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Sample records for acute toxicity skin

  1. Acute methyl salicylate toxicity complicating herbal skin treatment for psoriasis.

    PubMed

    Bell, Anthony J; Duggin, Geoffrey

    2002-06-01

    We present an interesting case of salicylism arising from the use of methyl salicylate as part of a herbal skin cream for the treatment of psoriasis. A 40-year-old man became quite suddenly and acutely unwell after receiving treatment from an unregistered naturopath. Methyl salicylate (Oil of Wintergreen) is widely available in many over the counter topical analgesic preparations and Chinese medicated oils. Transcutaneous absorption of the methyl salicylate was enhanced in this case due to the abnormal areas of skin and use of an occlusive dressing. The presence of tinnitus, vomiting, tachypnoea and typical acid/base disturbance allowed a diagnosis of salicylate toxicity to be made. Our patient had decontaminated his skin prior to presentation, limiting the extent of toxicity and was successfully treated with rehydration and establishment of good urine flow. PMID:12147116

  2. A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients

    PubMed Central

    Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.

    2013-01-01

    Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306

  3. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  4. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    PubMed

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  5. Beryllium Metal I. Experimental Results on Acute Oral Toxicity, Local Skin and Eye Effects, and Genotoxicity

    PubMed Central

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  6. Use of Axillary Deodorant and Effect on Acute Skin Toxicity During Radiotherapy for Breast Cancer: A Prospective Randomized Noninferiority Trial

    SciTech Connect

    Theberge, Valerie; Harel, Francois; Dagnault, Anne

    2009-11-15

    Purpose: To prospectively determine the effect of deodorant use on acute skin toxicity and quality of life during breast radiotherapy (RT). Methods and Materials: Before breast RT, 84 patients were randomly assigned to the deodorant group (n = 40) or the no-deodorant group (n = 44). The patients were stratified by axillary RT and previous chemotherapy. Toxicity evaluations were always performed by the principal investigator, who was unaware of the group assignment, at the end of RT and 2 weeks after completion using the Radiation Therapy Oncology Group acute skin toxicity criteria. Symptoms of acute skin toxicity (i.e., discomfort, pain, pruritus, sweating) and quality of life were self-evaluated. For each criterion, the point estimate of rate difference with the 95% one-sided upper confidence limit was computed. To claim noninferiority owing to deodorant use, the 95% one-sided upper confidence limit had to be lower than the noninferiority margin, fixed to 12.8%. Results: In the deodorant vs. no-deodorant groups, Grade 2 axillary radiodermatitis occurred in 23% vs. 30%, respectively, satisfying the statistical criteria for noninferiority (p = .019). Grade 2 breast radiodermatitis occurred in 30% vs. 34% of the deodorant vs. no-deodorant groups, respectively, also satisfying the statistical criteria for noninferiority (p = .049). Similar results were observed for the self-reported evaluations. The deodorant group reported less sweating (18% vs. 39%, p = .032). No Grade 3 or 4 radiodermatitis was observed. Conclusion: According to our noninferiority margin definition, the occurrence of skin toxicity and its related symptoms were statistically equivalent in both groups. No evidence was found to prohibit deodorant use (notwithstanding the use of an antiperspirant with aluminum) during RT for breast cancer.

  7. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

    PubMed Central

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C.; Liu, Stanley K.

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  8. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model.

    PubMed

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C; Liu, Stanley K

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  9. Standard or hypofractionated radiotherapy in the postoperative treatment of breast cancer: a retrospective analysis of acute skin toxicity and dose inhomogeneities

    PubMed Central

    2013-01-01

    Background To identify predictive factors of radiation-induced skin toxicity in breast cancer patients by the analysis of dosimetric and clinical factors. Methods 339 patients treated between January 2007 and December 2010 are included in the present analysis. Whole breast irradiation was delivered with Conventional Fractionation (CF) (50Gy, 2.0/day, 25 fractions) and moderate Hypofractionated Schedule (HS) (44Gy, 2.75Gy/day, 16 fractions) followed by tumour bed boost. The impact of patient clinical features, systemic treatments and, in particular, dose inhomogeneities on the occurrence of different levels of skin reaction has been retrospectively evaluated. Results G2 and G3 acute skin toxicity were 42% and 13% in CF patients and 30% and 7.5% in HS patients respectively. The retrieval and revaluation of 200 treatment plans showed a strong correlation between areas close to the skin surface, with inhomogeneities >107% of the prescribed dose, and the desquamation areas as described in the clinical records. Conclusions In our experience dose inhomogeneity underneath G2 – G3 skin reactions seems to be the most important predictor for acute skin damage and in these patients more complex treatment techniques should be considered to avoid skin damage. Genetic polymorphisms too have to be investigated as possible promising candidates for predicting acute skin reactions. PMID:23651532

  10. Factors of influence on acute skin toxicity of breast cancer patients treated with standard three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery (BCS)

    PubMed Central

    2012-01-01

    Purpose/Objectives Standard 3D-CRT after BCS may cause skin toxicity with a wide range of intensity including acute effects like erythema or late effects. In order to reduce these side effects it is mandatory to identify potential factors of influence in breast cancer patients undergoing standard three-dimensional conformal radiation therapy (3D-CRT) of the breast and modern systemic therapy. Materials/Methods Between 2006 and 2010 a total of 211 breast cancer patients (median age 52,4 years, range 24–77) after BCS consecutively treated in our institution with 3D-CRT (50 Gy whole breast photon radiotherapy followed by 16 Gy electron boost to the tumorbed) were evaluated with special focus on documented skin toxicity at the end of the 50 Gy-course. Standardized photodocumentation of the treated breast was done in each patient lying on the linac table with arms elevated. Skin toxicity was documented according to the common toxicity criteria (CTC)-score. Potential influencing factors were classified in three groups: patient-specific (smoking, age, breast size, body mass index = BMI, allergies), tumor-specific (tumorsize) and treatment-specific factors (antihormonal therapy with tamoxifen or aromatase inhibitors, chemotherapy). Uni- and multivariate statistical analyses were done using IBM SPSS version 19. Results After 50 Gy 3D-CRT to the whole breast 28.9% of all 211 patients had no erythema, 62.2% showed erythema grade 1 (G1) and 8.5% erythema grade 2. None of the patients had grade 3/4 (G3/4) erythema. In univariate analyses a significant influence or trend on the development of acute skin toxicities (erythema G0 versus G1 versus G2) was observed for larger breast volumes (p=0,004), smoking during radiation therapy (p=0,064) and absence of allergies (p=0,014) as well as larger tumorsize (p=0,009) and antihormonal therapy (p=0.005). Neither patient age, BMI nor choice of chemotherapy showed any significant effect on higher grade toxicity. In the multivariate

  11. Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus.

    PubMed

    Russi, Elvio G; Moretto, Francesco; Rampino, Monica; Benasso, Marco; Bacigalupo, Almalina; De Sanctis, Vitaliana; Numico, Gianmauro; Bossi, Paolo; Buglione, Michela; Lombardo, Antonino; Airoldi, Mario; Merlano, Marco C; Licitra, Lisa; Denaro, Nerina; Pergolizzi, Stefano; Pinto, Carmine; Bensadoun, Renè-Jean; Girolomoni, Giampiero; Langendijk, Johannes A

    2015-10-01

    The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics. PMID:26187236

  12. Acute toxicity and primary irritancy of alkylalkanolamines.

    PubMed

    Ballantyne, B; Leung, H W

    1996-12-01

    The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures. PMID:8948072

  13. [Acute toxic pneumopathies].

    PubMed

    Garnier, R

    1998-06-15

    The nature and extent of the acute injury due to toxic inhalants depend on the inhalant's solubility in water pH and chemical reactivity, on the aerodynamic diameter of particles (when the inhalant is an aerosol), and on the degree of exposure. Initial signs and symptoms indicate upper airways and bronchial irritation. Laryngeal oedema and (or) severe bronchospasm may be rapidly lethal. After cessation of exposure a transient improvement is generally observed; however a delayed pulmonary oedema may occur within the first 48 hours. On the following days, bacterial surinfection is a common complication. Possible long-term sequelae are reactive airways dysfunction syndrome and bronchiolitis obliterans. PMID:9781191

  14. Acute toxicity of gasoline and some additives

    SciTech Connect

    Reese, E.; Kimbrough, R.D.

    1993-12-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. 128 refs., 7 tabs.

  15. Acute toxicity of gasoline and some additives.

    PubMed Central

    Reese, E; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

  16. Acute Methylenedioxypyrovalerone Toxicity.

    PubMed

    Froberg, Blake A; Levine, Michael; Beuhler, Michael C; Judge, Bryan S; Moore, Philip W; Engebretsen, Kristin M; Mckeown, Nathanael J; Rosenbaum, Christopher D; Young, Amy C; Rusyniak, Daniel E

    2015-06-01

    The objective of this study was to characterize the acute clinical effects, laboratory findings, complications, and disposition of patients presenting to the hospital after abusing synthetic cathinone. We conducted a retrospective multicenter case series of patients with synthetic cathinone abuse by searching for the terms bath salts, MDPV, methylenedioxypyrovalerone, mephedrone, methcathinone, methylone, methedrone, and cathinone within the "agent" field of a national clinical toxicology database (ToxIC). The medical records of these patients were obtained and abstracted by investigators at each study site. Patients with confirmatory testing that identified a synthetic cathinone in either blood or urine were included in the series. Patients who had either an undetectable synthetic cathinone test or no confirmatory testing were excluded. A data abstraction sheet was used to obtain information on each patient. We entered data into an Excel spreadsheet and calculated descriptive statistics. We identified 23 patients with confirmed synthetic cathinone exposure--all were positive for methylenedioxyprovalerone (MDPV). Eighty-three percent were male and 74 % had recreational intent. The most common reported clinical effects were tachycardia (74 %), agitation (65 %), and sympathomimetic syndrome (65 %). Acidosis was the most common laboratory abnormality (43 %). Seventy-eight percent of patients were treated with benzodiazepines and 30 % were intubated. Ninety-six percent of patients were hospitalized and 87 % were admitted to the ICU. The majority (61 %) of patients was discharged home but 30 % required inpatient psychiatric care. There was one death in our series. The majority of patients presenting to the hospital after abusing MDPV have severe sympathomimetic findings requiring hospitalization. A number of these patients require inpatient psychiatric care after their acute presentation. PMID:25468313

  17. [Imaging in acute toxic encephalopathy].

    PubMed

    Dietemann, J-L; Botelho, C; Nogueira, T; Vargas, M I; Audibert, C; Abu Eid, M; Bogorin, A; Bernardo, R; Jacques, C; Kremer, S; Zöllner, G

    2004-09-01

    Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...). PMID:15545943

  18. Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase III Double-Blind, Randomized Trial From the North Central Cancer Treatment Group N06C4

    SciTech Connect

    Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

    2011-04-01

    Purpose: A two-arm, double-blind, randomized trial was performed to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials: Patients with ductal carcinoma in situ or invasive breast carcinoma who were undergoing external beam radiotherapy to the breast or chest wall were randomly assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was the provider-assessed maximal grade of Common Terminology Criteria for Adverse Events, version 3.0, radiation dermatitis. The secondary endpoints included provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or greater radiation dermatitis and adverse event monitoring. The patient-reported outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and a quality-of-life self-assessment. An assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results: A total of 176 patients were enrolled between September 21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no difference in the mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for Adverse Events toxicity was greater in the placebo group (p = .04), primarily from pruritus. For the patient-reported outcome measures, the maximum Skindex-16 score for the MMF group showed less itching (p = .008), less irritation (p = .01), less symptom persistence or recurrence (p = .02), and less annoyance with skin problems (p = .04). The group's maximal Skin Toxicity Assessment Tool score showed less burning sensation (p = .02) and less itching (p = .002). Conclusion: Patients receiving daily MMF during radiotherapy might experience reduced acute skin toxicity compared with patients receiving placebo.

  19. Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase 3 Double-Blind, Randomized Trial from the North Central Cancer Treatment Group N06C4

    PubMed Central

    Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

    2010-01-01

    Purpose A 2-arm, double-blinded, randomized trial to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma receiving external beam radiotherapy to breast or chest wall were randomly assigned to daily apply 0.1% MMF or placebo cream. Primary study end point was provider-assessed maximum grade of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation dermatitis. Secondary end points included provider-assessed CTCAE grade 3 or greater radiation dermatitis and adverse-event monitoring. Patient-reported outcome (PRO) measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and quality of life self-assessment. Assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results In total, 176 patients were enrolled from September 21, 2007 through December 7, 2007. The provider-assessed primary end point showed no difference in mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs 1.3 for placebo; P=.18). CTCAE toxicity was greater in placebo group (P=.04), primarily from pruritus. For PRO measures, the maximum Skindex-16 score for MMF group showed less itching (P=.008), less irritation (P=.01), less symptom persistence or recurrence (P=.02), and less annoyance with skin problems (P=.04); the group's maximum Skin Toxicity Assessment Tool score showed less burning sensation (P=.02) and less itching (P=.002). Conclusion Patients receiving daily MMF during radiotherapy may experience reduced acute skin toxicity in comparison to placebo. PMID:20800381

  20. Structural elucidation and estimation of the acute toxicity of the major UV-visible photoproduct of fludioxonil - detection in both skin and flesh samples of grape.

    PubMed

    Lassalle, Yannick; Nicol, Édith; Genty, Christophe; Bourcier, Sophie; Bouchonnet, Stéphane

    2015-06-01

    Ultraviolet (UV)-visible irradiation of fludioxonil was investigated with two photoreactors using either a mercury or xenon vapor lamp. In both cases, it led to the formation of only one photoproduct in significant amount: 2-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)-2-(nitrosomethylene)-4-oxobutanenitrile, which has been characterized using Liquid Chromatography - High Resolution - Tandem Mass Spectrometry (LC-HR-MS/MS) coupling. A photolysis pathway has been proposed to rationalize its formation in degassed water. In vitro bioassays on Vibrio fischeri bacteria showed that UV-vis irradiation of an aqueous solution of fludioxonil significantly increases its toxicity. Because no other by-product was detected in significant amount, the photoproduct mentioned above may be considered mainly responsible for this increase in toxicity. Grape berries treated with a 50 ppm aqueous solution of fludioxonil were submitted to UV-visible irradiation under laboratory conditions. The fungicide and photoproduct were detected in both skin and flesh of berries, even after they have been rinsed with water. The ability of the photoproduct to pass through the fruit skin is comparable with that of fludioxonil. These results are of concern for consumers because they mean that water tap rinsing does not lead to efficient removing of both compounds. PMID:26169141

  1. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

  2. Prospective Evaluation of Severe Skin Toxicity and Pain During Postmastectomy Radiation Therapy

    SciTech Connect

    Pignol, Jean-Philippe; Vu, Thi Trinh Thuc; Mitera, Gunita; Bosnic, Sandy; Verkooijen, Helena M.; Truong, Pauline

    2015-01-01

    Purpose: To prospectively capture acute toxicities and pain associated with postmastectomy radiation therapy (PMRT), to analyze patient and treatment risk factors for severe side effects. Methods and Materials: Women referred for PMRT were prospectively enrolled and assessed weekly during and after radiation therapy. The endpoint included severe National Cancer Institute Common Terminology Criteria for Adverse Effects grade 3 moist desquamation, other skin symptoms, and pain. Results: Of 257 patients, 73 (28.4%) experienced extensive moist desquamation, 84 (32.7%) Common Terminology Criteria for Adverse Effects skin toxicity grade 3, and 57 (22.2%) a pain impacting on daily life activities. Among symptoms only grade 3 moist desquamation was significantly associated with severe pain (P<.001). On multivariate analysis, smoking, high-energy photons, and skin bolus were significantly associated with severe moist desquamation. Skin toxicity doubled for smokers, with 40% severe pain, 48% grade 3 moist desquamation, and 64% grade 3 skin toxicity. Without skin bolus 4.2% had severe pain, none moist desquamation, and 2.1% grade 3 skin toxicity. When skin bolus was used on alternate days, the frequency increased to 15% for pain, 22% for moist desquamation, and 26% for grade 3 skin toxicity. When bolus was used daily, 32% had pain, 41% moist desquamation, and 47% grade 3 skin toxicity. Symptoms peaked 1 to 2 weeks after the end of PMRT. Conclusions: The present cohort study suggests excessive radiation toxicity after PMRT. Among factors associated with an increase of toxicity are smoking habits and the use of skin bolus.

  3. Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

    PubMed Central

    Kouloulias, Vassilis; Zygogianni, Anna; Kypraiou, Efrosini; Georgakopoulos, John; Thrapsanioti, Zoi; Beli, Ivelina; Mosa, Eftychia; Psyrri, Amanta; Antypas, Christos; Armbilia, Christina; Tolia, Maria; Platoni, Kalliopi; Papadimitriou, Christos; Arkadopoulos, Nikolaos; Gennatas, Costas; Zografos, George; Kyrgias, George; Dilvoi, Maria; Patatoucas, George; Kelekis, Nikolaos; Kouvaris, John

    2014-01-01

    AIM: To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS: We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS: The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ2 test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ2 test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION: There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions. PMID:25405195

  4. Evaluation of acute skin irritation and phototoxicity by aqueous and ethanol fractions of Angelica keiskei

    PubMed Central

    LEE, SANG-HAN

    2013-01-01

    In this study, to assess whether aqueous and ethanol fractions of Angelica keiskei induce acute skin irritation and phototoxicity, acute skin irritancy and phototoxicity tests were performed. The skin of rabbits or guinea pigs was treated with these fractions (100 mg/dose) and whether the animals sustained significant skin damage was determined. The data demonstrated that the aqueous and ethanol fractions of Angelica keiskei did not induce acute toxicity in the skin of the animals, as assessed by anatomical and pathological observations. The results from the present study suggest that these aqueous and ethanol fractions of Angelica keiskei have promising potential uses as cosmetic ingredients that do not induce significant levels of skin irritation or phototoxicity. PMID:23251240

  5. Acute and environmental toxicity studies with hexazinone.

    PubMed

    Kennedy, G L

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6479506

  6. Acute aquatic toxicity of biodiesel fuels

    SciTech Connect

    Wright, B.; Haws, R.; Little, D.; Reese, D.; Peterson, C.; Moeller, G.

    1995-12-31

    This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in a flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.

  7. Oritavancin for acute bacterial skin and skin structure infection

    PubMed Central

    Messina, Julia A.; Fowler, Vance G.; Corey, G. Ralph

    2015-01-01

    Introduction Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapidly bactericidal agent approved for the treatment of ABSSSI. Its prolonged half-life with one-time intravenous (IV) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of IV therapy. Areas covered This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/ pharmacokinetics, efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability. Expert Opinion If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged IV therapy, it will be sought as an alternative antibiotic therapy for ABSSSI. In addition, further clinical data demonstrating efficacy in gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market. PMID:25803197

  8. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    PubMed Central

    Korani, M; Rezayat, SM; Gilani, K; Bidgoli, S Arbabi; Adeli, S

    2011-01-01

    Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 μg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 μg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner. PMID:21720498

  9. [An acute toxicity study of bromantane].

    PubMed

    Bugaeva, L I; Verovskiĭ, V E; Iezhitsa, I N; Spasov, A A

    2000-01-01

    The toxicity of bromantan was evaluated by conventional acute tests (according to Belen'kiĭ) and by the behavioral activity data (according to Irvin). A method of integral graphical representation of the behavioral activity data is suggested, according to which the results are plotted as a "dose trajectory." Using the dose trajectory constructed for bromantan, the levels of therapeutic, toxic, and lethal doses were calculated. It was established that catecholaminergic effects account for the mechanism of therapeutic action of bromantan, while cholinergic effects determine the drug action in toxic doses. PMID:10763112

  10. ACUTE TOXICITY OF AMMONIA TO FATHEAD MINNOWS

    EPA Science Inventory

    The acute toxicity of ammonia to fathead minnows Pimephales promelas was measured in 35, 96-hour, flow-through tests. The fish were from both wild and hatchery-reared stocks, and ranged in size from 0.1 to 2.3 g. The 96-hour median lethal concentrations (LC50) ranged from 0.75 to...

  11. ACUTE TOXICITY OF AMMONIA TO RAINBOW TROUT

    EPA Science Inventory

    The acute toxicity of ammonia to hatchery-reared rainbow trout Salmo gairdneri was measured in 86 flow-through tests, 96 hours to 35 days long. Fish ranged in age from 1-day-old fry (<0.1 g) to 4-year-old adults (2.6 kg). The 96-hour median lethal concentrations (96-hour LC50) ra...

  12. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  13. Acute aquatic toxicity of alkyl phenol ethoxylates

    SciTech Connect

    Schueuermann G2 )

    1991-04-01

    The recently derived log Kow (octanol/water partition coefficient in logarithmic form) increment for a nonterminal oxyethylene unit was used to calculate a quantitative structure-activity relationships for literature data on the acute crustacean toxicity of polyoxyethylene surfactants. The resulting log Kow regression parameters are between the corresponding values for nonpolar and polar narcosis, which supports an interpretation of the surfactants' aquatic toxicity on the basis of another distinct mode of action. Furthermore, a comparison with calculated water solubility data indicates that for log Kow greater than 5 an aquatic toxicity decrease due to a solubility limit is expected, which gets support from two other sets on toxicity data of nonyl phenol polyethoxylates.

  14. Acute inhalation toxicity of carbonyl sulfide

    SciTech Connect

    Benson, J.M.; Hahn, F.F.; Barr, E.B.

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  15. Skin temperature recording with phosphors: toxicity studies on animals.

    PubMed

    Derse, P H; Alt, L L

    1966-08-20

    In a previous communication in this journal, a method was described for converting invisible thermal patterns of the human skin into a detailed visible picture. At that time, the question of possible toxicity of the thermographic phosphor was raised. Toxicity studies conducted on laboratory animals indicate that the probability of toxic side reactions resulting from the use of zinc-cadmium sulfide phosphor spray is very low. PMID:5943198

  16. Comparison of Provider-Assessed and Patient-Reported Outcome Measures of Acute Skin Toxicity During a Phase III Trial of Mometasone Cream Versus Placebo During Breast Radiotherapy: The North Central Cancer Treatment Group (N06C4)

    SciTech Connect

    Neben-Wittich, Michelle A.; Atherton, Pamela J.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Loprinzi, Charles L.; Burger, Kelli N.; Martenson, James A.; Miller, Robert C.

    2011-10-01

    Purpose: Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials: Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5-0.7, moderate; and >0.7, strong. Results: CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions: The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

  17. Acute and subchronic toxicity of sucralose.

    PubMed

    Goldsmith, L A

    2000-01-01

    The toxicity of sucralose has been evaluated in acute and subchronic toxicity studies. Acute oral toxicity studies in male and female mice and male rats documented no deaths or treatment-related signs at doses of 16g/kg for mice and 10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8 weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794-6406. There were no toxicologically significant effects observed at the 1.0% or 2.5% dietary levels. However, decreases in food consumption, body weight gain and selected organ weights and ratios as well as splenic and thymic histopathologic changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and female rats for 26 weeks investigated further the observations from the dietary study as well as general subchronic toxicity. The gavage study documented no sucralose-related toxicity. These results implicate the reduced palatability and digestibility of diets containing high concentrations of sucralose seen in the diet study as the cause for the decreased food consumption and other accompanying alterations. Dose selection for chronic toxicity studies in rats took into consideration the effect of high concentrations of sucralose on digestion and food consumption and the limitations that would be imposed on subsequent studies. In male and female dogs, no sucralose-related adverse effects were observed following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving doses of approximately 90, 300 and 900mg/kg/day respectively. These studies establish that sucralose is non-toxic in rodents following acute oral administration. The rat no-observed-adverse-effect level ranged between 2.5 and 5.0% following subchronic dietary administration. A 3.0% dietary concentration equivalent to a dose of 900mg

  18. Acute toxicity of selected crude and refined shale oil derived and petroleum-derived substances

    SciTech Connect

    Smith, L.H.; Haschek, W.M.; Witschi, H.

    1980-01-01

    General information was obtained on the toxicity of selected samples of crude Paraho shale oil and some of its derivatives, some crude petroleums, and 3 refined petroleum products. Five tests were used to determine the acute toxicity of these substances: acute lethality in mice following oral or intraperitoneal administration of a single dose; acute dermal toxicity of a single dose in rats; delayed-type allergic contact hypersensitivity in guinea pigs; primary eye irritation and primary skin irritation of a single dose in rabbits. Histopathologic changes induced in mice following intraperitoneal injection of a single large dose of crude shale oil and two of its hydrotreated derivatives were examined. Studies also have been initiated to examine the tumor inducing potential of selected samples. The test system used was the mouse lung adenoma bioassay. The present report describes our findings and shows that all compounds tested have very low or no acute toxic effects in laboratory animals.

  19. Measuring the acute toxicity of estuarine sediments

    SciTech Connect

    DeWitt, T.H.; Swartz, R.C.; Lanberson, J.O.

    1989-01-01

    Estuarine sediments frequently are repositories and sources of anthropogenic contaminants. Toxicity is one method of assessing the environmental quality of sediments, yet because of the extreme range of salinities that characterize estuaries few infaunal organisms have both the physiological tolerance and sensitivity to chemical contaminants to serve in estuarine sediment toxicity tests. The study describes research on the estuarine burrowing amphipod, Eohaustorius estuarius Bosworth, 1973, whose survival was >95% in control sediments across a 2 to 28% salinity range over 10-d periods. E. estuarius also was acutely sensitive to low sediment concentrations of the polycyclic aromatic hydrocarbon, fluoranthene (LC50 approximately = 10.6 mg/kg), and its sensitivity to fluoranthene was not affected by salinity. E. estuarius was almost as sensitive as Rhepoxynius abronius to fluoranthene and to field-collected sediments from Puget Sound urban and industrial bays. E. estuarius was also more tolerant of very fine, uncontaminated sediments than R. abronius. Furthermore, E. estuarius was more sensitive to sediments spiked with fluoranthene than the freshwater amphipod, Hyalella azteca. E. estuarius, and possibly other estuarine haustoriid species, appears to be an excellent candidate for testing the acute toxicity if estuarine and marine sediments.

  20. AUTOMATED SKIN SEGMENTATION IN ULTRASONIC EVALUATION OF SKIN TOXICITY IN BREAST CANCER RADIOTHERAPY

    PubMed Central

    Gao, Yi; Tannenbaum, Allen; Chen, Hao; Torres, Mylin; Yoshida, Emi; Yang, Xiaofeng; Wang, Yuefeng; Curran, Walter; Liu, Tian

    2013-01-01

    Skin toxicity is the most common side effect of breast cancer radiotherapy and impairs the quality of life of many breast cancer survivors. We, along with other researchers, have recently found quantitative ultrasound to be effective as a skin toxicity assessment tool. Although more reliable than standard clinical evaluations (visual observation and palpation), the current procedure for ultrasound-based skin toxicity measurements requires manual delineation of the skin layers (i.e., epidermis-dermis and dermis-hypodermis interfaces) on each ultrasound B-mode image. Manual skin segmentation is time consuming and subjective. Moreover, radiation-induced skin injury may decrease image contrast between the dermis and hypodermis, which increases the difficulty of delineation. Therefore, we have developed an automatic skin segmentation tool (ASST) based on the active contour model with two significant modifications: (i) The proposed algorithm introduces a novel dual-curve scheme for the double skin layer extraction, as opposed to the original single active contour method. (ii) The proposed algorithm is based on a geometric contour framework as opposed to the previous parametric algorithm. This ASST algorithm was tested on a breast cancer image database of 730 ultrasound breast images (73 ultrasound studies of 23 patients). We compared skin segmentation results obtained with the ASST with manual contours performed by two physicians. The average percentage differences in skin thickness between the ASST measurement and that of each physician were less than 5% (4.8 ± 17.8% and −3.8 ± 21.1%, respectively). In summary, we have developed an automatic skin segmentation method that ensures objective assessment of radiation-induced changes in skin thickness. Our ultrasound technology offers a unique opportunity to quantify tissue injury in a more meaningful and reproducible manner than the subjective assessments currently employed in the clinic. PMID:23993172

  1. 40 CFR 797.1400 - Fish acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish acute toxicity test. 797.1400 Section 797.1400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1400 Fish acute toxicity test. (a) Purpose. This...

  2. 40 CFR 797.1300 - Daphnid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Daphnid acute toxicity test. 797.1300 Section 797.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1300 Daphnid acute toxicity test. (a) Purpose....

  3. 40 CFR 795.120 - Gammarid acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Gammarid acute toxicity test. 795.120 Section 795.120 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional Environmental Effects Guidelines § 795.120 Gammarid acute toxicity test....

  4. 40 CFR 797.1930 - Mysid shrimp acute toxicity test.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Mysid shrimp acute toxicity test. 797.1930 Section 797.1930 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1930 Mysid shrimp acute toxicity test. (a)...

  5. 40 CFR 797.1050 - Algal acute toxicity test.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Algal acute toxicity test. 797.1050 Section 797.1050 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) ENVIRONMENTAL EFFECTS TESTING GUIDELINES Aquatic Guidelines § 797.1050 Algal acute toxicity test. (a) Purpose. The...

  6. Acute myelomonocytic leukaemia presenting as xanthomatous skin eruption

    PubMed Central

    O'Donnell, JR; Tansey, P; Chung, P; Burnett, AK; Thomson, J; McDonald, GA

    1982-01-01

    A case of acute myelomonocytic leukaemia (AMMOL) is reported in which skin infiltration with xanthomatous nodules was the presenting feature. The histological, including ultrastructural, appearances are described. Images PMID:6958680

  7. Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

    SciTech Connect

    Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

    1989-12-01

    The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

  8. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    PubMed

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements. PMID:20144136

  9. COMPARISON OF PROVIDER-ASSESSED AND PATIENT-REPORTED OUTCOME MEASURES OF ACUTE SKIN TOXICITY DURING A PHASE III TRIAL OF MOMETASONE CREAM VERSUS PLACEBO DURING BREAST RADIOTHERAPY: THE NORTH CENTRAL CANCER TREATMENT GROUP (N06C4)

    PubMed Central

    Neben-Wittich, Michelle A.; Atherton, Pamela J.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Loprinzi, Charles L.; Burger, Kelli N.; Martenson, James A.; Miller, Robert C.

    2012-01-01

    Purpose Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider–assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5–0.7, moderate; and >0.7, strong. Results CTCAE dermatitis moderately correlated with STATerythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity. PMID:20888137

  10. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  11. [Acute onset pulmonary toxicity associated to amiodarone].

    PubMed

    Ferreira, Pedro Gonçalo; Saraiva, Fátima; Carreira, Cláudia

    2012-01-01

    Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome. PMID:23211207

  12. Complementary and alternative medicine in reducing radiation-induced skin toxicity.

    PubMed

    Hu, Jennifer J; Cui, Tengjiao; Rodriguez-Gil, Jorge L; Allen, Glenn O; Li, Jie; Takita, Cristiane; Lally, Brian E

    2014-08-01

    Radiation therapy-induced acute and late effects, particularly skin toxicities, have significant impact on cancer patients' quality of life and long-term survival. To date, no effective topical agents have been routinely used in the clinical setting to prevent skin toxicity. Using SKH-hr1 hairless mice, we investigated two complementary and alternative medicine in their effects on inflammation and ionizing radiation (IR)-induced skin toxicity: Calendula officinalis (CO) and Ching Wan Hung (CWH). They were applied immediately following each IR dosing of 10 Gy/day for 4 days. Skin toxicity and inflammatory factors were evaluated at multiple time points up to 15 days post-radiation. Serum interleukin (IL)-1α, monocyte chemotactic protein-1 (MCP1), keratinocyte-derived chemokine (KC), and granulocyte colony-stimulating factor (G-CSF) were significantly induced by radiation. Both CO and CWH significantly inhibited IR-induced MCP1 (p < 0.01), KC (p < 0.05), and G-CSF (p < 0.001). IR-induced erythema and blood vessel dilation were significantly reduced by CWH (p < 0.001) but not by CO at day 10 post-IR. Both agents inhibited IR-induced IL-1α (p < 0.01), MCP1 (p < 0.05), and vascular endothelial growth factor (p < 0.05). There were continuous inhibitory effects of CWH on IR-induced skin toxicities and inflammation. In contrast, CO treatment resulted in skin reactions compared to IR alone. Our results suggest that both CO and CWH reduce IR-induced inflammation and CWH reduced IR-induced erythema. In summary, CWH showed promising effects in reducing IR-related inflammation and skin toxicities, and future proof-of-principal testing in humans will be critical in evaluating its potential application in preventing IR-induced skin toxicities. PMID:24792319

  13. Acute toxicity of methanol to mytilus edulis

    SciTech Connect

    Helmstetter, A.; Gamerdinger, A.P.; Pruell, R.J.

    1996-12-31

    Methanol is being promoted as an alternative fuel because of the clean air benefits of reduced carbon monoxide and other by-product emissions. In the event of an accidental spill or leakage from a storage tank, there is limited data available on the impact of alternative fuels on marine ecosystems. Before considering the impact of methanol on ecosystem processes, it is necessary to establish the acute toxicity. The blue mussel (Mytilus edulis) was selected for study because of its use as an indicator species of marine ecosystem health (Widdows and Donkin 1992). Our primary objective was to determine the LC-50 value of methanol to adult Mytilus edulis. We also not sublethal effects that were observed during the course of the 96-hr exposure. 16 refs., 1 fig. 3 tabs.

  14. Electrophiles and acute toxicity to fish.

    PubMed Central

    Hermens, J L

    1990-01-01

    Effect concentrations in fish LC50 tests with directly acting electrophiles are lower than those of unreactive chemicals that act by narcosis. LC50 values of more hydrophobic reactive chemicals tend to approach those of unreactive chemicals. Quantitative studies to correlate fish LC50 data to physical-chemical properties indicate that LC50 values of reactive chemicals depend on hydrophobicity as well as chemical reactivity. In this paper, several examples will be given of chemical structures that are known as direct electrophiles. This classification might be useful to identify chemicals that are more effective at lower concentrations than unreactive compounds. Chemicals that require bioactivation are not included because almost no information is available on the influence of bioactivation on acute toxic effects in aquatic organisms. PMID:2269228

  15. ACUTE AND CHRONIC TOXICITY STUDIES WITH MONOCHLOROBENZENE IN RAINBOW TROUT

    EPA Science Inventory

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity was monitored...

  16. Exploring waiving opportunities for mammalian acute systemic toxicity tests.

    PubMed

    Graepel, Rabea; Asturiol, David; Prieto, Pilar; Worth, Andrew P

    2016-07-01

    A survey was carried out to explore opportunities for waiving mammalian acute systemic toxicity tests. We were interested in finding out whether data from a sub-acute toxicity test could be used to predict the outcome of an acute systemic toxicity test. The survey was directed at experts in the field of toxicity testing, and was carried out in the context of the upcoming 2018 final registration deadline for chemicals under the EU REACH Regulation. In addition to the survey, a retrospective data analysis of chemicals that had already been registered with the European Chemicals Agency, and for which both acute and sub-acute toxicity data were available, was carried out. This data analysis was focused on chemicals that were administered via the oral route. The answers to the questionnaire showed a willingness to adopt waiving opportunities. In addition, the responses showed that data from a sub-acute toxicity test or dose-range finding study might be useful for predicting chemicals that do not require classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However, with the exception of substances that fall into the non-classified category, it is difficult to predict current acute oral toxicity categories. PMID:27494626

  17. [Acute toxicity testing (LD50) of Chinese mineral drugs].

    PubMed

    Yue, W; Liu, W H; Wang, L F; Fu, S X; Li, Y S; Kong, Z K; Tang, Z X; Chen, Z L

    1989-02-01

    Acute toxicity and LD50 of 62 mineral drugs were determined by ig, ip or iv in mice, in order to provide some guidelines for safety in clinical use, as well as for pharmacological and toxicological studies. In the present investigation, the difference in the acute toxicity and LD50 between raw drugs and medicines prepared by roasting is explained. PMID:2506896

  18. Oral Toxicity Study and Skin Sensitization Test of a Cricket.

    PubMed

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-04-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  19. Oral Toxicity Study and Skin Sensitization Test of a Cricket

    PubMed Central

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-01-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  20. Polymorphic Variants in Oxidative Stress Genes and Acute Toxicity in Breast Cancer Patients Receiving Radiotherapy

    PubMed Central

    Córdoba, Elisa Eugenia; Abba, Martín Carlos; Lacunza, Ezequiel; Fernánde, Eduardo; Güerci, Alba Mabel

    2016-01-01

    Purpose Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)–related response to radiotherapy injury in breast cancer patients undergoing RT. Materials and Methods Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction–based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects. Results Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment. Conclusion The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait. PMID:26790968

  1. Acute oral toxicity test of chemical compounds in silkworms.

    PubMed

    Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

    2016-02-01

    This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals. PMID:26971557

  2. Dalbavancin for the treatment of acute bacterial skin and skin structure infections.

    PubMed

    Esposito, Silvano; Noviello, Silvana; Leone, Sebastiano

    2015-12-01

    Dalbavancin is a novel parenteral lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults. Dalbavancin is highly active against common Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has a prolonged half-life that allows for once weekly dosing. Phase III trials have demonstrated non-inferiority compared with vancomycin/linezolid in the treatment of ABSSSIs, including those sustained by MRSA. PMID:26700080

  3. Assessment of dermal toxicity of nanosilica using cultured keratinocytes, a human skin equivalent model and an in vivo model.

    PubMed

    Park, Yoon-Hee; Kim, Ji Na; Jeong, Sang Hoon; Choi, Jae Eun; Lee, Seung-Ho; Choi, Byeong Hyeok; Lee, Jung Pyo; Sohn, Kyung Hee; Park, Kui Lea; Kim, Meyoung-Kon; Son, Sang Wook

    2010-01-12

    Assessments of skin irritation potentials are important aspects of the development of nanotechnology. Nanosilica is currently being widely used for commercial purposes, but little literature is available on its skin toxicity and irritation potential. This study was designed to determine whether nanosilica has the potential to cause acute cutaneous toxicity, using cultured HaCaT keratinocytes (CHK), a human skin equivalent model (HSEM), and invivo model. Nanosilica was characterized by scanning electron microscopy. We evaluated the cytotoxic effects of nanosilica on CHKs and the HSEM. In addition, we also investigated whether two commercially available nanosilicas with different sizes (7 and 10-20 nm) have different effects. To confirm invitro results, we evaluated the irritation potentials of nanosilicas on rabbit skin. Nanosilicas reduced the cell viabilities of CHKs in a dose-dependent manner. However, the HSEM revealed no irritation at 500 microg/ml of nanosilica. Furthermore, this result concurred with Draize skin irritation test findings. The present study data indicate that nanosilica does not cause acute cutaneous irritation. Furthermore, this study shows that the HSEM used provides more useful screening data than the conventional cell culture model on the relative toxicities of NPs. PMID:19850098

  4. ACUTE AND CHRONIC TOXICITY OF CHLORDANE TO FISH AND INVERTEBRATES

    EPA Science Inventory

    The acute and chronic toxicity of technical chlordane to bluegill (Lepomis macrochirus), fathead minnow (Pimephales promelas), brook trout (Salvelinus fontinalis), Daphnia magna, Hyallela azteca, and Chironomus No. 51 were determined with flow-through conditions. The purpose was ...

  5. Acute toxicity of dietary polybrominated biphenyls in Bobwhite Quail

    SciTech Connect

    Cottrell, W.O.; Ringer, R.K.; Babish, J.G.

    1984-09-01

    This investigation was undertaken to study the acute oral toxicity of PBB to Bobwhite Quail (Colinus virginianus). The median lethal dietary concentration (LC/sub 56/) of PBB was determined over 8 days and clinical signs of intoxication are described.

  6. METHODS FOR AQUATIC TOXICITY IDENTIFICATION EVALUATIONS: PHASE III TOXICITY CONFIRMATION PROCEDURES FOR SAMPLES EXHIBITING ACUTE AND CHRONIC TOXICITY

    EPA Science Inventory

    In 1989, the guidance document for acutely toxic effluents titled Methods for Aquatic Toxicity Identification Evaluations: Phase III Toxicity Confirmation Procedures was published (EPA, 1989D)This manual and its companion documents (EPA, 1991A; EPA, 1992; EPA, 1993A) are intended...

  7. Acute inhalation toxicity of silver nanoparticles.

    PubMed

    Sung, Jae Hyuck; Ji, Jun Ho; Song, Kyung Seuk; Lee, Ji Hyun; Choi, Kyung Hee; Lee, Sang Hee; Yu, Il Je

    2011-03-01

    The acute inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Seven-week-old rats, weighing approximately 218 g (males) and 153 g (females), were divided into four groups (five rats in each group): fresh-air control, low-dose (0.94 × 10(6) particle/cm(3), 76 µg/m(3)), middle-dose (1.64 × 10(6) particle/ cm(3), 135 µg/m( 3)), and high-dose (3.08 × 10(6) particle/cm(3), 750 µg/m(3)). The animals were then exposed to silver nanoparticles (average diameter 18-20 nm) for 4 hours in a whole-body inhalation chamber. The experiment was conducted following Organization Economic Cooperation and Development (OECD) test guideline 403 with the application of good laboratory practice (GLP). In addition to mortality and clinical observations, the body weights, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, and the organ weights measured. The lung function was also measured twice per week after the initial 4-hour exposure. No significant body weight changes or clinical changes were found during the 2-week observation period. The lung function tests also indicated no significant difference between the fresh air control and the exposed groups. Thus, LC50 silver nanoparticles are suggested for higher than 3.1 × 10(6) particles/cm(3) (750 µg/m(3)). PMID:20870693

  8. Skin temperature reveals the intensity of acute stress.

    PubMed

    Herborn, Katherine A; Graves, James L; Jerem, Paul; Evans, Neil P; Nager, Ruedi; McCafferty, Dominic J; McKeegan, Dorothy E F

    2015-12-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. PMID:26434785

  9. Skin temperature reveals the intensity of acute stress

    PubMed Central

    Herborn, Katherine A.; Graves, James L.; Jerem, Paul; Evans, Neil P.; Nager, Ruedi; McCafferty, Dominic J.; McKeegan, Dorothy E.F.

    2015-01-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. PMID:26434785

  10. Acute aquatic toxicity and biodegradation potential of biodiesel fuels

    SciTech Connect

    Haws, R.A.; Zhang, X.; Marshall, E.A.; Reese, D.L.; Peterson, C.L.; Moeller, G.

    1995-12-31

    Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicity tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.

  11. The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

    PubMed

    Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

    2014-12-01

    This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab. PMID:24930136

  12. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  13. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature.

    PubMed

    Salvo, N; Barnes, E; van Draanen, J; Stacey, E; Mitera, G; Breen, D; Giotis, A; Czarnota, G; Pang, J; De Angelis, C

    2010-08-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance-and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials.For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase II and phase III trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6).In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on

  14. ECVAM's ongoing activities in the area of acute oral toxicity.

    PubMed

    Kinsner-Ovaskainen, Agnieszka; Bulgheroni, Anna; Hartung, Thomas; Prieto, Pilar

    2009-12-01

    The 7th Amendment of the Cosmetics Directive (2003/15/EC) set up timelines for banning animal testing and marketing of cosmetic products and their ingredients tested on animals. For most of the human health effects, including acute toxicity, the deadline for these bans was in March 2009. Moreover, the new Regulation EC 1907/2006 on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) provided a strong impetus towards the application of alternative approaches to reduce the number of animals used for toxicological testing. Therefore, the European Centre for the Validation of Alternative Methods (ECVAM) is currently putting considerable effort into developing and validating alternative methods in the field of acute toxicity. The main activities in this area include: (1) the Integrated Project ACuteTox, funded by the European Commission's 6th Framework Programme in 2005 with the aim to develop and pre-validate a testing strategy to fully replace acute oral toxicity testing in vivo; (2) a follow-up validation study to assess the predictive capacity of the validated BALB/3T3 Neutral Red Uptake cytotoxicity assay to discriminate between toxic/hazardous (LD(50)<2,000 mg/kg) substances and substances not classified for acute toxicity (LD(50)>2,000 mg/kg); (3) an approach to identify compounds with LD(50)>2,000 mg/kg using information from 28-days repeated dose toxicity studies. PMID:19591916

  15. A comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; Schalie, W.H. van der; Leather, G.R.

    1995-05-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus calyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photobacterium phosphoreum--Microtox{reg_sign} test, and a mixture of bacterial species--the Polytox{reg_sign} test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriodaphnia dubia), green algae (Selenastrum capricornutum), fathead minnows (Pimephales promelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC50/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  16. Comparison of standard acute toxicity tests with rapid-screening toxicity tests

    SciTech Connect

    Toussaint, M.W.; Shedd, T.R.; VanDerSchal, W.H.; Leather, G.R.

    1995-10-01

    This study compared the relative sensitivity of five inexpensive, rapid toxicity tests to the sensitivity of five standard aquatic acute toxicity tests through literature review and testing. The rapid toxicity tests utilized organisms that require little culturing or handling prior to testing: a freshwater rotifer (Branchionus ccalyciflorus); brine shrimp (Artemia salina); lettuce (Lactuca sativa); and two microbial tests (Photo bacterium phosphoreum - Microtox test, and a mixture of bacterial species - the polytox test). Standard acute toxicity test species included water fleas (Daphnia magna and Ceriadaphnta dubia), green algae (Setenastrum capricarnutum), fathead minnows (Pimephalespromelas), and mysid shrimp (Mysidopsis bahia). Sensitivity comparisons between rapid and standard acute toxicity tests were based on LC5O/EC50 data from 11 test chemicals. Individually, the lettuce and rotifer tests ranked most similar in sensitivity to the standard tests, while Microtox fell just outside the range of sensitivities represented by the group of standard acute toxicity tests. The brine shrimp and Polytox tests were one or more orders of magnitude different from the standard acute toxicity tests for most compounds. The lettuce, rotifer, and Microtox tests could be used as a battery for preliminary toxicity screening of chemicals. Further evaluation of complex real-world environmental samples is recommended.

  17. Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

    USGS Publications Warehouse

    Dahlich, G.M.; Larson, R.E.; Gingerich, W.H.

    1982-01-01

    The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity. Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish. The LC50 of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.

  18. Towards a scheme of toxic equivalency factors (TEFs) for the acute toxicity of PAHs in sediment.

    PubMed

    Fisher, Tom T; Law, Robin J; Rumney, Heather S; Kirby, Mark F; Kelly, Carole

    2011-11-01

    Toxic equivalency factors/quotients (TEF/TEQs) express the toxicity of complex mixtures. For PAHs, TEF values are available for assessing their carcinogenic potential and are expressed as benzo[a]pyrene equivalents. This study develops a similar approach for their acute toxicity in sediments. Acute toxicity (10 day EC₅₀) values were generated using the marine amphipod Corophium volutator bioassay for twelve low molecular weight PAHs. The results ranged from 24 to > 1000 mg/Kg sediment dry weight for 4-methyldibenzothiophene and anthracene, respectively. Phenanthrene was used as the reference compound (TEF=1) and so the TEQ values derived are expressed as phenanthrene equivalents. In order to illustrate the applicability of this approach to the development of marine indicators we plotted TEQ values for acute toxicity to UK environmental monitoring data. Further work is required to validate the TEF values produced and to extend the TEQ approach to include a wider range of low molecular weight PAHs. PMID:21885125

  19. Acute toxicity of seeds of the sapodilla (Achras sapota L.).

    PubMed

    Singh, P D; Simon, W R; West, M E

    1984-01-01

    An aqueous extract of the sapodilla seed (Achras sapota L.) was acutely toxic to mice and rats (i.p. LD50 = 190 and 250 mg/kg, respectively) with symptoms of dyspnoea, apnoea and convulsions. Soxhlet extraction and chromatographic separation of the seed constituents yielded a brown amorphous solid containing saponin. This was heat-stable and toxic by the i.p. route (LD50 = 30-50 mg/kg) but non-toxic by the oral route in mice and rats. It is proposed that the toxicity of the sapodilla seed is due mainly to the saponin content. PMID:6719472

  20. Acute toxicity of 2-butyne-1,4-diol in laboratory animals.

    PubMed

    Jedrychowski, R A; Czajkowska, T; Stetkiewicz, J; Stetkiewicz, I

    1992-04-01

    Acute toxicity of 2-butyne-1,4-diol (BYD) was evaluated in laboratory animals. The evaluation involved acute oral and dermal toxicity in rats, dermal and ocular irritation in rabbits and skin sensitization in guinea pigs. The oral LD50 values for BYD were 132 mg kg-1 in male rats and 176 mg kg-1 in female rats. Post-mortem histology showed severe damage in lungs, liver and kidneys. In surviving rats, moderate to severe degenerative changes were observed in the liver but only mild lesions in the kidneys. In acute dermal toxicity studies the test chemical was applied either as a solid substance or as 40% aqueous solution at a dose of 5 g kg-1 for 24 h. Within 48 h of application of the diluted test material, half of the rats died. Liver and kidneys were the primary targets and different stages of degeneration, including necrosis, were observed. No deaths occurred after application of the solid substance. In rabbits, BYD was slightly irritant to skin and eyes. No allergic contact dermatitis was observed in guinea pigs. PMID:1556377

  1. Acute-toxicity evaluation of nitroaromatic compounds. Final report, 29 Sep 89-29 Sep 90

    SciTech Connect

    FitzGerald, G.B.; Austin, A.; DiGuilio, N.

    1991-03-01

    The nitroaromatics 1,3-dinitrobenzene (DNB), 1,2,5-trinitrobenzene (TNB) and N-methyl-n,2,4,6-tetranitroaniline (tetryl) have been detected as environmental contaminants of water and soil near production waste sites and at military test grounds. Acute toxicity evaluations were carried out with these compounds to develop environmental and health effects criteria. Dermal and eye irritation tests and acute dermal sensitization (Buehler) tests in guinea pigs were conducted according to EPA standard protocols. The sensitization tests showed that DNB and tetryl are not skin sensitizers while TNB caused a mild allergic reaction. None of these compounds produced skin irritation but positive (DNB) to severe (TNB, tetryl) eye irritation potentials were observed.

  2. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed. PMID:27084183

  3. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    SciTech Connect

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  4. Acute toxicity of trichloroethylene to saltwater organisms

    SciTech Connect

    Ward, G.S.; Tolmsoff, A.J.; Petrocelli, S.R.

    1986-12-01

    Trichloroethylene (TCE) is a chlorinated aliphatic hydrocarbon primarily utilized for vapor-phase degreasing in the fabricated metals industry. Other applications include cold-metal cleaning and use in the manufacture of organic chemicals. TCE enters the environment as a result of volatilization during its production and through its industrial uses. TCE has been detected in aquatic environments and organisms at part-per-trillion (pptr) concentrations. Although TCE is indicated to be widely distributed, relatively limited data exist on the acute effects of TCE on aquatic organisms, especially saltwater species. Results of static acute tests of TCE with a saltwater alga, invertebrate, and fish are reported here to enhance the data base.

  5. Acute inhalation toxicity of cotton plant dusts.

    PubMed Central

    Rylander, R; Snella, M C

    1976-01-01

    The number of free lung-cells was studied in guinea-pigs after acute exposure to extracts of various cotton dusts. A good correlation was found between the increase in number of leucocytes in the airways and the number of Gram-negative bacteria in the different dusts. Experiments using the Shwartzmann reaction and the Limulus titration test demonstrated a relationship between the content of different endotoxins in the dusts and the pulmonary reaction. A model for the acute exposure effects after exposure to cotton dust is proposed. PMID:963002

  6. Resolving some practical questions about Daphnia acute toxicity tests

    SciTech Connect

    Barera, Y.; Adams, W.J.

    1981-10-01

    Acute toxicity tests were performed with six age groups of Daphnia magna, ranging from less than or equal to6 h to 216 h, and with five chemicals, selected on the basis of their physical and chemical properties as well as their acute toxicity to D. magna. The age of the daphnids did not significantly alter the 48-h EC/sub 50/ values for the chemicals tested. The maximum difference observed in the 48-h EC/sub 50/ values between the 6-h and 216-h age groups was a factor of 3.9 for linear alkylbenzene sulfonate (LAS). For purposes of standardization, it appears that D. magna up to 48 h of age at the beginning of the test can be used to conduct acute toxicity tests with most chemicals. The results of static acute toxicity tests conducted with butylbenzyl phthalate (BBP) and D. magna in the presence and absence of several commonly used solvents indicate that the acute toxicity of this chemical is not altered by the use of a solvent carrier. The 48-h EC/sub 50/ value for BBP without a solvent was 1.0 mg/L, compared with a range of 1.6 to 2.2 mg/L when acetone, dimethylformamide, ethanol, or triethylene glycol were used as solvent carriers. The acute toxicities of the solvents in the absence of BBP were also determined for D. magna. The values ranged from 9.3 to 52.4 g/L. The results of static acute tests performed with D. magna and BBP in the presence of various concentrations of daphnid foods (algae or trout chow), indicate that the 48-h EC/sub 50/ values increase proportionally with an increase in food concentrations. These results suggest that acute toxicity tests with D. magna should be conducted in the presence of food with chemicals with a high Ksigma if the results are to be used to select the test concentrations for a chronic study with daphnids. The type of food and the concentration used in the acute test should be the same as those used in a chronic test.

  7. Acute toxicity and QSAR of chlorophenols on Daphnia magna

    SciTech Connect

    Devillers, J.; Chambon, P.

    1986-10-01

    Chlorophenols which are released into natural waters from various industrial processes and from agricultural uses have been recognized as a group of chemical substances potentially hazardous to the aquatic environment. Therefore it is important to estimate their toxic impact on biota. Thus, the scope of this research was to obtain acute toxicity data for seventeen chlorophenols towards Daphnia magna and to explore the possibilities of deriving QSAR's (quantitative structure-activity relationship) from the above values.

  8. Acute toxicity of peracetic acid to fish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA; also called peroxyacetic acid) is a promising new therapeutant for parasites and fungus. It is registered with the U.S. Environmental Protection Agency (EPA) as an antimicrobial compound approved for indoor use on hard, non-porous surfaces. This study determined the acute toxi...

  9. ACUTE TOXICITY OF AQUEOUS AND CHIRNONOMUS DECORUS

    EPA Science Inventory

    Fourth instar larvae of the midge, Chironomus decorus, were exposed copper in water and copper in food and substrate (bound forms). opper present in aqueous forms was more toxic than when it was present in bound forms. he relationship between copper in water and copper in midges ...

  10. Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

    PubMed

    Costa-Silva, J H; Lima, C R; Silva, E J R; Araújo, A V; Fraga, M C C A; Ribeiro E Ribeiro, A; Arruda, A C; Lafayette, S S L; Wanderley, A G

    2008-03-28

    Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity. PMID:18281172

  11. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization. PMID:27125562

  12. Jet fuel toxicity: skin damage measured by 900-MHz MRI skin microscopy and visualization by 3D MR image processing.

    PubMed

    Sharma, Rakesh; Locke, Bruce R

    2010-09-01

    The toxicity of jet fuels was measured using noninvasive magnetic resonance microimaging (MRM) at 900-MHz magnetic field. The hypothesis was that MRM can visualize and measure the epidermis exfoliation and hair follicle size of rat skin tissue due to toxic skin irritation after skin exposure to jet fuels. High-resolution 900-MHz MRM was used to measure the change in size of hair follicle, epidermis thickening and dermis in the skin after jet fuel exposure. A number of imaging techniques utilized included magnetization transfer contrast (MTC), spin-lattice relaxation constant (T1-weighting), combination of T2-weighting with magnetic field inhomogeneity (T2*-weighting), magnetization transfer weighting, diffusion tensor weighting and chemical shift weighting. These techniques were used to obtain 2D slices and 3D multislice-multiecho images with high-contrast resolution and high magnetic resonance signal with better skin details. The segmented color-coded feature spaces after image processing of the epidermis and hair follicle structures were used to compare the toxic exposure to tetradecane, dodecane, hexadecane and JP-8 jet fuels. Jet fuel exposure caused skin damage (erythema) at high temperature in addition to chemical intoxication. Erythema scores of the skin were distinct for jet fuels. The multicontrast enhancement at optimized TE and TR parameters generated high MRM signal of different skin structures. The multiple contrast approach made visible details of skin structures by combining specific information achieved from each of the microimaging techniques. At short echo time, MRM images and digitized histological sections confirmed exfoliated epidermis, dermis thickening and hair follicle atrophy after exposure to jet fuels. MRM data showed correlation with the histopathology data for epidermis thickness (R(2)=0.9052, P<.0002) and hair root area (R(2)=0.88, P<.0002). The toxicity of jet fuels on skin structures was in the order of tetradecane

  13. Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

    SciTech Connect

    Holland, J.M.

    2001-01-16

    Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

  14. Acute toxicity of pinnatoxins E, F and G to mice.

    PubMed

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group. PMID:22813782

  15. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia

    PubMed Central

    Hijiya, Nobuko; van der Sluis, Inge M.

    2016-01-01

    Abstract Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with asparaginase use include hypersensitivity (clinical and subclinical), pancreatitis, thrombosis, encephalopathy, and liver dysfunction. Depending on the nature and severity of the toxicity, asparaginase therapy may be altered or discontinued in some patients. Clinical hypersensitivity is the most common asparaginase-associated toxicity requiring treatment discontinuation, occurring in up to 30% of patients receiving Escherichia coli–derived asparaginase. The ability to rapidly identify and manage asparaginase-associated toxicity will help ensure patients receive the maximal benefit from asparaginase therapy. This review will provide an overview of the common toxicities associated with asparaginase use and recommendations for treatment management. PMID:26457414

  16. INTERSPECIES CORRELATION ESTIMATIONS: ACUTE TOXICITY TO AQUATIC ORGANISMS

    EPA Science Inventory

    Predictive toxicological models, including estimates of uncertainty, are necessary to address the trend towards probability-based ecological risk assessments. A method and software were developed to aid in estimating acute toxicity of chemicals to species where data is lacking, p...

  17. ACUTE TOXICITY OF PARA-NONYLPHENOL TO SALTWATER ANIMALS

    EPA Science Inventory

    ?para-Nonylphenol (PNP), a mixture of alkylphenols used in producing nonionic surfactants, is distributed widely in surface waters and aquatic sediments, where it can affect saltwater species. This article describes a database for acute toxicity of PNP derived for calculating a n...

  18. ACUTE TOXICITY AND BIOCONCENTRATION OF ENDOSULFAN-EXPOSED ESTUARINE ANIMALS

    EPA Science Inventory

    Acute (96-h) flow-through toxicity tests with endosulfan (Thiodan) were conducted with several estuarine animals. The test species and their 96-h lethal concentration for 50 percent of the organisms (LC50) values were: pink shrimp (Penaeus duorarum), 0.04 micrograms/litre; grass ...

  19. Acute toxicity of peracetic acid (PAA) to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

  20. Management of Skin Toxicity Associated with Cetuximab Treatment in Combination with Chemotherapy or Radiotherapy

    PubMed Central

    Barone, Carlo Antonio; Girolomoni, Giampiero; Russi, Elvio Grazioso; Merlano, Marco Carlo; Ferrari, Daris; Maiello, Evaristo

    2011-01-01

    Background. Cetuximab was demonstrated by clinical trials to improve response rate and survival of patients with metastatic and nonresectable colorectal cancer or carcinoma of the head and neck. Appropriate management of skin toxicity associated with epidermal growth factor receptor inhibitor (EGFR-i) therapy is necessary to allow adequate drug administration and to improve quality of life and outcomes. Methods. A group of Italian Experts produced recommendations for skin toxicity management using the RAND/UCLA Appropriateness Method. Statements were generated on the basis of a systematic revision of the literature and voted twice by a panel of 40 expert physicians; the second vote was preceded by a meeting of the panelists. Results. Skin toxicity included skin rash, skin dryness, pruritus, paronychia, hair abnormality, and mucositis. Recommendations for prophylaxis and therapeutic interventions for each type of toxicity were proposed. Conclusions. Interventions that were considered appropriate to improve compliance and outcomes of cancer patients treated with EGFR-i were identified. PMID:21273511

  1. Acute toxicity of karlotoxins to mice

    PubMed Central

    Place, Allen R.; Munday, R.; Munday, J.S.

    2015-01-01

    Karlotoxins, polyketide derivatives produced by the dinoflagellate Karlodinium veneficum, are associated with fish kills in temperate estuaries world wide. In this study, the acute effects of 3 pure karlotoxin analogs (KmTx 1, KmTx 3 and KmTx 2) have been examined in mice. Transient lethargy and increased respiratory rates were observed soon after dosing with the karlotoxins by intraperitoneal injection, but no deaths were recorded in animals dosed with KmTx 2 at up to 500 μg/kg or with KmTx 1 or KmTx 3 at up to 4000 μg/kg. Animals dosed intraperitoneally with KmTx 1 and KmTx 3 at 4000 μg/kg showed a pronounced decrease in food and water intake, lasting 3–4 days after dosing, accompanied by a significant decrease in body weight. After this time, the lost body weight was regained and the behavior and appearance of the mice remained normal throughout the following 10 day observation period. No effects were seen in mice dosed orally with KmTx 1 or KmTx 3 at a dose of 4000 μg/kg. It is concluded that contamination of seafood if it were to occur with these karlotoxins is unlikely to pose a major risk of acute intoxication in consumers. PMID:25150200

  2. Topical tacrolimus does not negatively impact acute skin wound healing.

    PubMed

    Namkoong, Sun; Chung, Jimin; Yoo, Jiyeon; Jung, Minyoung; Gye, Jiwon; Kim, Ji Seok; Kim, Jee Young; Ahn, Sung Ku; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2013-05-01

    Despite the increasing use of topical tacrolimus, there is little information about its effect on skin wound healing. To determine effects on acute cutaneous wound healing, two full-thickness skin wounds were imparted on the backs of 45 hairless mice, which were then divided into vehicle-, topical tacrolimus- and topical steroid-treated group. Each drug was topically applied once daily. The wound area was assessed by using dermoscopic images every two days after wounding. At 3, 7 and 11 days after wounding, 10 wounds in each group were collected for semi-quantitative analysis of histological features including re-epithelialization, polymorphonuclear leucocytes, fibroblasts and collagen. We also checked the mRNA expression levels of EGF, TGF-β, TNF-α and IL-1α. While topical application of clobetasol propionate was found to delay re-epithelialization and infiltration of polymorphonuclear leucocyte, topical treatment with tacrolimus showed patterns similar to that of the vehicle. In the tacrolimus-treated group, mRNA expression levels of IL-1α and TGF-β were slightly decreased, while the others were similar with the vehicle-treated group. Unlike steroid, topical tacrolimus, therefore, did not disturb the wound healing process in a murine skin wound model. PMID:23614749

  3. Acute toxicity value extrapolation with fish and aquatic invertebrates

    USGS Publications Warehouse

    Buckler, D.R.; Mayer, F.L.; Ellersieck, Mark R.; Asfaw, A.

    2005-01-01

    Assessment of risk posed by an environmental contaminant to an aquatic community requires estimation of both its magnitude of occurrence (exposure) and its ability to cause harm (effects). Our ability to estimate effects is often hindered by limited toxicological information. As a result, resource managers and environmental regulators are often faced with the need to extrapolate across taxonomic groups in order to protect the more sensitive members of the aquatic community. The goals of this effort were to 1) compile and organize an extensive body of acute toxicity data, 2) characterize the distribution of toxicant sensitivity across taxa and species, and 3) evaluate the utility of toxicity extrapolation methods based upon sensitivity relations among species and chemicals. Although the analysis encompassed a wide range of toxicants and species, pesticides and freshwater fish and invertebrates were emphasized as a reflection of available data. Although it is obviously desirable to have high-quality acute toxicity values for as many species as possible, the results of this effort allow for better use of available information for predicting the sensitivity of untested species to environmental contaminants. A software program entitled "Ecological Risk Analysis" (ERA) was developed that predicts toxicity values for sensitive members of the aquatic community using species sensitivity distributions. Of several methods evaluated, the ERA program used with minimum data sets comprising acute toxicity values for rainbow trout, bluegill, daphnia, and mysids provided the most satisfactory predictions with the least amount of data. However, if predictions must be made using data for a single species, the most satisfactory results were obtained with extrapolation factors developed for rainbow trout (0.412), bluegill (0.331), or scud (0.041). Although many specific exceptions occur, our results also support the conventional wisdom that invertebrates are generally more sensitive to

  4. Acute toxicity of cyanogen chloride to Daphnia magna

    SciTech Connect

    Kononen, D.W.

    1988-09-01

    The destruction of cyanide in waste waters by chlorination has been shown to result in the formation of the extremely toxic compound, cyanogen chloride. Industrial cyanide-containing waste waters may be treated by a batch chlorination process under highly alkaline conditions prior to being discharged into a receiving water systems. Alternatively, if the concentration of cyanide is relatively low, and such waste waters may be diverted to municipal waste treatment facilities where they may be subjected to a process of chlorination which may not be sufficient for the complete oxidative destruction of the available cyanide. Although a large body of literature exists concerning the toxicity of HCN and metallic cyanide compounds to aquatic organisms, there is a comparative scarcity of information concerning cyanogen chloride toxicity. This study was designed to determine the acute toxicity of CNCl to Daphnia magna neonates under static bioassay conditions.

  5. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    PubMed Central

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  6. Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

    SciTech Connect

    Dorn, Paige L.; Corbin, Kimberly S.; Al-Hallaq, Hania; Hasan, Yasmin; Chmura, Steven J.

    2012-05-01

    Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV

  7. Acute toxicity of saline produced waters to marine organisms

    SciTech Connect

    Pillard, D.A.; Evans, J.M.; DuFresne, D.L.

    1996-11-01

    Produced waters from oil and gas drilling operations are typically very saline, and may cause acute toxicity to marine organisms due imbalances as well as to an excess or deficiency of to osmotic specific common ions. In order to better understand the relationship between toxicity and ion concentration, laboratory toxicity tests were conducted using mysid shrimp (Mysidopsis bahia), sheepshead minnow, (Cyprinodon variegatus), and inland silvemide (Menidia beryllina). For each species the ionic concentration of standard laboratory water was proportionally increased or decreased to produce test solutions with a range of salinities. Individual ions (sodium, potassium, calcium, magnesium, strontium, chloride, bromide, sulfate, bicarbonate, and borate) were also manipulated to examine individual ion toxicity. Organisms were exposed for 48 hours. The three test species differ in their tolerance of salinity. Mysid shrimp show a marked decrease in survival at salinities less than approximately 5 ppt. Both fish species tolerated low salinity water, however, silversides were less tolerant of saline waters (salinity greater than 40 ppt). There were also significant differences in the responses of the organisms to different ions. The results show that salinity of the test solution may play an important role in the responses of the organisms to produced water effluent. Predictable toxicity/ion relationships developed in this study can be used to estimate whether toxicity in produced water is a result of common ions, salinity, or some other unknown toxicant.

  8. Acute toxicity of nickel nanoparticles in rats after intravenous injection

    PubMed Central

    Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2014-01-01

    This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

  9. Management of Normal Tissue Toxicity Associated With Chemoradiation (Primary Skin, Esophagus, and Lung)

    PubMed Central

    Yazbeck, Victor Y.; Villaruz, Liza; Haley, Marsha; Socinski, Mark A.

    2016-01-01

    Nearly one quarter of patients with lung cancer present with locally advanced disease where concurrent chemoradiotherapy is the current standard of care for patients with good performance status. Cisplatin-based concurrent chemoradiotherapy consistently showed an improvement in survival compared with sequential chemoradiotherapy, at the expense of an increase in the toxicity profile. Over the past decades, several encouraging biomarkers such as transforming growth factor-beta and radioprotective agents such as amifostine were studied but without reaching approval for patient care. We reviewed the prevalence and risk factors for different adverse effects associated with the combined chemoradiotherapy modality, especially dermatitis, mucositis, esophagitis, and pneumonitis. These adverse effects can further be divided into acute, subacute, and chronic. Dermatitis is usually rare and responds well to topical steroids and usual skin care. Acute esophagitis occurs in 30% of patients and is treated with proton pump inhibitors, promotility agents, local anesthetic, and dietary changes. Radiation pneumonitis is a subacute complication seen in 15% of patients and is usually managed with steroids. Chronic adverse effects such as radiation fibrosis and esophageal stricture occur approximately 6 months after completion of radiation therapy and are usually permanent. In this review, complications of chemoradiotherapy for patients with locally advanced lung cancer are delineated, and approaches to their management are described. Given that treatment interruption is associated with a worse outcome, patients are aggressively treated with a curative intent. Therefore, planning for treatment adverse effects improves patient tolerance, compliance, and outcome. PMID:23708070

  10. Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

    PubMed

    Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

    2016-06-01

    The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques. PMID:27113229

  11. Acute effects of cigarette smoke exposure on experimental skin flaps

    SciTech Connect

    Nolan, J.; Jenkins, R.A.; Kurihara, K.; Schultz, R.C.

    1985-04-01

    Random vascular patterned caudally based McFarlane-type skin flaps were elevated in groups of Fischer 344 rats. Groups of rats were then acutely exposed on an intermittent basis to smoke generated from well-characterized research filter cigarettes. Previously developed smoke inhalation exposure protocols were employed using a Maddox-ORNL inhalation exposure system. Rats that continued smoke exposure following surgery showed a significantly greater mean percent area of flap necrosis compared with sham-exposed groups or control groups not exposed. The possible pathogenesis of this observation as well as considerations and correlations with chronic human smokers are discussed. Increased risks of flap necrosis by smoking in the perioperative period are suggested by this study.

  12. Skin nodules in a patient with acute lymphoblastic leukaemia

    PubMed Central

    Le Clech, Lenaïg; Hutin, Pascal; Le Gal, Solène; Guillerm, Gaëlle

    2014-01-01

    Opportunistic infections cause a significant morbidity and mortality in immunocompromised patients. We describe the case of a patient with skin fusariosis and a probable cerebral toxoplasmosis after UCB stem cell transplantation for B-cell acute lymphoblastic leukaemia. Fusarium species (spp) infections are difficult to treat. To date, there has been no consensus on the treatment of fusariosis and the management of its side effects. Given the negative pretransplant Toxoplasma serology in this case, identifying the origin of the Toxoplasma infection was challenging. All usual transmission routes were screened for and ruled out. The patient's positive outcome was not consistent with that of the literature reporting 60% mortality due to each infection. PMID:24408938

  13. Racial Variations in Radiation-Induced Skin Toxicity Severity: Data From a Prospective Cohort Receiving Postmastectomy Radiation

    SciTech Connect

    Wright, Jean L.; Takita, Cristiane; Reis, Isildinha M.; Zhao, Wei; Lee, Eunkyung; Hu, Jennifer J.

    2014-10-01

    Purpose: Radiation-induced skin toxicity is one of the most symptomatic side effects of postmastectomy radiation therapy (PMRT). We sought to determine whether the severity of acute skin toxicity was greater in black patients in a prospective cohort receiving PMRT and to identify other predictors of more severe skin toxicity. Methods and Materials: We evaluated the first 110 patients in an ongoing prospective study assessing radiation-induced skin toxicity in patients receiving PMRT. We recorded patient demographics, body mass index (BMI), and disease and treatment characteristics. Logistic regression analyses were conducted to evaluate the effect of potential predictors on the risk of skin toxicity. Results: A total of 23.6% respondents self-identified as black, 5.5% as non-Hispanic white, 69.1% as Hispanic white, and 1.8% as other; 57% were postmenopausal, and 70.9% had BMI of >25. Median chest wall dose was 50 Gy, and mastectomy scar dose was 60 Gy. Most patients, 95.5%, were treated with a 0.5-cm bolus throughout treatment. There were no significant differences in patient characteristics in black versus non-black patients. At RT completion, moist desquamation was more common in black patients (73.1% vs 47.6%, respectively, P=.023), in postmenopausal patients (63.5% vs 40.4%, respectively, P=.016), and in those with BMI of ≥25 (60.3% vs 37.5%, respectively, P=.030). On multivariate analysis, the effects of black race (odds ratio [OR] = 7.46, P=.031), BMI ≥25 (OR = 2.95, P=.043) and postmenopausal status (OR = 8.26, P=.004) remained significant risk factors for moist desquamation. Conclusions: In this prospectively followed, racially diverse cohort of breast cancer patients receiving PMRT delivered in a uniform fashion, including the routine use of chest wall boost and bolus, black race, higher BMI, and postmenopausal status emerged as significant predictors of moist desquamation. There was a high frequency of moist desquamation, particularly in those

  14. Dermal toxicity elicited by phthalates: evaluation of skin absorption, immunohistology, and functional proteomics.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Hung, Yi-Yun; Lin, Chwan-Fwu; Fang, Jia-You

    2014-03-01

    The toxicity of phthalates is an important concern in the fields of environmental health and toxicology. Dermal exposure via skin care products, soil, and dust is a main route for phthalate delivery. We had explored the effect of topically-applied phthalates on skin absorption and toxicity. Immunohistology, functional proteomics, and Western blotting were employed as methodologies for validating phthalate toxicity. Among 5 phthalates tested, di(2-ethylhexyl)phthalate (DEHP) showed the highest skin reservoir. Only diethyl phthalate (DEP) and dibutyl phthalate (DBP) could penetrate across skin. Strat-M(®) membrane could be used as permeation barrier for predicting phthalate penetration through skin. The accumulation of DEHP in hair follicles was ∼15nmol/cm(2), which was significantly greater than DBP and DEP. DBP induced apoptosis of keratinocytes and fibroblasts via caspase-3 activation. This result was confirmed by downregulation of 14-3-3 and immunohistology of TUNEL. On the other hand, the HSP60 overexpression and immunostaining of COX-2 suggested inflammatory response induced by DEP and DEHP. The proteomic profiling verified the role of calcium homeostasis on skin inflammation. Some proteins investigated in this study can be sensitive biomarkers for dermal toxicity of phthalates. These included HSPs, 14-3-3, and cytokeratin. This work provided novel platforms for examining phthalate toxicity on skin. PMID:24384410

  15. Acute and subchronic toxicity of danshensu in mice and rats.

    PubMed

    Gao, Yonglin; Liu, Zhifeng; Li, Guisheng; Li, Chunmei; Li, Min; Li, Bafang

    2009-06-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from Salvia miltiorrhiza root, and is the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases. It has been reported to have potential protective effects from oxidative injury. However, there is a little information about its possible toxicity. In this study, acute and subchronic toxicity of danshensu in mice and rats have been evaluated. In the acute study, danshensu intraveniouslly administered to rats failed to induce any signs of toxicity or mortality up to a maximum practical dosage of 1500 mg/kg body weight. Test substance administered acutely to mice caused dose-dependent general behavior adverse effects and mortality with the medial lethal dose of 2356.33 mg/kg. The no observed adverse effect level and the lowest observed adverse effect level were 1835 mg/kg and 2000 mg/kg, respectively. In the subchronic study, rats were tested by daily intraperitoneal injection of danshensu at the doses of 50, 150, and 450 mg/kg for 90 days, resulting in no mortality, no changes in body weight, food consumption, hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology. The only treatment-related finding was transient writhing response observed in the 450 mg/kg group after administration. PMID:19778213

  16. Improvement of acute cadmium toxicity by pretreatment with copper salt

    SciTech Connect

    Li, D.; Katakura, M.; Sugawara, N.

    1995-06-01

    The toxicity of Cd compounds has been thoroughly reviewed. Furthermore, modification of the toxicity by other metals is well known. For example, pre-treatment with Zn significantly decreases the lethality of Cd. Testicular injuries induced by Cd are improved by simultaneous injection of Zn or Se. Thus, such preventive action might be expected as a result of prior or simultaneous injection of Cu salts. Hill et al (1963) reported that supplementation of the basal diet (1 ppm Cu) with 40 ppm copper sulphate markedly reduced Cd-induced lethality. Gunn and Gould (1970) reported that Cu affords protection against testicular injuries caused by Cd. Recently, Kaji et al (1992) found that Cu could prevent Cd cytotoxicity in cultured vascular endothelial cells. On the other hand, Irons and Smith (1976) reported previously that injection of Cu along with Cd decreases the binding of Cd to hepatic metallothionein (MT) and increases the toxicity of the Cd. An interactive increase in toxicity caused by a similar mechanism was observed in embryonic chick bone treated with both Cd and Cu in a culture system. Accordingly, we should accumulate further data to understand the preventive effect of Cu against Cd toxicity. The aim of this study was to determine the effect of Cu pretreatment on the acute toxicity of Cd in mice. We focused on two organs, the liver and testis. 17 refs., 4 tabs.

  17. Acute Radiation Disease : Cutaneous Syndrome and Toxic properties of Radiomimetics -Radiation Neurotoxins and Hematotoxins.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava

    Cutaneous injury is an important complication of a general or local acute irradiation. A type of a skin and tissues lesions depends on a type, intensity, and period of irradiation. Also, the clinical picture, signs, and manifestations of the cutaneous syndrome depend on a type of the radiation toxins circulated in lymph and blood of irradiated mammals. Radiation Toxins were isolated from lymph of the mammals that were irradiated and developed different forms of the Acute Radiation Syndromes (ARS) -Cerebrovascular, Cardiovascular, Gastrointestinal, and Hematopoietic. Radiation Toxins can be divided into the two important types of toxins (Neu-rotoxins and Hematotoxins) or four groups. The effects of Radiation Neurotoxins include severe damages and cell death of brain, heart, gastrointestinal tissues and endothelial cells of blood and lymphatic vessels. The hematotoxicity of Hematotoxic Radiation Toxins includes lym-phopenia, leukopenia, thrombocytopenia, and anemia in the blood circulation and transitory lymphocytosis and leukocytosis in the Central Lymphatic System. In all cases, administration of the Radiomimetics (Radiation Toxins) intramuscularly or intravenously to healthy, radiation naive mammals had induced and developed the typical clinical manifestations of the ARS. In all cases, administration of Radiomimetics by subtoxic doses had demonstrated development of typical clinical signs of the cutaneous syndrome such as hair loss, erythema, swelling, desqua-mation, blistering and skin necrosis. In animal-toxic models, we have activated development of the local skin and tissue injury after injection of Radiation Toxins with cytoxic properties.

  18. Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

    PubMed

    Wik, Anna; Dave, Göran

    2006-09-01

    Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be <40 times a predicted environmental concentration based on reports on the concentration of a tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment. PMID:16466775

  19. Acute and delayed toxicities of total body irradiation

    SciTech Connect

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  20. Acute inhalation toxicity testing: considerations of technical and regulatory aspects.

    PubMed

    Pauluhn, J; Bury, D; Föst, U; Gamer, A; Hoernicke, E; Hofmann, T; Kunde, M; Neustadt, T; Schlede, E; Schnierle, H; Wettig, K; Westphal, D

    1996-01-01

    The EU regulatory statute for the acute hazard identification of chemicals requires selection of the two most appropriate routes of administration. Testing employing the oral route is mandatory, whereas selection of the dermal or inhalation route requires expert judgement, i.e. considerations of structural alerts with regard to the inherent acute inhalation toxicity as well as the likelihood of dermal and inhalation exposure, respectively. Currently, testing of chemicals requires acute inhalation exposure of 4-h and 1-h durations according the EU classification and labelling and UN Transport Guidelines, respectively. The analysis made revealed that 1-h exposures appear to add little knowledge in addition to existing 4-h LC50 values and a default value of 4 should be used for conversion of 4-h to 1-h LC50 values, independently of the physical state of the chemical. Therefore, also the unit of concentration of exposure atmospheres should be independent of nominal features of the test substance. Hence, the preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking into account the overall variability of acute toxicity data the recommendations given are classification into the following groups of 4-h LC50 values: < or = 0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made concerning vapours and aerosols with regard to units and conversion factors from 4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable. Further differentiation of classification is not indicated due to technical variability of acute inhalation testing and resolution of the acute bioassay. PMID:9010579

  1. Acute and Sub-Acute Toxicity Studies of Plumeria alba Linn. (Apocynaceae) Hydroalcoholic Extract in Rat

    PubMed Central

    Tessou, K. Z.; Lawson-Evi, P.; Metowogo, K.; Diallo, A.; Eklu-Gadegkeku, K.; Aklikokou, K.; Gbeassor, M.

    2013-01-01

    Plumeria alba Linn (Apocynaceae) is used in Togolese traditional medicine to treat diabetes mellitus and wounds. The present investigation was carried out to evaluate the toxicity of hydroalcoholic extract of Plumeria alba roots in Sprague Dawley rats. The acute toxicity test was conducted by administering orally dose of 5 g/Kg. General behavior and mortality were examined for up to 14 days. The sub-acute toxicity test was performed by daily gavage at 250, 500 and 1000 mg/Kg for 28 days. Body weight and blood glucose were measured weekly. Hematological and biochemical parameters, relative organ weight were determined at the end of the 28 days administration. In acute study, no adverse effect of the extract was observed at 5.0 g/Kg. Sub-acute oral administration of the extract at the dose up to 1000 mg/Kg did not induce death or significant changes in body weight, relative weight of vital organs, hematological parameters and was not associated with liver and kidney toxicity. PMID:24711763

  2. Acute toxicity of 50 metals to Daphnia magna.

    PubMed

    Okamoto, Akira; Yamamuro, Masumi; Tatarazako, Norihisa

    2015-07-01

    Metals are essential for human life and physiological functions but may sometimes cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were < 100 µg l(-1) ; EC50s of 13 elements (Al, Sc, Cr, Co, Ni, Zn, Se, Rb, Y, Rh, Pt, Tl and Pb) were between 100 and 1000 µg l(-1) ; EC50s of 14 elements (Li, V, Mn, Fe, Ge, As, In, Sn, Sb, Te, Cs, Ba, W and Ir) were between 1,001 and 100,000 µg l(-1) ; EC50s of six elements (Na, Mg, K, Ca, Sr and Mo) were > 100,000 µg l(-1) ; and. 7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd adhered to the body of D. magna and physically retarded the movement of D. magna. These metals formed hydroxides after adjusting the pH. Therefore, here, we distinguished this physical effect from the physiological toxic effect. The acute toxicity results of 40 elements obtained in this study were not correlated with electronegativity. Similarly, the acute toxicity results of metals including the rare metals were also not correlated with first ionization energy, atomic weight, atomic number, covalent radius, atomic radius or ionic radius. PMID:25382633

  3. Oritavancin: a review in acute bacterial skin and skin structure infections.

    PubMed

    Syed, Yahiya Y; Scott, Lesley J

    2015-11-01

    Oritavancin (Orbactiv(®)) is a new generation lipoglycopeptide approved for use in adult patients with acute bacterial skin and skin structure infections (ABSSSI). It is administered as a single 1200 mg intravenous infusion over 3 h. In phase 3 trials in adult patients with ABSSSI, oritavancin was noninferior to vancomycin in terms of a composite outcome (cessation of spreading or reduction in the size of the baseline lesion, absence of fever and no rescue antibacterials required; primary endpoint) assessed at an US FDA-recommended early timepoint of 48-72 h after initiation of treatment. Oritavancin was also noninferior to vancomycin in terms of a ≥20 % reduction in the baseline lesion size at the early timepoint and clinical cure rate 7-14 days after the end of treatment. Oritavancin was generally well tolerated in the phase 3 trials, with most treatment-emergent adverse reactions being mild in severity. The most common adverse events occurring in oritavancin recipients were nausea, headache, vomiting, limb and subcutaneous abscesses, and diarrhoea. Oritavancin offers a number of potential advantages, including a convenient single dose treatment that may shorten or eliminate hospital stays, a reduction in healthcare resource utilization and cost, no need for dosage adjustment in patients with mild to moderate hepatic or renal impairment, no need for therapeutic drug monitoring, and elimination of compliance concerns. Therefore, oritavancin is a useful treatment option for adults with ABSSSI. PMID:26464319

  4. Clinical efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI)

    PubMed Central

    Leuthner, Kimberly D; Buechler, Kristin A; Kogan, David; Saguros, Agafe; Lee, H Stephen

    2016-01-01

    Acute bacterial skin and skin structure infections (ABSSSI) are a common disease causing patients to seek treatment through the health care system. With the continued increase of drug-resistant bacterial pathogens, these infections are becoming more difficult to successfully cure. Lipoglycopeptides have unique properties that allow the drug to remain active toward both common and challenging pathogens at the infected site for lengthy periods of time. Dalbavancin, a new lipoglycopeptide, provides two unique dosing regimens for the treatment of ABSSSI. The original regimen of 1,000 mg intravenous infusion followed by a 500 mg intravenous infusion after a week has been shown as safe and effective in multiple, randomized noninferiority trials. These studies also demonstrated that dalbavancin was similar to standard regimens in terms of both safety and tolerability. Recently a single 1,500 mg dose was demonstrated to be equivalent to the dalbavancin two-dose regimen for treating ABSSSI. With the introduction of dalbavancin, clinicians have the option to provide an intravenous antimicrobial agent shown to be as effective as traditional therapies, without requiring admission into the hospitals or prescribing a medication which may not be utilized optimally. Further understanding of dalbavancin and its unusual properties can provide unique treatment situations with potential benefits for both the patient and the overall health care system, which should be further explored. PMID:27354809

  5. Dalbavancin for the treatment of acute bacterial skin and skin structure infections

    PubMed Central

    Ramdeen, Sheena; Boucher, Helen W

    2015-01-01

    Introduction Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI. Areas covered A literature search of published pharmacologic and clinical data was conducted to review the chemistry, pharmacodynamics, and pharmacokinetics of dalbavancin. We also discuss its development process, highlighting efficacy and safety data from pertinent clinical trials and the role it could play in the current clinical landscape. Expert opinion DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin’s non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited. PMID:26239321

  6. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  7. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested. PMID:19038451

  8. Identifying and designing chemicals with minimal acute aquatic toxicity

    PubMed Central

    Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

    2015-01-01

    Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

  9. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

    PubMed Central

    Sim, Kae Shin; Abdul Wahab, Norhanom

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  10. Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor.

    PubMed

    Teoh, Wuen Yew; Sim, Kae Shin; Moses Richardson, Jaime Stella; Abdul Wahab, Norhanom; Hoe, See Ziau

    2013-01-01

    Gynura bicolor (Compositae) which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water) of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116), one human breast adenocarcinoma cell line (MCF7), and one human normal colon cell line (CCD-18Co) were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay), possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor. PMID:24369485

  11. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  12. Accuracy of Chronic Aquatic Toxicity Estimates Determined from Acute Toxicity Data and Two Time–Response Models.

    EPA Science Inventory

    Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of...

  13. DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

    EPA Science Inventory

    Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

  14. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    USGS Publications Warehouse

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  15. Assessing acute toxicities of pre- and post-treatment industrial wastewaters with Hydra attenuata: A comparative study of acute toxicity with the fathead minnow, Pimephales promelas

    SciTech Connect

    Fu, L.J.; Staples, R.E.; Stahl, R.G. Jr. . Haskell Lab. for Toxicology and Industrial Medicine)

    1994-04-01

    This study was undertaken to (a) determine wastewater treatment effectiveness using two freshwater organisms, (b) compare acute toxicity results from the two species exposed to the wastewaters, and (c) link acute and potential developmental toxicity of wastewaters in one organism. The acute toxicities of several pretreatment and post-treatment industrial waste-water samples wee evaluated with adult Hydra attenuata and fathead minnows. The acute LC50s agreed closely when results in Hydra attenuata were compared with those from fathead minnow tests. Acute LC50s ranged from 3 to >100% of samples with hydra, and from 1.0 to >100% of sample with fathead minnows. The results provided strong evidence of treatment effectiveness because toxicity decreased with progressive stages of treatment. Previously the Hydra Developmental Toxicity Assay was used as a prescreen mainly for in vitro assessment of developmental toxicity with pure compounds and to prioritized toxicants according to selective toxicity to the developing embryo. Recently the authors modified the assay for testing natural waters and wastewaters; hence, some of the wastewater samples also were tested for their developmental toxicity. In this case, the relative selective toxicity of these wastewater samples ranged from 0.7 to 2.1, indicating that no sample was uniquely toxic to the developing embryo, although acute toxicity was manifested. Overall, their results indicate the Hydra Assay functions appropriately in assessments of acute and developmental toxicity of industrial wastewaters and may be a simple and useful tool in a battery of tests for broader scale detection of environmental hazards.

  16. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. PMID:26256397

  17. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    PubMed Central

    Jani, Nihar; Niazi, Masooma; Lvovsky, Dmitry

    2016-01-01

    Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses. PMID:27042361

  18. Acute skin lesions due to localized ``hot particle`` radiation exposures

    SciTech Connect

    Baum, J.W.; Carsten, A.L.; Kaurin, D.G.L.; Schaefer, C.W.

    1996-06-01

    Purpose of the studies was to determine incidence and severity of lesions resulting from localized deposition of dose to the skin from small (<0.5 mm) discrete radioactive particles. Hanford mini-swine were exposed to localized doses from 0.2 to over 600 Gy (averaged over 1 cm{sup 2} at 70{mu}m depth) from isotopes having max beta particle energies from about 0.3-3 MeV. Incidence of erythema and scabs (indicating ulceration) were scored routinely for up to 71 days post-irradiation. Responses followed normal probability distributions, and thus, no true threshold could be defined. Ten and 50% incidence rates were deduced using probit analyses. Lowest dose producing 10% incidence was about 1 Gy for exposures to Yb-175 (0.5 MeV max energy) beta particles. Severity of lesions was estimated using diameters and persistence. From preliminary considerations of probability of induction, size, and persistence of acute lesions, a special limit for hot particle exposures in the range of 5-50 Gy may be reasonable, with an action level between about 1 Gy and the limit.

  19. Cesium in mammals: acute toxicity, organ changes and tissue accumulation

    SciTech Connect

    Pinsky C.; Bose, R.; Taylor, J.R.; McKee, J.S.C.; Lapointe, C.; Birchall, J.

    1981-01-01

    The acute toxicity of cesium given intraperitoneally (IP) as CsCl in mice is characterized by autonomic upset and by a multiphasic excitant-depressant action on the central nervous system. The predominantly depressant action can progress to respiratory embarrassment, cyanosis, spinal convulsions and death. Light microscopy of mice treated with 2.0 mEq Cs/sup +/ kg/sup -1/ IP for 14 days showed lymphoid hyperplasia in small intestine. Measurement of tissue cesium by the proton-induced x-ray emission (PIXE) technique is convenient and reproducible. Cesium displays a generalized bioactivity that merits further study.

  20. Prediction of the Daphnia acute toxicity from heterogeneous data.

    PubMed

    Faucon, J C; Bureau, R; Faisant, J; Briens, F; Rault, S

    2001-07-01

    Two descriptors (log(P(ow)), 'hardness') were selected to predict the Daphnia acute toxicity of a training set of heterogeneous chemical compounds. The data were extracted from 523 notification files about new chemicals stored at the French Department of Environment. The selection of the descriptors was carried out using a statistical method coupling ordinary least square (OLS) regression and genetic algorithm (GA). The validity limits for the final equation are discussed by comparing the actual and predicted activities of several compounds. The study points out the interest of the 'hardness' parameter for quantitative structure-activity relationships (QSAR) with a heterogeneous data set. PMID:11459146

  1. Decontamination Efficacy and Skin Toxicity of Two Decontaminants against Bacillus anthracis

    PubMed Central

    Stratilo, Chad W.; Crichton, Melissa K. F.; Sawyer, Thomas W.

    2015-01-01

    Decontamination of bacterial endospores such as Bacillus anthracis has traditionally required the use of harsh or caustic chemicals. The aim of this study was to evaluate the efficacy of a chlorine dioxide decontaminant in killing Bacillus anthracis spores in solution and on a human skin simulant (porcine cadaver skin), compared to that of commonly used sodium hypochlorite or soapy water decontamination procedures. In addition, the relative toxicities of these decontaminants were compared in human skin keratinocyte primary cultures. The chlorine dioxide decontaminant was similarly effective to sodium hypochlorite in reducing spore numbers of Bacillus anthracis Ames in liquid suspension after a 10 minute exposure. After five minutes, the chlorine dioxide product was significantly more efficacious. Decontamination of isolated swine skin contaminated with Bacillus anthracis Sterne with the chlorine dioxide product resulted in no viable spores sampled. The toxicity of the chlorine dioxide decontaminant was up to two orders of magnitude less than that of sodium hypochlorite in human skin keratinocyte cultures. In summary, the chlorine dioxide based decontaminant efficiently killed Bacillus anthracis spores in liquid suspension, as well as on isolated swine skin, and was less toxic than sodium hypochlorite in cultures of human skin keratinocytes. PMID:26394165

  2. Decontamination Efficacy and Skin Toxicity of Two Decontaminants against Bacillus anthracis.

    PubMed

    Stratilo, Chad W; Crichton, Melissa K F; Sawyer, Thomas W

    2015-01-01

    Decontamination of bacterial endospores such as Bacillus anthracis has traditionally required the use of harsh or caustic chemicals. The aim of this study was to evaluate the efficacy of a chlorine dioxide decontaminant in killing Bacillus anthracis spores in solution and on a human skin simulant (porcine cadaver skin), compared to that of commonly used sodium hypochlorite or soapy water decontamination procedures. In addition, the relative toxicities of these decontaminants were compared in human skin keratinocyte primary cultures. The chlorine dioxide decontaminant was similarly effective to sodium hypochlorite in reducing spore numbers of Bacillus anthracis Ames in liquid suspension after a 10 minute exposure. After five minutes, the chlorine dioxide product was significantly more efficacious. Decontamination of isolated swine skin contaminated with Bacillus anthracis Sterne with the chlorine dioxide product resulted in no viable spores sampled. The toxicity of the chlorine dioxide decontaminant was up to two orders of magnitude less than that of sodium hypochlorite in human skin keratinocyte cultures. In summary, the chlorine dioxide based decontaminant efficiently killed Bacillus anthracis spores in liquid suspension, as well as on isolated swine skin, and was less toxic than sodium hypochlorite in cultures of human skin keratinocytes. PMID:26394165

  3. Acute and subacute toxicity of 10B-paraboronophenylalanine

    SciTech Connect

    Taniyama, K.; Fujiwara, H.; Kuno, T.; Saito, N.; Shuntoh, H.; Sakaue, M.; Tanaka, C. )

    1989-07-01

    The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.

  4. Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    PubMed

    Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

    2013-08-01

    The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. PMID:23606235

  5. Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

    SciTech Connect

    Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia; Skliarenko, Julia; Craig, Tim; Le, Lisa W.; Brierley, James; Wong, Rebecca; Dinniwell, Robert; Bayley, Andrew J.; Dawson, Laura A.; Ringash, Jolie; Krzyzanowska, Monika K.; Moore, Malcolm J.; Chen, Eric X.; Easson, Alexandra M.; Kassam, Zahra; Cho, Charles; Kim, John

    2014-11-01

    Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were

  6. Comparative acute toxicity and primary irritancy of the ethylidene and vinyl isomers of norbornene.

    PubMed

    Ballantyne, B; Myers, R C; Klonne, D R

    1997-01-01

    The acute toxicity and primary irritancy of the industrial chemicals 5-ethylidene-2-norbornene (ENB) and 5-vinyl-2-norbornene (VNB) were studied. They are of moderate acute peroral toxicity in the rat, with LD50 values for ENB of 2.54 (male) and 5.66 (female) ml kg(-1), and for VNB of 5.90 (male) and 11.9 (female) ml kg(-1). Percutaneous toxicity is slight in the rabbit by 24-h occluded contact, with no mortalities for ENB up to 8.0 ml kg(-1) and only one mortality (male) at 16.0 ml kg(-1) VNB. Dynamically generated saturated vapor atmosphere LT50 values for ENB in the rat were 75 (male) and 125 (female) min, and for VNB they were 28 (male) and 37 (female) min. The 4-h LC50 values for ENB were 2717 (male) and 3015 (female) ppm, and for VNB they were 2231 (male) and 2518 (female) ppm. Intravenously, the ENB LD50 ranged from 0.09 (male rabbit) to 0.11 ml kg(-1) (female); corresponding LD50 values for VNB were 0.10-0.05 mg kg(-1). Acute neurotoxic signs were seen by the intravenous and inhalation routes of exposure, including tremors, ataxia and convulsions; the latter were sufficient to cause vertebral column luxation or fracture, producing spinal cord compression and resultant hindlimb paralysis. Both ENB and VNB are moderately irritating to the skin (rabbit), causing erythema and edema, but not necrosis. Both materials cause slight conjunctival hyperemia and chemosis in rabbits, but not corneal injury. PMID:9285533

  7. [Acute Toxicity of Coptis chinensis Rhizome Extracts to Daphnia carinata].

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-10-01

    Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems. PMID:26841628

  8. INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

  9. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. PMID:26429932

  10. Skin Toxicity Determined In vitro by Three-Dimensional, Native-State Histoculture

    NASA Astrophysics Data System (ADS)

    Li, Lingna; Margolis, Leonid B.; Hoffman, Robert M.

    1991-03-01

    We describe a gel-supported in vitro system for culturing skin samples in a three-dimensional native state. All the cell types of skin remain viable and maintain their native architecture for at least 10 days. The culture system is used for toxicity measurements by ascertaining cell viability using two fluorescent dyes: 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein acetoxymethyl ester, specific for living cells, and propidium iodide, specific for dead cells. Cell staining with the dyes is measured throughout the tissue block by confocal scanning fluorescence microscopy. The dose-response to three agents--ethanol, doxorubicin, and sodium hypochlorite--is shown and, in the case of sodium hypoclorite, compared to in vivo skin toxicity with a high correlation. We also demonstrate that the end point of [^3H]thymidine incorporation measured by histological autoradiography can be used to measure toxicity. Our results with the [^3H]thymidine end point demonstrate that the hair follicle cells are the most sensitive to doxorubicin. The native-state model for skin may be an effective replacement for animal systems and superior to the dispersed skin cell systems used previously. It can allow rapid, inexpensive measurements of the effect of manufactured products, drugs, and pollutants on skin.

  11. Skin toxicity determined in vitro by three-dimensional, native-state histoculture

    SciTech Connect

    Li, L.N.; Margolis, L.B.; Hoffman, R.M. )

    1991-03-01

    We describe a gel-supported in vitro system for culturing skin samples in a three-dimensional native state. All the cell types of skin remain viable and maintain their native architecture for at least 10 days. The culture system is used for toxicity measurements by ascertaining cell viability using two fluorescent dyes: 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein acetoxymethyl ester, specific for living cells, and propidium iodide, specific for dead cells. Cell staining with the dyes is measured throughout the tissue block by confocal scanning fluorescence microscopy. The dose-response to three agents--ethanol, doxorubicin, and sodium hypochlorite--is shown and, in the case of sodium hypochlorite, compared to in vivo skin toxicity with a high correlation. We also demonstrate that the end point of ({sup 3}H)thymidine incorporation measured by histological autoradiography can be used to measure toxicity. Our results with the ({sup 3}H)thymidine end point demonstrate that the hair follicle cells are the most sensitive to doxorubicin. The native-state model for skin may be an effective replacement for animal systems and superior to the dispersed skin cell systems used previously. It can allow rapid, inexpensive measurements of the effect of manufactured products, drugs, and pollutants on skin.

  12. Rapid creation of skin substitutes from human skin cells and biomimetic nanofibers for acute full-thickness wound repair.

    PubMed

    Mahjour, Seyed Babak; Fu, Xiaoling; Yang, Xiaochuan; Fong, Jason; Sefat, Farshid; Wang, Hongjun

    2015-12-01

    Creation of functional skin substitutes within a clinically acceptable time window is essential for timely repair and management of large wounds such as extensive burns. The aim of this study was to investigate the possibility of fabricating skin substitutes via a bottom-up nanofiber-enabled cell assembly approach and using such substitutes for full-thickness wound repair in nude mice. Following a layer-by-layer (L-b-L) manner, human primary skin cells (fibroblasts and keratinocytes) were rapidly assembled together with electrospun polycaprolactone (PCL)/collagen (3:1, w/w; 8%, w/v) nanofibers into 3D constructs, in which fibroblasts and keratinocytes were located in the bottom and upper portion respectively. Following culture, the constructs developed into a skin-like structure with expression of basal keratinocyte markers and deposition of new matrix while exhibiting good mechanical strength (as high as 4.0 MPa by 14 days). Treatment of the full-thickness wounds created on the back of nude mice with various grafts (acellular nanofiber meshes, dermal substitutes, skin substitutes and autografts) revealed that 14-day-cultured skin substitutes facilitated a rapid wound closure with complete epithelialization comparable to autografts. Taken together, skin-like substitutes can be formed by L-b-L assembling human skin cells and biomimetic nanofibers and they are effective to heal acute full-thickness wounds in nude mice. PMID:26187057

  13. Dexrazoxane Abrogates Acute Doxorubicin Toxicity in Marmoset Ovary1

    PubMed Central

    Salih, Sana M.; Ringelstetter, Ashley K.; Elsarrag, Mazin Z.; Abbott, David H.; Roti, Elon C. Roti

    2015-01-01

    ABSTRACT Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 μM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue. PMID:25609833

  14. Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary.

    PubMed

    Salih, Sana M; Ringelstetter, Ashley K; Elsarrag, Mazin Z; Abbott, David H; Roti, Elon C Roti

    2015-03-01

    Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 μM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue. PMID:25609833

  15. Safety assessment of aditoprim acute, subchronic toxicity and mutagenicity studies.

    PubMed

    Wang, Xu; Tan, Ziqiang; Pan, Yuanhu; Ihsan, Awais; Liu, Qianying; Huang, Lingli; Cheng, Guyue; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Yuan, Zonghui

    2015-11-01

    Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD50 calculated was 1400 mg kg(-1) body weight (BW) day(-1) in rats and 1130 mg kg(-1) BW day(-1) in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg(-1) diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg(-1) diet, and significant decrease in relative weights of livers in males in the 100 mg kg(-1) diet were noted. Histopathological observations revealed that the 1000 mg kg(-1) ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg(-1) diet, which is about 1.44-1.53 mg kg(-1) BW day(-1) in rats. PMID:25663419

  16. Acute oral toxicity of the herbicide BUREX EKO in pheasants.

    PubMed

    Legáth, J; Mlynarcíková, H; Svický, E; Lenhardt, L; Kacmár, P; Benová, K; Kovác, G

    1996-12-01

    The aim of this study was to determine the acute LD50, clinical symptoms and pathological changes of acute BUREX EKO intoxication in pheasants according to OECD No 205. Medium lethal dose (LD50) of BUREX EKO in pheasant is 3.84 ml/kg body weight with the upper level of reliability 4.50 ml and lower level of reliability 3.27 ml/kg body weight. As far as the calculation to the effective substance is concerned it is 1077 mg of chloridazone per kg body weight with the interval of reliability from 919 to 1263 mg/kg body weight. Calculated the effective substance of chloridazone (3.84 ml is LD50 of BUREX EKO which contains 1077 mg of chloridazone) BUREX EKO can be classified as the moderately toxic substance to pheasants. There were following clinical symptoms of the BUREX EKO intoxication in pheasants: apathy, drowsiness, incapability to move, ruffled feathers, slight diarrhoea, strenuous respiration, tonico-clonical cramps before death, decease with the head expressively bent rearwards. There was a relatively fast beginning of rigor mortis in dead pheasants. Pathologico-anatomical dissection of the pheasants obtained under conditions of acute intoxication did not reveal any changes on the organs of both experimental and control pheasants which would be immediately connected with the effect of the administered substance. Hyperaemia was recorded by histologico-pathological investigation of the liver and kidneys. No changes on the brain and intestine wall were recorded. PMID:9022351

  17. Use of drug therapy to manage acute cutaneous necrosis of the skin.

    PubMed

    Wallace, Jill S; Hall, John C

    2010-04-01

    Acute cutaneous necrosis is defined as a sudden onset of gangrenous skin changes in the skin, associated with significant morbidity and mortality. The following diseases are included in this discussion: coumadin necrosis, heparin necrosis, brown recluse spider bite, necrotizing fasciitis, vasculitis, pyoderma gangrenosum, calciphylaxis, clotting abnormalities and embolic phenomena. The importance of early diagnosis, early distinction and early drug therapy or drug withdrawal must match the diagnosis for maximal preservation of the skin and underlying tissue. PMID:20514791

  18. Influence of water quality parameters on acute silver toxicity

    SciTech Connect

    Bills, T.; Forsythe, B. II; Wenholz, M.; Jeffers, R.; Waldrop, V.; La Point, T.; Bens, C.; Cobb, G.; Klaine, S.J.

    1995-12-31

    The data to adequately characterize the influence of water quality on silver toxicity in freshwater are lacking or poorly developed. Current attempts to extrapolate existing data sets to many sites result in extremely low silver limits. The error associated with these extrapolations dictate that a silver toxicity data set, accounting for various water quality parameters, be generated. The interactive effects of chloride, hardness, alkalinity, total organic carbon, and pH on the acute toxicity of silver (AgNO{sub 3}) were measured using juvenile fathead minnows (Pimephales promelas) and Daphnia magna. The 96-hr LC50 for fathead minnows at the lowest tested levels of water quality parameters was 1.4 ug/L. At the highest levels tested, the 96-hr LC50 for fathead minnows was 3.8 ug/L. Preliminary results suggest the 48-hr LC50 values for Daphnia magna were similar to those of the fish. These results indicate a mitigating effect of certain water quality parameters.

  19. Acute toxicity of vanadium to the threespine stickleback, Gasterosteus aculeatus

    SciTech Connect

    Gravenmier, J.J.; Johnston, D.W.; Arnold, W.R.

    2005-02-15

    Vanadium is widely distributed, occurring in many types of minerals, coal, and petroleum. Anthropogenic sources of vanadium originate from the production, processing, and wastes of these materials. The aquatic toxicity of vanadium to fish species is not well characterized. This study focused on the three-spined stickleback, Gasterosteus aculeatus, a small and widely distributed euryhaline species of fish. The three-spined stickleback is used as an effluent-monitoring species in both Canada and the United States. Five 96-h static renewal acute toxicity tests were performed in moderately hard water with adult fish. The geometric mean and range of the five 96-h LC{sup 50}s based on measured concentrations of total vanadium in the test solution were 3.17 and 2.35-4.07 mg V/L, respectively. A conservative estimation of a safe concentration of vanadium that would not affect survival of adult three-spined sticklebacks over a 96-h exposure period in moderately hard water is approximately 0.30 mg V/L. A comparison with other fish species previously tested suggests that the three-spined stickleback is intermediate in sensitivity to vanadium. Information reported from this study may be useful in effluent toxicity identification evaluations and ecological risk assessments related to vanadium.

  20. Effect of Bra Use during Radiotherapy for Large-Breasted Women: Acute Toxicity and Treated Heart and Lung Volumes

    PubMed Central

    Keller, Lanea; Cohen, Randi; Sopka, Dennis M; Li, Tianyu; Li, Linna; Anderson, Penny R; Fowble, Barbara L.; Freedman, Gary M

    2012-01-01

    Purpose Large breast size presents special problems during radiation simulation, planning and patient treatment, including increased skin toxicity, in women undergoing breast-conserving surgery and radiotherapy (BCT). We report our experience using a bra during radiation in large-breasted women and its effect on acute toxicity and heart and lung dosimetry. Materials and methods From 2001 to 2006, 246 consecutive large-breasted women (bra size ≥ 38 and/or ≥ D cup) were treated with BCT using either 3D conformal (3D-CRT) or Intensity Modulated Radiation (IMRT). In 58 cases, at the physicians’ discretion, a custom-fit bra was used during simulation and treatment. Endpoints were acute radiation dermatitis, and dosimetric comparison of heart and lung volumes in a subgroup of 12 left-sided breast cancer patients planned with and without a bra. Results The majority of acute skin toxicities were grade 2 and were experienced by 90% of patients in a bra compared to 70% of patients not in a bra (p=0.003). On multivariate analysis significant predictors of grade 2/3 skin toxicity included 3D-CRT instead of IMRT (OR=3.9, 95% CI:1.8-8.5) and the use of a bra (OR=5.5, 95% CI:1.6-18.8). For left-sided patients, use of a bra was associated with a volume of heart in the treatment fields decreased by 63.4% (p=0.002), a volume of left lung decreased by 18.5% (p=0.25), and chest wall separation decreased by a mean of 1 cm (p=0.03). Conclusions The use of a bra to augment breast shape and position in large-breasted women is an alternative to prone positioning and associated with reduced chest wall separation and reduced heart volume within the treatment field. PMID:23459714

  1. [Acute Toxic Effects of Bromate on Aquatic Organisms].

    PubMed

    Wang, Zhi-wei; Liu, Dong-mei; Zhang, Wen-juan; Cui, Fu-yi

    2016-02-15

    Acute toxic effects of potassium bromate, sodium bromate and potassium bromide on luminescent bacteria, water flea, green alga and zebrafish were studied using standard toxic testing methods. The results showed that the pollutants had no effect on the luminous intensity of luminescent bacteria. The 96 h EC5. of potassium bromate on Scenedesmus obliquus was 738.18 mg x L(-1), 48 h EC50 on Daphnia magna and Moina was 154.01 mg x L(-1) was 161.80 mg x L(-1), while 48 h LC50 was 198 52 mg x L(-1), 175.68 mg x L(-1), and 96 h LC50 on zebrafish was 931.4 mg x L(-1). The 96 h EC50 of sodium bromate on Scenedesmus obliquus was 540.26 mg x L(-1), 48 h EC50 Daphnia magna and Moina was 127.90 mg x L(-1), 111.07 mg x L(-1), while 48 h LC50 was 161.80 mg x L(-1), 123.47 mg x L(-1), and 96 h LC50 on zebrafish was 1065.6 mg x L(-1). But the effects of potassium bromide on the above several kinds of aquatic organisms were far smaller than those of potassium bromate and sodium bromate. The toxic effects on test organisms were due to the impacts of bromate after the comparison of different pollutants, and the effects were more obvious with the increase of exposure time. The order of sensitivity to the toxic effects of bromate was Daphnia magna, Moina > Scenedesmus obliquus > zebrafish > Chlorella vulgaris, luminescent bacteria. PMID:27363170

  2. Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams

    PubMed Central

    2013-01-01

    Background and purpose The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. Materials and methods A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. Results All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. Conclusions The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy. PMID:23497676

  3. New developments in the treatment of acute bacterial skin and skin structure infections: considerations for the effective use of dalbavancin

    PubMed Central

    Juul, Janelle J; Mullins, Caitlin F; Peppard, William J; Huang, Angela M

    2016-01-01

    Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies. PMID:26937194

  4. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    PubMed

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  5. Acute and subchronic toxicity of ethylene glycol monobutyl ether.

    PubMed Central

    Tyler, T R

    1984-01-01

    The available information on the acute and subchronic toxicity of ethylene glycol monobutyl ether is reviewed. Data from animal studies have been examined from the standpoint of dose-response relationships and the sensitivity of various animal species, including man, to the effects of this chemical. In view of recent findings with other chemically related glycol ethers, particular attention has been given to possible adverse effects on blood and testicular tissue. In evaluating the hazard that this chemical may pose to man, consideration has been given to likely routes of exposure and its irritant properties. It is concluded that the available information continues to support the current ACGIH TWA8-TLV of 25 ppm with a STEL of 75 ppm. PMID:6499803

  6. Investigation of acute nanoparticulate aluminum toxicity in zebrafish.

    PubMed

    Griffitt, Robert J; Feswick, April; Weil, Roxana; Hyndman, Kelly; Carpinone, Paul; Powers, Kevin; Denslow, Nancy D; Barber, David S

    2011-10-01

    In freshwater fish, aluminum is a well-recognized gill toxicant, although responses are influenced by pH. Aluminum nanomaterials are being used in diverse applications that are likely to lead to environmental release and exposure. However, it is unclear if the effects of nanoparticulate aluminum are similar to those of other forms of aluminum or require special consideration. To examine the acute toxicological effects of exposure to aluminum nanoparticle (Al-NP)s, adult female zebrafish were exposed to either Al-NPs or aluminum chloride for up to 48 hours in moderately hard fresh water. Al-NPs introduced into test water rapidly aggregated and up to 80% sedimented from the water column during exposures. No mortality was caused by concentrations of Al-NP up to 12.5 mg/L. After exposure, tissue concentrations of aluminum, effects on gill morphology, Na+, K+ -ATPase (NKA) activity, and global gene expression patterns were examined. Exposure to both aluminum chloride and nanoparticulate aluminum resulted in a concentration dependent decrease in sodium potassium ATPase activity, although Al-NP exposure did not alter gill morphology as measured by filament widths. Decreased ATPase activity coincided with decreases in filamental NKA staining and mucous cell counts. Analysis of gill transcriptional responses demonstrated that exposure to 5 mg/L Al-NP only resulted in significant changes in expression of two genes, whereas aluminum chloride exposure significantly affected the expression of 105 genes. Taken together, these results indicate that nanoparticulate aluminum has little acute toxicity for zebrafish in moderately hard freshwater. PMID:21910207

  7. ORAL TOXICITY OF CARBON TETRACHLORIDE: ACUTE, SUBACUTE, AND SUBCHRONIC STUDIES IN RATS

    EPA Science Inventory

    The investigation was conducted to characterize the acute, subacute and subchronic toxic potency of ingested carbon tetrachloride (CCl4). In the first acute and subchronic toxicity study, male Sprague-Dawley rats of 300-350 g were gavaged with 0, 20, 40 or 80 mg CCl4/kg once dail...

  8. Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

  9. The acute toxicity of inhaled beryllium metal in rats

    SciTech Connect

    Haley, P.J.; Finch, G.L.; Hoover, M.D.; Cuddihy, R.G. )

    1990-01-01

    The authors exposed rats once by nose only for 50 min to a mean concentration of 800 [mu]g/m[sup 3] of beryllium metal to characterize the acute toxic effects within the lung. Histological changes within the lung and enzyme changes within bronchoalveolar lavage (BAL) fluid were evaluated at 3, 7, 10, 14, 31, 59, 115, and 171 days postexposure (dpe). Beryllium metal-exposed rats developed acute, necrotizing, hemorrhagic, exudative pneumonitis and intraalveolar fibrosis that peaked at 14 dpe. By 31 dpe, inflammatory lesions were replaced by minimal interstitial and intraalveolar fibrosis. Necrotizing inflammation was observed again at 59 dpe which progressed to chronic-active inflammation by 115 dpe. Low numbers of diffusely distributed lymphocytes were also present but they were not associated with granulomas as is observed in beryllium-induced disease in man. Lymphocytes were not elevated in BAL samples collected from beryllium-exposed rats at any time after exposure. Lactate dehydrogenase (LDH), [beta]-glucuronidase, and protein levels were elevated in BAL fluid from 3 through 14 dpe but returned to near normal levels by 31 dpe. LDH increased once again at 59 dpe and remained elevated at 171 dpe. [beta]-Glucuronidase and protein levels were slightly, but not significantly, elevated from 31 through 171 dpe.

  10. A successful approach to overcome imatinib-induced skin toxicity in a GIST patient.

    PubMed

    Desar, Ingrid M E; van Herpen, Carla M L; van Erp, Nielka P; Kaal, Suzanne E J; van de Kerkhof, Peter C M; van der Graaf, Winette T A

    2016-07-01

    Since the introduction of tyrosine kinase inhibitors in gastrointestinal stromal tumor patients, the median survival of patients has increased from less than 1 to more than 5 years. The chronic use of a tyrosine kinase inhibitor has an impact on quality of life because of its toxicity. Adequate supportive therapy is therefore important. We describe a female patient with a metastatic gastrointestinal stromal tumor. During treatment with the c-KIT inhibitor imatinib, she developed severe therapy-limiting skin toxicity. After several different supportive attempts, the combination of doxycycline and clemastine proved to be the solution, enabling successful chronic treatment with imatinib. Chronic use of doxycycline and clemastine is useful in the management of skin toxicity caused by c-KIT inhibitors, enabling the needed long-term use of these kind of anticancer drugs without hampering the quality of life. PMID:26982239

  11. Acute Toxicity and General Pharmacological Action of QGC EXT

    PubMed Central

    Lee, Jong Mi; Im, Wi Joon; Nam, Yoon Jin; Oh, Kyung Hoon; Lim, Jae Chun; Whang, Wan Kyunn

    2012-01-01

    It has been shown that QGC isolated and purified from Rumecis folium found protective effects of gastritis and esophagitis which EXT is an ethanol extract of it. We examined acute toxicity and the general pharmacological action of QGC EXT to search for any side effects of it in rats, mice, guinea pigs, and cats. In a single dose toxicity study, QGC EXT didn't show toxicological effects in rats and mice, and the LD50 was over 5 g/kg in both animals, and there were also no changes in weight, feed and water intake during these toxicological experimental periods. We examined the general pharmacological action on central controlled behavior responses, and peripheral organs including blood pressure, heart rate, respiration and gastrointestinal system, We found that there were no significant changes in body temperature, locomotors activity, stereotyped behaviors, sleeping time, and convulsion. In other studies, writhing reaction, normal body temperature, there did not appear to be any changes. The large intestine movement and electrical field stimulation-induced contraction was not changes by its EXT. In addition, the influences on blood pressure, heart rates, and respiration by QGC EXT were not found. These results indicate that QGC EXT may be very safe as a new drug, since its LD50 was very high over 5 g/kg and any side effects were not found. PMID:22416220

  12. Acute cardiopulmonary toxicity of inhaled aldehydes: role of TRPA1.

    PubMed

    Conklin, Daniel J

    2016-06-01

    Inhalation of high-level volatile aldehydes, as present in smoke from wildfires and in tobacco smoke, is associated with both acute and chronic cardiopulmonary morbidity and mortality, but the underlying mechanisms are unclear. The transient receptor potential ankyrin 1 (TRPA1) protein forms a cation channel (irritant receptor) that mediates tobacco smoke-induced airway and lung injury, yet the role of TRPA1 in the cardiovascular toxicity of aldehyde exposure is unclear. Physiologically, airway-located TRPA1 activation triggers an irritant response (e.g., coughing and "respiratory braking") that alters the rate and depth of breathing to reduce exposure. Acrolein (2-propenal), a volatile, unsaturated aldehyde, activates TRPA1. Acrolein was used as a chemical weapon in World War I and is present at high levels in wildfires and tobacco smoke. Acrolein is thought to contribute to pulmonary and cardiovascular injury caused by tobacco smoke exposure, although the role of TRPA1 in cardiovascular toxicity is unclear. This minireview addresses this gap in our knowledge by exploring literature and recent data indicating a connection between TRPA1 and cardiovascular as well as pulmonary injury due to inhaled aldehydes. PMID:27152448

  13. Skin toxicity in BRAF(V600) mutated metastatic cutaneous melanoma patients treated with vemurafenib

    PubMed Central

    Huszno, Joanna; Slomian, Grzegorz; Nieckula, Jaroslaw

    2016-01-01

    Introduction The use of orally available BRAF kinase inhibitor – vemurafenib is associated with numerous adverse skin reactions. Aim To assess the safety and early side effects of vemurafenib treatment in the unselected group of patients treated at the outpatient clinic, in particular the assessment of the incidence of skin cancer. Material and methods We carried out a systematic study of patients (pts) treated with vemurafenib. Skin toxicity during vemurafenib therapy was analyzed. Toxicity was determined on the basis of the toxicity scale CTCAE, version 4.0. Results The most common cutaneous side effects were hyperkeratotic perifollicular rash (69%) and photosensitivity (15%). Skin rash developed more frequently in the first month of treatment. Squamous cell carcinoma occurred in 38% of patients. Patients with skin cancer development during vemurafenib therapy had non-significantly longer overall survival (OS) than patients without skin cancer, p = 0.4. Skin cancer developed more often in women than in men (60% vs. 25%), p = 0.249. It was detected only in patients with normal weight compared to overweight patients (55% vs. 0), p = 0.09. The median OS was 26 months and median OS from the time of distant metastases diagnosis was 9.8 months. In patients with a low body mass index, shorter OS was observed, p = 0.09. Conclusions The incidence of squamous cell carcinoma was high (38%). This study has many limitations mostly due to a small group of patients. That is why the results should be taken into consideration with caution. The proper symptomatic treatment in cooperation with dermatologists allows to continue the vemurafenib therapy. PMID:26985180

  14. Severe toxicity of skin rash, fever and diarrhea associated with imatinib: case report and review of skin toxicities associated with tyrosine kinase inhibitors

    PubMed Central

    Huang, Xuan; Patel, Samir; Ahmed, Nasir; Seiter, Karen; Liu, Delong

    2008-01-01

    Chronic myeloid leukemia (CML) is characterized by a Philadelphia chromosome which contains an oncogene, bcr-abl. This oncogene encodes a tyrosine kinase which is constitutively activated. Imatinib, a tyrosine kinase inhibitor (TKI), has been widely used in the treatment of CML. Dasatinib and nilotinib were recently approved for the treatment of CML. Other TKIs, such as bosutinib, erlotinib, and sunitinib, are under study for the treatment of CML as well as other hematologic and solid malignancies. Skin rash has been reported as one of the most common side effects of the TKIs. Here we present a case of severe skin rash together with unusual symptoms of high fever and diarrhea induced by imatinib in a CML patient. The dermatologic toxicities from a variety of tyrosine kinase inhibitors are reviewed and general principles of management are also discussed. PMID:19920908

  15. Isolation and characterization of acutely toxic fractions in oil sands wastewater

    SciTech Connect

    Verbeek, A.; Mackay, W.; MacKinnon, M.

    1995-12-31

    Extraction of oil from oil sand using the hot water flotation method results in the production of large volumes of wastewater that are acutely toxic to aquatic organisms. At Syncrude Canada Ltd. and Suncor Oil Sands Group Inc., this wastewater is stored in large tailings ponds that must eventually be reclaimed. The acute toxicity of these wastewaters was assessed and the acutely toxic fractions were identified. Samples were collected from the surface and fine tails zones of the Syncrude and Suncor tailings ponds during the summers of 1991 and 1992. The Microtox bioassay was used to assess the acute toxicity before and after various treatments. Where significant reductions in acute toxicity were found, further acute toxicity tests were carried out using Daphnia magna and rainbow trout. The Microtox IC{sub 50} of all centrifuged tailings pond water samples varied between 26.5 and 46%. Daphnia LC{sub 50}s varied between 76 and 98% and a rainbow trout LC{sub 50} was 12.5 %. Organic compounds that have a non-polar component, as removed by solid phase extraction with C{sub 18} sorbent, accounted for all the acute toxicity (100%) of all samples. Organic ``acids``, as removed by precipitation at pH 2.5, also accounted for all the acute toxicity (100%) of all samples except those from pond 1A of Suncor. In pond 1A, organic ``acids`` accounted for approximately 55--60% of the acute toxicity, nonpolar organic volatile compounds accounted for approximately 20--35% and the balance of the acute toxicity was due to non-polar organic compounds that were neither volatile nor organic ``acids``, as removed by precipitation at pH 2.5.

  16. Evidence from a breast cancer hypofractionated schedule: late skin toxicity assessed by ultrasound

    PubMed Central

    2013-01-01

    Background Feasibility of whole breast hypofractionated radiotherapy schedules in breast conserving therapy is recognized however concerns remain about the role of the boost dose on the overall treatment’s potential toxicity. In this study we report on the possibility to quantitatively evaluate radiation induced toxicity in patients treated with an abbreviated course with major concern in the irradiated boost region. Methods Eighty-nine patients who underwent conservative surgery for early-stage breast cancer followed by adjuvant accelerated hypofractionated whole breast radiotherapy were included in this study to assess skin and subcutaneous tissue late toxicity by means of ultrasonographic quantitative examination. For each patient the skin thickness was measured at four positions: on the irradiated breast, in the boost region and in the corresponding positions in the contra-lateral not treated breast. All patients were scanned by the same radiologist to reduce potential inter-operator variability, the operator was blind to the scoring of the patient CTCv3 late toxicity as well as patient treatment characteristics. Ultrasound assessment and clinical evaluation were compared. Results The median time between the end of adjuvant radiotherapy and ultrasound examination was 20.5 months. The measured mean skin thickness in the irradiated breast was 2.13 ± 0.72 mm while in the mirror region of the contra-lateral healthy breast was 1.61 ± 0.29 mm. The measured mean skin thickness in the irradiated boost region was 2.25 ± 0.79 mm versus 1.63 ± 0.33 mm in the corresponding region of contra-lateral healthy breast. The mean increment in skin thickness respect to the counterpart in the healthy breast was 0.52 ± 0.67 mm and 0.62 ± 0.74 mm for the breast and the boost region respectively. A significant direct correlation was found between the increment in skin thickness in the irradiated breast and in the boost region with fibrosis (G ≥ 1). Conclusions In this study

  17. Comparative analysis of the acute response of zebrafish Danio rerio skin to two different bacterial infections.

    PubMed

    Lü, Aijun; Hu, Xiucai; Wang, Yi; Shen, Xiaojing; Zhu, Aihua; Shen, Lulu; Ming, Qinglei; Feng, Zhaojun

    2013-12-01

    Skin is an important innate immune organ in fish; however, little is known about the skin's immune response to infectious pathogens. We conducted a comparative analysis of the acute immune response of Zebrafish Danio rerio skin against gram-positive (Staphylococcus chromogenes) and gram-negative (Citrobacter freundii) bacterial infections. Gene expression profiles induced from the two different infections were identified by microarray hybridization, with many genes demonstrating an acute immune response in the skin. Differentially expressed genes were mainly involved in response to stress and stimulus, complement activation, acute-phase response, and defense and immune response. Compared with transcription patterns of skin from the two infections, a similar innate immunity (e.g., transferrin, coagulation factor, complements, and lectins) was observed but with different acute-phase genes (e.g., ceruloplasmin, alpha-1-microglobulin, vitellogenin, and heat shock protein). These results suggest that the skin of fish plays an important role in the innate immune responses to bacterial infection. PMID:24341765

  18. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  19. Acute toxicity of methyl mercury to the larval lamprey, Petromyzon marinus

    SciTech Connect

    Mallatt, J.; Barron, M.G.; McDonough, C.

    1986-08-01

    Mercury compounds pollute many aquatic habitats and are extremely toxic to aquatic organisms. Acute toxicity of waterborne methyl mercury has been studied in several teleost species. Lampreys are taxonomically distant from teleosts and are used for comparative toxicological purposes. Landlocked sea lampreys, Petromyzon marinus, inhabit the Great Lakes region, and their larvae (ammocoetes) burrow in stream sediments. In this study, the authors present toxicity curves for ammocoetes exposed acutely to methyl mercuric chloride solutions. Susceptibility was related to temperature and animal size.

  20. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    PubMed Central

    2012-01-01

    Background Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose) were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats. There were no delayed effects

  1. Transitions of care in the management of acute bacterial skin and skin structure infections: a paradigm shift.

    PubMed

    Verastegui, Jaime E; Hamada, Yukihiro; Nicolau, David P

    2016-08-01

    Acute bacterial skin and skin structure infections (ABSSSI) have evolved over a relatively short period of time to become one of the most challenging medical problems encountered in clinical practice. Notably the high incidence of methicillin-resistant S. aureus (MRSA) across the continuum of care has coincided with increased outpatient failures and higher rates of hospital admissions for parental antibiotic therapy. Consequently the management of ABSSSI constitutes a tremendous burden to the healthcare system in terms of cost of care and consumption of institutional and clinical resources. This perspective piece discusses current and new approaches to the management of ABSSSI in a hospital setting and the need for a multifaceted approach. Treatment strategies for the management through the utilization of observation units (OU), Outpatient Parental Antibiotic Therapy (OPAT), and newly developed antibiotics for the use against skin infections caused by Gram-positive bacteria will be discussed in the context of ABSSSI. PMID:27248789

  2. Comparative acute toxicity of potassium permanganate to nontarget aquatic organisms.

    PubMed

    Hobbs, Melissa S; Grippo, Richard S; Farris, Jerry L; Griffin, Billy R; Harding, Lora L

    2006-11-01

    Potassium permanganate (KMnO4) is used worldwide in freshwater pond aquaculture for treatment and prevention of waterborne external parasitic, bacterial, and fungal diseases. Nevertheless, KMnO4 has not been approved by the U.S. Food and Drug Administration, and insufficient information exists to allow evaluation of the environmental risk of KMnO4 exposures. Limited data exist concerning KMnO4 toxicity to nontarget species in systems receiving aquaculture effluent from treated ponds. The goal of this research is to generate effects data for use in developing an ecological risk assessment of KMnO4. Toxicity tests were used to compare the relative sensitivities of five standard aquatic test species to KMnO4. Acute toxicity test results using synthetic moderately hard water show static 96-h mean median lethal concentration (LC50) values +/- standard deviation (SD) of 0.058 +/- 0.006 mg/L for Ceriodaphnia dubia, 0.053 +/- 0.009 mg/L for Daphnia magna, 2.13 +/- 0.07 mg/L for Pimephales promelas, 4.74 +/- 1.05 mg/L for Hyalella azteca, and 4.43 +/- 0.79 mg/L for Chironomus tentans. Most of these values are below the recommended KMnO4 treatment rate of at least 2.0 mg/L or 2.5 times the water's potassium permanganate demand (PPD; an estimation of the available reducing agents in the exposure water), suggesting significant environmental risk. However, repeating these laboratory tests using pond water resulted in significantly reduced toxicity, with static 96-h mean LC50 values (+/-SD) of 2.39 +/- 0.36 mg/L for C. dubia, 1.98 +/- 0.12 mg/L for D. magna, 11.22 +/- 1.07 mg/L for P. promelas, 13.55 +/- 2.24 mg/L for H. azteca, and 12.30 +/- 2.83 mg/L for C. tentans. The PPD of synthetic moderately hard water was 0.329 +/- 0.114 mg/L; however, pond water PPD was 5.357 +/- 0.967 mg/L. The effective disease-treating dose based on 2.5 times the PPD would thus be 0.823 and 13.392 mg KMnO4/L, respectively, exceeding the LC50 for most of these nontarget organisms, even in pond water

  3. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  4. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. PMID:26697225

  5. Topical versus Systemic Antibiotics in the Treatment of Acute Superficial Skin Infections

    PubMed Central

    Belcon, Michael C.

    1979-01-01

    Use of antibiotics in some superficial skin infections is examined. The choice of a route of administration is dependent on a number of factors, including the site and extent of skin lesions, frequency of recurrence, and clinical and immunological state of the host. However, the consensus of various studies on the subject seem to indicate a preference for the systemic route in acute infectious dermatoses. PMID:423278

  6. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    PubMed Central

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  7. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  8. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    PubMed

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results. PMID:25694074

  9. Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer.

    PubMed

    Sun, Li-Min; Huang, Chih-Jen; Chen, Hsiao-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

    2016-01-01

    We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT. PMID:27158022

  10. Acute toxicity of biodiesel to freshwater and marine organisms

    SciTech Connect

    Reece, D.; Peterson, C.

    1995-11-01

    Biodiesel fuels are reported to be nontoxic resulting in less potential hazard to fish and other aquatic life in case of accidental spills. This paper reports on static tests with rapeseed methyl ester (RME) and rapeseed ethyl ester (REE) performed according to EPA/600/4-90/027. The acute aquatic toxicity tests were conducted with both rainbow trout and daphnia magna by CH2M Hill in Corvallis, Oregon under contract to the University of Idaho. The LC50 (the point at which 50% have died and 50% are still alive determined by interpolation) values for each of the substrates tested with daphnia magna in parts per million were as follows: control(table salt (NaCl)) = 3.7, D2 = 1.43, RME = 23, REE = 99, and Methyl Soyate = 332. Duplicate tests with rainbow trout were run with 10 organisms per replicate. LC50 numbers were not reported because of the failure to kill a sufficient number of fish at the concentrations tested, even with the diesel control fuel. The 20 percent and 50 percent blends had scattered losses of fish but none of the tests had less than 85 percent survival at any concentrations after 96 hours.

  11. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  12. High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

    SciTech Connect

    Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus; Schueler, Phillip; Herrmann, Markus Karl; Hennies, Steffen; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans

    2011-04-01

    Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

  13. Topical absorption and toxicity studies of jet fuel hydrocarbons in skin

    NASA Astrophysics Data System (ADS)

    Muhammad, Faqir

    Kerosene-based fuels have been used for many decades. Over 2 million military and civilian personnel each year are occupationally exposed to various jet fuel mixtures. Dermatitis is one of the major health concerns associated with these exposures. In the past, separate absorption and toxicity studies have been conducted to find the etiology of such skin disorders. There was a need for integrated absorption and toxicity studies to define the causative constituents of jet fuel responsible for skin irritation. The focus of this thesis was to study the percutaneous absorption and to identify the hydrocarbons (HC) causing irritation in jet fuels so that preventive measures could be taken in the future. The initial study was conducted to understand the possible mechanism for additive interactions on hydrocarbon absorption/disposition in silastic, porcine skin and isolated perfused porcine skin flap (IPPSF) models. The influence of JP-8 (100) additives (MDA, BHT, 8Q405) on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of HC absorption was evaluated. This study indicated that individual and combination of additives influenced marker disposition in different membranes. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption in IPPSF. The 8Q405 significantly reduced naphthalene content in dosed silastic and skin indicating a direct interaction between additive and marker HC. Similarly, the individual MDA and BHT significantly retained naphthalene in the stratum corneum of porcine skin, but the combination of both of these additives statistically decreased the marker retention in the stratum corneum suggesting a potential biological interaction. This study concluded that all components of a chemical mixture should be assessed since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture. However, this study indicated that the marker HC

  14. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. PMID:25791923

  15. Importance of structural information in predicting human acute toxicity from in vitro cytotoxicity data

    SciTech Connect

    Lee, Soyoung; Park, Keunwan; Ahn, Hee-Sung; Kim, Dongsup

    2010-07-15

    In this study, we tried to assess the utility of the structural information of drugs for predicting human acute toxicity from in vitro basal cytotoxicity, and to interpret the informative quality and the pharmacokinetic meaning of each structural descriptor. For this, human acute toxicity data of 67 drugs were taken from literature with their basal cytotoxicity data, and used to develop predictive models. A series of multiple linear regression analyses were performed to construct feasible regression models by combining molecular descriptors and cytotoxicity data. We found that although the molecular descriptors alone had only moderate correlation with human acute toxicity, they were highly useful for explaining the discrepancy between in vitro cytotoxicity and human acute toxicity. Among many possible models, we selected the most explanatory models by changing the number and the type of combined molecular descriptors. The results showed that our selected models had high predictive power (R{sup 2}: between 0.7 and 0.87). Our analysis indicated that those successful models increased the prediction accuracies by providing the information on human pharmacokinetic parameters which are the major reason for the difference between human acute toxicity and cytotoxicity. In addition, we performed a clustering analysis on selected molecular descriptors to assess their informative qualities. The results indicated that the number of single bonds, the number of hydrogen bond donors and valence connectivity indices are closely related to linking cytotoxicity to acute toxicity, which provides insightful explanation about human toxicity beyond cytotoxicity.

  16. Bilayer Cryogel Wound Dressing and Skin Regeneration Grafts for the Treatment of Acute Skin Wounds.

    PubMed

    Priya, S Geetha; Gupta, Ankur; Jain, Era; Sarkar, Joyita; Damania, Apeksha; Jagdale, Pankaj R; Chaudhari, Bhushan P; Gupta, Kailash C; Kumar, Ashok

    2016-06-22

    In this study, the potential of cryogel bilayer wound dressing and skin regenerating graft for the treatment of surgically created full thickness wounds was evaluated. The top layer was composed of polyvinylpyrrolidone-iodine (PVP-I) cryogel and served as the antiseptic layer, while the bottom regenerative layer was made using gelatin cryogel. Both components of the bilayer showed typical features of a cryogel interconnected macropore network, rapid swelling, high water uptake capacity of about 90%. Both PVP and gelatin cryogel showed high tensile strength of 45 and 10 kPa, respectively. Gelatin cryogel sheets were essentially elastic and could be stretched without any visible deformation. The antiseptic PVP-I layer cryogel sheet showed sustained iodine release and suppressed microbial growth when tested with skin pathogens (zone of inhibition ∼2 cm for sheet of 0.9 cm diameter). The gelatin cryogel sheet degraded in vitro in weeks. The gelatin cryogel sheet supported cell infiltration, attachment, and proliferation of fibroblasts and keratinocytes. Microparticles loaded with bioactive molecules (mannose-6-phosphate and human fibrinogen) were also incorporated in the gelatin cryogel sheets for their role in enhancing skin regeneration and scar free wound healing. In vivo evaluation of healing capacity of the bilayer cryogel was checked in rabbits by creating full thickness wound defect (diameter 2 cm). Macroscopic and microscopic observation at regular time intervals for 4 weeks demonstrated better and faster skin regeneration in the wound treated with cryogel bilayer as compared to untreated defect and the repair was comparable to commercial skin regeneration scaffold Neuskin-F. Complete skin regeneration was observed after 4 weeks of implantation with no sign of inflammatory response. Defects implanted with cryogel having mannose-6-phosphate showed no scar formation, while the wound treated with bilayer incorporated with human fibrinogen microparticles showed

  17. Acute toxicity by water containing hexavalent or trivalent chromium in native Brazilian fish, Piaractus mesopotamicus: anatomopathological alterations and mortality.

    PubMed

    Castro, Marcello Pardi; de Moraes, Flávio Ruas; Fujimoto, Rodrigo Yudi; da Cruz, Claudinei; Belo, Marco Antonio de Andrade; de Moraes, Julieta Rodini Engrácia

    2014-02-01

    This study evaluated the toxicity of hexavalent and trivalent compounds of chromium to the pacu, Piaractus mesopotamicus, in acute exposures of 96 h through mortality and histopathological responses. Hexavalent potassium dichromate was more toxic than trivalent compounds of chromium chloride, chromium oxide and chromium carbochelate. Sufficient mortalities occurred only with potassium dichromate to yield an LC50 value at 124.2 mg L(-1). Hexavalent chromium caused reversible and irreversible lesions, which may affect organ functionality. Histopathological evaluation showed that trivalent chromium caused lesions of lower severity. Pacu subjected to different concentrations of chromium carbochelate showed no histopathological changes in the kidneys, liver, skin and gills, being similar to those of the control fish. Among the three sources of Cr(3+), only chromium chloride at 200 mg L(-1) resulted in mortality, which reached 100 % within the first 18 h. These findings confirm that trivalent chromium, when administered within recommended levels, may be used safely in aquaculture. PMID:24346495

  18. Results of acute and chronic toxicity tests conducted at SRS NPDES outfalls, July--October 1991

    SciTech Connect

    Specht, W.L.

    1992-01-01

    Acute (48 hour LC50) and chronic (7-day reproductive impairment) toxicity tests were conducted on Ceriodaphnia dubia in water collected from 53 NPDES outfalls. All tests were conducted at the in-stream waste concentration. only 12 of the 53 outfalls showed no evidence of toxicity. Twenty-eight of the outfalls were acutely toxic, often producing 100% mortality during the first day of exposure. Fourteen outfalls had no discharge at the time of sampling and could not be tested. Three outfalls were not tested because their toxicity has been adequately characterized in other investigations. Elevated concentrations of total residual chlorine are suspected to be responsible for the observed toxicity of many NPDES outfalls, particularly the sanitary wastewater treatment plants. Chemical data from previous studies indicate that metals may also be present in toxic concentrations at many outfalls. Toxicity identification and reduction options are discussed.

  19. The impact of skin viability on drug metabolism and permeation -- BSA toxicity on primary keratinocytes.

    PubMed

    Haberland, A; Schreiber, S; Maia, C Santos; Rübbelke, M K; Schaller, M; Korting, H C; Kleuser, B; Schimke, I; Schäfer-Korting, M

    2006-04-01

    For testing cutaneous absorption of drugs, ingredients of cosmetics and also for risk assessment of industrial compounds predictable in vitro test protocols are under investigation using excised skin or reconstructed human epidermis. Since the metabolizing enzymes expressed by viable skin can influence the absorption behaviour of substances by changing their structure and thereby their physicochemical characteristics, the metabolic capacity should be considered in the design of the test protocols of compounds susceptible to metabolism. Then data, generated using viable reconstructed epidermis may reflect the in vivo situation. Interestingly, bovine serum albumin (BSA) commonly used in receptor media in permeation studies to facilitate solubility of highly lipophilic substances strongly inhibited the metabolism of topically applied prednicarbate in reconstructed epidermis. Here, we show that 5% BSA is toxic to reconstructed epidermis and keratinocytes which was consistent with the earlier findings. While media toxicity (deficiency media) was at least partly the cause of both apoptotic and necrotic processes in keratinocytes, BSA only slightly increased the rate of necrotic cells. Moreover, caspase inhibitors did not reduce BSA toxicity. Yet, the results show that BSA toxicity on keratinocytes has to be carefully considered if this protein is used in permeation studies with reconstructed epidermis. PMID:16182510

  20. ESTIMATION OF AQUATIC SPECIES SENSITIVITY USING INTERSPECIES CORRELATION AND ACUTE TO CHRONIC TOXICITY MODELS

    EPA Science Inventory

    Abstract for presentation

    Estimation of aquatic species sensitivity using interspecies correlation and acute to chronic toxicity models

    Determining species sensitivity of aquatic organisms to contaminants is a critical component of criteria development and ecolog...

  1. Assessing Contaminant Sensitivity of Endangered and Threatened Aquatic Species: Part I. Acute Toxicity of Five Chemicals

    EPA Science Inventory

    This paper reports on the results of acute toxicity tests conducted with common surrogate species, and several species of threatened and endangered species for which there were excess artificially propagated stock to allow direct testing.

  2. FISH ACUTE TOXICITY SYNDROMES IN THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS.

    EPA Science Inventory

    The focus of this report is to summarize the development and status of the fish acute toxicity syndrome (FATS) research effort. hus far, FATS associated with nonpolar narcotics, oxidative phosphorylation uncouplers, respiratory membrane irritants, acetylcholinesterase (AChE) inhi...

  3. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  4. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    PubMed Central

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  5. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

    PubMed

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents. PMID:27326543

  6. Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

    PubMed

    Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

    2015-06-01

    The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

  7. Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

    PubMed

    Maynard, Samuel K; Edwards, Peter; Wheeler, James R

    2014-07-01

    Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

  8. Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer.

    PubMed

    Takahashi, Naoki; Yamada, Yasuhide; Furuta, Koh; Nagashima, Kengo; Kubo, Akiko; Sasaki, Yusuke; Shoji, Hirokazu; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro

    2015-05-01

    Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients. PMID:25707609

  9. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  10. Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment.

    PubMed

    Atrux-Tallau, Nicolas; Romagny, Céline; Padois, Karine; Denis, Alain; Haftek, Marek; Falson, Françoise; Pirot, Fabrice; Maibach, Howard I

    2010-08-01

    Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach. PMID:20043170

  11. Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

    PubMed

    Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

    2014-12-01

    A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. PMID:25259848

  12. Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of “Zapote” Pouteria mammosa (L.) Cronquist

    PubMed Central

    Dutok, Carlos M. S.; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M. C.

    2015-01-01

    The common use of Pouteria mammosa (L.) Cronquist, “Mamey or Zapote,” in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating. PMID:26273696

  13. Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of "Zapote" Pouteria mammosa (L.) Cronquist.

    PubMed

    Dutok, Carlos M S; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M C

    2015-01-01

    The common use of Pouteria mammosa (L.) Cronquist, "Mamey or Zapote," in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating. PMID:26273696

  14. In Vitro Skin Models and Their Predictability in Defining Normal and Disease Biology, Pharmacology, and Toxicity.

    PubMed

    Danilenko, Dimitry M; Phillips, Gail D Lewis; Diaz, Dolores

    2016-06-01

    In vitro skin model systems are increasingly being used both in the early evaluation of therapeutic drug candidates and in confirmatory mechanistic studies. The most commonly used of these in vitro model systems are reconstituted human epidermis (RHE) models. These RHE models consist solely of epidermal keratinocytes, which comes with some limitations but also with the advantage of focusing toxicologic and pharmacologic evaluation on keratinocytes alone. RHE models can generally be implemented more quickly, easily, and reproducibly than in vivo models and can thus be used for high throughput compound screening while potentially reducing the need for animal studies. Histologic evaluation of RHE sections can be done quite easily, and the sections are very amenable to quantification via image analysis, including automated analysis. RHE model systems can provide very valuable early indications of therapeutic candidate biology, pharmacology, and toxicity; and early results have demonstrated that RHE models have been quite predictive for in vivo pharmacologic and toxicologic effects on the skin, including clinical skin toxicity. PMID:26940714

  15. Qsars for photoinduced toxicity: 1. acute lethality of polycyclic aromatic hydrocarbons to daphnia magna'

    SciTech Connect

    Mekenyan, O.G.; Ankley, G.T.; Veith, G.D.; Call, D.J.

    1994-01-01

    Research with a variety of aquatic species has shown that while polycyclic aromatic hydrocarbons (PAHs) are generally not acutely toxic in conventional laboratory tests, many are extremely toxic in the presence of sunlight. In an effort to develop a model for predicting which PAHs may exhibit photo-induced toxicity, Newsted and Giesy (1987) reported a parabolic relationship between the toxicity and the energy of the triplet state of a variety of PAHs. The authors have reexamined these data and propose a more mechanistic explanation for the prediction of photo-induced PAH toxicity. They sought a molecular descriptor which could be computed from structure rather than measured empirically.

  16. ACUTE TOXICITY OF SELECTED SUBSTITUTED PHENOLS, BENZENES AND BENZOIC ACID ESTERS TO FATHEAD MINNOWS 'PIMEPHALES PROMELAS'

    EPA Science Inventory

    Flow-through acute toxicity tests were conducted with 24 organic compounds using fathead minnows Pimephales promelas as test organisms. The tested toxicants consisted of 11 substituted phenols, four substituted benzenes and nine esters. The 96-h LC50 values determined for these c...

  17. COMPARATIVE ACUTE TOXICITIES OF SEVERAL PESTICIDES AND METALS TO MYSIDOPSIS BAHIA AND POSTLARVAL PENAEUS DUORARUM

    EPA Science Inventory

    Effects of toxic chemicals on estuarine and marine crustaceans are often evaluated using the mysid, Mysidopsis bahia. n a literature survey of results of acute toxicity tests with estuarine crustaceans, Mysidae and Penaeidae were generally the two most sensitive families. owever,...

  18. BEHAVIORAL TOXICITY OF ACUTE AND SUBACUTE EXPOSURE TO TRIETHYLTIN IN THE RAT

    EPA Science Inventory

    Triethyltin (TET), the most toxic of the alkyltin compounds is used industrially as both a catalyst and a biocide (NIOSH, 1976). Stoner et al. (1955) determined the acute toxicity of a series of alkyltins and reported that in the rat, the LD50 for TET was 5.7 mg/kg. Barnes and St...

  19. TLD skin dose measurements and acute and late effects after lumpectomy and high-dose-rate brachytherapy only for early breast cancer

    SciTech Connect

    Perera, Francisco . E-mail: francisco.perera@lrcc.on.ca; Chisela, Frank; Stitt, Larry; Engel, Jay; Venkatesan, Varagur

    2005-08-01

    lumpectomy site (p < 0.001). Grade 1 or more fibrosis, in 25 patients with a 60-month follow-up, occurred in 47.4% (9 of 19) of patients with a volume of 45 cm{sup 3} or less covered by the 100% isodose vs. 83.3% (5 of 6) of patients with a larger volume (p 0.180). Asymptomatic and biopsy-proven fat necrosis occurred in 5 patients. No significant differences in fat necrosis rates according to volume were detected. Conclusions: For high-dose-rate brachytherapy to the lumpectomy site, TLD skin dose was significantly related to acute skin reaction and to pigmentation and telangiectasia at 60 months. An acute skin reaction was also significantly associated with the development of telangiectasia at 60 months. TLD skin dose measurement may allow modification of the brachytherapy implant geometry (dwell times and position) to minimize late skin toxicity.

  20. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    PubMed Central

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes. PMID:25834395

  1. Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity.

    PubMed

    Mauro, Marcella; Crosera, Matteo; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Piero; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Filon, Francesca Larese

    2015-07-01

    Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs) have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1) and needle-abraded human skin (experiment 2). Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled-Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm⁻²), while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm⁻²) and those with intact skin (1.08 ± 0.20 ng·cm⁻²). To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue and propidium iodide (PI) uptake assays. The results indicate that a long exposure time (i.e., seven days) was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10-4 M, 95% CL = 0.8-1.9 × 10⁻⁴ M, MTT essay; 3.7 × 10⁻⁵ M, 95% CI = 2.2-6.1 × 10⁻⁵ M, AlamarBlue assay) that seems to be associated to necrotic events (EC50 value: 1.3 × 10⁻⁴ M, 95% CL = 0.9-1.9 × 10⁻⁴ M, PI assay). This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure. PMID:26193294

  2. Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

    PubMed Central

    Mauro, Marcella; Crosera, Matteo; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Piero; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Larese Filon, Francesca

    2015-01-01

    Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs) have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1) and needle-abraded human skin (experiment 2). Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2), while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2) and those with intact skin (1.08 ± 0.20 ng·cm−2). To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI) uptake assays. The results indicate that a long exposure time (i.e., seven days) was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay) that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay). This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure. PMID:26193294

  3. Acute toxicity of furazolidone on Artemia salina, Daphnia magna, and Culex pipiens molestus larvae

    SciTech Connect

    Macri, A.; Stazi, A.V.; Dojmi di Delupis, G.

    1988-10-01

    As a result of evidence of the ecotoxicity of nitrofurans, the acute toxicity of furazolidone was tested in vivo on two aquatic organisms, Artemia salina and Daphnia magna, which are both crustaceans. Toxicity studies were also performed on larvae of Culex pipiens molestus. Results indicated a significant toxicity of the compound on Culex pipiens and Daphnia magna, while Artemia salina proved to be the least sensitive.

  4. Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

    PubMed

    Giddings, Jeffrey; Gagne, James; Sharp, Janice

    2016-08-01

    A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. PMID:26762236

  5. Estimates of the spatial extent of acute toxicity in sediments of selected USA estuaries

    SciTech Connect

    Long, E.; Robertson, A.; Sloane, G.; Boswell, H.

    1995-12-31

    Acute toxicity has been measured in sediments collected during surveys of 18 estuaries in the USA. The spatial patterns, severity, and magnitude of toxicity have been determined during these surveys. Also, by weighting the toxicity data to the sizes of the sampling strata, the spatial extent of toxicity (expressed in kilometers{sup 2}) was estimated. The data from a battery of tests with different sensitivities were used to identify the relative severity of toxicity and to identify those areas that were most degraded. Accordingly, the spatial scales of toxicity within each estuary differed according to the sensitivities of the different tests. The spatial extent of toxicity measured in each standardized test was compared among different areas. For example, the results of the amphipod survival tests indicated that the spatial extent of toxicity ranged from 0.0% to over 85% among the different study areas.

  6. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    SciTech Connect

    Liu, T; Yang, X; Curran, W; Torres, M

    2014-06-15

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  7. A Study on Dosimetric Outcomes and Acute Toxicity of Post Mastectomy Adjuvant Hypofractionated Radiotherapy for Breast Cancer

    PubMed Central

    Deshmukh, Shivaprasad; Fernandes, Donald Jerard; Srinivasa, Vidyasagar Mamidipudi; Yathiraj, Prahlad Hiremagalur; Singh, Anshul; Reddy, Anusha

    2016-01-01

    Introduction Hypofractionated External Beam Radiotherapy (HFRT) is a relatively new adjuvant Radiotherapy (RT) schedule for breast cancers following breast conservation surgery and less commonly, following mastectomy. Here we report our experience on normal tissue exposure and acute toxicity of HFRT after mastectomy. Aim To assess the dosimetric outcomes and acute toxicity profile of adjuvant HFRT following mastectomy for breast cancer. Materials and Materials This prospective observational study considered consecutive patients planned for adjuvant HFRT (42.5 Gy in 16 sessions delivered over 3 weeks) to the chest wall with/without regional nodes between October 2014 and June 2015. The dosimetric parameters including dose homogeneity to the target volume and exposure to heart and lung were analyzed. Acute haematological and dermatological toxicity was recorded until upto three months after completion of RT. Results Among the 56 patients treated with HFRT, the mean age was 49 years (range: 28-69 years). Pathologically positive nodes and ≥pT3 primary was observed in 44 (78.6%) and 12 (21.4%) patients, respectively. Majority (87.5%) received prior adjunct chemotherapy. RT to the supraclavicular fossa was delivered for 39 (69.6%) patients. The mean V90 and V95 to the Planning Target Volume (PTV) were 95% (± 3.3%) and 93% (± 4%), respectively. The maximum dose received was on average 47.7 Gy (112%; range: 46.2-48.5 Gy). The mean lung dose was 10.2 Gy (± 3.5 Gy) and V20 was 20.9% (± 6%). The mean V25 to heart was 6.6% (± 4.8%) for left sided and 0% for right sided tumours (p=0.001). Acute skin toxicity peaked at completion of RT and was tolerable (grade 0, I, II and III reactions were 75%, 16% and 1.8%, respectively). No patient had ≥ grade III haematological toxicity, and treatment was not interrupted for any patient. Conclusion Adjuvant HFRT could be planned while meeting the dose constraints to normal tissues in all patients and was well tolerated, with mild

  8. Anti-epidermal growth factor receptor skin toxicity: a matter of topical hydration.

    PubMed

    Ferrari, Daris; Codecà, Carla; Bocci, Barbara; Crepaldi, Francesca; Violati, Martina; Viale, Giulia; Careri, Carmela; Caldiera, Sarah; Bordin, Veronica; Luciani, Andrea; Zonato, Sabrina; Cassinelli, Gabriela; Foa, Paolo

    2016-02-01

    Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response. PMID:26469836

  9. Contact toxicities of anuran skin alkaloids against the fire ant ( Solenopsis invicta)

    NASA Astrophysics Data System (ADS)

    Weldon, Paul J.; Cardoza, Yasmin J.; Vander Meer, Robert K.; Hoffmann, W. Clint; Daly, John W.; Spande, Thomas F.

    2013-02-01

    Nearly 500 alkaloids, representing over 20 structural classes, have been identified from the skin of neotropical poison frogs (Dendrobatidae). These cutaneous compounds, which are derived from arthropod prey of the frogs, generally are believed to deter predators. We tested the red imported fire ant ( Solenopsis invicta) for toxicosis following contact with 20 alkaloids (12 structural classes) identified from dendrobatids or other anurans. Individual ants forced to contact the dried residues of 13 compounds exhibited convulsions and/or reduced ambulation. We estimated the cutaneous concentrations of several compounds based on their reported recoveries from skin extracts of free-ranging frogs and our measurements of the skin surface areas of museum specimens. Pumiliotoxin 251D exhibited contact toxicity below its estimated cutaneous concentration in the Ecuadorian frog, Epipedobates anthonyi, an observation consistent with the hypothesized role of this compound in anuran chemical defense. Our results and those of a previous study of mosquitoes indicate that some anuran skin compounds function defensively as contact toxins against arthropods, permeating their exoskeleton.

  10. MOAtox: A comprehensive mode of action and acute aquatic toxicity database for predictive model development.

    PubMed

    Barron, M G; Lilavois, C R; Martin, T M

    2015-04-01

    The mode of toxic action (MOA) has been recognized as a key determinant of chemical toxicity and as an alternative to chemical class-based predictive toxicity modeling. However, the development of quantitative structure activity relationship (QSAR) and other models has been limited by the availability of comprehensive high quality MOA and toxicity databases. The current study developed a dataset of MOA assignments for 1213 chemicals that included a diversity of metals, pesticides, and other organic compounds that encompassed six broad and 31 specific MOAs. MOA assignments were made using a combination of high confidence approaches that included international consensus classifications, QSAR predictions, and weight of evidence professional judgment based on an assessment of structure and literature information. A toxicity database of 674 acute values linked to chemical MOA was developed for fish and invertebrates. Additionally, species-specific measured or high confidence estimated acute values were developed for the four aquatic species with the most reported toxicity values: rainbow trout (Oncorhynchus mykiss), fathead minnow (Pimephales promelas), bluegill (Lepomis macrochirus), and the cladoceran (Daphnia magna). Measured acute toxicity values met strict standardization and quality assurance requirements. Toxicity values for chemicals with missing species-specific data were estimated using established interspecies correlation models and procedures (Web-ICE; http://epa.gov/ceampubl/fchain/webice/), with the highest confidence values selected. The resulting dataset of MOA assignments and paired toxicity values are provided in spreadsheet format as a comprehensive standardized dataset available for predictive aquatic toxicology model development. PMID:25700118

  11. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    SciTech Connect

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-06-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity.

  12. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  13. Toxicity of 8-Hydroxyquinoline in Cryprinus carpio Using the Acute Toxicity Test, Hepatase Activity Analysis and the Comet Assay.

    PubMed

    Yan, Shuaiguo; Chen, Lili; Dou, Xiaofei; Qi, Meng; Du, Qiyan; He, Qiaoqiao; Nan, Mingge; Chang, Zhongjie; Nan, Ping

    2015-08-01

    To evaluate the environmental toxicity of 8-hydroxyquinoline (8-HOQ), an important industrial raw material found in China's major ornamental fish, Cryprinus carpio, using the acute toxicity test, hepatase activity analysis and the comet assay. The results indicated that 8-HOQ had significant acute toxicity in adult C. carpio with a 96 h-LC50 of 1.15 and 0.22 mg L(-1) hepatic quinoline residues as assessed by HPLC. 8-HOQ also induced genotoxicity in the form of strand breaks in the DNA of hepatic cells as shown by the comet assay. With regard to physiological toxicity, 8-HOQ induced a decrease in the activities of hepatic GOT and GPT with increased exposure concentration and time. These data suggest that 8-HOQ may be toxic to the health of aquatic organisms when accidentally released into aquatic ecosystems. The data also suggest that the comet assay may be used in biomonitoring to determine 8-HOQ genotoxicity and hepatic GPT and GOT activities may be potential biomarkers of physiological toxicity. PMID:26067700

  14. Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

    SciTech Connect

    Goyal, Sharad

    2011-02-01

    Purpose: Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. Methods and Materials: After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Results: Fourteen patients were identified to have received bevacizumab plus RT. All patients receivedbevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced {>=}Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Conclusion: Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

  15. Differentially expressed miRNAs in acute wound healing of the skin: a pilot study.

    PubMed

    Li, Ping; He, Quanyong; Luo, Chengqun; Qian, Liyuan

    2015-02-01

    The aim of the present study was to compare expression of microRNAs (miRNAs) from scar and normal skin areas in patients who suffered acute injuries in the skin. A total of 9 patients with acute injuries in the skin who received surgical treatment from December 2012 to March 2013 were included in this pilot study. Specimens from the hypertrophic scar and normal skin areas were obtained from the same patient during surgery. To screen for differentially expressed miRNAs, we applied 3 statistical methods, namely the traditional t test, the false discovery rate (FDR), and a novel sure independence screening procedure based on the distance correlation (DC-SIS). We examined the functional trends and metabolic and regulatory pathways for the target genes of the identified miRNAs, and explored interaction of these miRNAs in the implication of scar healing using Ingenuity Pathway Analysis. DC-SIS identified 18 differentially expressed miRNAs, 4 of which (miR-149, miR-203a, miR-222, miR-122) were also identified by FDR. The target genes of the 4 miRNAs exhibit a variety of biological functions, and are involved in various pathways such as mitogen-activated protein kinase, Wnt signaling, and focal adhesion. We identified 1 network in which 14 out of the 18 differentially expressed miRNAs were involved. Many of the miRNAs in the network target genes were involved in cell proliferation and apoptosis.In this pilot study, we identified several miRNAs exhibiting differential expression in patients who suffered acute injuries in the skin. Further studies on these miRNAs are needed to validate our findings and explore their roles in the wound healing process of the skin. PMID:25700309

  16. Acute Pain Speeds Skin Barrier Recovery in Healthy Men and Women

    PubMed Central

    Graham, Jennifer E.; Song, Sunmi; Engeland, Christopher G.

    2012-01-01

    Objective Psychological stress is known to impair skin barrier recovery, but little is known about the impact of pain on skin healing processes. Our primary goals were to examine the degree to which acute pain affects recovery from skin barrier disruption, and the potential mediating impact of cortisol and catecholamines. Methods Healthy non-smokers aged 18-43 (N=53, 65% women) underwent a 3-minute cold pressor pain stimulus to their foot. Tape-stripping of forearm skin occurred at two separate locations: before (site 1) and after (site 2) the pain stimulus. Transepidural water loss (TEWL) was assessed at baseline (pre-stripping), immediately post-stripping, and at 75 minutes to determine skin barrier recovery. Cortisol and catecholamine responses were obtained from multiple saliva and plasma samples, respectively. Results Contrary to expectations, greater pain was associated with faster skin barrier recovery, even after controlling for demographics, mood, anxiety, and other factors. Those who reported higher pain showed faster recovery at site 2 compared to a) individuals who experienced lower pain; and b) their own recovery at site 1. Greater increase in norepinephrine (but not in cortisol) was also associated with faster recovery at site 2, and mediated the impact of pain on recovery. Discussion Results bolster evidence that acute pain can affect immune-related processes. It is possible that acute pain may speed recovery from dermal abrasions, although pain is likely to impair recovery from more severe wounds. As pain is an important potential target for clinical intervention, further investigation of pain, stress, and healing processes is warranted. PMID:23148814

  17. Investigation of acute toxicity of chlorpyrifos-methyl on Nile tilapia (Oreochromis niloticus L.) larvae.

    PubMed

    Gül, Ali

    2005-04-01

    Chlorpyrifos-methyl, a wide-spectrum organophosphorus insecticide and potential toxic pollutant contaminating aquatic ecosystems, was investigated for acute toxicity. Larvae of the freshwater fish Nile tilapia (Oreochromis niloticus L.) were selected for the bioassay experiments. The experiments were repeated three times and the 96 h LC50 was determined for the larvae. The static test method for assessing acute toxicity was used. Water temperature was maintained at 25+/-1 degrees C. In addition, behavioral changes at each chlorpyrifos-methyl concentration were observed for the individual fish. Data obtained from the chlorpyrifos-methyl acute toxicity tests were evaluated using Finney's probit analysis statistical method. The 96 h LC50 value for Nile tilapia larvae was calculated to be 1.57 mg/l. PMID:15722087

  18. Acute management of skin tears: a change in practice pilot study.

    PubMed

    Vandervord, John G; Tolerton, Sarah K; Campbell, Peter A; Darke, Jan M; Loch-Wilkinson, Anna-Marie V

    2016-02-01

    Skin tears are an increasingly common injury occurring in the elderly population and have significant associated morbidity secondary to poor wound healing, prolonged hospital stays and reduced mobility. There has been a shift in practice for the acute management of skin tears within our institution, which has resulted in improved outcomes and reduced morbidity for this common and debilitating injury. Review of past and current practices including cost analyses has led to the establishment of a management protocol for the hospital and wider area health service with the aim to reduce the burden of disease amongst our ever-expanding elderly population. PMID:24612698

  19. ACUTE AND CHRONIC PARATHION TOXICITY TO FISH AND INVERTEBRATES

    EPA Science Inventory

    Acute and chronic aquatic bioassays were conducted with a variety of organisms using parathion (0,0-diethyl 0-(p-nitrophenyl) phosphorothioate) as the challenge compound. Acute LC50 values ranged from a low of 0.38 micrograms/l in invertebrates to a high of 2.0 mg/l in freshwater...

  20. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products. PMID:25510780

  1. A study of the pharmacologic control of blood flow to acute skin flaps using xenon washout. Part I

    SciTech Connect

    Hendel, P.M.; Lilien, D.L.; Buncke, H.J.

    1983-03-01

    This study was undertaken to understand the control mechanisms differentiating circulation to normal skin and acute skin flaps. The approach was to compare the effects of systemic vasoactive drugs on skin blood flow in rats in acute skin flaps and identical areas of control skin. With this model it was felt that systemic changes would affect both areas equally and any difference in response would be due to vascular control mechanisms unique to the flap. Xenon washout by percutaneous injection was chosen to measure blood flow. The results of over 8000 observations in these studies were: 1. Vasodilation enhances blood flow and flap survival. 2. Vasoconstriction decreases blood flow. 3. Depletion of sympathetic nerve terminals enhances blood flow and flap survival. 4. The acute flap is less sensitive to systemic alpha-agonists than control skin. 5. The acute flap is less sensitive to vasodilators acting at the receptor-site level than control skin. 6. Total sympathetic denervation does not occur. 7. Biologic increases in area of flap survival did occur in drug dose ranges predicted by xenon washout measurements in this model. These findings indicate that the vessels in an acutely raised skin flap have a greater vasospastic tone than is optimal for maximum nutrient blood flow. One explanation consistent with these findings is offered in which the mechanism responsible for this tone is the release of catecholamines from the sympathetic nerve terminals after the flap has been raised.

  2. Biomarkers of skin toxicity induced by anti-epidermal growth factor receptor antibody treatment in colorectal cancer

    PubMed Central

    Kubo, Akiko; Hashimoto, Hironobu; Takahashi, Naoki; Yamada, Yasuhide

    2016-01-01

    Skin toxicity is a common symptom of anti-epidermal growth factor receptor (EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer (the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing (EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients. PMID:26811634

  3. Application of OECD Guideline 423 in assessing the acute oral toxicity of moniliformin.

    PubMed

    Jonsson, Martina; Jestoi, Marika; Nathanail, Alexis V; Kokkonen, Ulla-Maija; Anttila, Marjukka; Koivisto, Pertti; Karhunen, Pirkko; Peltonen, Kimmo

    2013-03-01

    Moniliformin is a Fusarium mycotoxin highly prevalent in grains and grain-based products worldwide. In this study, the acute oral toxicity of moniliformin was assessed in Sprague-Dawley male rats according to OECD Guideline 423 with a single-dose exposure. Clinical observations and histopathological changes were recorded together with the excretion of moniliformin via urine and feces, utilizing a novel liquid chromatography-mass spectrometry method. According to our study, moniliformin is acutely toxic to rats with a rather narrow range of toxicity. Moniliformin can be classified into category 2 (LD(50) cut-off value 25 mg/kg b.w.), according to the Globally Harmonized System for the classification of chemicals. The clinical observations included muscular weakness, respiratory distress and heart muscle damage. Pathological findings confirmed that heart is the main target tissue of acute moniliformin toxicity. A significant proportion (about 38%) of the administered moniliformin was rapidly excreted in urine in less than 6 h. However, the toxicokinetics of the majority of the administered dose still requires clarification, as the total excretion was only close to 42%. Considering the worldwide occurrence of moniliformin together with its high acute toxicity, research into the subchronic toxicity is of vital importance to identify the possible risk in human/animal health. PMID:23201451

  4. Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.

    PubMed

    Kuehne, Andreas; Emmert, Hila; Soehle, Joern; Winnefeld, Marc; Fischer, Frank; Wenck, Horst; Gallinat, Stefan; Terstegen, Lara; Lucius, Ralph; Hildebrand, Janosch; Zamboni, Nicola

    2015-08-01

    Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance. PMID:26190262

  5. Acute toxicity of commonly used forestry herbicide mixtures to Ceriodaphnia dubia and Pimephales promelas.

    PubMed

    Tatum, Vickie L; Borton, Dennis L; Streblow, William R; Louch, Jeffrey; Shepard, James P

    2012-12-01

    Because many herbicides selectively control specific species or types of vegetation, they are often applied as mixtures to achieve better control over undesirable vegetation. When herbicides are applied in forest ecosystems, streams, ponds, and other bodies of water are typically protected by buffer zones in which no herbicide is applied. However, in some landscapes, small wetlands and streams are difficult to see and avoid, thus the potential acute toxicity of herbicide mixtures to aquatic organisms is of interest, yet it has not been well-studied. We examined the acute toxicity of 23 different herbicide mixtures to Ceriodaphnia dubia and fathead minnows (Pimephales promelas) at environmentally relevant concentrations, and, where possible, characterized mixture interactions using Marking's Additive Index. Maximum exposure concentrations were equivalent to applying the maximum allowable rate for each component directly to the surface of a 6-in. deep pond with no dissipation following application. Under the conditions of this study, herbicide formulations containing Accord Concentrate (glyphosate), Arsenal AC (imazapyr), Chopper (imazapyr), Escort (metsulfuron methyl), Oust XP (sulfometuron methyl), and Velpar L (hexazinone) were not associated with appreciable acute toxicity to fathead minnows or C. dubia when used alone or in mixtures with each other and various surfactants and adjuvants. Herbicide mixtures for which Additive Indexes could be calculated exhibited primarily antagonistic or simple additive toxicity. In the few cases where synergistic toxicity was observed, the degree of synergism was slight, never exceeding approximately twice the effect estimated based on additive toxicity. Based on the results of this study, neither acute toxicity nor enhanced acute aquatic toxicity due to synergistic mixture effects appears to be a significant concern for applications of the herbicide mixtures most commonly used in forestry. PMID:21384491

  6. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin

    PubMed Central

    Ma, Li-wen; Liu, Juan; Zhang, Jia-an; Xu, Yang; Wu, Di; Permatasari, Felicia

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. PMID:27478534

  7. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin.

    PubMed

    Zhou, Bing-Rong; Ma, Li-Wen; Liu, Juan; Zhang, Jia-An; Xu, Yang; Wu, Di; Permatasari, Felicia; Luo, Dan

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm(2)) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. PMID:27478534

  8. Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.

    PubMed

    Taylor, M S; Daniels, A U; Andriano, K P; Heller, J

    1994-01-01

    Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10147175

  9. Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

    SciTech Connect

    Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.

    1995-12-31

    The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA`s Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity.

  10. Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity against Rhipicephalus microplus in rats.

    PubMed

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P < 0.05) and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. PMID:24883331

  11. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

    PubMed Central

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate) with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P < 0.05) and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg) of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity. PMID:24883331

  12. A novel colorimetric biosensor for monitoring and detecting acute toxicity in water.

    PubMed

    Zhai, Junfeng; Yong, Daming; Li, Jing; Dong, Shaojun

    2013-01-21

    This work presents a new colorimetric microorganism biosensor for monitoring and detecting acute toxicity in water, where prussian blue (PB) is used as the colorimetric indicator and E. coli as the model bacterial. In this biosensor, the electron mediator, ferricyanide, accepts electrons from E. coli during respiration to produce ferrocyanide, which subsequently reacts with ferric ions to yield PB, a famous material with a blue color. Since toxicants can inhibit the respiratory activity of E. coli and then reduce the ferrocyanide and consequent PB production, toxicity can be easily detected by measuring the decrease in the production of PB induced by toxicants. Three important toxicants, 3,5-dichlorophenol (DCP), As(3+), Cr(6+) are tested and the detection limits are 3.2, 25, and 3.2 ppm, respectively. Moreover, we could identify the yellow green to dark green color change by naked eye even at concentrations as low as 12.5 ppm for both DCP and Cr(6+). Subsequently, the acute toxicities of groundwater and south lake water are successfully determined by this sensor. This biosensor is rapid, sensitive and cost-effective, and can thus be regarded as a promising biosensor for giving an early warning of acute water toxicity. PMID:23187797

  13. Acute toxicity of Headline® fungicide to Blanchard's cricket frogs (Acris blanchardi).

    PubMed

    Cusaac, J Patrick W; Morrison, Shane A; Belden, Jason B; Smith, Loren M; McMurry, Scott T

    2016-04-01

    Previous laboratory studies have suggested that pyraclostrobin-containing fungicide formulations are toxic to amphibians at environmentally relevant concentrations. However, it is unknown if all pyraclostrobin formulations have similar toxicity and if toxicity occurs in different amphibian species. We investigated the acute toxicity of two formulations, Headline(®) fungicide and Headline AMP(®) fungicide, to Blanchard's cricket frogs (Acris blanchardi) based on a direct overspray scenario. In addition, we examined body residues of fungicide active ingredients in A. blanchardi following direct exposure to Headline AMP fungicide. Headline fungicide and Headline AMP fungicide had similar toxicity to A. blanchardi with calculated median lethal doses of 2.1 and 1.7 µg pyraclostrobin/cm(2), respectively, which are similar to the suggested maximum label rate in North American corn (2.2 and 1.52 µg pyraclostrobin/cm(2), respectively). Tissue concentrations of pyraclostrobin were lower than predicted based on full uptake of a direct dose, and did not drop during the first 24 h after exposure. Headline fungicides at corn application rates are acutely toxic to cricket frogs, but acute toxicity in the field will depend on worst-case exposure. PMID:26707241

  14. Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection.

    PubMed

    Cates, Jordan E; Mitrani-Gold, Fanny S; Li, Gang; Mundy, Linda M

    2015-08-01

    A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials. PMID:25987628

  15. Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection

    PubMed Central

    Cates, Jordan E.; Li, Gang; Mundy, Linda M.

    2015-01-01

    A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials. PMID:25987628

  16. Safety, Tolerability, and Efficacy of GSK1322322 in the Treatment of Acute Bacterial Skin and Skin Structure Infections

    PubMed Central

    Corey, Ralph; O'Riordan, William D.; Dumont, Etienne; Jones, Lori S.; Kurtinecz, Milena; Zhu, John Z.

    2014-01-01

    GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a ≥20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01209078 and at http://www.gsk-clinicalstudyregister.com [PDF113414].) PMID:25136015

  17. Acute Iodine Toxicity From a Suspected Oral Methamphetamine Ingestion

    PubMed Central

    Bulloch, Marilyn N

    2014-01-01

    BACKGROUND Iodine is a naturally occurring element commercially available alone or in a multitude of products. Iodine crystals and iodine tincture are used in the production of methamphetamine. Although rarely fatal, iodine toxicity from oral ingestion can produce distressing gastrointestinal symptoms and systemic symptoms, such as hypotension and tachycardia, from subsequent hypovolemia. OBJECTIVE The objective of this case report is to describe a case of iodine toxicity from suspected oral methamphetamine ingestion. CASE REPORT A male in his early 20’s presented with gastrointestinal symptoms, chills, fever, tachycardia, and tachypnea after orally ingesting a substance suspected to be methamphetamine. The patient had elevated levels of serum creatinine, liver function tests, and bands on arrival, which returned to within normal limits by day 4 of admission. Based on the patient’s narrow anion gap, halogen levels were ordered on day 3 and indicated iodine toxicity. This is thought to be the first documented case of iodine toxicity secondary to suspected oral methamphetamine abuse. CONCLUSION Considering that the incidence of methamphetamine abuse is expected to continue to rise, clinicians should be aware of potential iodine toxicity in a patient with a history of methamphetamine abuse. PMID:25452705

  18. Ratios between acute aquatic toxicity and effects on population growth rates in relation to toxicant mode of action

    SciTech Connect

    Roex, E.W.M.; Gestel, C.A.M. Van; Wezel, A.P. Van; Straalen, N.M. Van

    2000-03-01

    Environmental risk assessment of chemicals is mostly based on the results of standardized toxicity tests. To obtain environmental quality criteria, extrapolation factors are used that depend on the amount and quality of available data. These extrapolation factors do not, however, take into account the mode of action of the compound tested or the life history of the test organism. In this study, the authors analyzed the variability in acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action. Chemicals were classified as nonpolar narcotics, polar narcotics, specifically acting compounds, and heavy metals. As an acute endpoint, the LC50 was used; as a chronic endpoint, the lowest test concentration at which the natural rate of population increase (r) is affected, or LOEC(r), was used. Data were derived from the on-line literature. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class. For the other classes, the variation in ACRs is larger. Fish species especially show a relatively large ACR. For heavy metals, differences in the mode of action may play an important role in explaining differences in ACRs. For the other three classes, however, it is less reliable to predict chronic toxicity using the results of acute tests. In general, differences in species sensitivity rather than in mode of action for the chemical seem to determine differences in ACRs.

  19. Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations.

    PubMed

    Case, M T; Smith, J K; Nelson, R A

    Because of an apparent typographic error in a US patent, there has been some confusion as to the acute oral toxicity of danthron and danthron in combination with dioctyl sodium sulfosuccinate (DSS). Acute oral toxicity studies in mice revealed LD50 values of greater than 7 gm/kg for danthron, 2.64 gm/kg for DSS and 3.42 gm/kg for danthron/DSS mixture (1:2 ratio). These results indicate that the lethality of these compounds is in the gm/kg range and not in the mg/kg range. A one year chronic toxicity study of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations in dogs failed to reveal any toxic effects. In particular, there was no evidence of hepatotoxicity or of any changes in the myenteric plexuses in the chronically treated dogs. PMID:90594

  20. Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

    PubMed

    Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

    2016-02-01

    Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers. PMID:26408031

  1. Acute toxicity and accumulation of zinc in the crayfish, Orconectes virilis (Hagen)

    SciTech Connect

    Not Available

    1986-09-01

    Zinc produces acute toxicity to freshwater organisms over a range of concentrations from 90 to 58, 100..mu..g Zn/L; with the range of acute median effect concentrations being similar for freshwater fish and invertebrates. The capacity to regulate internal zinc concentrations in decapod crustaceans has been described. Studies with the crayfish Austropotambius pallipes suggested a relatively high degree of tolerance to zinc by this animal. The present study is designed to describe the toxicity of zinc to the crayfish Orconectes virilis over a 2-wk exposure period. In addition, whole animal and tissue analyses were performed on the test organisms and compared to previous results.

  2. Persistent cerebellar dysfunction following acute lithium toxicity: A report of two cases

    PubMed Central

    Banwari, Girish; Chaudhary, Pradhyuman; Panchmatia, Ankit; Patel, Nisheet

    2016-01-01

    Neurological disturbances caused by lithium range from simple side effects such as benign tremor to acute reversible neurotoxicity. Rarely, lithium is reported to cause irreversible, permanent neurological sequelae most commonly manifested as cerebellar dysfunction, although other presentations have also been described. We report two cases of persistent cerebellar syndrome following acute lithium toxicity and discuss them in the light of existing literature on the subject. PMID:27298510

  3. Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

    SciTech Connect

    Katayama, Sonja; Striecker, Thorbjoern; Kessel, Kerstin; Sterzing, Florian; Habl, Gregor; Edler, Lutz; Debus, Juergen; Herfarth, Klaus

    2014-11-15

    Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

  4. A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute pancreatitis

    PubMed Central

    Johnson, P. Connor; Phillips, Kristy M.; O'Donnell, Walter J.

    2015-01-01

    We present a case of suspected linezolid toxicity in a 34-year-old man with sickle cell disease and line-related vancomycin-resistant enterococcal bacteremia and tricuspid valve endocarditis. The patient developed sudden-onset hypoglycemia, lactic acidosis, and acute pancreatitis 11 days after initiation of linezolid. All adverse effects quickly resolved with drug cessation. The pathophysiology underlying this triad of linezolid toxicity is unclear, but may be related to mitochondrial dysfunction. PMID:26424943

  5. A mitogen-activated protein kinase kinase inhibitor induced compound skin toxicity with oedema in metastatic malignant melanoma.

    PubMed

    Thomas, C L; Mortimer, P S; Larkin, J M; Basu, T N; Gore, M E; Fearfield, L

    2016-04-01

    We report three cases of skin toxicity associated with oral mitogen-activated protein kinase kinase (MEK) inhibitor treatment for metastatic malignant melanoma (MM). All three patients developed oedema, and a single patient experienced eyelash trichomegaly. This is the first known report of eyelash trichomegaly secondary to MEK inhibitor use. We also discuss possible mechanisms for MEK inhibitor-associated oedema development. This series supports the role of the dermatologist in the screening and management of patients in the rapidly developing oncology setting, as new targeted agents can give rise to marked skin toxicity. PMID:26411345

  6. Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections

    PubMed Central

    Urbina, Olatz; Ferrández, Olivia; Espona, Mercè; Salas, Esther; Ferrández, Irene; Grau, Santiago

    2013-01-01

    Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need. PMID:23589680

  7. ACUTE TOXICITY OF AMMONIA AND NITRITE TO CUTTHROAT TROUT FRY

    EPA Science Inventory

    The toxicity of ammonia and of nitrite was tested on cutthroat trout (Salmo clarki) fry (1-3 g) for periods up to a month in eight laboratory flow-through bioassays. Median lethal concentration (LC50) values for ammonia (mg/liter un-ionized NH3) were 0.5-0.8 for 96 hours, and 0.3...

  8. Acute toxicity of organic solvents on Artemia salina

    SciTech Connect

    Barahona-Gomariz, M.V.; Sanz-Barrera, F.; Sanchez-Fortun, S. )

    1994-05-01

    Organic solvents can make their way into the environment as industrial wastes and components of pesticide formulation. In laboratory bioassays, the use of organic formulations. In laboratory bioassays, the use of organic solvents is often unavoidable, since many pesticides and organic pollutants have low water solubility and must be dissolved in organic solvents prior to addition into experimental systems. In the toxicant bioassays, invertebrates with special reference to aquatic arthropod species are of recent interest as test models due to the need for developing nonmammalian test systems. Toxic effects of organic solvents have been tested with a few aquatic species, but information on the comparative toxicity of solvents towards Artemia salina is not available. Artemia salina have, within recent years, gained popularity as test organisms for short-term toxicity testing. Because Artemia salina exhibit rapid development and growth within 48 hr after hatch, their potential as a model organism for toxicology screening has been considered. To do this, synchronous populations of Artemia salina at different development intervals must be available.

  9. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

  10. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

  11. [Acute poisoning with selected hepatotoxic agents: biochemistry of toxic effect, clinical symptoms and treatment].

    PubMed

    Rusiński, Piotr; Kołaciński, Zbigniew

    2003-01-01

    The paper discusses etiopathogenesis, clinical symptoms and treatment in acute poisoning with hepatotoxic agents. The liver is a critical organ in acute poisoning with Amanita phalloides, carbon tetrachloride, iron compounds and isonicotinic acid hydrazide. Based on literature reports and own experience the authors present the current outlook on the specific treatment of acute poisoning with these xenobiotics. Special consideration was given to biochemical etiopathogenesis of hepatoxicity: oxidative stress, lipid peroxidation and impaired homeostasis of calcium ions and glutathione. Basic principles were also discussed of conservative treatment in hepatic encephalopathy due to toxic liver necrosis. PMID:14569886

  12. Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.

    PubMed

    Jung, Ji-Yong; Oh, Jang-Hee; Kim, Yeon Kyung; Shin, Mi Hee; Lee, Dayae; Chung, Jin Ho

    2012-03-01

    Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation. PMID:22379342

  13. Acute bilateral ureteral obstruction secondary to guaifenesin toxicity.

    PubMed

    Cockerill, Patrick A; de Cógáin, Mitra R; Krambeck, Amy E

    2013-10-01

    Several medications or their metabolites have been associated with urolithiasis, although overall they remain an infrequent cause of urolithiasis. Guaifenesin stones were originally reported as complexed with ephedrine, and subsequent reports have demonstrated pure guaifenesin stones, occurring after long term abuse. We report a case of a 23-year-old male who ingested a large, one time dose of guaifenesin, resulting in acute bilateral ureteral obstruction, which, to our knowledge, is the first such reported case in the literature. PMID:24128843

  14. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    SciTech Connect

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  15. Correlation Between Acute and Late Toxicity in 973 Prostate Cancer Patients Treated With Three-Dimensional Conformal External Beam Radiotherapy

    SciTech Connect

    Jereczek-Fossa, Barbara A.; Zerini, Dario; Fodor, Cristiana

    2010-09-01

    Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. Results: Multivariate analysis showed that age {<=}65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). Conclusion: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

  16. Acute toxicity of mosquitocidal compounds to young mosquitofish, Gambusia affinis.

    PubMed

    Tietze, N S; Hester, P G; Hallmon, C F; Olson, M A; Shaffer, K R

    1991-06-01

    Toxicity of Florida mosquito larvicides and adulticides to 3-5 day old Gambusia affinis was determined in the laboratory. After 24-h exposure, the larvicides, temephos, fenoxycarb and petroleum distillates had LC50 values of 5.60, 1.05 and 593.4 ppm, respectively. After 24 h the adulticides resmethrin, fenthion, naled and malathion had LC50 values of 0.007, 2.94, 3.50 and 12.68 ppm, respectively. The only compound toxic to young mosquitofish at maximum field application rates was resmethrin. However, in the light of earlier tests, aerially applied adulticides generally reach the water surface at reduced concentrations and thus probably pose little or no risk to mosquitofish populations. PMID:1716659

  17. Acute Toxicity of Sodium Fluorescein to Ashy Pebblesnails Fluminicola fuscus

    USGS Publications Warehouse

    Stockton, Kelly A.; Moffitt, Christine M.; Blew, David L.; Farmer, C. Neil

    2011-01-01

    Water resource agencies and groundwater scientists use fluorescein dyes to trace ground water flows that supply surface waters that may contain threatened or endangered mollusk species. Since little is known of the toxicity of sodium fluorescein to mollusks, we tested the toxicity of sodium fluorescein to the ashy pebblesnail Fluminicola fuscus. The pebblesnail was selected as a surrogate test species for the threatened Bliss Rapid snail Taylorcocha serpenticola that is endemic to the Snake River and its tributaries in the Hagerman Valley, Idaho. In laboratory tests, we expose replicated groups of snails to a series of concentrations of fluorescein in a static 24 h exposure at 15 degrees C. Following the exposure, we removed snails, rinsed them, and allowed a 48 h recovery in clean water before recording mortality. We estimated 377 mg/L as the median lethal dose. Mortality to snails occurred at concentrations well above those expected in test wells during the monitoring efforts.

  18. Determination of acute toxicity of polychlorinated biphenyls to photobactrium phosphoreum

    SciTech Connect

    Chu, S.; Xu, X.; He, Y.

    1997-02-01

    Polychlorinated biphenyls (PCBs) are a highly lipophilic group of global pollutants, consisting of 209 congeners. PCBs were discovered before the turn of the century and their usefulness for industry, because of their physical properties, was recognized early. The distribution of PCBs in the environment was not noticed until Jensen and his colleagues found PCBs in wildlife samples. Since then, investigations in many parts of the world have revealed the widespread distribution of PCBs in environmental samples and PCVs are persistent and accumulate in food webs. Thus, determination of toxicities of commercial PCB mixtures and PCB congeners are required. Toxicity tests using luminous bacteria have shown high correlation to traditional bioassays. This study compared the EC50 values of the commercial mixtures, PCB3 and PCB5, with those of Aroclor 1242 and Aroclor 1254. 12 refs., 2 tabs.

  19. Acute tellurium toxicity from ingestion of metal-oxidizing solutions.

    PubMed

    Yarema, Mark C; Curry, Steven C

    2005-08-01

    Tellurium is an element used in the vulcanization of rubber and in metal-oxidizing solutions to blacken or tarnish metals. Descriptions of human toxicity from tellurium ingestion are rare. We report the clinical course of 2 children who ingested metal-oxidizing solutions containing substantial concentrations of tellurium. Clinical features included vomiting, black discoloration of the oral mucosa, and a garlic odor to the breath. One patient developed corrosive injury to the esophagus secondary to the high concentration of hydrochloric acid in the solution. Both patients recovered without serious sequelae, which is typical of tellurium toxicity. An awareness of situations in which children may be exposed to tellurium and its clinical presentation may assist clinicians in the diagnosis of this rare poisoning. PMID:15995006

  20. Possible Role of Interleukin-31/33 Axis in Imatinib Mesylate-Associated Skin Toxicity

    PubMed Central

    Musolino, Caterina; Allegra, Alessandro; Mannucci, Carmen; Russo, Sabina; Alonci, Andrea; Maisano, Valerio; Calapai, Gioacchino; Gangemi, Sebastiano

    2015-01-01

    Imatinib mesylate is a small-molecule tyrosine kinase inhibitor (TKi) designed to target c-ABL and BCR-ABL, approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Adverse cutaneous reactions induced by imatinib are frequent, generally moderate, and dose-dependent. The aim of this work was to investigate the possible contribution of interleukin (IL)-33 and IL-31, cytokines involved in disorders associated with itching, in the pathogenesis of pruritus in a patient undergoing imatinib mesylate treatment. His IL-31 and IL-33 serum levels were significantly higher than in the control group (respectively 96.6 pg/mL vs. 7.623±7.681 pg/mL and 27.566 pg/mL vs. 6.170±7.060 pg/mL). In light of these findings, imatinib mesylate-related symptoms of dermatologic toxicities might be related to the release of IL-31 and IL-33. In particular, it is supposable that TKi usage could cause keratinocyte injury, the release of IL-33, and the consequent interaction with its receptor on mast cells that induces the secretion of several factors capable of causing skin manifestations, including IL-31, a known pruritus-inducing cytokine. This report, to the best of our knowledge, is the first work describing the possible involvement of the IL-31/IL-33 axis in the pathogenesis of skin side effects related to imatinib mesylate treatment. PMID:26316486

  1. Acute toxicity screening of sediments utilizing Chydorus sphaericus

    SciTech Connect

    Campbell, M.G.S.; Crisman, T.; Bitton, G.; Delfino, J.

    1997-08-01

    Out of over 165 species of organisms that have been proposed for use in toxicity bioassays only a few are invertebrates and even fewer have ever been cultured in the laboratory. Many of the invertebrates that have been applied in sediment toxicity tests are not benthic organisms and possess few characteristics of the ideal sediment bioassay organism. Some tests species have limited ecological ranges; some may not be widely available for testing and many are not easily maintained in the laboratory. In addition, some traditional sediment toxicity tests utilize organisms that spend no part or only part of their life cycle in contact with sediment constituents, and therefore lack, in some degree, ecological relevance. The study reported involved the development and evaluation of a 48-hour lethality bioassay employing the benthic cladoceran, Chydorus sphaericus. The bioassay is ecologically relevant because the test organism is ubiquitous and it lives associated with sediments in freshwater aquatic environments. The bioassay was evaluated by direct comparison with standard bioassays using sediment samples collected from hazardous waste sites in Florida.

  2. Case of acute lead toxicity associated with Ayurvedic supplements.

    PubMed

    Breyre, Amelia; Green-McKenzie, Judith

    2016-01-01

    Use of traditional folkloric remedies not disclosed to the physician may be difficult to identify as a source of lead toxicity. This report illustrates the presentation of a 26-year-old man who, during his 1 month vacation in India, was treated for low back pain with Ayurvedic herbal medicine. On his return to the USA, he presented to the emergency department with epigastric pain, weight loss, dark stools, nausea and vomiting. He was admitted and noted to be anaemic with a blood lead level (BLL) of 94.8 µg/dL. Peripheral blood smear demonstrated basophilic stippling. Chelation therapy with succimer was initiated. The patient became asymptomatic within months. Three years later, he remained asymptomatic with BLL <20 µg/dL. Physicians should be cognisant of potential toxicity from these Ayurvedic medications and have a heightened level of suspicion for lead toxicity in the face of anaemia and abdominal pain without obvious cause. PMID:27364782

  3. Reduction of acute photodamage in skin by topical application of a novel PARP inhibitor.

    PubMed

    Farkas, Beatrix; Magyarlaki, Marta; Csete, Bela; Nemeth, Jozsef; Rabloczky, Gyorgy; Bernath, Sandor; Literáti Nagy, Peter; Sümegi, Balazs

    2002-03-01

    The ultraviolet (UV) components of sunlight induce damage to the DNA in skin cells, which is considered to be the initiating step in the harmful biological effects of UV radiation. Repair of DNA damage results in the formation of single-strand DNA breaks, which activate the nuclear poly(ADP-ribose) polymerase (PARP). Overactivation of PARP worsens the oxidative cell damage and impairs the energy metabolism, raising the possibility that moderation of PARP activation following DNA damage may protect skin cells from UV radiation. The topical effects of the novel PARP inhibitor O-(3-pyperidino-2-hydroxy-1-propyl) pyridine-3-carboxylic acid amidoxime monohydrochloride (BGP-15M) were investigated on UV-induced skin damage in a hairless mouse model. For evaluation of the UV-induced acute photodamage to the skin and the potential protective effect of BGP-15M, DNA injury was detected by measuring the formation of single-strand DNA breaks and counting the resulting sunburn (apoptotic) cells. The ADP-ribosylation of PARP was assessed by Western blot analysis and then quantified. In addition, the UV-induced immunosuppression was investigated by the immunostaining of tumor necrosis factor alpha and interleukin-10 expressions in epidermal cells. The signs of inflammation were examined clinically and histochemically. Besides its primary effect in decreasing the activity of nuclear PARP, topically applied BGP-15M proved to be protective against solar and artificial UV radiation-induced acute skin damage. The DNA injury was decreased (P<0.01). An inhibition of immunosuppression was observed by down-regulation of the epidermal production of cytokines IL-10 and TNFalpha. In the mouse skin, clinical or histological signs of UV-induced inflammation could not be observed. These data suggest that BGP-15M directly interferes with UV-induced cellular processes and modifies the activity of PARP. The effects provided by topical application of the new PARP-regulator BGP-15M indicate that it

  4. Acute toxicities of five commonly used antifouling booster biocides to selected subtropical and cosmopolitan marine species.

    PubMed

    Bao, Vivien W W; Leung, Kenneth M Y; Qiu, Jian-Wen; Lam, Michael H W

    2011-05-01

    Since 1990s, various booster biocides have been increasingly used as substitutes of organotins. However, knowledge about their toxicities on tropical/sub-tropical marine species is significantly lacking. This study comprehensively investigated the acute toxicities of copper, tributyltin (TBT), and five commonly used booster biocides including Irgarol, diuron, zinc pyrithione (ZnPT), copper pyrithione (CuPT) and chlorothalonil on the growth or survival of 12 marine species in which eight of them are native species of subtropical Hong Kong. We found that Irgarol was more toxic than TBT on the growth of autotrophic species. The toxicity of CuPT was comparable to that of TBT on almost all test species, while it showed higher toxicity than TBT on medaka fish larvae. As the usage of these biocides is expected to further increase worldwide, accurate assessments of their ecological risks are required for better informed decision on their management. This study provided useful datasets for such purposes. PMID:21420693

  5. Primary chemical and physical characterization of acute toxic components in wastewaters

    SciTech Connect

    Svenson, A.; Linlin, Z.; Kaj, L. )

    1992-10-01

    A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.

  6. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    PubMed

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-01

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis. PMID:27251985

  7. Pharmacokinetic-Pharmacodynamic Analysis for Efficacy of Ceftaroline Fosamil in Patients with Acute Bacterial Skin and Skin Structure Infections

    PubMed Central

    Hammel, Jeffrey P.; Van Wart, Scott A.; Rubino, Christopher M.; Reynolds, Daniel K.; Forrest, Alan; Drusano, George L.; Khariton, Tatiana; Friedland, H. David; Riccobene, Todd A.; Ambrose, Paul G.

    2014-01-01

    Ceftaroline is a cephalosporin with broad-spectrum in vitro activity against pathogens commonly associated with acute bacterial skin and skin structure infections (ABSSSI), including methicillin-resistant Staphylococcus aureus. Ceftaroline fosamil, the prodrug of ceftaroline, is approved for the treatment of patients with ABSSSI. Using data from the microbiologically evaluable population from two phase 2 and two phase 3 randomized, multicenter, double-blind studies of patients with ABSSSI, an analysis examining the relationship between drug exposure, as measured by the percentage of time during the dosing interval that free-drug steady-state concentrations remain above the MIC (f%T>MIC), and clinical and microbiological responses was undertaken. The analysis population included 526 patients, of whom 423 had infections associated with S. aureus. Clinical and microbiological success percentages were 94.7 and 94.5%, respectively, among all of the patients and 95.3 and 95.7%, respectively, among those with S. aureus infections. Univariable analysis based on data from all of the patients and those with S. aureus infections demonstrated significant relationships between f%T>MIC and microbiological response (P < 0.001 and P = 0.026, respectively). Multivariable logistic regression analyses demonstrated other patient factors in addition to f%T>MIC to be significant predictors of microbiological response, including age and infection type for all of the patients evaluated and age, infection type, and the presence of diabetes mellitus for patients with S. aureus infections. Results of these analyses confirm that a ceftaroline fosamil dosing regimen of 600 mg every 12 h provides exposures associated with the upper plateau of the pharmacokinetic-pharmacodynamic relationship for efficacy. PMID:25367904

  8. Pharmacokinetic-pharmacodynamic analysis for efficacy of ceftaroline fosamil in patients with acute bacterial skin and skin structure infections.

    PubMed

    Bhavnani, Sujata M; Hammel, Jeffrey P; Van Wart, Scott A; Rubino, Christopher M; Reynolds, Daniel K; Forrest, Alan; Drusano, George L; Khariton, Tatiana; Friedland, H David; Riccobene, Todd A; Ambrose, Paul G

    2015-01-01

    Ceftaroline is a cephalosporin with broad-spectrum in vitro activity against pathogens commonly associated with acute bacterial skin and skin structure infections (ABSSSI), including methicillin-resistant Staphylococcus aureus. Ceftaroline fosamil, the prodrug of ceftaroline, is approved for the treatment of patients with ABSSSI. Using data from the microbiologically evaluable population from two phase 2 and two phase 3 randomized, multicenter, double-blind studies of patients with ABSSSI, an analysis examining the relationship between drug exposure, as measured by the percentage of time during the dosing interval that free-drug steady-state concentrations remain above the MIC (f%T>MIC), and clinical and microbiological responses was undertaken. The analysis population included 526 patients, of whom 423 had infections associated with S. aureus. Clinical and microbiological success percentages were 94.7 and 94.5%, respectively, among all of the patients and 95.3 and 95.7%, respectively, among those with S. aureus infections. Univariable analysis based on data from all of the patients and those with S. aureus infections demonstrated significant relationships between f%T>MIC and microbiological response (P < 0.001 and P = 0.026, respectively). Multivariable logistic regression analyses demonstrated other patient factors in addition to f%T>MIC to be significant predictors of microbiological response, including age and infection type for all of the patients evaluated and age, infection type, and the presence of diabetes mellitus for patients with S. aureus infections. Results of these analyses confirm that a ceftaroline fosamil dosing regimen of 600 mg every 12 h provides exposures associated with the upper plateau of the pharmacokinetic-pharmacodynamic relationship for efficacy. PMID:25367904

  9. Profile of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections

    PubMed Central

    Hall, Ronald G; Michaels, Heidi N

    2015-01-01

    Tedizolid phosphate is the first once-daily oxazolidinone approved by the United States Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections (ABSSSI). It is more potent in vitro than linezolid against methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive pathogens causing ABSSSI, even retaining activity against some linezolid-resistant strains. Tedizolid is approximately 90% protein bound, leading to lower free-drug concentrations than linezolid. The impact of the effect of food, renal or hepatic insufficiency, or hemodialysis on tedizolid’s pharmacokinetic have been evaluated, and no dosage adjustment is needed in these populations. In animal and clinical studies, tedizolid’s effect on bacterial killing is optimized by the free-drug area under the curve to minimum inhibitory concentration ratio (fAUC/MIC). The 200 mg once-daily dose is able to achieve the target fAUC/MIC ratio in 98% of simulated patients. Two Phase III clinical trials have demonstrated the noninferiority of tedizolid 200 mg once daily for 6 days to linezolid 600 mg twice daily for 10 days. In vitro, animal, and clinical studies have failed to demonstrate that tedizolid inhibits monoamine oxidase to a clinically relevant extent. Tedizolid has several key advantages over linezolid including once daily dosing, decreased treatment duration, minimal interaction with serotonergic agents, possibly associated with less adverse events associated with the impairment of mitochondrial protein synthesis (eg, myelosuppression, lactic acidosis, and peripheral/optic neuropathies), and retains in vitro activity against linezolid-resistant gram-positive bacteria. Economic analyses with tedizolid are needed to describe the cost-effectiveness of this agent compared with other options used for ABSSSI, particularly treatment options active against MRSA. PMID:25960671

  10. Comparative acute and subchronic toxicity of ethylene glycol monopropyl ether and ethylene glycol monopropyl ether acetate.

    PubMed Central

    Katz, G V; Krasavage, W J; Terhaar, C J

    1984-01-01

    The acute toxicity of ethylene glycol monopropyl ether (EGPE) and ethylene glycol monopropyl ether acetate (EGPEA) was determined in a series of standardized tests. The oral LD50 in rats was 3089 and 9456 mg/kg EGPE and EGPEA, respectively. Skin irritation was slight following an occluded single dose application of either compound to the guinea pig abdomen. The dermal LD50 for guinea pigs was 1 to 5 mL/kg and greater than 20 mL/kg EGPE and EGPEA, respectively. EGPE produced a very weak positive sensitization response in one of five guinea pigs. No positive response was elicited when 10 guinea pigs were similarly challenged with EGPEA. EGPE produced transient moderate to severe eye irritation in rabbits while EGPEA produced slight eye irritation. Subchronic toxicity was determined in a series of oral and inhalation studies. Groups of 10 male rats were dosed with 15, 7.5, 3.75 or 1.88 mmole/kg EGPE and 30, 15 or 7.5 mmole/kg EGPEA by gavage 5 days/week for 6 weeks. Hemoglobinuria was seen at least once at all dose levels of both compounds. EGPE had little effect on feed consumption or body weight gain, while body weight gain was reduced in the two high dose groups exposed to EGPEA and feed consumption was reduced at all dose levels. Hematologic changes were seen at all dose levels of both compounds. Absolute and/or relative spleen weights were increased at all but the lowest EGPE dose level and at all EGPEA dose levels. Gross and histopathologic examinations revealed significant effects on the spleen of animals exposed to EGPE and on the spleen, liver, kidney and testes of animals exposed to EGPEA. The no-observed effect level (NOEL) for splenic changes was 1.88 mmole/kg EGPE. A NOEL for hematology was not established. The NOEL for liver and testicular changes were 15 and 7.5 mmole/kg EGPEA, respectively while a NOEL for hematologic, splenic and renal changes was not established. Groups of 10 rats (5M, 5F) were exposed to 800, 400, 200 or 100 ppm EGPE or EGPEA 6 hr

  11. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    EPA Science Inventory

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  12. Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels

    EPA Science Inventory

    Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...

  13. The value of acute toxicity testing of pharmaceuticals for estimation of human response.

    PubMed

    Barle, Ester Lovšin; Looser, Roland; Cerne, Manica; Bechter, Rudolf

    2012-04-01

    The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID:22306828

  14. ACUTE TOXICITY OF METHYL-PARATHION IN WETLAND MESOCOSMS: INFLUENCE OF AQUATIC PLANTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The acute toxicity of methyl-parathion (MeP) introduced into constructed wetlands for the purpose of assessing the importance of emergent vegetation was tested using Hyalella azecta (Crustacea: Amphipoda). A vegetated (90% cover, mainly Juncus effuses) and a non-vegetated wetland (each with a water...

  15. ACUTE TOXICITY AND BEHAVIORAL EFFECTS OF ACRYLATES AND METHACRYLATES TO JUVENILE FATHEAD MINNOWS (JOURNAL VERSION)

    EPA Science Inventory

    Acrylate and methacrylate esters are reactive monomers that are used primarily in the synthesis of acrylic plastics and polymers. Ninety-six hour flow-through acute toxicity tests were conducted with fathead minnows (Pimephales promelas) using 6 acrylates and 6 methacrylates. Nin...

  16. ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

    EPA Science Inventory

    Walker, Calvin C., James T. Winstead, Steven S. Foss, Janis C. Kurtz, James Watts, Jeanne E. Scott and William S. Fisher. In press. Acute and Chronic Toxicity of Brevetoxin to Oysters and Grass Shrimp (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November ...

  17. EXTRAPOLATION OF ACUTE TOXICITY AMONG AQUATIC SPECIES BASED ON MECHANISM OF ACTION

    EPA Science Inventory

    Presentation provides inter-species QSARs for acute toxicity to ciliates, fish and daphnia...The inter-species QSARs can be also useful in the analysis of the relative species sensitivity to a variety of pollutants and will be useful in assisting in risk assessments of potential ...

  18. Acute toxicity of praziquantel (an anthelmintic) to grass carp and golden shiners

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Praziquantel is an anthelmintic that can be applied to the water to kill tapeworm and trematode parasites in fish. Effective praziquantel treatment rates have been determined but there is little information on the toxicity of this chemical to fish hosts of the parasites. Acute praziquantel toxicit...

  19. ACUTE TOXICITIES OF SELECTED HEAVY METALS TO THE SOFTSHELL CLAM, 'MYA ARENARIA'

    EPA Science Inventory

    Static acute toxicity bioassays with adult softshell clams and salts of copper, cadmium, zinc, lead, manganese, and nickel were conducted at 30 o/oo salinity and 22C. Concentrations fatal to 50% in 168 hours, in mg/l (ppm) metal added at start, were 0.035 for Cu, 0.150 for Cd, 1....

  20. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    EPA Science Inventory

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  1. EVALUATION OF MINIMUM DATA REQUIREMENTS FOR ACUTE TOXICITY VALUE EXTRAPOLATION WITH AQUATIC ORGANISMS

    EPA Science Inventory

    Buckler, Denny R., Foster L. Mayer, Mark R. Ellersieck and Amha Asfaw. 2003. Evaluation of Minimum Data Requirements for Acute Toxicity Value Extrapolation with Aquatic Organisms. EPA/600/R-03/104. U.S. Environmental Protection Agency, National Health and Environmental Effects Re...

  2. Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products contai...

  3. THE ACUTE TOXICITY OF PRAZIQUANTEL TO GRASS CARP AND GOLDEN SHINERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute praziquantel toxicity and no observable effect concentrations (NOEC), were determined in the laboratory for grass carp and golden shiners, two commercially raised cyprinids known to harbor Asian tapeworm Bothriocephalus acheilognathi. Praziquantel is an anthelmintic used to treat fish with ta...

  4. Acute and chronic toxicity of lead in water and diet to the amphipod Hyalella azteca

    USGS Publications Warehouse

    Besser, J.M.; Brumbaugh, W.G.; Brunson, E.L.; Ingersoll, C.G.

    2005-01-01

    We evaluated the influence of waterborne and dietary lead (Pb) exposure on the acute and chronic toxicity of Pb to the amphipod Hyalella azteca. Test solutions were generated by a modified diluter with an extended (24-h) equilibration period. Acute (96-h) toxicity of Pb varied with water hardness in the range of 71 to 275 mg/L as CaCO3, despite similar dissolved Pb concentrations. Acute toxicity was greatest in soft test water, with less than 50% survival at the lowest dissolved Pb concentration (151 ??g/L). Survival also was significantly reduced in medium-hardness water but not in hard test water. In chronic (42-d) studies, amphipods were exposed to waterborne Pb and fed either a control diet or a diet equilibrated with waterborne Pb levels. For animals fed the control diet, the median lethal concentration (LC50) for Pb was 24 ??g/L (as dissolved Pb), and significant reductions in survival occurred at 16 ??g/L. Exposure to Pb-treated diets significantly increased toxicity across a wide range of dissolved Pb concentrations, with a LC50 of 16 ??g/L and significant reductions in growth and reproduction at 3.5 ??g/L. Significant effects on growth and reproduction occurred at dissolved Pb concentrations close to the current U.S. chronic water-quality criterion. Our results suggest that both aqueous- and dietary-exposure pathways contribute significantly to chronic Pb exposure and toxic effects in aquatic biota. ?? 2005 SETAC.

  5. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    PubMed

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. PMID:22440551

  6. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  7. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

    PubMed Central

    Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  8. Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice.

    PubMed

    Sim, K S; Sri Nurestri, A M; Sinniah, S K; Kim, K H; Norhanom, A W

    2010-01-01

    Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

  9. Fatality due to acute systemic fluoride poisoning following a hydrofluoric acid skin burn.

    PubMed

    Tepperman, P B

    1980-10-01

    Reports indicate that death due to hydrofluoric acid exposure is usually the result of inhalation of vapor causing pulmonary edema and fluoride poisoning. Absorption via the skin route of fluoride ion sufficient to cause serious systemic problems and even death has rarely been reported. A fatality resulting from a severe facial burn, which produced acute systemic fluoride poisoning with profound hypocalcemia and hypomagnesemia, is presented. The importance of proper personal protective equipment as well as the immediate initiation of first aid and appropriate medical measures, including the monitoring and replacement of serum calcium and magnesium, are emphasized. PMID:7431138

  10. Acute and subacute oral toxicity of Litsea elliptica Blume essential oil in rats.

    PubMed

    Budin, Siti Balkis; Siti Nor Ain, Seri Masran; Omar, Baharuddin; Taib, Izatus Shima; Hidayatulfathi, Othman

    2012-10-01

    Litsea elliptica Blume has been traditionally used to treat headache, fever, and stomach ulcer, and has also been used as an insect repellent. The acute and subacute toxicities of L. elliptica essential oil were evaluated orally by gavage in female Sprague-Dawley rats. For the acute toxicity study, L. elliptica essential oil was administered in doses from 500 to 4000 mg/kg (single dose), and in the subacute toxicity test, the following doses were used: 125, 250, and 500 mg/kg, for 28 consecutive days. In the acute toxicity study, L. elliptica essential oil caused dose-dependent adverse behaviours and mortality. The median lethal dose value was 3488.86 mg/kg and the acute non-observed-adversed-effect level value was found to be 500 mg/kg. The subacute toxicity study of L. elliptica essential oil did not reveal alterations in body weight, and food and water consumptions. The haematological and biochemical analyses did not show significant differences between control and treated groups in most of the parameters examined, except for the hemoglobin, mean cell hemoglobin concentration, mean cell volume, mean cell hemoglobin, serum albumin, and serum sodium. However, these differences were still within the normal range. No abnormalities or histopathological changes were observed in the liver, pancreatic islet of Langerhans, and renal glomerulous and tubular cells of all treated groups. In conclusion, L. elliptica essential oil can be classified in the U group, which is defined as a group unlikely to present an acute hazard according to World Health Organization (WHO) classification. PMID:23024045

  11. Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

    USGS Publications Warehouse

    Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

    2015-01-01

    The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

  12. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite.

    PubMed

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-01-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration

  13. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    NASA Astrophysics Data System (ADS)

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

  14. Drug-induced skin toxicity and clinical nursing of VitK cream on colorectal cancer patients.

    PubMed

    Li, Ai-Min; Miao, Jin-Hong; Liu, Hui; Ma, Yao-Zhen; Sun, Zhen-Chang

    2015-07-01

    To discuss the impact of 0.1% vitamin K1 (VitK1) cream on cetuximab-induced skin toxicity for colorectal cancer patients. 60 colorectal cancer patients with cetuximab therapy after hospitalization, were divided into experimental group (Ward A) and control group (Ward B) according to personnel sequential number, with 30 cases in each group. Routine nursing was implemented on control group. For experimental group, on the routine nursing basis, 0.1% VitK1 cream was smeared on face, neck, chest, back and nail (toenail) edge with three times one day at the application of cetuximab day. After cetuximab applied in 8 weeks, both skin itch and dry skin for patients in experimental group were significantly improved compared those in control group, showing statistically significant difference (W=708.000, P=0.001: W=662. 500, P=0.000). 0.1% VitK1 cream was conducive to improve both skin itch and dry skin symptoms in the cetuximab-induced skin toxicity for colorectal cancer patients. PMID:26431649

  15. [Association between mthfr gene polymorphisms and toxicity of HDMTX chemotherapy in acute lymphocytic leukemia].

    PubMed

    Liu, Jing-Xia; Chen, Jie-Ping; Tan, Wen; Lin, Dong-Xin

    2008-06-01

    This study was aimed to investigate the association between mthfr gene polymorphisms and toxicity of HDMTX in acute lymphocytic leukemia patients. A total of 44 patients were selected, and DNA was extracted from their peripheral blood. PCR-RFLP was used to determine the genotypes of mthfr. The toxicity response of patients received HDMTX chemotherapy was observed. The results showed that the toxicity of HDMTX to carriers of the variant allele at codon 677 (CT or TT) increased, as compared with individuals with the common CC genotype (OR = 3.75, 95% CI 1 - 14, p = 0.04). In contrast, the toxicity of HDMTX to ALL patients with the variant allele at codon 1298 (AC or CC) decreased as compared with the common AA genotype carriers (OR = 0.12, 95% CI: 0.026 - 0.564, p = 0.007). As compared with carriers of the variant allele at coden 1298 (AC or CC), the toxicity of HDMTX to patients with TT genotype at 677 and AA genotype at 1298 increased (OR = 16.5, 95% CI: 0.026 - 0.564). It is concluded that mthfr gene polymorphisms associate with the toxicity of HDMTX chemotherapy in acute lymphocytic leukemia. PMID:18549614

  16. Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy

    PubMed Central

    Chavan, Swapnil; Friedman, Ran; Nicholls, Ian A.

    2015-01-01

    A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. PMID:26006240

  17. Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

    PubMed

    Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

    2011-11-01

    Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios. PMID:21789673

  18. Acute benzodiazepine toxicity exacerbated by concomitant oral olanzapine.

    PubMed

    Hoffmann, Marc S; Overman, Michael J; Nates, Joseph L

    2016-04-01

    Improvements in antiemetic therapy constitute a major advance in oncology. A recent poll of the oncology community by the American Society of Clinical Oncology ranked it as one of the top 5 advances in cancer in the last 50 years. Emetogenicity of chemotherapy is defined by risk of emesis in the patient given no antiemetics; high-risk regimens cause nausea and vomiting in >90% of patients, moderate risk in 30%-90%, and low risk in <30%. This risk profile serves as the basis for empiric antiemetic prophylaxis and offers alternatives to refractory patients. Modern antiemetic prophylaxis is extremely effective for high-risk chemotherapy, reducing the risk for breakthrough nausea and vomiting to 0%-13% in the acute setting (<24 hours from receipt of chemotherapy) and to 25%-30% in the delayed setting (24-72 hours from receipt of chemotherapy). PMID:27152518

  19. Tigriopus fulvus: The interlaboratory comparison of the acute toxicity test.

    PubMed

    Faraponova, Olga; Giacco, Elisabetta; Biandolino, Francesca; Prato, Ermelinda; Del Prete, Francesco; Valenti, Alessandra; Sarcina, Stefania; Pasteris, Andrea; Montecavalli, Adele; Comin, Stefano; Cesca, Claudia; Francese, Marco; Cigar, Monica; Piazza, Veronica; Falleni, Fabrizio; Lacchetti, Ines

    2016-02-01

    The paper reports the results of an interlaboratory comparison involving 11 laboratories, with the objectives of apply and validate a new standardized ecotoxicological method on marine crustacean Tigriopus fulvus. Copper was chosen as reference toxicant as indicated in the official method. The results of two independent tests performed by all the participants, demonstrated that the new method is simple, fast and easy to learn. This is confirmed even by the values of z-score index calculated for each laboratory and the relative coefficient of variation (CV) which are 6.32% after 24h, 6.56 after 48h and 35.3% after 96h, mentioned in the ISO standards for the precision of interlaboratory assays. Therefore its use could be recommended in environmental studies and monitoring. PMID:26584461

  20. Acute aquatic toxicity of nine alcohol ethoxylate surfactants to fathead minnow and Daphnia magna

    SciTech Connect

    Wong, D.C.L.; Dorn, P.B.; Chai, E.Y.

    1995-12-31

    The aquatic toxicity of nine commercial-grade alcohol ethoxylate surfactants was studied in acute exposures to fathead minnow (Pimephales promelas) and Daphnia magna. All studies were conducted in accordance with USEPA TSCA Good Laboratory Practice Standards. Mean measured surfactant concentrations in exposure solutions showed good agreement with nominal concentrations for both fathead minnow and daphnid tests. Surfactant recoveries ranged from 59 to 97% and 67 to 106% in the fathead minnow and daphnid solutions, respectively. The response of both species to the surfactants was generally similar with the daphnids being slightly more sensitive to a few surfactants. Surfactant toxicity tended to increase with increasing alkyl chain lengths. The effect of low average EO groups on increased surfactant toxicity was more evident in the daphnid exposures. Quantitative structure-activity relationship (QSAR) models were developed form the data which relates surfactant structure to toxicity. The models predict increasing toxicity with decreasing EO number and increasing alkyl chain length. The models also indicate that alkyl chain length has a greater effect on toxicity than EO groups. Further, the models indicate that both species did not differ markedly in their sensitivity to alkyl chain length effects, while the number of EO groups had a stronger effect on daphnids than fathead minnow. Good agreement was found between QSAR model-predicted toxicity and reported toxicity values from the literature for several surfactants previously studied.

  1. Joint acute toxicity of the herbicide butachlor and three insecticides to the terrestrial earthworm, Eisenia fetida.

    PubMed

    Wang, Yanhua; Cang, Tao; Yu, Ruixian; Wu, Shenggan; Liu, Xinju; Chen, Chen; Wang, Qiang; Cai, Leiming

    2016-06-01

    The herbicide butachlor and three insecticides phoxim, chlorpyrifos, and lambda-cyhalotrhin are widely used pesticides with different modes of action. As most previous laboratory bioassays for these pesticides have been conducted solely based on acute tests with a single compound, only limited information is available on the possible combined toxicity of these common chemicals to soil organisms. In this study, we evaluated their mixture toxicity on the terrestrial earthworm, Eisenia fetida, with binary, ternary, and quaternary mixtures. Two different types of bioassays were employed in our work, including a contact filter paper toxicity test and a soil toxicity test. Mixture toxicity effects were assessed using the additive index method. For all of the tested binary mixtures (butachlor-phoxim, butachlor-chlorpyrifos, and butachlor-lambda-cyhalothrin), significant synergistic interactions were observed after 14 days in the soil toxicity assay. However, greater additive toxicity was found after 48 h in the contact toxicity bioassay. Most of the ternary and quaternary mixtures exhibited significant synergistic effects on the worms in both bioassay systems. Our findings would be helpful in assessing the ecological risk of these pesticide mixtures to soil invertebrates. The observed synergistic interactions underline the necessity to review soil quality guidelines, which are likely underestimating the adverse combined effects of these compounds. PMID:26946506

  2. Effects of Treatment Intensification on Acute Local Toxicity During Radiotherapy for Head and Neck Cancer: Prospective Observational Study Validating CTCAE, Version 3.0, Scoring System

    SciTech Connect

    Palazzi, Mauro Tomatis, Stefano; Orlandi, Ester; Guzzo, Marco; Sangalli, Claudia; Potepan, Paolo; Fantini, Simona; Bergamini, Cristiana; Gavazzi, Cecilia; Licitra, Lisa; Scaramellini, Gabriele; Cantu', Giulio; Olmi, Patrizia

    2008-02-01

    Purpose: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. Methods and Materials: Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventional fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. Results: Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the 'low-burden' class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the 'high-burden' class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. Conclusions: The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant.

  3. Development of a salinity/toxicity relationship to predict acute toxicity of saline waters to freshwater organisms. Interim final report, June 1990-March 1992

    SciTech Connect

    Mount, D.R.; Gulley, D.D.

    1992-04-01

    Discharge of produced water to surface waters is generally regulated as part of the NPDES permit problem and, therefore, may be subject to discharge limits for aquatic toxicity. Most produced waters contain elevated (relative to fresh water) concentrations of major ions (e.g., sodium, chloride) that can be toxic to fresh water organisms regardless of other organic and inorganic constituents. The objective of the research was to develop a Salinity/Toxicity Relationship (STR) that predicts the acute toxicity of saline waters to freshwater organisms based on the concentrations of major ions in solution. Laboratory toxicity tests were conducted to measure the acute toxicity of major ions to three freshwater species (Ceriodaphnia dubia, Daphnia magna, and fathead minnows). These laboratory toxicity data were then incorporated into multi-variate logistic regression equations that predict the acute toxicity of any combination of major ions. Logistic regression equations represented the toxicity data quite well, generally explaining in excess of 80 percent of the overall variance in survival. Application of the Ceriodaphnia STR to field data collected from surface waters receiving produced water discharges showed very strong correlation of STR predictions with the results of toxicity tests conducted on field-collected samples.

  4. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose

    PubMed Central

    Hunter, Laura J; Wood, David M; Dargan, Paul I

    2011-01-01

    The nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, anti-inflammatory and antipyretic actions. They are commonly taken in overdose in many areas of the world. The majority of patients with acute NSAID overdose will remain asymptomatic or develop minor self-limiting gastrointestinal symptoms. However, serious clinical sequelae have been reported in patients with acute NSAID overdose and these include convulsions, metabolic acidosis, coma and acute renal failure. There appear to be some differences between the NSAIDs in terms of the relative risk of these complications; in particular mefenamic acid is most commonly associated with convulsions. The management of these serious clinical features is largely supportive and there are no specific antidotes for acute NSAID toxicity. PMID:27147851

  5. Daily baseline skin care in the prevention, treatment, and supportive care of skin toxicity in oncology patients: recommendations from a multinational expert panel

    PubMed Central

    Bensadoun, René-Jean; Humbert, Phillipe; Krutman, Jean; Luger, Thomas; Triller, Raoul; Rougier, André; Seite, Sophie; Dreno, Brigitte

    2013-01-01

    Skin reactions due to radiotherapy and chemotherapy are a significant problem for an important number of cancer patients. While effective for treating cancer, they disturb cutaneous barrier function, causing a reaction soon after initiation of treatment that impacts patient quality of life. Managing these symptoms with cosmetics and nonpharmaceutical skin care products for camouflage or personal hygiene may be important for increasing patient self-esteem. However, inappropriate product choice or use could worsen side effects. Although recommendations exist for the pharmaceutical treatment of skin reactions, there are no recommendations for the choice or use of dermatologic skin care products for oncology patients. The present guidelines were developed by a board of European experts in dermatology and oncology to provide cancer care professionals with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin care management of cutaneous toxicities associated with radiotherapy and systemic chemotherapy, including epidermal growth factor inhibitors and monoclonal antibodies. The experts hope that these recommendations will improve the management of cutaneous side effects and hence quality of life for oncology patients. PMID:24353440

  6. Daily baseline skin care in the prevention, treatment, and supportive care of skin toxicity in oncology patients: recommendations from a multinational expert panel.

    PubMed

    Bensadoun, René-Jean; Humbert, Phillipe; Krutman, Jean; Luger, Thomas; Triller, Raoul; Rougier, André; Seite, Sophie; Dreno, Brigitte

    2013-01-01

    Skin reactions due to radiotherapy and chemotherapy are a significant problem for an important number of cancer patients. While effective for treating cancer, they disturb cutaneous barrier function, causing a reaction soon after initiation of treatment that impacts patient quality of life. Managing these symptoms with cosmetics and nonpharmaceutical skin care products for camouflage or personal hygiene may be important for increasing patient self-esteem. However, inappropriate product choice or use could worsen side effects. Although recommendations exist for the pharmaceutical treatment of skin reactions, there are no recommendations for the choice or use of dermatologic skin care products for oncology patients. The present guidelines were developed by a board of European experts in dermatology and oncology to provide cancer care professionals with guidance for the appropriate use of non-pharmaceutical, dermocosmetic skin care management of cutaneous toxicities associated with radiotherapy and systemic chemotherapy, including epidermal growth factor inhibitors and monoclonal antibodies. The experts hope that these recommendations will improve the management of cutaneous side effects and hence quality of life for oncology patients. PMID:24353440

  7. Acute and chronic toxicity of selected disinfection byproducts to Daphnia magna, Cyprinodon variegatus, and Isochrysis galbana.

    PubMed

    Fisher, Daniel; Yonkos, Lance; Ziegler, Gregory; Friedel, Elizabeth; Burton, Dennis

    2014-05-15

    Ballast water treatment has become a major issue in the last decade due to the problem of invasive species transported and released by the uptake and discharge of ballast water for shipping operations. One of the important issues considering ballast water treatment is to determine whether treated ballast water, once discharged, is safe to the aquatic environment. The International Maritime Organization (IMO) Marine Environmental Protection Committee (MEPC) has determined that prior to approval of a ballast water management system, aquatic toxicity data must be available for both the active substance and relevant byproducts. Many proposed ballast water treatment systems use chlorine as the active ingredient. Although there are sufficient toxicity data concerning active substances such as chlorine, there are limited toxicity data concerning disinfection (halogenated) byproducts including dibromochloromethane, four haloacetic acids and sodium bromate. Acute and chronic toxicity were determined for these disinfection byproducts (DBPs). Acute toxicity values ranged from 96-h LC50s of 46.8 mg/l for Daphnia magna for both dibromochloromethane and sodium bromate to a 96-h LC50 of 376.4 mg/l for Cyprinodon variegatus for tribromoacetic acid. Acute Isochrysis galbana population growth effect values ranged from a 72-h EC10 of 39.9 mg/l for dichloroacetic acid to a 72-h EC50 of 15,954 mg/l for sodium bromate. Chronic toxicity mortality/reproduction effects values for D. magna ranged from a 21-d IC25 of 160.9 mg/l for tribromoacetic acid to a 21-d LOEC of 493.0 mg/l for trichloroacetic acid. Chronic toxicity mortality/growth values for C. variegatus ranged from a 32-d IC25 of 246.8 mg/l for trichloroacetic acid to a 32-d LOEC of 908.1 mg/l for tribromoacetic acid. I. galbana 96-h chronic population growth effects values ranged from an EC10 of 38.5 mg/l for trichloroacetic acid to an LOEC of 500.0 mg/l for tribromoacetic acid. Acute to chronic ratios for all of these

  8. Acute Toxicity Assessment of Reactive Red 120 to Certain Aquatic Organisms.

    PubMed

    Darsana, R; Chandrasehar, G; Deepa, V; Gowthami, Y; Chitrikha, T; Ayyappan, S; Goparaju, A

    2015-11-01

    Laboratory experiments were conducted to evaluate the acute toxicity of a widely used textile dye namely Reactive Red 120 (RR 120) on certain aquatic species such as Pseudokirchneriella subcapitata (green alga), Lemna gibba (duck weed), Daphnia magna (water flea) and Oncorhynchus mykiss (Rainbow trout). All experiments were performed as per the OECD Guidelines for Testing of Chemicals. The toxicity end points of EC50, LC50, NOEC and LOEC for RR 120 were determined with 95% confidence limits using TOX STAT version 3.5. The EC50 of RR 120 for green alga, duck weed and water flea are >100.00, 64.34, 10.40 mg L(-1), respectively and LC50 for Rainbow trout is 78.84 mg L(-1). Based on the results, the test item RR 120 could be classified as non-toxic to green alga, harmful to duck weed and Rainbow trout, toxic to water flea. PMID:26350898

  9. Acute toxicity study of the oil from Azadirachta indica seed (neem oil).

    PubMed

    Gandhi, M; Lal, R; Sankaranarayanan, A; Banerjee, C K; Sharma, P L

    1988-01-01

    The seed oil of Azadirachta indica (neem oil) is well known for its medicinal properties in the indigenous Indian system of medicine. Its acute toxicity was documented in rats and rabbits by the oral route. Dose-related pharmacotoxic symptoms were noted along with a number of biochemical and histopathological indices of toxicity. The 24-h LD50 was established as 14 ml/kg in rats and 24 ml/kg in rabbits. Prior to death, animals of both species exhibited comparable pharmacotoxic symptoms in order and severity, with lungs and central nervous system as the target organs of toxicity. Edible mustard seed oil (80 ml/kg) was tested in the same manner to document the degree to which the physical characteristics of an oil could contribute to the oral toxicity of neem oil. PMID:3419203

  10. Assessment of acute toxicity of carbofuran in Macrobrachium olfersii (Wiegmann, 1836) at different temperature levels.

    PubMed

    Barbieri, Edison; Moreira, Priscila; Luchini, Luiz Alberto; Hidalgo, Karla Ruiz; Muñoz, Alejandro

    2016-01-01

    Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity - median lethal concentration - of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L(-1), respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control. PMID:23847016

  11. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    PubMed

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide. PMID:17716846

  12. Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice.

    PubMed

    Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran

    2016-12-01

    Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100mg/kg body weight (BW) and examined for 2weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10mg/kg BW for 4weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140nm and -44mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p<0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. PMID:27612832

  13. Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses.

    PubMed

    Pinto, Flávia Cristina Morone; De-Oliveira, Ana Cecília A X; De-Carvalho, Rosangela R; Gomes-Carneiro, Maria Regina; Coelho, Deise R; Lima, Salvador Vilar C; Paumgartten, Francisco José R; Aguiar, José Lamartine A

    2016-02-10

    The acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of BC were studied. Cytotoxicity of BC was evaluated in cultured C3A hepatoma cells (HepG2/C3A) using a lactate dehydrogenase (LDH) activity assay. Acute toxicity was tested in adults Wistar rats treated with a single dose of BC. The genotoxicity of BC was evaluated in vivo by the micronucleus assay. BC (0.33-170 μg/mL) added to C3A cell culture medium caused no elevation in LDH release over the background level recorded in untreated cell wells. The treatment with the BC in a single oral dose (2000 mg/kg body weight) caused no deaths or signs of toxicity. BC attenuated CP-induced and inhibition the incidence of MNPCE (female: 46.94%; male: 22.7%) and increased the ratio of PCE/NCE (female: 46.10%; male: 35.25%). There was no alteration in the LDH release in the wells where C3A cells were treated with increasing concentrations of BC compared to the wells where the cells received the cell culture medium only (background of approximately 20% cell death), indicated that in the dose range tested BC was not cytotoxic. BC was not cytotoxic, genotoxic or acutely toxic. BC attenuated CP-induced genotoxic and myelotoxic effects. PMID:26686163

  14. Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish.

    PubMed

    Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto

    2016-08-15

    Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a(fh318). After treatment with 1mM sodium arsenite, the survival of nrf2a(fh318) larvae was significantly shorter than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. PMID:27306194

  15. Acute oral toxicity of sodium cyanide in birds

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

    1986-01-01

    Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

  16. Metal uptake and acute toxicity in zebrafish: common mechanisms across multiple metals.

    PubMed

    Alsop, Derek; Wood, Chris M

    2011-10-01

    Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca(2+) uptake, copper and nickel also decreased Ca(2+) uptake, suggesting that the epithelial transport of all these metals is through Ca(2+) pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca(2+) levels, indicating that the reduction of Ca(2+) uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na(+), which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K(+) were also observed, although they were not as pronounced or frequent as Na(+) losses. None of the metals tested inhibited Na(+) uptake in zebrafish (Na(+) uptake was in fact increased with exposure) and the observed losses of Na(+), K(+), Ca(2+) and Mg(2+) were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na(+)). PMID:21820385

  17. Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae).

    PubMed

    Wang, Ning; Ingersoll, Christopher G; Hardesty, Douglas K; Ivey, Christopher D; Kunz, James L; May, Thomas W; Dwyer, F James; Roberts, Andy D; Augspurger, Tom; Kane, Cynthia M; Neves, Richard J; Barnhart, M Chris

    2007-10-01

    The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 microg Cu/L (except 15 microg Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were <45 microg Cu/L or <12 mg N/L and were often at or below the final acute values (FAVs) used to derive the U.S. Environmental Protection Agency 1996 acute water quality criterion (WQC) for copper and 1999 acute WQC for ammonia. However, the chlorine EC50s for mussels generally were >40 microg/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. PMID:17867873

  18. Acute toxicity modeling of rainbow trout and silver sea bream exposed to waterborne metals.

    PubMed

    Liao, C M; Lin, M C

    2001-01-01

    Of three proposed acute toxicity models, the uptake-depuration (UD) model, the time-integrated concentration (TIC) model, and the concentration-time (CT) model are derived and verified with acute toxicity data to estimate the internal residues of waterborne metals in fish as a function of a few constants and variables. The main factors are the exposure time, the external exposure concentration, the bioconcentration factor (BCF), and the depuration rate constant (k2). The UD model is based on the concept of residue levels at the cell membrane well correlating with the whole-body concentrations, whereas the TIC and the CT models are based on the idea of irreversible inhibition of the enzyme acetylcholinesterase (AChE) governing the metal acute toxicity in that metals in the entire fish or in the aqueous phase can be described by the critical area under the time-concentration curve that is associated with a critical TIC of toxicant in the target tissue. A highly significant correlation (r2 > 0.9) was found between predictions and LC50(t) data for both the TIC and the CT models, indicating successfully describe 4- to 18-d LC50(t) data of arsenic (As), cobalt (Co), copper (Cu), and Co/Cu mixture in rainbow trout (Oncorhyuchus mykiss) and of Cu in fingerlings and subadults of silver sea bream (Sparus sarba). The time-dependent lethal internal concentration at the site of action that causes 50% mortality is also predicted for a given compound and species. It concludes that the TIC and the CT models can be applied to regulate the acute toxicity and to estimate incipient LC50 values and internal residues of waterborne metals in fish. PMID:11501285

  19. Acute and chronic toxicity of the benzoylurea pesticide, lufenuron, in the fish, Colossoma macropomum.

    PubMed

    Rafaela Leão Soares, Priscila; Lucas Corrêa de Andrade, André; Pinheiro Santos, Thamiris; Caroline Barros Lucas da Silva, Stephannie; Freitas da Silva, Jadson; Rodrigues Dos Santos, Amanda; Hugo Lima da Silva Souza, Elton; Magliano da Cunha, Franklin; Wanderley Teixeira, Valéria; Sales Cadena, Marilia Ribeiro; Bezerra de Sá, Fabrício; Bezerra de Carvalho Júnior, Luiz; Gonçalves Cadena, Pabyton

    2016-10-01

    Lufenuron is a benzoylurea insecticide that interfere in chitin synthesis in insects. Although lufenuron is widely used in agriculture and aquaculture, rare are studies described that relates to possible toxic effects in fish. This work aimed to evaluate acute and chronic toxic effects of benzoylurea pesticide (lufenuron) on biological parameters of Colossoma macropomum (Tambaqui). In the acute test, juveniles of Tambaqui were divided into control group and five experimental groups with exposure from 0.1 to 0.9 mg/L of lufenuron for 96 h. Animals were also submitted to chronic toxicity test for four months in concentrations of 0.1 and 0.3 mg/L of lufenuron, the concentration used in the treatment of ectoparasites in fish and 50% of LC50 96 h, respectively. The presence of hemorrhages was observed in eyes, fins and operculum of fish exposed to 0.7 and 0.9 mg/L of lufenuron. Histological analysis showed changes in the morphology of fish gills submitted to acute toxicity test, as lamellar aneurysm and blood congestion inside lamellae. Lufenuron promoted damage in fish retina as in ability to respond to stimuli in photoreceptors and in ON-bipolar cells in acute test. In chronic test, blood glucose analysis and morphometric parameters showed no significant differences (p > 0.05). In general, Tambaqui exhibited behaviors associated with stress when exposed to lufenuron. Thus, lufenuron showed several toxic effects in relation to biological parameters in Tambaqui. This concerns about the use and discard of lufenuron, and indicates the requirement of environmental actions to prevent potential contamination of aquatic biota. PMID:27448754

  20. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  1. Acute toxicity of mixture of acetaminophen and ibuprofen to Green Neon Shrimp, Neocaridina denticulate.

    PubMed

    Sung, Hung-Hung; Chiu, Yuh-Wen; Wang, Shu-Yin; Chen, Chien-Min; Huang, Da-Ji

    2014-07-01

    In recent years, numerous studies have indicated that various long-term use drugs, such as antibiotics or analgesics, not only cannot be completely decomposed via sewage treatment but also exhibit biological toxicity if they enter the environment; thus, the release of these drugs into the environment can damage ecological systems. This study sought to investigate the acute toxicity of two commonly utilized analgesics, ibuprofen (IBU) and acetaminophen (APAP), to aquatic organisms after these drugs have entered the water. To address this objective, the acute toxicity (median lethal concentration, LC₅₀, for a 96-h exposure) of IBU alone, APAP alone, and mixtures containing different ratios of IBU and APAP in green neon shrimp (Neocaridina denticulata) were measured. The results of four tests revealed that the 96-h LC₅₀ values for IBU and APAP alone were 6.07 mg/L and 6.60 mg/L, respectively. The 96-h LC₅₀ for a 1:1 mixture of IBU and APAP was 6.23 mg/L, and the toxicity of this mixture did not significantly differ from the toxicity of either drug alone (p<0.05). The experimental results for mixtures containing unequal ratios of IBU and APAP indicated that mixtures with high APAP concentrations and low IBU concentrations exhibited markedly greater toxicity in N. denticulata (LC₅₀=4.78 mg/L) than APAP or IBU alone. However, mixtures with high IBU concentrations and low APAP concentrations exhibited lower toxicity in N. denticulata (LC₅₀=6.78 mg/L) than IBU or APAP alone. This study demonstrated that different mixtures of IBU and APAP were associated with different toxic effects in green neon shrimp. PMID:24860956

  2. Kinetics, intermediates and acute toxicity of arsanilic acid photolysis.

    PubMed

    Zhu, Xiang-Dong; Wang, Yu-Jun; Liu, Cun; Qin, Wen-Xiu; Zhou, Dong-Mei

    2014-07-01

    Arsanilic acid (4-amino phenyl arsenic acid, ASA) is widely used in poultry production as feed additives, while most of ASA in the feed is excreted in the animal manure and released into the environment. However, the environmental behaviors of ASA were not well understood. In the present study, the photolysis behaviors of ASA and the toxicity of its metabolites to luminescent bacterium were studied. The results showed that ASA could be photodegraded and this process was strongly affected by solution pH, humic acid and dissolved oxygen. Upon UV irradiation for 360 min, ASA could be completely eliminated, but the reduction of total organic carbon (TOC) was not significant. In addition, NH4(+) ions and inorganic arsenic including arsenite and arsenate were identified as the predominant end-products. The conversion of ASA included both direct and indirect photolysis involving radicals, and its possible photolysis pathways were proposed on the basis of the identified intermediates. Unfortunately, higher adverse effects of the conversion products of ASA on bacteria were observed during the photolysis reaction. The results of present study might be helpful for assessing the environmental persistence and risks of ASA. PMID:24405966

  3. Acute ecological toxicity and environmental persistence of simulants

    SciTech Connect

    Cataldo, D.A.; Ligotke, M.W.; McVeety, B.D.; Fellows, R.J.; Bolton, H. Jr.; Li, S.W.; Van Voris, P.; Wentsel, R.S.

    1988-06-01

    The objectives of these studies are to establish the comparative environmental behavior and chemical fate of chemical simulants. Laboratory studies were undertaken to establish: (1) deposition efficiency (deposition velocities, Vd) for receptor surfaces including plant foliage and soils; (2) dose/response relationships for important environmental components including plants and soil microflora; and (3) the environmental persistence of the simulants. Chemical agent simulants are employed for a range of testing and training activities where use of chemical agents is less than suitable from a safety and environmental standpoint. A variety of chemical simulant materials are used to simulate either nerve agents or blister agents. The following research describes the environmental effects and persistence of four simulants. These are the nerve agent stimulants diisopropyl methylphosphonate (DIMP), diisopropyl fluorophosphate (DFP), and bis (2-ethylhexyl) phosphonate (BIS), and the mustard stimulant 2-chloroethyl ethyl sulfide (CEES). The vapor pressures for DIMP, DFP, and CEES are relatively high, reported to be 0.17, 0.58 and 3.4 mm Hg, respectively; while that of BIS is substantially less at 5.8 /times/ 10/sup /minus/5/ mm Hg at 25/degree/C. The chemical characteristics of DFP and CEES are very similar to G/VX-agents and mustard, respectively, and are employed for materials evaluation under controlled conditions. However, their toxicity precludes their use in the environment. DIMP and BIS are currently used for testing in the open air. 3 figs., 3 tabs.

  4. In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models

    PubMed Central

    García, Marta; Llames, Sara; García, Eva; Meana, Alvaro; Cuadrado, Natividad; Recasens, Mar; Puig, Susana; Nagore, Eduardo; Illera, Nuria; Jorcano, José Luis; Del Rio, Marcela; Larcher, Fernando

    2010-01-01

    In vivo studies of UVB effects on human skin are precluded by ethical and technical arguments on volunteers and inconceivable in cancer-prone patients such as those affected with Xeroderma Pigmentosum (XP). Establishing reliable models to address mechanistic and therapeutic matters thus remains a challenge. Here we have used the skin-humanized mouse system that circumvents most current model constraints. We assessed the UVB radiation effects including the sequential changes after acute exposure with respect to timing, dosage, and the relationship between dose and degree-sort of epidermal alteration. On Caucasian-derived regenerated skins, UVB irradiation (800 J/m2) induced DNA damage (cyclobutane pyrimidine dimers) and p53 expression in exposed keratinocytes. Epidermal disorganization was observed at higher doses. In contrast, in African descent–derived regenerated skins, physiological hyperpigmentation prevented tissue alterations and DNA photolesions. The acute UVB effects seen in Caucasian-derived engrafted skins were also blocked by a physical sunscreen, demonstrating the suitability of the system for photoprotection studies. We also report the establishment of a photosensitive model through the transplantation of XP-C patient cells as part of a bioengineered skin. The inability of XP-C engrafted skin to remove DNA damaged cells was confirmed in vivo. Both the normal and XP-C versions of the skin-humanized mice proved proficient models to assess UVB-mediated DNA repair responses and provide a strong platform to test novel therapeutic strategies. PMID:20558577

  5. Acute and chronic effects of sulfur mustard on the skin: a comprehensive review.

    PubMed

    Ghanei, Mostafa; Poursaleh, Zohreh; Harandi, Ali Amini; Emadi, Seyed Emad; Emadi, Seyed Naser

    2010-12-01

    Sulfur mustard (2,2-dichlorodiethyl sulfide, SM) is one of the vesicant classes of chemical warfare agents that causes blistering in the skin and mucous membranes, where it can have lingering long-term effects for up to ten years (1). SM was employed extensively by the Iraqi army against not only Iranian soldiers but also civilians between 1983 and 1988, resulting in over 100,000 chemical casualties. Approximately 45,000 victims are still suffering from long-term effects of exposure (2,3). More than 90% of the patients exposed to SM exhibit various cutaneous lesions in the affected area. The human skin can absorb approximately 20% of the SM through exposure. Up to 70% of the chemical is concentrated in the epidermis and the remainder in the basement membrane and in the dermis (4).Sulfur mustard exists in different physical states. The liquid form of SM evaporates slowly in cold weather and can penetrate through the clothing, thereby increasing exposure. However, the gas form readily diffuses in the air and it can be inhaled, leading to systemic absorption. In addition, warm temperatures are ideal conditions that liquid SM present in the clothing of the exposed individual could be converted to gas form. SM-induced clinical cutaneous symptoms include itching and burning. Other clinical findings include erythema or painless sunburn, bulla, hypo- and hyper pigmentation in both exposed and unexposed areas (5,6) The mechanism and biochemical cascade of SM-induced cutaneous manifestations are not completely understood but several published pathways support many of the know facts. Our current understanding fails to explain the time interval between the acute chemical exposure and the late-onset and delayed tissue damage (7,8). The aim of this article is to review the acute and long-term cutaneous findings resulting from SM exposure. Also, cellular and molecular mechanism involved in SM-induced skin pathology have been discussed. PMID:20868209

  6. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  7. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    SciTech Connect

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  8. Assessing contaminant sensitivity of endangered and threatened aquatic species: Part I. Acute toxicity of five chemicals

    USGS Publications Warehouse

    Dwyer, F.J.; Mayer, F.L.; Sappington, L.C.; Buckler, D.R.; Bridges, C.M.; Greer, I.E.; Hardesty, D.K.; Henke, C.E.; Ingersoll, C.G.; Kunz, J.L.; Whites, D.W.; Augspurger, T.; Mount, D.R.; Hattala, K.; Neuderfer, G.N.

    2005-01-01

    Assessment of contaminant impacts to federally identified endangered, threatened and candidate, and state-identified endangered species (collectively referred to as "listed" species) requires understanding of a species' sensitivities to particular chemicals. The most direct approach would be to determine the sensitivity of a listed species to a particular contaminant or perturbation. An indirect approach for aquatic species would be application of toxicity data obtained from standard test procedures and species commonly used in laboratory toxicity tests. Common test species (fathead minnow, Pimephales promelas; sheepshead minnow, Cyprinodon variegatus; and rainbow trout, Oncorhynchus mykiss) and 17 listed or closely related species were tested in acute 96-hour water exposures with five chemicals (carbaryl, copper, 4-nonylphenol, pentachlorophenol, and permethrin) representing a broad range of toxic modes of action. No single species was the most sensitive to all chemicals. For the three standard test species evaluated, the rainbow trout was more sensitive than either the fathead minnow or sheepshead minnow and was equal to or more sensitive than listed and related species 81% of the time. To estimate an LC50 for a listed species, a factor of 0.63 can be applied to the geometric mean LC50 of rainbow trout toxicity data, and more conservative factors can be determined using variance estimates (0.46 based on 1 SD of the mean and 0.33 based on 2 SD of the mean). Additionally, a low- or no-acute effect concentration can be estimated by multiplying the respective LC50 by a factor of approximately 0.56, which supports the United States Environmental Protection Agency approach of multiplying the final acute value by 0.5 (division by 2). When captive or locally abundant populations of listed fish are available, consideration should be given to direct testing. When direct toxicity testing cannot be performed, approaches for developing protective measures using common test

  9. Acute Toxicity Prediction in Multiple Species by Leveraging Mechanistic ToxCast Mitochondrial Inhibition Data and Simulation of Oral Bioavailability.

    PubMed

    Bhhatarai, Barun; Wilson, Daniel M; Bartels, Michael J; Chaudhuri, Shubhra; Price, Paul S; Carney, Edward W

    2015-10-01

    There is great interest in assessing the in vivo toxicity of chemicals using nonanimal alternatives. However, acute mammalian toxicity is not adequately predicted by current in silico or in vitro approaches. Mechanisms of acute toxicity are likely conserved across invertebrate, aquatic, and mammalian species, suggesting that dose-response concordance would be high and in vitro mechanistic data could predict responses in multiple species under conditions of similar bioavailability. We tested this hypothesis by comparing acute toxicity between rat, daphnia, and fish and by comparing their respective acute data to inhibition of mitochondria membrane potential (MMP) using U.S. Environmental Protection Agency ToxCast in vitro high-throughput screening data. Logarithmic scatter plots of acute toxicity data showed a clear relationship between fish, daphnia, and intravenous rat but not oral rat data. Similar plots versus MMP showed a well-delineated upper boundary for fish, daphnia, and intravenous data but were scattered without an upper boundary for rat oral data. Adjustments of acute oral rat toxicity values by simulating fractional absorption and CYP-based metabolism as well as removing compounds with hydrolyzable linkages or flagged as substrates for glucuronidation delineated an upper boundary for rat oral toxicity versus MMP. Mitochondrial inhibition at low concentrations predicted highly acutely toxic chemicals for fish and daphnia but not the rat where toxicity was often attenuated. This use of a single high-throughput screening assay to predict acute toxicity in multiple species represents a milestone and highlights the promise of such approaches but also the need for refined tools to address systemic bioavailability and the impact of limited absorption and first pass metabolism. PMID:26139166

  10. Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

    PubMed

    Cho, MyoungLae; Shin, Gi-Hae; Kim, Jae-Min; Lee, Jin-Ha; Park, Sun-Ok; Lee, Sang-Jong; Shin, HyunMu; Lee, Boo-Yong; Kang, Il-Jun; Lee, Ok-Hwan

    2016-06-01

    The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats. PMID:26925497

  11. Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment

    SciTech Connect

    McKim, J.M.; Bradbury, S.P.; Niemi, G.J.

    1987-04-01

    Implementation of the Toxic Substances Control Act of 1977 creates the need to reliably establish testing priorities because laboratory resources are limited and the number of industrial chemicals requiring evaluation is overwhelming. The use of quantitative structure activity relationship (QSAR) models as rapid and predictive screening tools to select more potentially hazardous chemicals for in-depth laboratory evaluation has been proposed. Further implementation and refinement of quantitative structure-toxicity relationships in aqueous toxicology and hazard assessment requires the development of a mode-of-action database. With such a database, a qualitative structure-activity relationship can be formulated to assign the proper mode of action, and respective QSAR, to a given chemical structure. In this review, the development of fish acute toxicity syndromes (FATS), which are toxic-response sets based on various behavioral and physiological-biochemical measurements, and their projected use in the mode-of-action database are outlined. Using behavioral parameters monitored in the fathead minnow during acute toxicity testing, FATS associated with acetylcholinesterase (AChE) inhibitors and narcotics could be reliably predicted. However, compounds classified as oxidative phosphorylation uncouplers or stimulants could not be resolved. Refinement of this approach by using respiratory-cardiovascular responses in the rainbow trout, enabled FATS associated with AChE inhibitors, convulsants, narcotics, respiratory blockers, respiratory membrane irritants, and uncouplers to be correctly predicted.

  12. Acute and chronic oral toxicity of a partially purified plaunotol extract from Croton stellatopilosus Ohba.

    PubMed

    Chaotham, Chatchai; Chivapat, Songpol; Chaikitwattana, Anan; De-Eknamkul, Wanchai

    2013-01-01

    Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD₅₀ = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11-1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550-1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans. PMID:24286075

  13. Acute toxicity of eight oil spill response chemicals to temperate, boreal, and Arctic species.

    PubMed

    Hansen, Bjørn Henrik; Altin, Dag; Bonaunet, Kristin; Overjordet, Ida Beathe

    2014-01-01

    The objectives of this study were to (1) determine the acute toxicity of selected shoreline washing agents (SWA) and dispersants, and (2) assess interspecies differences in sensitivity to the products. Eight shoreline washing agents (Hela saneringsvæske, Bios, Bioversal, Absorrep K212, and Corexit 9580) and chemical dispersants (Corexit 9500, Dasic NS, and Gamlen OD4000) were tested on five marine species, algae Skeletonema costatum, planktonic copepod species Acartia tonsa (temperate species), Calanus finmarchicus (boreal species) and Calanus glacialis (Arctic species), and benthic amphipod Corophium volutator. For most products, A. tonsa was the most sensitive species, whereas C. volutator was the least sensitive; however, these species were exposed through different media (water/sediment). In general, all copepod species displayed a relatively similar sensitivity to all products. However, A. tonsa was somewhat more sensitive than other copepods to most of the tested products. Thus, A. tonsa appears to be a candidate species for boreal and Arctic copepods for acute toxicity testing, and data generated on this species may be used as to provide conservative estimates. The benthic species (C. volutator) had a different sensitivity pattern relative to pelagic species, displaying higher sensitivity to solvent-based SWA than to water-based SWA. Comparing product toxicity, the dispersants were in general most toxic while the solvent-based SWA were least toxic to pelagic species. PMID:24754387

  14. Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

    2011-05-01

    From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

  15. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems. PMID:27539747

  16. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    PubMed

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg(-1) for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg(-1) of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg(-1) of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender. PMID:24369482

  17. Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

    PubMed Central

    Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

    2013-01-01

    The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender. PMID:24369482

  18. Acute fibrinous organising pneumonia: a manifestation of trimethoprim-sulfamethoxazole pulmonary toxicity.

    PubMed

    Jamous, Fady; Ayaz, Syed Zain; Choate, Jacquelyn

    2014-01-01

    A 50-year-old man was treated with trimethoprim-sulfamethoxazole (TMP-SMX) for acute arthritis of his right big toe. Within a few days, he developed dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. Symptoms improved with discontinuation of the antibiotic but worsened again with its reintroduction. An open lung biopsy was performed. We describe the workup performed and the factors that pointed to a final diagnosis of TMP-SMX-related pulmonary toxicity in the form of acute fibrinous organising pneumonia. PMID:25355746

  19. Emergency planning and the acute toxic potency of inhaled ammonia.

    PubMed Central

    Michaels, R A

    1999-01-01

    Ammonia is present in agriculture and commerce in many if not most communities. This report evaluates the toxic potency of ammonia, based on three types of data: anecdotal data, in some cases predating World War 1, reconstructions of contemporary industrial accidents, and animal bioassays. Standards and guidelines for human exposure have been driven largely by the anecdotal data, suggesting that ammonia at 5,000-10,000 parts per million, volume/volume (ppm-v), might be lethal within 5-10 min. However, contemporary accident reconstructions suggest that ammonia lethality requires higher concentrations. For example, 33,737 ppm-v was a 5-min zero-mortality value in a major ammonia release in 1973 in South Africa. Comparisons of secondary reports of ammonia lethality with original sources revealed discrepancies in contemporary sources, apparently resulting from failure to examine old documents or accurately translate foreign documents. The present investigation revealed that contemporary accident reconstructions yield ammonia lethality levels comparable to those in dozens of reports of animal bioassays, after adjustment of concentrations to human equivalent concentrations via U.S. Environmental Protection Agency (EPA) procedures. Ammonia levels potentially causing irreversible injury or impairing the ability of exposed people to escape from further exposure or from coincident perils similarly have been biased downwardly in contemporary sources. The EPA has identified ammonia as one of 366 extremely hazardous substances subject to community right-to-know provisions of the Superfund Act and emergency planning provisions of the Clean Air Act. The Clean Air Act defines emergency planning zones (EPZs) around industrial facilities exceeding a threshold quantity of ammonia on-site. This study suggests that EPZ areas around ammonia facilities can be reduced, thereby also reducing emergency planning costs, which will vary roughly with the EPZ radius squared. Images Figure 1

  20. Species comparison of acute inhalation toxicity of ozone and phosgene

    SciTech Connect

    Hatch, G.E.; Slade, R.; Stead, A.G.; Graham, J.A.

    1986-01-01

    A comparison of the concentration-response effects of inhaled ozone (O/sub 3/) and phosgene (COCl/sub 2/) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl/sub 2/ and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl/sub 2/-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm O3 and above, while rabbits responded only at 2.0 ppm O3. Phosgene similarly affected mice, hamsters, and rats at 0.2 ppm and above, while guinea pigs and rabbits were affected at 0.5 ppm and above. Percent recovery of lavage fluid varied significantly between species, guinea pigs having lower recovery than other species with both gases. Lavage fluid recovery was lower following exposure to higher levels of O3 but not COCl/sub 2/. Results of this study indicate that significant species differences are seen in the response to low levels of O3 and COCl/sub 2/. These differences do not appear to be related in a simple manner to body weight.

  1. Acute toxicity of cadmium and sodium pentachlorophenate to daphnids and fish

    SciTech Connect

    Hall, W.S.; Paulson, R.L.; Hall, L.W. Jr.; Burton, D.T.

    1986-08-01

    When estimating the toxicity of effluents it is desirable to use organisms sensitive to a wide range of pollutants. Currently, the US Environmental Protection Agency (US EPA) recommends the use of Daphnia pulex, Daphnia magna, and Pimephales promelas to assess the toxicity of freshwater effluents. Ceriodaphnia sp. has also received increased attention as a standard toxicity test organism due to its sensitivity, short generation time, and ubiquitous distribution. Comparison of toxicity data generated by different investigators is often difficult because of differences in test procedures, dilution waters, or nutritional history of test organisms. The primary objectives of this research were to compare the sensitivity of Daphnia magna, Daphnia pulex, Ceriodaphnia reticulata, and Pimephales promelas to the reference toxicants CdCl/sub 2/ and sodium pentachlorophenate (NaPCP) and to compare results with those obtained by other investigators. A secondary objective of this study was to evaluate the effect of different dilution waters on the acute toxicity of these reference toxicants to the above test organisms.

  2. Clinical & pathological features of acute toxicity due to Cassia occidentalis in vertebrates.

    PubMed

    Vashishtha, V M; John, T J; Kumar, Amod

    2009-07-01

    Cassia occidentalis is an annual shrub found in many countries including India. Although bovines and ovines do not eat it, parts of the plant are used in some traditional herbal medicines. Several animal studies have documented that fresh or dried beans are toxic. Ingestion of large amounts by grazing animals has caused serious illness and death. The toxic effects in large animals, rodents and chicken are on skeletal muscles, liver, kidney and heart. The predominant systems involved depend upon the animal species and the dose of the beans consumed. Brain functions are often affected. Gross lesions at necropsy consist of necrosis of skeletal muscle fibres and hepatic centrilobular necrosis; renal tubular necrosis is less frequent. Muscle and liver cell necrosis is reflected in biochemical abnormalities. The median lethal dose (LD(50)) is 1 g/kg for mice and rats. Toxicity is attributed to various anthraquinones and their derivatives and alkaloids, but the specific toxins have not been identified. Data on human toxicity are extremely scarce. This review summarizes information available on Cassia toxicity in animals and compares it with toxic features reported in children. The clinical spectrum and histopathology of C. occidentalis poisoning in children resemble those of animal toxicity, affecting mainly hepatic, skeletal muscle and brain tissues. The case-fatality rate in acute severe poisoning is 75-80 per cent in children. PMID:19700797

  3. Toxicity of adipic acid.

    PubMed

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests. PMID:12024802

  4. Acute toxicity of PCB congeners to Daphnia magma and Pimephales promelas

    SciTech Connect

    Dillon, T.M. ); Burton, W.D.S. )

    1991-02-01

    The acute toxicity (EC50/LC50) of commercial PCB mixtures has been reported to range from 2.0 to 283 ug/L. Because PCBs are very hydrophobic most biological studies have utilized a carrier solvent to facilitate introduction of PCBs into aqueous solution. As a result, biological effects are often reported at exposure concentrations exceeding water solubility. The purpose of this work was to evaluate the comparative toxicity of selected PCB congeners without carrier solvents. These tests were conducted on early life stages of two sensitive freshwater organisms, Daphnia magna and Pimephales promelas.

  5. [Empirical therapeutic approach to infection by resistant gram positive (acute bacterial skin and skin structure infections and health care pneumonia). Value of risk factors].

    PubMed

    González-DelCastillo, J; Núñez-Orantos, M J; Candel, F J; Martín-Sánchez, F J

    2016-09-01

    Antibiotic treatment inadequacy is common in these sites of infection and may have implications for the patient's prognosis. In acute bacterial skin and skin structure infections, the document states that for the establishment of an adequate treatment it must be assessed the severity, the patient comorbidity and the risk factors for multidrug-resistant microorganism. The concept of health care-associated pneumonia is discussed and leads to errors in the etiologic diagnosis and therefore in the selection of antibiotic treatment. This paper discusses how to perform this approach to the possible etiology to guide empirical treatment. PMID:27608306

  6. Acute and subacute toxicity study of 1,8-cineole in mice

    PubMed Central

    Xu, Jiao; Hu, Zhi-Qiang; Wang, Chuan; Yin, Zhong-Qiong; Wei, Qin; Zhou, Li-Jun; Li, Li; Du, Yong-Hua; Jia, Ren-Yong; Li, Mei; Fan, Qiao-Jia; Liang, Xiao-Xia; He, Chang-Liang; Yin, Li-Zi

    2014-01-01

    The effects of acute and subacute toxicity of 1,8-cineole in Kunming mice were studied. After acute oral administration, the LD50 value (95% CL) was 3849 mg/kg (3488.8~4247.1 mg/kg). In the subacute toxicity study, there were no significant differences in body weight and relative organ weight between the control group and 1,8-cineole treatment groups. The histopathological examinations showed that granular degeneration and vacuolar degeneration appeared in liver and kidney tissue after administration of high dose of 1,8-cineole. Under electron microscopy, a series of ultrastructural changes were observed: The electron microscopy assays indicated that the influence of 1,8-cineole on the target organ at the subcellular level were mainly on the mitochondria, endoplasmic reticulum and other membrane type structure of liver and kidney. PMID:24817945

  7. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy.

    PubMed

    Mei, Lin; Ontiveros, Evelena P; Griffiths, Elizabeth A; Thompson, James E; Wang, Eunice S; Wetzler, Meir

    2015-07-01

    Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies. PMID:25614322

  8. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day. PMID:23353547

  9. Acute and Subacute Toxicity Studies on Rutin-Rich Tartary Buckwheat Dough in Experimental Animals.

    PubMed

    Suzuki, Tatsuro; Morishita, Toshikazu; Noda, Takahiro; Ishiguro, Koji

    2015-01-01

    In order to investigate the toxicity of rutin-rich dough from the Tartary buckwheat variety 'Manten-Kirari,' acute and subacute toxicity studies (10,000 and 5,000 mg/kg flour, respectively) were performed using rats. In the acute toxicity study, no toxic symptoms were observed and no rats died during the test. Body weight in the 'Manten-Kirari'-treated group was not significantly different when compared with that of the control group. On pathologico-anatomic observation, no unusual symptoms were observed in the 'Manten-Kirari'-treated group when compared with the control group. In the subacute toxicity study, no toxic symptoms were observed and no rats died during the test. Body weight and food intake in the 'Manten-Kirari'-treated and common buckwheat groups were not significantly different when compared with the control group. However, some investigated properties, such as urine protein and serum albumin, were significantly different in the 'Manten-Kirari' and common buckwheat groups when compared with the control group. However, these changes were not caused by toxicity, but by transient changes. On pathologico-anatomic observation, some abnormalities were observed in the liver, kidneys, heart, lung, bronchi and pituitary gland in some rats. However, the incidental rates in the 'Manten-Kirari' and common buckwheat groups did not differ when compared to controls. Therefore, these abnormalities may be caused by natural generation. Based on these results, we concluded that dough at a dose of 5,000 mg flour/kg is at a non effect level. PMID:26052149

  10. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  11. The acute whole effluent toxicity of storm water from an international airport

    SciTech Connect

    Fisher, D.J.; Turley, S.D.; Turley, B.S.; Yonkos, L.T.; Ziegler, G.P.; Knott, M.H.

    1995-06-01

    In October 1990, the US Environmental Protection Agency promulgated application requirements with deadlines for storm-water discharges associated with industrial activity and certain municipal systems. Major airports have a number of hydrocarbon-based contaminants that could appear in storm-water runoff. In addition, ethylene, diethylene, and propylene glycol deicing and anti-icing mixtures are used during freezing and near-freezing weather. The objective of this study was to characterize the potential acute impact on aquatic life from industrial storm-water discharges from an international airport. Samples from winter storm events caused acute toxicity to both the fathead minnow (Pimephales promelas) and the daphnid (Daphnia magna), with LC50 values for both species as low as 1.0 and 2.0% effluent. The toxicity of the samples was due to the various glycol-based deicer/anti-icer mixtures used during these events. High oxygen demands and elevated total nitrogen levels are other potential problems during anti-icing/deicing activities. Samples from rain events during the nonwinter months at the airport did not cause acute toxicity unless associated with fuel spills. As a result of this study, a new discharge permit has been issued for this airport, requiring the implementation of plans for the collection and recycling and/or disposal of the deicer/anti-icer mixtures.

  12. Protective Effects of Lactobacillus plantarum CCFM8610 against Acute Cadmium Toxicity in Mice

    PubMed Central

    Zhai, Qixiao; Wang, Gang; Zhao, Jianxin; Liu, Xiaoming; Zhang, Hao

    2013-01-01

    This study evaluated the protective effects of Lactobacillus plantarum CCFM8610, a selected probiotic with good cadmium binding capacity, against acute cadmium toxicity in mice. Ninety mice were divided into prevention and therapy groups. In the prevention groups, CCFM8610 was administered at 109 CFU once daily for 7 days, followed by a single oral dose of cadmium chloride at 1.8 mg cadmium for each mouse. In the therapy groups, the same dose of CCFM8610 was administered for 2 days after an identical single dose of cadmium exposure. Mice that received neither cadmium nor culture or that received cadmium alone served as negative and positive controls, respectively. The effects of both living and dead CCFM8610 on cadmium ion concentrations in feces, liver, and kidney were determined. Moreover, the alterations in reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and histopathology in the liver and kidney were investigated. The results showed that compared to the mice that received cadmium only, CCFM8610 treatment can effectively decrease intestinal cadmium absorption, reduce tissue cadmium accumulation, alleviate renal and hepatic oxidative stress, and ameliorate hepatic histopathological changes. Living CCFM8610 administered after cadmium exposure offered the most significant protection. Our results suggested that CCFM8610 is more effective against acute cadmium toxicity than a simple antioxidant treatment due to its special physiological functions and that it can be considered a new dietary therapeutic strategy against acute cadmium toxicity. PMID:23263961

  13. Acute toxicities to larval rainbow trout of representative compounds detected in Great Lakes fish

    SciTech Connect

    Edsall, C.C. )

    1991-02-01

    In recent years the National Fisheries Research Center-Great Lakes has ranked the potential hazard to fish and invertebrates of various chemical compounds detected in two Great Lakes fishes - lake trout, Salvelinus namaycush, and walleye. Stizostedion vitreum vitreum. This hazard assessment has included the identification of the potential sources of the compound, determination of the occurrence and abundance of the compounds in Great Lakes fish, and the determination of acute toxicities of representative compounds of 19 chemical classes. The author focuses on four of the classes. The PAHs are products of fuel combustion and components of fossil fuels. The other three classes principally originate from industrial applications (alkyl halides), as fossil fuels, insecticides, solvents, and in perfumes (cyclic alkanes); and as herbicides and insecticides (heterocyclic nitrogen compounds). The authors purpose is to report results of static acute toxicity tests in which larval rainbow trout (Oncorhynchus mykiss) were used as the test fish and to compare results of acute toxicity tests with previous studies.

  14. Enantioselective bioactivity, acute toxicity and dissipation in vegetables of the chiral triazole fungicide flutriafol.

    PubMed

    Zhang, Qing; Hua, Xiu-de; Shi, Hai-yan; Liu, Ji-song; Tian, Ming-ming; Wang, Ming-hua

    2015-03-01

    The enantioselective bioactivity, acute toxicity and stereoselective degradation of the chiral triazole fungicide flutriafol in vegetables were investigated for the first time using the (R)-, (S)- and rac-flutriafol. The order of the bioactivity against five target pathogens (Rhizoctonia solani, Alternaria solani, Pyricularia grisea, Gibberella zeae, Botrytis cinerea) was found to be (R)-flutriafol>rac-flutriafol>(S)-flutriafol. The fungicidal activity of (R)-flutriafol was 1.49-6.23 times higher than that of (S)-flutriafol. The (R)-flutriafol also showed 2.17-3.52 times higher acute toxicity to Eisenia fetida and Scenedesmus obliquus than (S)-flutriafol. The stereoselective degradation of flutriafol in tomato showed that the active (R)-flutriafol degraded faster, resulting in an enrichment of inactive (S)-form, and the half-lives were 9.23 d and 10.18 d, respectively. Inversely, the (S)-flutriafol, with a half-life of 4.76 d, was preferentially degraded in cucumber. In conclusion, the systemic assessments of the triazole fungicide flutriafol stereoisomers on the enantioselective bioactivity, acute toxicity and environmental behavior may have implications for better environmental and ecological risk assessment. PMID:25463219

  15. [Alteration of the acute toxicity and various pharmacologic effects of streptomycin sulfate by calcium 4'-phosphopantothenate].

    PubMed

    Dorofeev, B F; Korablev, M V; Kopelevich, V M

    1983-10-01

    The effect of calcium 4'-phosphopantothenate (CPP) on acute toxicity of streptomycin and the decrease by the antibiotic of the muscle working capacity, "holes" reflex, body temperature and oxygen intake was studied on 258 albino mice weighing 22-26 g. Medical calcium pantothenate (CPA) was used for control purposes. CPP is an antagonist of streptomycin sulfate. In a dose of 1/10 or 1/5 of the LD50 injected intraperitoneally CPP lowered acute toxicity of streptomycin and prevented its effect in a dose of 0.11--1.1 g/kg injected subcutaneously on the muscle working capacity, "holes" reflex and body temperature. The spectrum index of the CPP antitoxic effect was equal to 22.5. By its acute toxicity CPP (LD50 1.18 +/- 0.07 g/kg) did not differ from CPA (LD50 1.25 +/- 0.08 g/kg). The efficacy of CPP, by its antitoxic spectrum, was 1.8 times higher than that of CPA. CPA lowered the streptomycin effect on the "holes" reflex and body temperature, while CPP prevented it. Both the drugs did not influence the decrease in the oxygen consumption induced by streptomycin. PMID:6651265

  16. Artemia salina as test organism for assessment of acute toxicity of leachate water from landfills.

    PubMed

    Svensson, B M; Mathiasson, L; Mårtensson, L; Bergström, S

    2005-03-01

    Artemia salina has, for the first time, been used as test organism for acute toxicity of leachate water from three landfills (the municipal landfills at Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in different ways in a pilot plan). Artemia can tolerate the high concentrations of chloride ions found in such waters. Large differences in toxicities were found, the leachate from Siauliai being the most toxic one. To increase the selectivity in the measurements, a fractionation was done by using ion exchange to separate ammonium/ammonia and metal ions from the leachate, and activated carbon adsorbents for organic pollutants. The influence of some metals and phenol compounds on the toxicity was investigated separately. It was found that most of the toxicity emanated from the ammonium/ammonia components in the leachate. However, there was also a significant contribution n from organic pollutants, other than phenol compounds, since separate experiments had in this latter case indicated negligible impact. The concentrations of metals were at a level, shown by separate experiments, where only small contribution to the toxicity could be expected. PMID:15869192

  17. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    PubMed

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. PMID:24934557

  18. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    PubMed Central

    Zhao, Xinyan; Dong, Tao

    2013-01-01

    A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU) obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety. PMID:24300075

  19. Acute Toxicity Comparison of Single-Walled Carbon Nanotubes in Various Freshwater Organisms

    PubMed Central

    Chung, Young Shin; Kim, Tae Gyu; Kim, Jin Kwon; Lee, Ji Hyun; Lee, Yong Hwa; Kang, Sung Wook

    2015-01-01

    While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50) of 29.99 and 30.96 mg/L, respectively, representing “acute category 3” in the Globally Harmonized System (GHS) of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish. PMID:25654094

  20. Acute toxicity comparison of single-walled carbon nanotubes in various freshwater organisms.

    PubMed

    Sohn, Eun Kyung; Chung, Young Shin; Johari, Seyed Ali; Kim, Tae Gyu; Kim, Jin Kwon; Lee, Ji Hyun; Lee, Yong Hwa; Kang, Sung Wook; Yu, Il Je

    2015-01-01

    While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50) of 29.99 and 30.96 mg/L, respectively, representing "acute category 3" in the Globally Harmonized System (GHS) of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish. PMID:25654094

  1. Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

    PubMed

    Gissi, F; Binet, M T; Adams, M S

    2013-11-01

    Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute

  2. Acute Toxicity and Bioaccumulation of Chloroform to Four Species of Freshwater Fish

    SciTech Connect

    ,

    1980-08-01

    Acute toxicity of chloroform to four species of freshwater fish was studied in flow-through 96-hr toxicity tests. Chloroform is toxic to fish in the tens of parts per million, a concentration well above that which would be expected to be produced under normal power plant chlorination conditions. Investigations of acute toxicity of chloroform and the bioaccumulation of chlorinated compounds in tissues of fish revealed differences in tolerance levels and tissue accumulations. Mean 96-hr LC{sub 50}s for chloroform were 18 ppm for rainbow trout and bluegill, 51 ppm for largemouth bass and 75 ppm for channel catfish. Mortalities of bluegill and largemouth bass occurred during the first 4 hr of exposure while rainbow trout and channel catfish showed initial tolerance and mortalities occurred during the latter half of the 96-hr exposure. Rainbow trout had the highest level of chloroform tissue accumulation, 7 {micro}g/g tissue, catfish the second highest, 4 {micro}g/g tissue, followed by bluegill and largemouth bass which each accumulated about 3 {micro}g/g tissue. Accumulation of chloroform was less than one order of magnitude above water concentrations for all species.

  3. Evaluation of Acute and Chronic Toxicities of the Water Extract from Ziziphus attopensis Pierre

    PubMed Central

    Sireeratawong, Seewaboon; Vannasiri, Supaporn; Nanna, Urarat; Singhalak, Tipaya; Jaijoy, Kanjana

    2012-01-01

    We studied an acute and chronic oral toxicity of the extract from Ziziphus attopensis (ZA) in male and female SD rats according to the OECD guidelines. After a single oral administration of ZA 5 g/kg body weight, measurement of the body and organs, necropsy, and health monitoring were performed. The body and organ weights and behavior were not changed relative to the control rats indicating that ZA does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with ZA at the doses of 1, 2, 4, and 8 g/kg body weight for 180 days. Body weight changes, hematological and biochemical parameters, organ weights, gross finding, and histopathology examination were monitored during the experimental period. The results did not show any differences from the control groups. Analyses of these results with the information of signs, behavior, and health monitoring can lead to a conclusion that the long-term oral administration of ZA for 180 days does not cause chronic toxicity. PMID:22474597

  4. Consideration of reactivity to acute fish toxicity of α,β-unsaturated carbonyl ketones and aldehydes.

    PubMed

    Furuhama, A; Aoki, Y; Shiraishi, H

    2012-01-01

    To understand the key factor for fish toxicity of 11 α,β-unsaturated carbonyl aldehydes and ketones, we used quantum chemical calculations to investigate their Michael reactions with methanethiol or glutathione. We used two reaction schemes, with and without an explicit water molecule (Scheme-1wat and Scheme-0wat, respectively), to account for the effects of a catalytic water molecule on the reaction pathway. We determined the energies of the reactants, transition states (TS), and products, as well as the activation energies of the reactions. The acute fish toxicities of nine of the carbonyl compounds were evaluated to correlate with their hydrophobicities; no correlation was observed for acrolein and crotonaldehyde. The most toxic compound, acrolein, had the lowest activation energy. The activation energy of the reaction could be estimated with Scheme-1wat but not with Scheme-0wat. The complexity of the reaction pathways of the compounds was reflected in the difficulty of the TS structure searches when Scheme-1wat was used with the polarizable continuum model. The theoretical estimations of activation energies of α,β-unsaturated carbonyl compounds with catalytic molecules or groups including hydrogen-bond networks may complement traditional tools for predicting the acute aquatic toxicities of compounds that cannot be easily obtained experimentally. PMID:22150015

  5. Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3 academic hospitals.

    PubMed

    Jang, Hak-Soo; Kim, Jung-Youn; Choi, Sung-Hyuk; Yoon, Young-Hoon; Moon, Sung-Woo; Hong, Yun-Sik; Lee, Sung-Woo

    2013-10-01

    Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased. PMID:24133344

  6. Effect of copper status on acute toxicity of cocaine in rats

    SciTech Connect

    Smith, J.C.; Reddy, P.P.; Seung, S.K.; Combs, G.F.; Dulin, A.M.; Danford, D.E. )

    1989-02-09

    Both copper (Cu) nutriture and cocaine (Coc) ingestion have been shown to affect cardiovascular integrity. Therefore, the purpose of these studies was to determine if Cu status affects the acute toxicity of Coc. 20 weanling male rats (45 {plus minus} 5 g) were randomly assigned to 2 groups, 1 fed a copper deficient (CuD) (<1ppmCu) and the other a copper supplemented (CuS) diet (ca.6ppm, Cu). After 7 wks, the rats, paired for Cu status, were injected (ip) with Coc-HCl at reported LD{sub 50} doses ranging from 80-90 mg/kg bw. The CuD was established by cardiac hypertrophy, depressed hematocrit, lowered serum, liver and heart Cu compared to the CuS controls. The acute toxicity resulted in tachycardia and hyperactivity followed by ataxia with isolated muscle twitchings and violent grand-mal type seizures. For those animals that died, death was apparently due to respiratory arrest followed by ventricular fibrillation; animals that survived were killed by exsanguination. The severity of toxicity was greater for the CuD rats as evidenced by 100% exhibiting seizures compared to 80% for the CuS group. In addition, the incidence of death was 60% for the CuD group compared to 20% for the CuS rats. Although these results suggest that CuD exacerbates the toxic effects of Coc, it is not established that the effects are specific for this essential nutrient.

  7. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    PubMed

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals. PMID:25754724

  8. Acute and sub-chronic toxicity of aqueous extracts of Chenopodium ambrosioides leaves in rats.

    PubMed

    da Silva, Marcel Gianni C; Amorim, Raimundo Neilson L; Câmara, Carlos C; Fontenele Neto, José Domingues; Soto-Blanco, Benito

    2014-09-01

    The present study aimed to evaluate the toxicity of aqueous extract of Chenopodium ambrosioides leaves. To measure acute toxicity, rats were administered 0, 0.3, 1.0, or 3.0 g/kg of aqueous extract from C. ambrosioides leaves by gavage. To analyze sub-chronic toxicity, rats were treated by oral gavage for 15 consecutive days with 0, 0.3, or 1.0 g/kg of extract of C. ambrosioides leaves. No animals from either trial exhibited any signs of toxicity. In the acute study, the highest dose of the extract led to an increase in the serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) and a decrease in the serum levels of urea. In the sub-chronic test, rats treated with 1.0 g/kg for 15 days exhibited increased serum ALT activity and creatinine levels and mild cytoplasmic vacuolation of hepatocytes. The results indicate that aqueous extract from C. ambrosioides leaves produce slight hepatotoxic lesions in rats. PMID:24892475

  9. Acute toxicity of some hydrazine compounds to salamander larvae, Ambystoma spp

    SciTech Connect

    Slonim, A.R.

    1986-11-01

    Although hydrazine compounds have been used extensively by industry for a very long time, they have become important in recent years as propellants for aerospace operations. The study of hydrazine compounds in this laboratory began about two decades ago and developed into a large pharmacological and toxicological research program that included also environmental considerations. Subsequently, acute toxicity studies were conducted on the common guppy (Lebistes reticulatus Peters) using four hydrazine compounds of interest. The toxicity of these propellants were evaluated next on other species of aquatic organisms such as mosquito fish (Gambusia affinis) and amphibians. Two different studies were conducted on amphibians: One utilized amphibian eggs and the other amphibian larvae. The larvae of spotted and marbled salamanders (Ambystoma maculatum and A. opacum, respectively) were used primarily in numerous static bioassays to determine the acute toxicity of hydrazine, UDMH and Aerozine-50 on these organisms. The remaining larvae were used in other tests mainly to corroborate previous experimental results (e.g., to see whether toxicity is affected by organism size, aeration of test solutions, and water hardness). The results on the larvae are presented in this paper.

  10. Acute Toxicity and Genotoxicity of Carbendazim, Main Impurities and Metabolite to Earthworms (Eisenia foetida).

    PubMed

    Huan, Zhibo; Luo, Jinhui; Xu, Zhi; Xie, Defang

    2016-01-01

    The acute toxicity and genotoxicity of carbendazim, two impurities (3-amino-2-hydroxyphenazine and 2,3-diaminophenazine) and one metabolite (2-aminobenzimidazole) to Eisenia foetida were assessed using artificial soil test and comet assay respectively. Acute toxicity results showed carbendazim was moderately toxic to the earthworms with 14 day-LC50 of 8.6 mg/kg dry soil while 3-amino-2-hydroxyphenazine, 2,3-diaminophenazine, and 2-aminobenzimidazole were of low toxicity with 14 day-LC50 values of 19.0, 14.9, and 27.7 mg/kg dry soil respectively (nominal concentration). The olive tail moment and percentage of DNA in the tail were used as genotoxicity indices, and carbendazim could significantly induce DNA damage to the earthworm coelomocytes with obviously positive dose- and duration-response relationships while the other three substances showed similar (p = 0.05) genotoxicity results to the negative controls in all of the tests. PMID:26370277

  11. The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

    NASA Technical Reports Server (NTRS)

    Carter, V. L., Jr.; Bafus, D. A.; Warrington, H. P.; Harris, E. S.

    1974-01-01

    Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

  12. FISH ACUTE TOXICITY SYNDROMES: APPLICATION TO THE DEVELOPMENT OF MECHANISM-SPECIFIC QSARS (QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS)

    EPA Science Inventory

    Predictive models based on quantitative structure activity relationships (QSARs), are used as rapid screening tools to identify potentially hazardous chemicals. Several QSARs are now available that predict the acute toxicity of narcotic-industrial chemicals. Predictions for compo...

  13. SIMULTANEOUS MULTIPLE SPECIES TESTING: ACUTE TOXICITY OF 13 CHEMICALS TO 12 DIVERSE FRESHWATER AMPHIBIAN, FISH, AND INVERTEBRATE FAMILIES

    EPA Science Inventory

    The test series developed methods for testing a compliment of aquatic organisms in a single test that satisfies the freshwater acute toxicity requirements for setting water quality criteria. Species tested included fathead minnows Pimephales promelas, rainbow trout Salmo gairdner...

  14. Influence of water hardness and sulfate on the acute toxicity of chloride to sensitive freshwater invertebrates.

    PubMed

    Soucek, David J; Linton, Tyler K; Tarr, Christopher D; Dickinson, Amy; Wickramanayake, Nilesh; Delos, Charles G; Cruz, Luis A

    2011-04-01

    Total dissolved solids (TDS) represent the sum of all common ions (e.g., Na, K, Ca, Mg, chloride, sulfate, and bicarbonate) in freshwater. Currently, no federal water quality criteria exist for the protection of aquatic life for TDS, but because the constituents that constitute TDS are variable, the development of aquatic life criteria for specific ions is more practical than development of aquatic life criteria for TDS. Chloride is one such ion for which aquatic life criteria exist; however, the current aquatic life criteria dataset for chloride is more than 20 years old. Therefore, additional toxicity tests were conducted in the current study to confirm the acute toxicity of chloride to several potentially sensitive invertebrates: water flea (Ceriodaphnia dubia), fingernail clams (Sphaerium simile and Musculium transversum), snail (Gyraulus parvus), and worm (Tubifex tubifex), and determine the extent to which hardness and sulfate modify chloride toxicity. The results indicated a significant ameliorating effect of water hardness (calcium and magnesium) on chloride toxicity for all species tested except the snail; for example, the 48-h chloride median lethal concentration (LC50) for C. dubia at 50 mg/L hardness (977 mg Cl(-) /L) was half that at 800 mg/L hardness (1,836 mg Cl(-) /L). Conversely, sulfate over the range of 25 to 600 mg/L exerted a negligible effect on chloride toxicity to C. dubia. Rank order of LC50 values for chloride at a given water hardness was in the order (lowest to highest): S. simile < C. dubia < M. transversum < G. parvus < T. tubifex. Results of the current study support the contention that the specific conductivity or TDS concentration of a water body alone is not a sufficient predictor of acute toxicity and that knowledge of the specific ion composition is critical. PMID:21191883

  15. Increased RO concentrate toxicity following application of antiscalants - acute toxicity tests with the amphipods Gammarus pulex and Gammarus roeseli.

    PubMed

    Feiner, Mona; Beggel, Sebastian; Jaeger, Nadine; Geist, Juergen

    2015-02-01

    In reverse osmosis, a frequently used technology in water desalination processes, wastewater (RO concentrate) is generated containing the retained solutes as well as so-called antiscalants (AS), i.e. chemical substances that are commonly applied to prevent membrane-blocking. In this study, a risk assessment of a possible discharge of concentrate into a small stream was conducted. The acute toxicity of two concentrates containing two different ASs and of concentrate without AS to the amphipods Gammarus pulex and Gammarus roeseli was studied. Mortality of gammarids exposed to the concentrate without AS was not different to the control, whereas concentrates including ASs caused mortality rates up to 100% at the highest test concentrations after 168 h. Resulting EC50-values were 36.2-39.4% (v/v) after 96 h and 26.6-58.0% (v/v) after 168 h. These results suggest that the ecotoxicological relevance of antiscalants is greater than currently assumed. PMID:25476491

  16. Acute toxicity of binary and ternary mixtures of Cd, Cu, and Zn to Daphnia magna.

    PubMed

    Meyer, Joseph S; Ranville, James F; Pontasch, Mandee; Gorsuch, Joseph W; Adams, William J

    2015-04-01

    Standard static-exposure acute lethality tests were conducted with Daphnia magna neonates exposed to binary or ternary mixtures of Cd, Cu, and Zn in moderately hard reconstituted water that contained 3 mg dissolved organic carbon/L added as Suwannee River fulvic acid. These experiments were conducted to test for additive toxicity (i.e., the response to the mixture can be predicted by combining the responses obtained in single-metal toxicity tests) or nonadditive toxicity (i.e., the response is less than or greater than additive). Based on total metal concentrations (>90% dissolved) the toxicity of the tested metal mixtures could be categorized into all 3 possible additivity categories: less-than-additive toxicity (e.g., Cd-Zn and Cd-Cu-Zn mixtures and Cd-Cu mixtures when Cu was titrated into Cd-containing waters), additive toxicity (e.g., some Cu-Zn mixtures), or more-than-additive toxicity (some Cu-Zn mixtures and Cd-Cu mixtures when Cd was titrated into Cu-containing waters). Exposing the organisms to a range of sublethal to supralethal concentrations of the titrated metal was especially helpful in identifying nonadditive interactions. Geochemical processes (e.g., metal-metal competition for binding to dissolved organic matter and/or the biotic ligand, and possibly supersaturation of exposure waters with the metals in some high-concentration exposures) can explain much of the observed metal-metal interactions. Therefore, bioavailability models that incorporate those geochemical (and possibly some physiological) processes might be able to predict metal mixture toxicity accurately. PMID:25336231

  17. An Evaluation of Select Test Variables Potentially Affecting Acute Oil Toxicity.

    PubMed

    Echols, Brandi S; Smith, A; Gardinali, P; Rand, G

    2016-02-01

    In the wake of the Deepwater Horizon incident (2010) in the Gulf of Mexico, an abundance of research studies have been performed, but the methodologies used have varied making comparisons and replication difficult. In this study, acute toxicity tests with mysids and inland silversides were performed to examine the effect of different variables on test results. The toxicity test variables evaluated in this study included (1) open versus closed static test chambers, (2) natural versus artificial diluent, (3) aerated versus nonaerated test solution, and (4) low versus medium energy water-accommodated (WAF) mixing energies. The use of tests using natural or artificial diluent showed no difference in either toxicity test or analytical chemistry results. Based on median lethal concentrations (LC50) of WAFs of unweathered oil (MASS), mysid tests performed in closed chambers were approximately 41 % lower than LC50 values from open-chamber studies, possibly a result of the presence of low-molecular weight volatile aromatics (i.e., naphthalenes). This research also showed that using a medium-energy WAF (with a 20–25 % vortex) increases the number of chemical components compared with low-energy WAF, thus affecting the composition of the exposure media and increasing toxicity. The comparison of toxic units as a measure of the potential toxicity of fresh and weathered oils showed that weathered oils (e.g., Juniper, CTC) are less toxic than the unweathered MASS oil. In the event of future oil spills, these variables should be considered to ensure that data regarding the potential toxicity and environmental risk are of good quality and reproducible. PMID:26467150

  18. Modified skin window technique for the extended characterisation of acute inflammation in humans

    PubMed Central

    Marks, D. J. B.; Radulovic, M.; McCartney, S.; Bloom, S.; Segal, A. W.

    2009-01-01

    Objective To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. Subjects 15 healthy subjects and 5 Crohn’s patients. Treatment Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 μg/ml interleukin-8 (IL-8). Methods Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. Results Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn’s patients, notably PKC α/β hyperphosphorylation (11.3 ± 3.1 vs 1.2 ± 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. Conclusions The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators. PMID:17522815

  19. Comparative toxicities of bismuth oxybromide and titanium dioxide exposure on human skin keratinocyte cells.

    PubMed

    Gao, Xiaoya; Wang, Yawen; Peng, Shiqi; Yue, Bin; Fan, Caimei; Chen, Weiyi; Li, Xiaona

    2015-09-01

    Nano-sized bismuth oxybromide (BiOBr) particles are being considered for applications within the semiconductor industry. However, little is known about their potential impact on human health. In this study, we comparatively investigated the cytotoxicity of BiOBr and titanium dioxide (TiO2) nanoparticles (NPs) using human skin keratinocyte cell line (HaCaT) as a research model. Results indicate that lamellar-shaped BiOBr (length: 200 nm, width: 150 nm, and an average thickness: around 15 nm) has less toxic effects on cell viability and intracellular organelles than TiO2 (P25) NPs. BiOBr mainly induced late cell apoptosis, while for TiO2, both early apoptosis and late apoptosis were involved. Cell cycle arrest was found in cells on both NPs exposure, and more prominent in TiO2-treated cells. More cellular uptake was achieved after TiO2 exposure, particularly at 10 μg mL(-1), presence of TiO2 resulted in more than 2-fold increase in cellular granularity compared with BiOBr. Furthermore, TiO2 had a high potential to generate intracellular reactive oxygen species (ROS) in cells, where a 2.7-fold increase in TiO2 group and 2.0-fold increase in BiOBr group at the same concentration of 25 μg mL(-1). Higher cellular uptake and ROS stimulation should contribute to the more hazards of TiO2 than BiOBr NPs. This knowledge is a crucial component in the environmental and human hazard assessment of BiOBr and TiO2 NPs. PMID:25917605

  20. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  1. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    PubMed Central

    2011-01-01

    Purpose To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Methods Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Results Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Conclusion Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted. PMID:21466696

  2. Evaluation of the detoxication efficiencies for acrylonitrile wastewater treated by a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT) process: Acute toxicity and zebrafish embryo toxicity.

    PubMed

    Na, Chunhong; Zhang, Ying; Deng, Minjie; Quan, Xie; Chen, Shuo; Zhang, Yaobin

    2016-07-01

    Acrylonitrile (ACN) wastewater generated during ACN production has been reported to be toxic to many aquatic organisms. However, few studies have evaluated toxicity removal of ACN wastewater during and after the treatment process. In this study, the detoxication ability of an ACN wastewater treatment plant (WWTP) was evaluated using Daphnia magna, Danio rerio and zebrafish embryo. This ACN WWTP has a combined anaerobic oxic-aerobic biological fluidized tank (A/O-ABFT) process upgraded from the traditional anaerobic oxic (A/O) process. Moreover, the potential toxicants of the ACN wastewaters were identified by gas chromatography-mass spectrometry (GC-MS). The raw ACN wastewater showed high acute and embryo toxicity. 3-Cyanopyridine, succinonitrile and a series of nitriles were detected as the toxic contributors of ACN wastewater. The A/O process was effective for the acute and embryo toxicity removal, as well as the organic toxicants. However, the A/O effluent still showed acute and embryo toxicity which was attributed by the undegraded and the newly generated toxicants during the A/O process. The residual acute and embryo toxicity as well as the organic toxicants in the A/O effluent were further reduced after going through the downstream ABFT process system. The final effluent displayed no significant acute and embryo toxicity, and less organic toxicants were detected in the final effluent. The upgrade of this ACN WWTP results in the improved removal efficiencies for acute and embryo toxicity, as well as the organic toxicants. PMID:27037768

  3. ORAL TOXICITY OF 1,3-DICHLOROPROPANE: ACUTE, SHORT-TERM, AND LONG-TERM STUDIES IN RATS

    EPA Science Inventory

    The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil...

  4. Acute phase response in toxicity studies. I. Survey of beagle dogs subjected to single-dose toxicity studies.

    PubMed

    Hoshiya, T; Watanabe, D; Akagi, K; Mizoguchi, Y; Kamiya, K; Mizuguchi, H; Kumahara, M; Toya, H; Nagashima, Y; Okaniwa, A

    2001-05-01

    In the field of routine single-dose toxicity studies, we occasionally meet with transient leukocytosis associated with an increase in fibrinogen in beagle dogs within a few days after treatment with the test article. Only a little is known, however, about the toxicological significance of these changes. However, these changes were thought to belong to the category of "Acute Phase Response, APR," which has been known for a long time in connection with injury, trauma or infection. Aiming at proper understanding of these experiences, we surveyed 25 single-dose toxicity studies (7 intravenous bolus, 5 intravenous infusion, 12 oral and 1 subcutaneous treatment, hereafter referred to simply as i.v. bolus, i.v. infusion, oral and s.c.) in beagle dogs, provided with data from hematological examinations. We set the following criteria as a positive response in the present survey: increases of 50% or more in either or both WBC or fibrinogen compared to the predosing value, transiently from Day 1 to Day 3 of the study. Among 25 studies surveyed, about 1/2 of the studies exhibited increases of 50% or more in either or both fibrinogen or WBC counts compared to the predosing values showing dose-dependency transiently on Day 1 or Day 2. These changes were remarkable after intravenous application. Oral application produced similar effects, although the incidence and severity were low compared to the i.v. routes. Regarding blood chemical and hematological changes other than changes in fibrinogen and WBC counts, there were no essential differences between the groups of studies with and without the changes in fibrinogen and WBC counts. These changes were thought to be characteristic and to have occurred as incidents unrelated to other changes. The reported changes seen in single-dose toxicity studies may belong to the category of APR as the non-specific mechanism of living bodies as stated by Burns et al. (1996). PMID:11429972

  5. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.3

    EPA Science Inventory

    Information on the acute toxicity to multiple species is needed for the assessment of the risks to, and the protection of, individuals, populations, and ecological communities. However, toxicity data are limited for the majority of species, while standard test species are general...

  6. Acute toxicity of firefighting chemical formulations to four life stages of fathead minnow

    USGS Publications Warehouse

    Gaikowski, Mark P.; Hamilton, Steve J.; Buhl, Kevin J.; McDonald, Susan F.; Summers, Cliff H.

    1996-01-01

    Laboratory studies were conducted with four early life stages of fathead minnow,Pimephales promelas,to determine the acute toxicity of five firefighting chemical formulations in standardized soft and hard water. Egg, fry, 30-day posthatch, and 60-day posthatch life stages were tested with three fire retardants (Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F) and two fire-suppressant foams (Phos-Chek WD-881 and Ansul Silv-Ex). Fry were generally the most sensitive life stage tested, whereas the eggs were the least sensitive life stage. Formulation toxicity was greater in hard water than in soft water for all life stages tested. Fire-suppressant foams were more toxic than the fire retardants. The 96-hr LC50s derived for fathead minnows were rank ordered from the most toxic to the least toxic formulation as follows: Phos-Chek WD-881 (13a??32 mg/liter) > Silv-Ex (19a??32 mg/liter) > Fire-Trol GTS-R (135a??787 mg/liter) > Phos-Chek D75-F (168a??2250 mg/liter) > Fire-Trol LCG-R (519a??6705 mg/liter) (ranges are the lowest and highest 96-hr LC50for each formulation). (C) 1996 Academic Press, Inc.

  7. Acute, mutagenicity, teratogenicity and subchronic oral toxicity studies of diaveridine in rodents.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Cao, Xingyuan

    2015-09-01

    Diaveridine (DVD) is a member of the 2,4-pyrimidinediamine class of dihydrofolate reductase inhibitors. It is used in combination with sulfaquinoxaline as an antiprotozoal agent in animals for the prophylaxis and treatment of coccidiosis and leucocytozoonosis. Herein, we report a complete toxicological safety assessment of DVD for clinical use. The study of toxicity, genetic toxicity (mammalian erythrocyte micronucleus assay, mice sperm abnormality test and in vivo chromosome aberration test of mammalian bone marrow), 90-day sub-chronic toxicity and teratogenicity test were performed. In the acute oral toxicity tests, median lethal dose, LD50, was more than 2378mg/kg body weight in Sprague Dawley rats (1025mg/kg body weight in ICR mice). The testing results for three terms of mutagenicity toxicity (mouse chromosome aberration, erythrocyte micronucleus and sperm abnormality) were all negative at 128-512mg/kg body weight. For 90-day feeding of DVD at the dosage of 10mg/kg body weight in both male and female SD rats, no signs of toxicological effects were detected. Meanwhile, for teratogenicity test in female SD rats at the dosage of 37mg/kg body weight, there were no toxicological signs observed. Thus, our results suggested that the DVD is safe when administered orally in rats at 10mg/kg body weight per day. PMID:26397222

  8. Acute toxicity and aqueous solubility of some condensed thiophenes and their microbial metabolites

    SciTech Connect

    Seymour, D.T.; Hrudey, S.E.; Fedorak, P.M.; Verbeek, A.G.

    1997-04-01

    Petroleum or creosote contamination of surface waters, soils, or groundwaters introduces countless aromatic compounds to these environments. Among these are condensed thiophenes that were shown to be oxidized to sulfoxides, sulfones, and 2,3-diones by microbial cultures. In this study, the acute toxicities of 12 compounds (benzothiophene, benzothiophene sulfone, benzothiophene-2,3-diones, dibenzothiophene, dibenzothiophene sulfoxide, and dibenzothiophene sulfone) were determined by the Microtox{reg_sign} and Daphnia magna bioassays. To aid in determining the toxicities, the solubilities of many of these compounds were determined, which showed that the oxidized compounds were much more water soluble than the parent thiophenes. In nearly every case, the oxidized compounds were less toxic than their parent thiophenes. The Microtox method was more sensitive than the D. magna bioassay, but in general, there was a good correlation between toxicities measured by the two tests. Samples were removed from batch cultures of a Pseudomonas strain capable of oxidizing the thiophenes, and these samples were subjected to Microtox bioassays. These experiments showed that the toxicities of the culture supernatants decreased with incubation time.

  9. Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Ingersoll, C.G.; Hardesty, D.K.; Ivey, C.D.; Kunz, J.L.; May, T.W.; Dwyer, F.J.; Roberts, A.D.; Augspurger, T.; Kane, C.M.; Neves, R.J.; Barnhart, M.C.

    2007-01-01

    The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 ??g Cu/L (except 15 ??g Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were 40 ??g/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. ?? 2007 SETAC.

  10. Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae)

    USGS Publications Warehouse

    Wang, N.; Augspurger, T.; Barnhart, M.C.; Bidwell, Joseph R.; Cope, W.G.; Dwyer, F.J.; Geis, S.; Greer, I.E.; Ingersoll, C.G.; Kane, C.M.; May, T.W.; Neves, R.J.; Newton, T.J.; Roberts, A.D.; Whites, D.W.

    2007-01-01

    The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., ???90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. ?? 2007 SETAC.

  11. Whole acute toxicity removal from industrial and domestic effluents treated by electron beam radiation: emphasis on anionic surfactants

    NASA Astrophysics Data System (ADS)

    Moraes, M. C. F.; Romanelli, M. F.; Sena, H. C.; Pasqualini da Silva, G.; Sampa, M. H. O.; Borrely, S. I.

    2004-09-01

    Electron beam radiation has been applied to improve real industrial and domestic effluents received by Suzano wastewater treatment plant. Radiation efficacy has been evaluated as toxicity reduction, using two biological assays. Three sites were sampled and submitted for toxicity assays, anionic surfactant determination and electron beam irradiation. This paper shows the reduction of acute toxicity for both test-organisms, the marine bacteria Vibrio fischeri and the crustacean Daphnia similis. The raw toxic effluents exibitted from 0.6 ppm up to 11.67 ppm for anionic surfactant before being treated by the electron beam. Radiation processing resulted in reduction of the acute toxicity as well as surfactant removal. The final biological effluent was in general less toxic than other sites but the presence of anionic surfactants was evidenced.

  12. A biology-based dynamic approach for the reconciliation of acute and chronic toxicity tests: application to Daphnia magna.

    PubMed

    Zaldívar, José-Manuel; Baraibar, Joaquín

    2011-03-01

    There is the need to integrate existing toxicity data in a coherent framework for extending their domain of applicability as well as their extrapolation potential. This integration would also reduce time and cost-consuming aspects of these tests and reduce animal usage. In this work, based on data extracted from literature, we have assessed the advantages that a dynamic biology-toxicant fate coupled model for Daphnia magna could provide when assessing toxicity data, in particular, the possibility to obtain from short-term (acute) toxicity test long-term (chronic) toxicity values taking into account the inherent variability of D. magna populations and the multiple sources of data. The results show that this approach overcomes some of the limitations of existing toxicity tests and that the prediction errors are considerably reduced when compared with the factor from 2 to 5 obtained using acute-to-chronic ratios. PMID:21168184

  13. Acute toxicity of subcutaneously administered depleted uranium and the effects of CBMIDA in the simulated wounds of rats.

    PubMed

    Fukuda, Satoshi; Ikeda, Mizuyo; Nakamura, Mariko; Yan, Xueming; Xie, Yuyuan

    2009-04-01

    We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wound model (experiment I), and the effects of a chelating agent, catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA), on the removal and damages caused by uranium by local treatment for wounds in rats (experiment II). Experiment I: To examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg kg-1 DU in a solution of pH 1 and 7. The rats were killed 1, 3, 6, and 24 h after DU injection. The DU (pH 1) injection site on the skin was altered markedly by acid burn, and the chemical action of uranium compared with that of DU (pH 7). After the injection of 4 mg kg-1 DU (pH 1), about 60% of the uranium was retained 1-3 h at the injected sites and then decreased to 16% at 24 h. However, the concentration of uranium in the injected site after 16 mg kg-1 DU (pH 1) injection did not change significantly. Urinary excretion rates of uranium (pH 1) increased in a time-independent manner after the injection. Depositions of uranium in the liver, kidneys and femur were found at 1 h after DU injection, and the results of serum and urinary examinations indicated that severe damage in the organs, including the kidney, was induced. The results of the DU (pH 7) were useful for estimating the chemical toxicity of uranium. Experiment II: The effects of CBMIDA by local treatment for wounds with DU were examined. CBMIDA (480 mg kg-1) was infused into the DU-injected site 0, 10, 30, 60, 120 min, and 24 h after the subcutaneous injection of 4 mg kg-1 DU (pH 1 and 7). The uranium at the injected sites decreased to 4-17% of that at 24 h in the DU (pH 1) group without CBMIDA treatment in experiment I, when it was administered within 120 min after DU injection. In addition, CBMIDA had excellent efficacy in excreting the uranium in urine and feces and decreasing the concentrations of uranium in the kidneys and

  14. Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

    PubMed

    Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

    2013-09-01

    The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. PMID:23764236

  15. Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

    SciTech Connect

    Amsbaugh, Mark J.; Grosshans, David R.; McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita

    2012-08-01

    Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

  16. Acute toxicity of 2,4,6-trinitrotoluene in earthworm (Eisenia andrei).

    PubMed

    Robidoux, P Y; Hawari, J; Thiboutot, S; Ampleman, G; Sunahara, G I

    1999-11-01

    2,4,6-Trinitrotoluene (TNT) is an worldwide recalcitrant environmental contaminant and is toxic to a number of organisms including humans. This study examines the acute effects (lethal and biomass changes) of TNT on the oligochaetes species Eisenia andrei, using the 3-day filter paper, and the 7- and 14-day direct contact spiked soil (OECD artificial and forest soil) toxicity tests. Studies using the filter paper test indicated that the lethality of TNT could be detected in the range 1.5 to 14.2 microg/cm(2), with significant biomass (body weight) changes occurring at the lowest concentration. Acute effects (lethality) could not be measured when earthworms were placed on filter paper containing a saturated aqueous solution of TNT. This may indicate that with these exposure conditions, TNT may have been adsorbed to the filter paper, and that this matrix should be saturated with TNT before becoming available to the earthworms. Spiked soil toxicity tests indicated that the E. andrei lethality by TNT was >1.5 times higher when earthworms were exposed to TNT-spiked forest soil (LOEC:260 mg/kg; LC(50) 14 days 222.4 mg/kg) than to spiked OECD artificial soil (LOEC:420 mg/kg; LC(50) 14 days: 364.9 mg/kg). The sublethal effect on biomass change at the selected TNT concentrations in soil was not significant compared to controls. Results indicate that the bioanalytical methods described in this article could be used as TNT toxicity assessment tools. This soil quality test method gives valuable information for the screening of soil toxicity. PMID:10581125

  17. Safety Evaluation of Yukmijihwang-tang: Assessment of Acute and Subchronic Toxicity in Rats

    PubMed Central

    Ha, Hyekyung; Lee, Jun Kyoung; Lee, Ho Young; Koh, Woo Suk; Seo, Chang Seob; Lee, Mi-Young; Huang, Dae Sun; Shin, Hyeunkyoo

    2011-01-01

    Yukmijihwang-tang (YMJ; Liu wei di huang tang (China), Rokumigan (Japan)) has been used in the treatment of diseases including renal disorder, cognitive vitality, and diabetes mellitus. However, there is very little information regarding the toxicity of YMJ to give an assurance of safety for clinical treatment. To provide safety information for YMJ, we evaluated its acute and sub-chronic toxicity in rats. The single-dose toxicity of YMJ was examined using Sprague-Dawley rats. Rats were treated with YMJ extract orally at 0, 500, 1000, or 2000 mg/kg body weight. After a single administration, clinical signs were observed every day for two weeks, and body weights were measured five times, including an initial measurement on day 1 (the day of administration). In the sub-chronic oral toxicity study, YMJ was administered to rats at 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. Mortalities, clinical signs, body weight changes, food and water consumption, ophthalmologic findings, urinalysis, hematological and biochemical parameters, gross findings, organ weights, and histological examination were monitored during the study period. We found no mortality and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute and sub-chronic studies following oral administration in the rat at up to 2000 mg/kg/day YMJ. YMJ may not have any single-dose toxicity; the LD50 of YMJ was over 2000 mg/kg, and it is safe for rats. The no-observed-adverse-effect-level (NOAEL) was considered to be 2000 mg/kg/day. PMID:21234385

  18. Acute embryo toxicity and teratogenicity of three potential biofuels also used as flavor or solvent.

    PubMed

    Bluhm, Kerstin; Seiler, Thomas-Benjamin; Anders, Nico; Klankermayer, Jürgen; Schaeffer, Andreas; Hollert, Henner

    2016-10-01

    The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC50: 83mg/L) compared to 2-MTHF (LC50: 2980mg/L), 2-MF (LC50: 405mg/L) and water accommodated fractions of the reference fuels including gasoline (LC50: 244mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. PMID:27243931

  19. Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach.

    PubMed

    Vukov, Oliver; Smith, D Scott; McGeer, James C

    2016-01-01

    The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60mg CaCO3 mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23°C. Acute toxicity tests were done with <24h old neonates for 48h in the case of D. pulex and with 2-9 days old offspring for 96h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5-2.0mM), Na (0.5-2.0mM) and Mg (0.125-0.5mM). The effect of pH (6.5-8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (LogK values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The logK value for Dy(3+) toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific water quality guidelines and

  20. Could hydroxyethyl starch be a therapeutic option in management of acute aluminum phosphide toxicity?

    PubMed

    Marashi, Sayed Mahdi; Arefi, Mohammad; Behnoush, Behnam; Nasrabad, Mahdi Ghazanfari; Nasrabadi, Zeynab Nasri

    2011-04-01

    Acute aluminum phosphide poisoning is a serious toxicity and results in high mortality rate despite the progress of critical care. After ingestion, phosphine gas is released and absorbed quickly, causing systemic poisoning and cell hypoxia. Excessive thirst, severe hypotension, arrhythmias, tachypnea, and severe metabolic acidosis are the common clinical manifestations. We think acute metabolic response which characteristically occurs in severe injury also happens in aluminum phosphide poisoning. Necropsy examinations indicate congestion in almost all vital organs because of leakage of fluids from intravascular to extravascular space. The most favorable type of fluid for intravascular volume resuscitation persists and is disputed. Colloids remain in the intravascular space rather than crystalloids, and provide more rapid hemodynamic stabilization. Furthermore, hydroxyethyl starch solution may have other benefits e.g. it can reduce the extra vascular leak of albumin and fluids from an endothelial injury site. As refractory hypotension and cardiovascular collapse, because leakage of fluids from intravascular to extravascular space are common cause of death in this toxicity, we propose that hydroxyethyl starch can dominate this refractory hypotension and consequently acute metabolic response. PMID:21288649

  1. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

    PubMed Central

    Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A.

    2015-01-01

    Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg. PMID:27047139

  2. Acute toxicity study and antipyretic effect of the brown alga Turbinaria conoides (J. Agardh) Kuetz.

    PubMed

    Kumar, S Sadish; Kumar, Y; Khan, M S Y; Anbu, J; Sam, K G

    2009-01-01

    The active principles of brown alga, Turbinaria conoides (J.Agardh) Kuetz. (Sargassaceae) was extracted with n-hexane, cyclohexane, methanol and ethanol-water (1:1) and investigated for acute toxicity and antipyretic activity. Phytochemical analysis of the extracts revealed the presence of steroids, flavonoids and reducing sugars. Acute toxicity study was performed in Wistar rats after administration of extracts orally. No mortality was observed up to the dose of 5 g/kg for methanol and ethanol-water (1:1) extracts whereas n-hexane and cyclohexane extracts were found to be toxic at the dose levels of 1 g/kg and 2 g/kg respectively. In biochemical analysis, n-hexane, cyclohexane and ethanol-water (1:1) extracts caused a significant (P<0.01) increase in serum cholesterol, protein and alkaline phosphatase levels. In haematological studies, a significant difference was observed for cyclohexane and ethanol-water (1:1) extracts in polymorphs, lymphocytes and eosinophils when compared to the control. Antipyretic activity of extracts (100-400 mg/kg doses) was carried out on yeast-induced pyrexia in rats. Cyclohexane extract exhibited more significant antipyretic activity (P<0.01) than the other extracts at a dose of 200 mg/kg (54.43%), which was comparable to that of paracetamol at a dose of 33 mg/kg. The findings validated the use of this brown alga in traditional cure of children's fever. PMID:20448848

  3. Acute toxic effects of fenpyroximate acaricide on Guppy (Poecilia reticulata Peters, 1859).

    PubMed

    Doğan, Nesli; Yazıcı, Zehra; Şişman, Turgay; Aşkin, Hakan

    2013-09-01

    Fenpyroximate (FP), an acaricide, is widely used in the prevention of acarids (mites) in fruit plant gardens. In this study, the acute toxic effects of different concentrations of FP were investigated using adult guppy (Poecilia reticulata Peters, 1859). Guppy adults were exposed to a range of FP concentrations (25, 50, 75, 100, 125, and 150 µg/L) during 48 h. Static method, which is one of the acute toxicity experiments, has been used in this study. According to probit analysis, the 48-h median lethal concentration (LC50) value of FP at 26°C was found to be 72.821 µg/L. Sublethal exposures were predetermined based on 48-h LC50 value. Guppies were exposed to low concentrations (15, 25, and 50 µg/L) of FP for 48 h. Signs of paralysis and behavior deformations were monitored every 12 h in a number of live and dead adults. Low concentrations of FP were also responsible for erratic swimming, loss of equilibrium, and being lethargic. Liver histology revealed several pathological damages including congestion, picnotic nucleus, sinusoidal dilatation, increase in melanomacrophagic centers, and endothelial degeneration. Finally, the toxicity test results provided 48-h LC50 value for FP, and low concentrations of FP can be highly detrimental to guppy adults with clear evidence of behavioral and histologic effects. PMID:22508399

  4. Chemical composition, protoscolicidal effects and acute toxicity of Pistacia atlantica Desf. fruit extract.

    PubMed

    Mahmoudvand, Hossein; Kheirandish, Farnaz; Ghasemi Kia, Mehdi; Tavakoli Kareshk, Amir; Yarahmadi, Mohammad

    2016-05-01

    The present study was designed to evaluate the chemical composition and scolicidal effects of Pistacia atlantica Desf. extract against protoscoleces of hydatid cysts and its acute toxicity in mice model. Various concentrations of the methanolic extract (5-50 mg/mL) were used for 10-60 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1%). Acute toxicity was also determined in mice model. The main components were β-myrcene (41.4%), α-pinene (32.48%) and limonene (4.66%). Findings demonstrated that P. atlantica extract at the concentrations of 25 and 50 mg/mL after 20 and 10 min of exposure killed 100% protoscoleces. The LD50 of the intraperitoneal injection of the P. atlantica methanolic extract was 2.43 g/kg and the maximum non-fatal dose was 1.66 g/kg. Obtained results showed the potential of P. atlantica extract as a natural source with no significant toxicity for the production of new scolicidal agent to use in hydatid cyst surgery. PMID:26252652

  5. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    PubMed

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients. PMID:18977273

  6. In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

    PubMed

    Hwang, Yoonha; Ahn, Jinhyo; Mun, Jungho; Bae, Sangyoon; Jeong, Young Uk; Vinokurov, Nikolay A; Kim, Pilhan

    2014-05-19

    The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process. PMID:24921268

  7. Acute toxicity of fire-control chemicals, nitrogenous chemicals, and surfactants to rainbow trout

    USGS Publications Warehouse

    Buhl, K.J.; Hamilton, S.J.

    2000-01-01

    Laboratory studies were conducted to determine the acute toxicity of three ammonia-based fire retardants (Fire-Trol LCA-F, Fire-Trol LCM-R, and Phos-Chek 259F), five surfactant-based fire-suppressant foams (FireFoam 103B, FireFoam 104, Fire Quench, ForExpan S, and Pyrocap B-136), three nitrogenous chemicals (ammonia, nitrate, and nitrite), and two anionic surfactants (linear alkylbenzene sulfonate [LAS] and sodium dodecyl sulfate [SDS]) to juvenile rainbow trout Oncorhynchus mykiss in soft water. The descending rank order of toxicity (96-h concentration lethal to 50% of test organisms [96-h LC50]) for the fire retardants was as follows: Phos-Chek 259F (168 mg/L) > Fire-Trol LCA-F (942 mg/L) = Fire-Trol LCM-R (1,141 mg/L). The descending rank order of toxicity for the foams was as follows: FireFoam 103B (12.2 mg/L) = FireFoam 104 (13.0 mg/L) > ForExpan S (21.8 mg/L) > Fire Quench (39.0 mg/L) > Pyrocap B-136 [156 mg/L). Except for Pyrocap B-136, the foams were more toxic than the fire retardants. Un-ionized ammonia (NH3; 0.125 mg/L as N) was about six times more toxic than nitrite (0.79 mg/L NO2-N) and about 13,300 times more toxic than nitrate (1,658 mg/L NO3-N). Linear alkylbenzene sulfonate (5.0 mg/L) was about five times more toxic than SDS (24.9 mg/L). Estimated total ammonia and NH3 concentrations at the 96-h LC50s of the fire retardants indicated that ammonia was the primary toxic component in these formulations. Based on estimated anionic surfactant concentrations at the 96-h LC50s of the foams and reference surfactants, LAS was intermediate in toxicity and SDS was less toxic to rainbow trout when compared with the foams. Comparisons of recommended application concentrations to the test results indicate that accidental inputs of these chemicals into streams require substantial dilutions (100-1,750-fold to reach concentrations nonlethal to rainbow trout.

  8. A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

    SciTech Connect

    Dragun, Anthony E.; Quillo, Amy R.; Riley, Elizabeth C.; Roberts, Teresa L.; Hunter, Allison M.; Rai, Shesh N.; Callender, Glenda G.; Jain, Dharamvir; McMasters, Kelly M.; Spanos, William J.

    2013-03-01

    Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patients were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes.

  9. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    PubMed

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). PMID:26590695

  10. Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions.

    PubMed

    Jour, George; Glitza, Isabella C; Ellis, Rachel M; Torres-Cabala, Carlos A; Tetzlaff, Michael T; Li, Janet Y; Nagarajan, Priyadharsini; Huen, Auris; Aung, Phyu P; Ivan, Doina; Drucker, Carol R; Prieto, Victor G; Rapini, Ronald P; Patel, Anisha; Curry, Jonathan L

    2016-08-01

    Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy. PMID:27086658

  11. Predictive Factors for Acute and Late Urinary Toxicity After Permanent Prostate Brachytherapy: Long-Term Outcome in 712 Consecutive Patients

    SciTech Connect

    Keyes, Mira Miller, Stacy; Moravan, Veronika; Pickles, Tom; McKenzie, Michael; Pai, Howard; Liu, Mitchell; Kwan, Winkle; Agranovich, Alexander; Spadinger, Ingrid; Lapointe, Vincent; Halperin, Ross; Morris, W. James

    2009-03-15

    Purpose: To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity, associated predictive factors, and resolution of International Prostate Symptom Score (IPSS) in 712 consecutive prostate brachytherapy patients. Methods and Materials: Patients underwent implantation between 1998 and 2003 (median follow-up, 57 months). The IPSS and RTOG toxicity data were prospectively collected. The patient, treatment, and implant factors were examined for an association with urinary toxicity. The time to IPSS resolution was examined using Kaplan-Meier curves, and multivariate modeling of IPSS resolution was done using Cox proportional hazards regression analysis. Logistic regression analysis was used to examine the factors associated with urinary toxicity. Results: The IPSS returned to baseline at a median of 12.6 months. On multivariate analysis, patients with a high baseline IPSS had a quicker resolution of their IPSS. Higher prostate D90 (dose covering 90% of the prostate), maximal postimplant IPSS, and urinary retention slowed the IPSS resolution time. The rate of the actuarial 5-year late urinary (>12 months) RTOG Grade 0, 1, 2, 3, and 4 was 32%, 36%, 24%, 6.2%, and 0.1%, respectively. At 7 years, the prevalence of RTOG Grade 0-1 was 92.5%. Patients with a larger prostate volume, greater number of needles, greater baseline IPSS, and use of hormonal therapy had more acute toxicity. On multivariate analysis, the significant predictors for late greater than or equal to RTOG toxicity 2 were a greater baseline IPSS, maximal postimplant IPSS, presence of acute toxicity, and higher prostate V150 (volume of the prostate covered by 150% of the dose). More recently implanted patients had less acute urinary toxicity and patients given hormonal therapy had less late urinary toxicity (all p < 0.02). Conclusion: Most urinary symptoms resolved within 12 months after prostate brachytherapy, and significant long-term urinary toxicity was very low

  12. Technique, outcomes, and acute toxicities in adults treated with proton beam craniospinal irradiation

    PubMed Central

    Barney, Christian L.; Brown, Aaron P.; Grosshans, David R.; McAleer, Mary Frances; de Groot, John F.; Puduvalli, Vinay; Tucker, Susan L.; Crawford, Cody N.; Gilbert, Mark R.; Brown, Paul D.; Mahajan, Anita

    2014-01-01

    Background Proton craniospinal irradiation (p-CSI) has been proposed to reduce side effects associated with CSI. We evaluated acute toxicities and preliminary clinical outcomes in a series of adults treated with p-CSI. Methods We reviewed medical records for 50 patients (aged 16–63 y) with malignancies of varying histologies treated consecutively with vertebral body-sparing p-CSI at MD Anderson Cancer Center from 2007 to 2011. Median CSI and total boost doses were 30.6 and 54 Gy. Forty patients received chemotherapy, varying by histology. Median follow-up was 20.1 months (range, 0.3–59). Results Median doses to the thyroid gland, pituitary gland, hypothalamus, and cochleae were 0.003 Gy–relative biological effectiveness (RBE; range, 0.001–8.5), 36.1 Gy-RBE (22.5–53.0), 37.1 Gy-RBE (22.3–54.4), and 33.9 Gy-RBE (22.2–52.4), respectively. Median percent weight loss during CSI was 1.6% (range, 10% weight loss to 14% weight gain). Mild nausea/vomiting was common (grade 1 = 46%, grade 2 = 20%); however, only 5 patients experienced grade ≥2 anorexia (weight loss >5% baseline weight). Median percent baseline white blood cells, hemoglobin, and platelets at nadir were 52% (range, 13%–100%), 97% (65%–112%), and 61% (10%–270%), respectively. Four patients developed grade ≥3 cytopenias. Overall and progression-free survival rates were 96% and 82%, respectively, at 2 years and 84% and 68% at 5 years. Conclusions This large series of patients treated with p-CSI confirms low rates of acute toxicity, consistent with dosimetric models. Vertebral body-sparing p-CSI is feasible and should be considered as a way to reduce acute gastrointestinal and hematologic toxicity in adults requiring CSI. PMID:24311638

  13. Development of a QSAR for worst case estimates of acute toxicity of chemically reactive compounds.

    PubMed

    Freidig, A P; Dekkers, S; Verwei, M; Zvinavashe, E; Bessems, J G M; van de Sandt, J J M

    2007-05-15

    Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in vitro data for classification and labelling regarding acute toxicity. For this purpose, a large existing database containing in vitro and in vivo data was analysed. For more than 300 compounds in the database, relations between in vitro cytotoxicity and rat or mouse intravenous and oral in vivo LD50 values were re-evaluated and the possibilities for definition of mechanism based chemical subclasses were investigated. A high in vitro-in vivo correlation was found for chemicals classified as irritants. This can be explained by a shared unspecific cytotoxicity of these compounds which will act as the predominant mode of action for both endpoints, irritation and acute toxicity. For this subclass, which covered almost 40% of all compounds in the database, the LD50 values after intravenous dosing could be predicted with high accuracy. A somewhat lower accuracy was found for the prediction of oral LD50 values based on in vitro cytotoxicity data. Based on this successful correlation, a classification and labelling scheme was developed, that includes a hazard based definition of the applicability domain (irritants) and a prediction of the labelling of compounds for their acute iv and oral toxicity. The scheme was tested by an external validation. PMID:17462838

  14. Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

    PubMed

    Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

    2012-11-01

    The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time. PMID:22940740

  15. Acute Amiodarone Pulmonary Toxicity after Drug Holiday: A Case Report and Review of the Literature

    PubMed Central

    Abuzaid, Ahmed; Saad, Marwan; Ayan, Mohamed; Kabach, Amjad; Mahfood Haddad, Toufik; Smer, Aiman; Arouni, Amy

    2015-01-01

    Amiodarone is reported to cause a wide continuum of serious clinical effects. It is often challenging to detect Amiodarone-induced pulmonary toxicity (AIPT). Typically, the diagnosis is made based on the clinical settings and may be supported by histopathology results, if available. We describe a 57-year-old patient who developed severe rapidly progressive respiratory failure secondary to AIPT with acute bilateral infiltrates and nodular opacities on chest imaging. Interestingly, Amiodarone was discontinued 3 weeks prior to his presentation. He had normal cardiac filling pressures confirmed by echocardiography. To our knowledge, this is the first case of isolated acute lung injury induced by Amiodarone, three weeks after therapy cessation, with adequate clinical improvement after supportive management and high dose steroid therapy. PMID:26075108

  16. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation. PMID:12722156

  17. MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients.

    PubMed

    Chiusolo, Patrizia; Reddiconto, Giovanni; Farina, Giuliana; Mannocci, Alice; Fiorini, Alessia; Palladino, Mariangela; La Torre, Giuseppe; Fianchi, Luana; Sorà, Federica; Laurenti, Luca; Leone, Giuseppe; Sica, Simona

    2007-12-01

    Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse free survival and event free survival between homozygous wild-type and variant patients in both polymorphisms were not significantly different. However, we observed an association between 677TT variant and survival in a subset of ALL patients homogenously treated with MTX-based maintenance (p=0.02). In the same subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment (p=0.003). PMID:17512587

  18. Acute toxicity screening of Hanford Site waste grouts using aquatic invertebrates

    SciTech Connect

    Rebagay, T.V.; Dodd, D.A.; Lockrem, L.L.; Powell, W.J.; Voogd, J.A.

    1993-11-01

    Waste grouts prepared by mixing a simulated nonradioactive liquid waste with a dry solids blend consisting of cement, fly ash, and clay were screened for their acute toxicity using aquatic invertebrates (D. magna, D. pulex, and C. dubia) as test organisms and a fluorogenic substrate (4-methylumbelliferyl b-d galactoside) as the toxic stress indicator. After one hour of exposing juvenile daphnids to grout extracts of varying concentrations, followed by a 15-minute reaction with the fluorogenic substrate, the degree of in vivo enzymatic inhibition was measured by the number of resulting fluorescent daphnids. The effective concentration at which 50% of the daphnids were adversely affected (EC50) values calculated by probit analysis were 2,877 mg/L, 2,983 mg/L, and 3,174 mg/L for D. pulex, D. magna, and C. dubia, respectively. The results indicated that the grout extracts studied are nonhazardous and not dangerous to daphnids.

  19. Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

    PubMed Central

    Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

    2016-01-01

    We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P < 0.05) 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity. PMID:26981538

  20. Correlation between heavy metal acute toxicity values in Daphnia magna and fish

    SciTech Connect

    Khangarot, B.S.; Ray, P.K.

    1987-04-01

    In the toxicant bioassays, invertebrates with special reference to aquatic arthropod species have been of recent interest as test models due to the need for developing nonmammalian tests system. The cladoceran Daphnia magna bioassays have several practical advantages. D. magna has been used as a useful test species and its sensitivity to environmental pollutants have been recognized as a general representative of other freshwater zooplankton species. The objectives of this study were to determine the acute toxicity of various heavy metals to Daphnia magna for 48 h of exposure and to compare these values with the existing LC50 values for rainbow trout (Salmo gairdneri); which is commonly used as a test animal in aquatic bioassay studies.

  1. Acute toxic effects of sustained-release verapamil in chronic renal failure.

    PubMed

    Pritza, D R; Bierman, M H; Hammeke, M D

    1991-10-01

    Four hypertensive patients with chronic renal insufficiency or end-stage renal disease who were treated with sustained-release verapamil hydrochloride subsequently developed acute toxic effects. All four patients developed varying degrees of atrioventricular heart block, hypotension, hyperkalemia, metabolic acidosis, and hepatic dysfunction. Supportive treatment consisted of intravenous catecholamines, sodium polystyrene sulfonate, and dialysis, and all patients recovered completely without any residual hepatic or cardiac disease. Patients with renal impairment who are treated with sustained-release verapamil may accumulate verapamil or its metabolites and develop toxic side effects. We conclude that sustained-release verapamil should be used with caution in this patient population and that patients should be closely monitored for adverse cardiovascular, metabolic, and hepatic side effects. PMID:1843183

  2. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  3. Acute toxic effects of two lampricides on twenty-one freshwater invertebrates

    USGS Publications Warehouse

    Rye, Robert P., Jr.; King, Everett Louis, Jr.

    1976-01-01

    We conducted laboratory static bioassays to determine acute toxicity of two lampricides -- a 70% 2-aminoethanol salt of 5,2'dichloro-4'-nitrosalicylanilide (Bayer 73) and a mixture containing 98% 3-trifluoromethyl-4-nitrophenol (TFM) and 2% Bayer 73 (TFM-2B) -- to 21 freshwater invertebrates. LC50 values were determined for 24-h exposure periods at 12.8 C. Organisms relatively sensitive to Bayer 73 were a turbellarian (Dugesia tigrina), aquatic earthworms (Tubifex tubifex and Lumbriculus inconstans), snails (Physa sp.) and (Pleurocera sp.), a clam (Eliptio dilatatus), blackflies (Simulium sp.), leeches (Erpobdellidae), and a daphnid (Daphnia pulex). The invertebrates most sensitive to TFM-2B were turbellarians, aquatic earthworms (Tubifex), snails (Physa), blackflies, leeches, and burrowing mayflies (Hexagenia sp.). Bayer 73 was generally much more toxic to the test organisms than TFM-2B. At lampricidal concentrations, TFM-2B was more highly selective than Bayer 73 against larval sea lampreys (Petromyzon marinus).

  4. [Pharmacological correction of toxic liver damage in patients with heavy forms of acute ethanol intoxication].

    PubMed

    Shikalova, I A; Shilov, V V; Vasil'ev, S A; Batotsyrenov, B V; Loladze, A T

    2012-01-01

    The efficiency of using remaxol and ademethionine in the therapy of patients with heavy acute alcohol intoxication on the background of toxic liver damage has been studied. The administration of remaxol led to improvement of the clinical treatment of alcohol intoxication, which is manifested by a decrease in the rate and duration of delirium tremens (from 33.9 to 10.8%), frequency of secondary lung disorders (from 18.5 to 3.1%), duration of stay in hospital (from 7.3 +/- 0.6 to 5.6 +/- 0.3 days), and total therapy duration (from 11.8 +/- 1.05 to 5.6 +/- 0.3 days). The results of biochemical investigations confirmed that remaxol and ademethionine provide effective treatment of the toxic liver damage. Remaxol decreases the degree of metabolic disorders to a greater extent than does ademethionine. PMID:22702109

  5. Acute toxicities to larval rainbow trout of representative compounds detected in Great Lakes fish

    USGS Publications Warehouse

    Edsall, Carol Cotant

    1991-01-01

    In recent years the National Fisheries Research Center-Great Lakes has ranked the potential hazard to fish and invertebrates of various chemical compounds detected in two Great Lakes fishes-- lake trout, Salvelinus namaycush, and walleye, Stizostedion vitreum vitreum (Hesselberg and Seelye 1982). This hazard assessment has included the identification of the potential sources of the compounds, determination of the occurrence and abundance of the compounds in Great Lakes fish, and the determination of acute toxicities of representative compounds of 19 chemical classes (Passino and Smith 1987a). In further studies Smith et al. (1988) focused on 6 of the 19 classes of compounds using the zooplankter Daphnia pulex as the test organism. They ranked the six classes as follows (in decreasing order of toxicity): polycyclic aromatic hydrocarbons (PAHs), alkyl halides, nitrogen-containing compounds, cyclic alkanes, heterocyclic nitrogen compounds, and silicon-containing compounds.

  6. Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb.

    PubMed

    Singh, G D; Ganjoo, M; Youssouf, M S; Koul, A; Sharma, R; Singh, S; Sangwan, P L; Koul, S; Ahamad, D B; Johri, R K

    2009-10-01

    Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as "Kacip Fatimah". Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women's health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns. PMID:19654032

  7. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Vesprini, Danny; Catton, Charles; Jacks, Lindsay; Lockwood, Gina; Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig; Bristow, Robert G.

    2012-06-01

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts

  8. Acute toxicity, antiedematogenic activity, and chemical constituents of Palicourea rigida Kunth.

    PubMed

    Alves, Vanessa G; da Rosa, Elisa A; de Arruda, Laura L M; Rocha, Bruno A; Bersani Amado, Ciomar A; Santin, Silvana M O; Pomini, Armando M; da Silva, Cleuza C

    2016-03-01

    The phytochemical study of the leaves, roots, and flowers of Palicourea rigida led to the isolation of the triterpenes betulinic acid (1) and lupeol (2), the diterpene phytol (3), and the iridoid glycosides sweroside (4) and secoxyloganin (5). These compounds were identified using NMR 1H and 13C and comparing the spectra with published data. We studied the antiedematogenic activity of crude extracts from the organs, and of different fractions, in mice and found that the n-hexane fraction of the leaf extract significantly inhibited the ear edema resulting from croton oil administration. The crude extract from leaves was not acutely toxic to the mice. PMID:26927220

  9. A confirmatory study of the up-and-down method for acute oral toxicity testing.

    PubMed

    Bruce, R D

    1987-01-01

    Ten materials have been tested in parallel both by the "classical" method for acute oral toxicity (LD50) and by the up-and-down method. Materials tested included laundry and dishwashing detergents, a shampoo, a flavor, potassium hydroxide, and caffeine. All testing was done in Sprague-Dawley rats. Excellent agreement was seen between the two methods. The classical method typically used 40 to 50 animals while the up-and-down method required only six to nine animals per material. PMID:3556826

  10. Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic

    PubMed Central

    2014-01-01

    Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8

  11. Acute toxicity, brine shrimp cytotoxicity, anthelmintic and relaxant potentials of fruits of Rubus fruticosus Agg

    PubMed Central

    2013-01-01

    Background Rubus fruticosus is used in tribal medicine as anthelmintic and an antispasmodic. In the current work, we investigated the anthelmintic and antispasmodic activities of crude methanol extract of fruits of R. fruticosus on scientific grounds. Acute toxicity and brine shrimp cytotoxicity activity of the extract were also performed. Methods Acute toxicity study of crude methanol extract of R. fruticosus was performed on mice. In vitro Brine shrimp cytotoxicity assay was performed on shrimps of Artemia salina. In vitro Anthelmintic activity was tested against Raillietina spiralis and Ascaridia galli. Relaxant activities were tested on spontaneous rabbits’ jejunal preparations. Calcium chloride curves were constructed to elucidate possible mode of action of the extract. Results LD 50 of the extract for acute toxicity studies was 887.75 ± 9.22 mg/ml. While CC 50 of the extract for Brine shrimps cytotoxicity assay was 13.28 ± 2.47 μg/ml. Test samples of crude methanolic extract of R. fruticosus (Rf.Cr) at concentration 20 mg/ml showed excellent anthelmintic activity against Raillietina spiralis. Anthelmintic activity was 1.37 times of albendazole against the Raillietina spiralis at concentration 40 mg/ml. At higher concentration (40 mg/ml), Rf.Cr has 89. 83% parasiticidal activity. The mean EC50 relaxation activity for spontaneous and KCl-induced contractions was 7.96 ± 0.1 and 6.45 ± 0.29 mg/ml, respectively. EC 50 (Log[Ca++]M) for control calcium chloride curves was −1.75 ± 0.01 vs. EC 50 −1.78 ± 0.06 in the presence of 3.0 mg/ml of Rf.Cr. Similarly, EC 50(Log[Ca++]M) in the absence and presence of verapamil (0.1 μM) were −2.46 ± 0.01 and −1.72 ± 0.02, respectively. Conclusions The anthelmintic and relaxant activities explained traditional uses of R. fruticosus on scientific grounds. Relaxant activity follows the inhibition of voltage gated channels. Although the plant extract has cytotoxic effects, yet it is

  12. Acute lethal toxicity of some reference chemicals to freshwater fishes of Scandinavia

    SciTech Connect

    Oikari, A.O.J.

    1987-07-01

    Relevance of the choice of a test organism intended to be representative for a given environment seems to be under continual debate in aquatic ecotoxicology. For instance, it is commonly argue that acute toxicity tests with rainbow trout, the species most often recommended as a standard cold water teleost, were not representative for Nordic countries because the species is an alien in local faunas. A comparative study with several freshwater species was therefore initiated to clarify the validity of this assumption. As a first approximation, standard LC 50 assays were conducted. The species used were chosen only on the basis of their local availability, i.e, they randomly represented the fish fauna of Nordic inland waters. Furthermore, inter-species variation of toxicity response was compared with certain other, quantitatively more important, intra-species sources of variability affecting the toxicity of chemicals. Use of reference toxicants has been recommended as a means of standardizing bioassays. Compounds, characteristic of effluents from the pulp and paper industry, were selected for the present study. The toxicity of organic acids such a phenols and resin acids, as well as that of pupmill effluents, strongly depends on water pH. Because of the possibility that species differences could exist in this respect, effects of water acidity on toxicity of these types of substances to a randomly selected local species was investigated. Finally, as an example of the biological source of assay variability, the effect of yolk absorption was studied with a subsequent crisis period due to moderate starvation under laboratory conditions.

  13. Combined anaerobic-ozonation process for treatment of textile wastewater: removal of acute toxicity and mutagenicity.

    PubMed

    Punzi, Marisa; Nilsson, Filip; Anbalagan, Anbarasan; Svensson, Britt-Marie; Jönsson, Karin; Mattiasson, Bo; Jonstrup, Maria

    2015-07-15

    A novel set up composed of an anaerobic biofilm reactor followed by ozonation was used for treatment of artificial and real textile effluents containing azo dyes. The biological treatment efficiently removed chemical oxygen demand and color. Ozonation further reduced the organic content of the effluents and was very important for the degradation of aromatic compounds, as shown by the reduction of UV absorbance. The acute toxicity toward Vibrio fischeri and the shrimp Artemia salina increased after the biological treatment. No toxicity was detected after ozonation with the exception of the synthetic effluent containing the highest concentration, 1 g/l, of the azo dye Remazol Red. Both untreated and biologically treated textile effluents were found to have mutagenic effects. The mutagenicity increased even further after 1 min of ozonation. No mutagenicity was however detected in the effluents subjected to longer exposure to ozone. The results of this study suggest that the use of ozonation as short post-treatment after a biological process can be beneficial for the degradation of recalcitrant compounds and the removal of toxicity of textile wastewater. However, monitoring of toxicity and especially mutagenicity is crucial and should always be used to assess the success of a treatment strategy. PMID:25781375

  14. The effects of fasting on the acute oral toxicity of nine chemicals in the rat.

    PubMed

    Dashiell, O L; Kennedy, G L

    1984-12-01

    Nine chemicals, with a range from extremely to slightly toxic, were used to measure the oral LD50 in both fasted (24-h) and non-fasted rats. Each chemical was tested as a solution or suspension in corn oil, responses within 14 days post-treatment were evaluated, and LD50S were calculated. Hexachlorophene was more toxic in non-fasted rats. The LD50 values for tetraethyl lead, methomyl and hexamethylenediamine were essentially the same in both fasted and non-fasted rats. Adiponitrile, bromobenzene, caffeine, carbon tetrachloride and N-butyl-1,6-hexamediamine yielded lower LD50 values in fasted rats. The use of non-fasted rats in acute oral toxicity determinations allows both the establishment of relative potency and the estimation of dosage levels for further repeated dose oral studies. The LD50 values obtained were generally (7 of 9) higher in non-fasted rats, but the magnitude of the differences was not great enough to suggest routine use of both fasted and non-fasted rats in oral toxicity studies. PMID:6520321

  15. Temperature-dependent acute toxicity of methomyl pesticide on larvae of 3 Asian amphibian species.

    PubMed

    Lau, Edward Tak Chuen; Karraker, Nancy Elizabeth; Leung, Kenneth Mei Yee

    2015-10-01

    Relative to other animal taxa, ecotoxicological studies on amphibians are scarce, even though amphibians are experiencing global declines and pollution has been identified as an important threat. Agricultural lands provide important habitats for many amphibians, but often these lands are contaminated with pesticides. The authors determined the acute toxicity, in terms of 96-h median lethal concentrations, of the carbamate pesticide methomyl on larvae of 3 Asian amphibian species, the Asian common toad (Duttaphrynus melanostictus), the brown tree frog (Polypedates megacephalus), and the marbled pygmy frog (Microhyla pulchra), at 5 different temperatures (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) to examine the relationships between temperature and toxicity. Significant interspecific variation in methomyl sensitivity and 2 distinct patterns of temperature-dependent toxicity were found. Because high proportions of malformation among the surviving tadpoles were observed, a further test was carried out on the tree frog to determine effect concentrations using malformation as the endpoint. Concentrations as low as 1.4% of the corresponding 96-h median lethal concentrations at 25 °C were sufficient to cause malformation in 50% of the test population. As the toxicity of pesticides may be significantly amplified at higher temperatures, temperature effects should not be overlooked in ecotoxicological studies and derivation of safety limits in environmental risk assessment and management. PMID:25959379

  16. Acute toxicity of nitrofurazone to channel catfish Ictalurus punctatus, and goldfish, Carassius auratus

    SciTech Connect

    Wise, M.L.; Stiebel, C.L.; Grizzle, J.M.

    1987-01-01

    Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) is a nitrofuran, a group of organic compounds which have inhibitory activity against many Gram-negative and Gram-positive bacteria and against some protozoan parasites. Although not approved by the United States Food and Drug Administration for use with food fish, nitrofurazone has been found effective in fish against external and internal infections by various species of Aeromonas, Pseudomonas and myxobacteria and can be administered either as a food additive or as a bath treatment. Attempts to control the microsporidian parasite Pleistophora ovariae in golden shiners, Notemigonus crysoleucas, with nitrofurazone met with equivocal results. The following experiment was performed to determine acute toxicity, including lesions, of nitrofurazone to channel catfish, Ictalurus punctatus, and goldfish, carassius auratus, fingerlings. Toxicity of nitrofurazone to channel catfish was determined with low dissolved oxygen concentrations (2 mg/L) to simulate conditions frequently encountered in channel catfish culture. Information abut toxic levels of drugs and the lesions occurring in exposed fish is important to determine the safety of treatment levels and the effects of toxic concentrations.

  17. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use.

    PubMed

    Kalsi, Sarbjeet S; Wood, David M; Dargan, Paul I

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  18. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

    PubMed Central

    Kalsi, Sarbjeet S.; Wood, David M.; Dargan, Paul I.

    2011-01-01

    Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine. The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma. Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine. In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity. PMID:24149025

  19. Protective effect of berberine on doxorubicin‑induced acute hepatorenal toxicity in rats.

    PubMed

    Chen, Xueyan; Zhang, Yu; Zhu, Zhongning; Liu, Huanlong; Guo, Huicai; Xiong, Chen; Xie, Kerang; Zhang, Xiaofei; Su, Suwen

    2016-05-01

    Doxorubicin (DOX), a potent broad‑spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non‑target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX‑induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX‑induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX‑induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX‑induced hepatorenal toxicity in clinical practice. PMID:27035423

  20. Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

    SciTech Connect

    Meyer, Francois; Fortin, Andre; Wang, Chang Shu; Liu, Geoffrey

    2012-03-15

    Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help

  1. Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

    PubMed Central

    Pushkin, Richard; Barriere, Steven L.; Corey, G. Ralph; Stryjewski, Martin E.

    2015-01-01

    Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm2 and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin. PMID:26248356

  2. Comprehensive mollusk acute toxicity database improves the use of Interspecies Correlation Estimation (ICE) models to predict toxicity of untested freshwater and endangered mussel species

    EPA Science Inventory

    Interspecies correlation estimation (ICE) models extrapolate acute toxicity data from surrogate test species to untested taxa. A suite of ICE models developed from a comprehensive database is available on the US Environmental Protection Agency’s web-based application, Web-I...

  3. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  4. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

    PubMed

    Tanuja Yadav; Mishra, Shivangi; Das, Shefali; Aggarwal, Shikha; Rani, Vibha

    2015-01-01

    Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those. PMID:25555260

  5. Acute and subacute dermal toxicity of Break-Free CLP: a weapons cleaning and maintenance compound.

    PubMed

    Arfsten, D P; Johnson, E W; Thitoff, A R; Jung, A E; Still, K R; Brinkley, W W; Schaeffer, D J; Jederberg, W W; Bobb, A J

    2005-01-01

    Break-Free CLP((R)) is a commercial cleaning, lubricating and preserving compound used in both the military and civilian sectors for maintenance of small- and large-caliber weapons. Like many commercial mixtures, there is very little information available on the toxicity of Break-Free CLP. Studies were conducted to characterize the biological effects of single or repeat dermal application of Break-Free CLP to the clipped backs of CD-1 mice. Break-Free CLP was applied neat, 50 microl three times of week for up to 2 weeks. Foci of epithelial ulceration were observed in skin sections from 22% of Break-Free CLP-treated animals in conjunction with markedly thickened epithelium suggesting that robust epithelial regeneration was occurring in these animals. Skin histopathology of Break-Free CLP-treated animals closely matched the histopathology from mice treated repeatedly with 2% croton oil in acetone (dermal irritation positive control). Serum alkaline phosphatase activity was significantly (P < 0.05) lower for mice treated with Break-Free CLP, 2% croton oil or 7,12-dimethylbenz[a]anthracene (DMBA) compared with negative and vehicle control mice. Skin nitric oxide (NO) levels were not significantly elevated for mice treated with Break-Free CLP but were significantly elevated for mice treated with dermal irritation positive control compound DMBA. The cumulative skin changes in Break-Free CLP-treated animals support conducting a subchronic dermal application study. The observed decreases in serum alkaline phosphatase activity suggest that future studies should include the liver and bone as possible target organs. Additionally, dermal penetration studies could provide key health risk assessment information for characterizing the potential health risks associated with chronic dermal exposure to Break-Free CLP. PMID:16025432

  6. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    PubMed

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. PMID:21309017

  7. Influence of dissolved organic matter on acute toxicity of zinc to larval fathead minnows (Pimephales promelas).

    PubMed

    Bringolf, Robert B; Morris, Brady A; Boese, Connie J; Santore, Robert C; Allen, Herbert E; Meyer, Joseph S

    2006-10-01

    We conducted laboratory toxicity tests in support of the development of a biotic ligand model (BLM) to predict acute toxicity of zinc (Zn) to fathead minnows (Pimephales promelas). To test the effect of dissolved organic matter (DOM) on Zn toxicity, we exposed larval fathead minnows to Zn in water containing elevated concentrations of dissolved organic carbon (DOC) in 96-h static-renewal toxicity tests. We tested DOM isolated from four surface waters: Cypress Swamp, Delaware; Edisto River, South Carolina; Suwannee River, Georgia; and Wilmington, Delaware, wastewater treatment effluent. The DOM isolates from the Edisto River and Wilmington wastewater treatment effluent contained elevated concentrations of NaCl (20-110x control NaCl) due to the use of a Na+-exchange resin to remove Ca2+ and Mg2+ during the DOM isolation process. Therefore, we also performed Zn toxicity tests in which we added up to 20 mM NaCl to exposure solutions containing Cypress Swamp and Suwannee River DOM. A threshold concentration of 11 mg DOC/L was needed to decrease Zn toxicity, after which the 96 h Zn LC50 was positively correlated with DOC concentration. Elevated NaCl concentrations did not alter Zn toxicity in the presence of DOM. In conjunction with data from other studies with fish and invertebrates, results of this study were used to calibrate Version 2.1.1 of the Zn BLM. BLM-predicted LC50s for our exposure waters containing elevated DOM concentrations were within the range of acceptable deviation relative to the observed LC50s (i.e., 0.5-2x observed LC50s); however, BLM-predicted LC50s for our exposure waters containing < 1 mg DOC/L were 2-3x lower than the observed LC50s (i.e., the BLM over-predicted the toxicity). Therefore, the current composite-species BLM for Zn could be improved for fathead minnows if that species were modeled separately from the other species used to calibrate Version 2.1.1. PMID:16788742

  8. Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats.

    PubMed

    Traesel, Giseli Karenina; de Souza, Juliane Coelho; de Barros, Aline Lima; Souza, Marcos Alexandre; Schmitz, Wanderley Onofre; Muzzi, Rozanna Marques; Oesterreich, Silvia Aparecida; Arena, Arielle Cristina

    2014-12-01

    Acrocomia aculeata, popularly known as “bocaiúva”, is a species used for nutritional purposes and for the treatment of various diseases, as it has, among other things, high levels of antioxidant compounds. This study aimed to assess the toxicological profile of A. aculeata, through acute and subacute toxicity tests. Male and female rats (Wistar) received by gavage 2000 mg/kg of oil extracted from the pulp of A. aculeata (OPAC) for the acute toxicity test and 125, 250, 500 or 1000 mg/kg of OPAC for subacute toxicity test. In the acute toxicity study no mortality or behavioral changes were observed in rats treated with 2000 mg/kg, indicating that the LD50 is higher than this dose. In the subacute toxicity test, the tested doses produced no significant changes in hematological, biochemical or histopathological parameters in the animals exposed. These results demonstrate the absence of acute and subacute toxicity after oral exposure to A. aculeata oil in rats. However, further studies in animals and in humans are needed in order to have sufficient safety evidence for its use in humans. PMID:25445758

  9. Immediate skin grafting of sub-acute and chronic wounds debrided by hydrosurgery.

    PubMed

    Vanwijck, R; Kaba, L; Boland, S; Gonzales y Azero, M; Delange, A; Tourbach, S

    2010-03-01

    A wound bed may be prepared by various non-surgical debridements using autolytic, biological or enzymatic techniques. These are all effective in selective wounds but tend to be time consuming. Surgical debridement is not selective since healthy collateral tissue is also removed. Physical debridement uses whirlpool therapy to slough off necrotic tissues - the saline which comes out of the hand piece if vapourized over the wound - and therefore disseminates contaminated droplets. Hydrosurgery combines physical and surgical debridement but does not have their drawbacks. Water dissection works by using a high-pressure jet of sterile saline that travels parallel to the wound and creates a Venturi effect, thus enabling the selective removal of necrotic tissues without dissemination of contaminants. In this study, the authors report on 167 sub-acute and chronic wounds from 155 patients treated under general anaesthesia by hydrosurgery (Versajet). Of these, 95% of the debrided wounds were immediately covered with an autologous meshed graft. Compared to other debridement techniques, hydrosurgery has two main advantages: namely its tissue selectivity and its high percentage of successful engraftment after immediate skin grafting. PMID:19196559

  10. Field and laboratory tests on acute toxicity of cadmium to freshwater crayfish

    SciTech Connect

    Not Available

    1986-09-01

    Environmental regulatory standards for cadmium (EPA 1980), like those for most pollutants, are based on acute, laboratory toxicity tests of single species. Such tests can be conducted rapidly and inexpensively in comparison to acute or chronic field studies, but their validity has often been questioned. Laboratory-based criteria are subject to two criticisms: (1) chemical and physical conditions differ greatly in degree and variability from laboratory to field, and (2) species are not isolated, but live in an ecosystem of interacting taxa and biofeedback. To investigate the validity of basing field toxicity standards on laboratory data, the authors subjected the freshwater crayfish Orconectes immunis for 96 h to various levels of cadmium in laboratory aquaria and experimental ponds. The study was designed to evaluate in part the first criticism of lab-based criteria. The studies were conducted concurrently with similar short-term experiments on the fathead minnow, Pimephales promelas, and coincided with studies of chronic cadmium stress on fathead minnows in experimental ponds.

  11. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    PubMed

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. PMID:27208746

  12. Acute toxicity of runoff from sealcoated pavement to Ceriodaphnia dubia and Pimephales promelas.

    PubMed

    Mahler, Barbara J; Ingersoll, Christopher G; Van Metre, Peter C; Kunz, James L; Little, Edward E

    2015-04-21

    Runoff from coal-tar-based (CT) sealcoated pavement is a source of polycyclic aromatic hydrocarbons (PAHs) and N-heterocycles to surface waters. We investigated acute toxicity of simulated runoff collected from 5 h to 111 days after application of CT sealcoat and from 4 h to 36 days after application of asphalt-based sealcoat containing about 7% CT sealcoat (AS/CT-blend). Ceriodaphnia dubia (cladocerans) and Pimephales promelas (fathead minnows) were exposed in the laboratory to undiluted and 1:10 diluted runoff for 48 h, then transferred to control water and exposed to 4 h of ultraviolet radiation (UVR). Mortality following exposure to undiluted runoff from unsealed asphalt pavement and UVR was ≤10% in all treatments. Test organisms exposed to undiluted CT runoff samples collected during the 3 days (C. dubia) or 36 days (P. promelas) following sealcoat application experienced 100% mortality prior to UVR exposure; with UVR exposure, mortality was 100% for runoff collected across the entire sampling period. Phototoxic-equivalent PAH concentrations and mortality demonstrated an exposure-response relation. The results indicate that runoff remains acutely toxic for weeks to months after CT sealcoat application. PMID:25860716