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Sample records for 90-day inhalation toxicity

  1. Inhalation toxicity study of disk-shaped potassium octatitanate particles (terracess TF) in rats following 90 days of aerosol exposure.

    PubMed

    Sakai, Seiya; Inada, Kousuke; Tanaka, Akira K; Kelly, David P; Sykes, Greg P; Lee, K P

    2010-01-01

    Since fibrous particles such as asbestos and some man-made fibers (MMF) have been known to produce carcinogenic or fibrogenic effects, disk-shaped potassium octatitanate (POT) particles (trade name: Terracess TF) were manufactured as nonfibrous particles. A 90-day inhalation toxicity study of Terracess TF was performed to evaluate comparative inhalation toxicity of the disk shape with a fibrous shape that was previously evaluated. Four groups of 20 male and 15 female rats each were exposed to Terracess TF aerosols at concentrations of 0, 2, 10, or 50 mg/m(3) for 90 days. Ten male and 10 female rats per group were sacrificed at 90 days of exposure. After 90 days of exposure, 5 male rats per group were sacrificed at 3 wk of recovery period and 4-5 male rats per group or 5 female rats per group were sacrificed at 15 wk of recovery for lung clearance and histopathology. The mass median aerodynamic equivalent diameter (MMAED) of the aerosols of test materials ranged from 2.5 to 2.9 microm. There were no test-substance-related adverse effects on clinical observations. At the end of the 90-day exposure, a slight increase in lung-to-body weight ratios was observed at 50 mg/m(3) in male but not in female rats. However, lung weights were within normal limits after 3- or 15-wk recovery periods. Microscopically, inhaled Terracess TF particles were mostly phagocytized by free alveolar macrophages (AMs) in the alveolar airspaces and alveolar walls maintained normal structure at 2 and 10 mg/m(3). At 50 mg/m(3), some alveoli were distended and filled with aggregates of particle-laden AMs. The alveolar walls showed slight type II pneumocyte hyperplasia, but neither proliferative inflammation nor alveolar fibrosis was present at 50 mg/m(3). The clearance half-times for Terracess TF were estimated to be in the order of 6 to 9 mo for the 50-mg/m(3) group and 2 to 3 mo for the 10- and 2-mg/m(3) groups. The lung responses and lung clearance rate were comparable to those of "nuisance

  2. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  3. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  4. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  5. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and control groups is required. (D) Each animal shall be assigned a unique identification number. Dead... substance shall be measured in the animal's breathing zone. During the exposure period, the actual... provided the mixture at the animal's breathing zone is analogous to the formulation; the grounds for...

  6. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) should be used for each test group. (B) If interim sacrifices are planned, the number of animals shall be increased by the number of animals scheduled to be sacrificed before the completion of the study. (C) To... substance should be used, if possible throughout the duration of the......

  7. 90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in rats.

    PubMed

    Christian, Brian J; Bechtel, David H

    2014-12-01

    The subchronic (90-day) toxicity of a "core" version of EPG was assessed in rats. Crl:CD-1®(ICR)BR rats (70/sex) received diets containing a constant level of 5% EPG (w/w) or adjusted to deliver 0 (control), 0.5, 1, or 2g/kg of body weight/day (g/kg bw/day). Subsets of animals from each group (20/sex) were evaluated after 30 days (interim sacrifice); the remainder after 90 days. EPG intake at all dose levels was associated with lower mean liver vitamin E levels; liver vitamin A and serum vitamin D were also lower, but less consistently. Animals given 5% EPG had higher fecal output (males) and cholesterol (males and females) without corresponding changes in serum cholesterol. Urinary pH was also mildly lower in males given 5% EPG. However, detailed evaluation of general health and assessment of blood, organs and tissues showed no evidence that EPG administration compromised the nutritional requirements of the animals, caused a state of fat-soluble vitamin deficiency, or caused' toxicity to any organ system. Based on the results of this study, it was not possible to establish a no-observable-effect level (NOEL). The possible effect of EPG on vitamin levels in the absence of any clinical signs of deficiency was not considered "adverse" per se. As such, the 2g/kg and 5% EPG level were considered to represent a no-observable-adverse-effect levels (NOAELs). PMID:25497991

  8. The 90-day oral toxicity of d-psicose in male Wistar rats

    PubMed Central

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-01-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD50 = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days. PMID:22448098

  9. The 90-day oral toxicity of d-psicose in male Wistar rats.

    PubMed

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-03-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD(50) = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days.

  10. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  11. A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps cicadae (Ascomycetes) in Rats.

    PubMed

    Chen, Yen-Lien; Yeh, Shu-Hsing; Lin, Ting-Wei; Chen, Chin-Chu; Chen, Chin-Shuh; Kuo, Chia-Feng

    2015-01-01

    Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food. PMID:26559863

  12. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    PubMed

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys.

  13. Safety assessment of dietary bamboo charcoal powder: a 90-day subchronic oral toxicity and mutagenicity studies.

    PubMed

    Zhenchao, Jia; Yuting, Zhong; Jiuming, Yan; Yedan, Lu; Yang, Song; Jinyao, Chen; Lishi, Zhang

    2015-01-01

    Vegetable carbon has been used as food additive in EU (E153) and China for many years; however, no experimental data have been available on its dietary safety. This study was designed to evaluate the subchronic toxicity and genotoxicity of bamboo charcoal powder (BCP). In the study of subchronic oral toxicity, BCP was administered orally at doses of 2.81, 5.62, and 11.24 g/kg BW for 90 days to SD rats. Additional satellite groups from the control group and high dose group were observed for a 28-day recovery period. At the end of the treatment and recovery periods, animals were sacrificed, and their organs were weighed and blood samples were collected. The toxicological endpoints observed included clinical signs, food consumption, body and organ weights, hematological and biochemical parameters, macroscopic and microscopic examinations. The results showed no significant differences between the BCP treated groups and control group. The genotoxicity of BCP was assessed with the Salmonella typhimurium mutagenicity assay (Ames test) and a combination of comet assay and mammalian erythrocyte micronucleus protocol. The results did not reveal any genotoxicity of BCP. Based on our study, the no-observed-adverse-effect level (NOAEL) for BCP is 11.24 g/kg BW/day.

  14. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    PubMed

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys. PMID:23444337

  15. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats.

    PubMed

    Werley, Michael S; Kirkpatrick, Dan J; Oldham, Michael J; Jerome, Ann M; Langston, Timothy B; Lilly, Patrick D; Smith, Donna C; Mckinney, Willie J

    2016-01-01

    A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1-4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  16. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats

    PubMed Central

    Werley, Michael S.; Kirkpatrick, Dan J.; Oldham, Michael J.; Jerome, Ann M.; Langston, Timothy B.; Lilly, Patrick D.; Smith, Donna C.; Mckinney, Willie J.

    2016-01-01

    Abstract A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1–4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  17. Toxicity of Carbon Nanotubes in the Lungs of Mice 7 and 90 Days After Intratracheal Instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2002-01-01

    Single-walled carbon nanotubes have many potential applications in the electronic, computer, and aerospace industries. Because unprocessed nanotubes could become airborne and potentially reach the lungs, their pulmonary toxicity was investigated. The three products studied were made by different methods, and contained different types and amounts of residual catalytic metals. Mice were each intratracheally instilled once with 0,0.1 or 0.5 mg of nanotubes, a carbon black negative control, or a quartz positive control, and killed for histopathological study 7 d or 90 d after the treatment. All nanotube products induced epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7 -d groups. These lesions persisted and were worse in the 90-d groups. We found that, if nanotubes reach the lung, they can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  18. Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice

    SciTech Connect

    Boorman, G.A.; Uraih, L.C.; Gupta, B.N.; Bucher, J.R.

    1987-06-01

    B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eight (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.

  19. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    PubMed Central

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  20. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

    PubMed

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  1. 90-day dermal toxicity study and neurotoxicity evaluation of nitromusks in the albino rat.

    PubMed

    Ford, R A; Api, A M; Newberne, P M

    1990-01-01

    Musk ketone, musk xylene, musk tibetene and moskene, synthetic musks used in fragrances, were applied dermally to rats in daily doses of 240 (musk ketone and musk xylene only), 75, 24 or 7.5 mg/kg body weight for 90 days. The chemically related musk ambrette, a known neurotoxin in rats, was used as a positive control. While musk ambrette was clearly neurotoxic and caused testicular atrophy, as had been previously reported, the other compounds tested caused neither effect. The only effects of application of these materials were some organ weight changes at the higher doses, but these were not associated with histopathological changes in any of the tissues. The no-effect levels were: musk ketone, 75 mg/kg for males and females; musk xylene, 75 mg/kg for males and 24 mg/kg for females; moskene, 24 mg/kg for males and 75 mg/kg (highest dose administered) for females; and musk tibetene, 75 mg/kg (highest dose) for males and females.

  2. Toxicity of 2,4,4{prime}-trichlorobiphenyl in rats following 90-day dietary exposure

    SciTech Connect

    Chu, I.; Villeneuve, D.C.; Yagminas, A.; Lecavalier, P.; Poon, R.

    1996-10-25

    The toxicity of 2,4,4{prime}-trichlorobiphenyl (PCB 28) was investigated in rats after a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for 13 wk. Growth rate and food consumption were not affected by treatment, and no clinical signs of toxicity were observed. Mottled liver was noted in both control and PCB-treated males, but was found with increased incidence in the highest treatment group. Increased urinary ascorbic acid and hepatic microsomal ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both sexes. The vitamin A content in liver, lung, and kidney was not significantly affected by treatment. Analysis of brain biogenic amines showed a decreased dopamine concentration in the substantial nigra region of female rats receiving 0.5 ppm PCB 28 and higher doses. Female rats appeared top be more sensitive than males to the neurochemical effects of PCB 28. Dose-dependent histologic changes were observed in the thyroid and liver, with biologically significant changes occurring at 5.0 ppm and above. Based on these data, the no-observable-adverse-effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet or 36 {mu}g/kg body weight/d. 26 refs., 6 figs., 3 tabs.

  3. Safety assessment of essential oil from Minthostachys verticillata (Griseb.) Epling (peperina): 90-days oral subchronic toxicity study in rats.

    PubMed

    Escobar, Franco Matías; Sabini, María Carola; Cariddi, Laura Noelia; Sabini, Liliana Inés; Mañas, Fernando; Cristofolini, Andrea; Bagnis, Guillermo; Gallucci, Mauro Nicolas; Cavaglieri, Lilia Renée

    2015-02-01

    Minthostachys verticillata (Lamiaceae), popularly known as peperina is largely used in popular medicine for its digestive, carminative, antispasmodic and antirheumatic properties. There are no reports of repeated exposure toxicity to guarantee their safety. The present study investigated the chemical composition, analyzed by GC-FID, and the 90-day toxicity and genotoxicity effect of M. verticillata essential oil (Mv-EO), using Wistar rats as test animals. The rats were divided into four groups (5 rats/sex/group) and Mv-EO was administered on diet at doses of 0, 1, 4 and 7 g/kg feed. The main components of Mv-EO were pulegone (64.65%) and menthone (23.92%). There was no mortality, adverse effects on general conditions or changes in body weight, food consumption and feed conversion efficiency throughout the study in male and female rats. Subchronic administration of Mv-EO did not alter the weights, morphological and histopathological analyses of liver, kidney and intestine. Genotoxicity was tested by micronucleus and comet assays. Mv-EO up to a concentration of 7 g/kg feed for 90 days did not exert a cyto-genotoxic effect on the bone marrow and cells blood of Wistar rats. These results suggest that Mv-EO appears to be safe and could be devoid of any toxic risk.

  4. A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiatica.

    PubMed

    Park, Byung-Gyu; Lee, Hyun-Sun; Jung, Sung-Hoon; Hong, Chung-Oui; Won, Hye-Jin; Park, Ho-Young; Ryu, Yung-Sun; Lee, Sung-Joon; Kim, Kyoung-Heon; Park, Kuen-Woo; Lee, Kwang-Won

    2007-12-01

    Plantago asiatica is distributed widely in East Asia. Since ancient times it has been used as a diuretic to treat acute urinary infections, and as an antiinflammatory, antiasthmatic, antioxidant, antibacterial, antihyperlipidemic and antihepatitis drug. The major compound, plantamajoside from P. asiatica, which is used as a marker compound in chemotaxonomic studies, was reported to have antibacterial activity, inhibition activity against cAMP phosphodiesterase and 5-lipoxygenase and antioxidant activity. However, there are no reports on the safety of plantamajoside. This study assessed the toxic effects of plantamajoside concentrate (PC), the purity of which was above 80%, in rats following administration at dose levels of 0, 500, 1000 and 2000 mg/kg body weight/day for 13 weeks, as recommended by the OECD guidelines. The results showed that there were no differences in body weight, food intake, water consumption, relative organ weight or the hematological and serum biochemical values among the different dosage groups. No death or abnormal clinical signs were observed during the experimental period. Therefore, the results suggested that no observed adverse effect level (NOAEL) of the PC in rats after oral administration is considered to be greater than 2000 mg/kg in rats under the conditions employed in this study. PMID:17622978

  5. A 90-day subchronic oral toxicity study of triterpene-enriched extract from Alismatis Rhizoma in rats.

    PubMed

    Huang, Ming-Qing; Xu, Wen; Wu, Shui-Shen; Lu, Jin-Jian; Chen, Xiu-Ping

    2013-08-01

    Alismatis Rhizoma has been used in East Asia as a traditional treatment for various illnesses and symptoms, and the presence of protostane-type triterpenes has been claimed to provide health benefits. To investigate the subchronic toxicity of triterpene-enriched extract from Alismatis Rhizoma (TEAR), a 90-day oral toxicity study was conducted in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and received doses of 0, 360, 720, and 1440 mg/kg/d of TEAR for 90 days. Daily clinical observations as well as weekly measurement of body weight and food consumption were conducted. Blood samples were obtained on day 91 to measure changes in hematology and biochemistry. Urine samples were collected on days 0 and 91 for urinalysis. At necropsy, selected organs were weighed and recorded, and histological examination was performed. No mortality or obvious treatment-related clinical signs, hematology, urinalysis parameters, and macroscopic or microscopic examinations were observed. Differences in weight gain, food consumption, biochemistry, and relative organ weight between the treated group and the control group were not considered treatment-related. On the basis of these findings, the no-observed-adverse-effect level for TEAR was 1440 mg/kg/d in both sexes. PMID:23684999

  6. In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

    PubMed

    Kim, Jin Sik; Sung, Jae Hyuck; Choi, Byung Gil; Ryu, Hyeon Yeol; Song, Kyung Seuk; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Lee, Gun Ho; Jeon, Kisoo; Ahn, Kang Ho; Yu, Il Je

    2014-03-01

    Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the

  7. A 90-day subchronic toxicity study with sodium formononetin-3'-sulphonate (Sul-F) delivered to dogs via intravenous administration.

    PubMed

    Li, Chunmei; Li, Guisheng; Gao, Yonglin; Sun, Chengfeng; Wang, Xiaoyan

    2016-06-01

    Sodium formononetin-3'-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs.

  8. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    PubMed Central

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  9. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats.

    PubMed

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  10. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation.

    PubMed

    Lam, Chiu-Wing; James, John T; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-09-01

    O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

  11. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-01-01

    O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

  12. A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Shin, Sung-Sup; Meang, Eun Ho; Hong, Jeong-sup; Park, Jong-Il; Kim, Su-Hyon; Koh, Sang-Bum; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Jong-Yun; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. PMID:25565828

  13. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Hunter, Robert L.

    2004-01-01

    Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.

  14. Safety assessment of EPA-rich oil produced from yeast: Results of a 90-day subchronic toxicity study.

    PubMed

    MacKenzie, Susan A; Belcher, Leigh A; Sykes, Greg P; Frame, Steven R; Mukerji, Pushkor; Gillies, Peter J

    2010-12-01

    The safety of eicosapentaenoic acid (EPA) oil produced from genetically modified Yarrowia lipolytica yeast was evaluated following 90 days of exposure. Groups of rats received 0 (olive oil), 98, 488, or 976 mg EPA/kg/day, or GRAS fish oil or deionized water by oral gavage. Rats were evaluated for in-life, neurobehavioral, anatomic and clinical pathology parameters. Lower serum cholesterol (total and non-HDL) was observed in Medium and High EPA and fish oil groups. Lower HDL was observed in High EPA and fish oil males, only at early time points. Liver weights were increased in High EPA and Medium EPA (female only) groups with no associated clinical or microscopic pathology findings. Nasal lesions, attributed to oil in the nasal cavity, were observed in High and Medium EPA and fish oil groups. No other effects were attributed to test oil exposure. Exposure to EPA oil for 90 days produced no effects at 98 mg EPA/kg/day and no adverse effects at doses up to 976 mg EPA/kg/day. The safety profile of EPA oil was comparable to that of GRAS fish oil. These results support the use of EPA oil produced from yeast as a safe source for use in dietary supplements.

  15. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  16. Safety assessment of the fermented Phylloporia ribis (Lonicera japonica Thunb.) mycelia by oral acute toxicity study in mice and 90-day feeding study in rats.

    PubMed

    Lu, Lianhua; Fan, Yiou; Yao, Wenhuan; Xie, Wei; Guo, Jie; Yan, Yan; Yang, Fei; Xu, Lingchuan

    2014-07-01

    Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.

  17. A 90-Day Dietary Toxicity Study of Genetically Modified Rice T1C-1 Expressing Cry1C Protein in Sprague Dawley Rats

    PubMed Central

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study. PMID:23300690

  18. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    PubMed

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  19. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  20. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  1. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats

    PubMed Central

    Sato, Makoto; Todoriki, Setsuko; Takahashi, Tetsuyuki; Hafez, Ezar; Takasu, Chie; Uehara, Hisanori; Yamakage, Kohji; Kondo, Takashi; Matsumoto, Kozo; Furuta, Masakazu; Izumi, Keisuke

    2015-01-01

    A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females. PMID:26028819

  2. A 90-day repeated dose oral (gavage) toxicity study of perfluorohexanoic acid (PFHxA) in rats (with functional observational battery and motor activity determinations).

    PubMed

    Chengelis, Christopher P; Kirkpatrick, Jeannie B; Radovsky, Ann; Shinohara, Motoki

    2009-06-01

    Possible toxic effects of perfluorohexanoic acid (PFHxA) were evaluated when administered orally by gavage to rats at levels up to 200mg/kg/day for 90 days. Lower body weight gains were noted in the 10, 50 and 200mg/kg/day group males (not dose-responsive) throughout dosing. Other changes included lower red blood cell parameters, higher reticulocyte counts and lower globulin in the 200mg/kg/day group males and females, higher liver enzymes in males at 50 and 200mg/kg/day, lower total protein and higher albumin/globulin ratio, and lower cholesterol, calcium in males at 200mg/kg/day. Minimal centrilobular hepatocellular hypertrophy was present in 200mg/kg/day group males and correlated with higher liver weights and slightly higher peroxisome beta oxidation activity at the end of the dosing period. Based on liver histopathology and liver weight changes, the no-observed-adverse-effect level (NOAEL) for oral administration was 50mg/kg/day for males and 200mg/kg/day for females.

  3. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    PubMed

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. PMID:26993751

  4. Evaluation of the safety and nutritional equivalence of a genetically modified cottonseed meal in a 90-day dietary toxicity study in rats.

    PubMed

    Dryzga, M D; Yano, B L; Andrus, A K; Mattsson, J L

    2007-10-01

    Meal prepared from Cry1F/Cry1Ac transgenic/genetically modified cottonseed (WIDESTRIKE Insect Protection, hereafter referred to as WIDESTRIKE) was compared to cottonseed meal prepared from four conventionally bred lines of cotton (three commercial non-transgenic line controls (PHY72, PHY78 and 98M-2983), and a near isoline non-transgenic control (PSC355) in a 90-day dietary study to evaluate safety and nutritional equivalence. Diets were formulated with 10% WIDESTRIKE cottonseed meal equivalent to 7,235 mg/kg/day for males and 7,935 mg/kg/day for females. Animals were evaluated by cage-side and hand-held detailed clinical observations, body weight, and feed consumption. Functional tests, motor activity and ophthalmic examinations were conducted pre-exposure and prior to study termination. Standard hematology, clinical chemistry, prothrombin time and urinalysis parameters were evaluated. All rats had a complete necropsy and selected organs were weighed. Histopathologic examinations were performed on all rats fed the diets containing the near isoline non-transgenic control or WIDESTRIKE. Following 90 days of feeding, no adverse effects were observed during the conduct of clinical observations or in any of the parameters measured in this study. This study demonstrated that rodent diets prepared with 10% cottonseed meal from WIDESTRIKE cottonseeds do not produce any untoward effects and are nutritionally equivalent to cottonseed meals prepared from other, non-transgenic cottonseeds.

  5. Metabonomics study of transgenic Bacillus thuringiensis rice (T2A-1) meal in a 90-day dietary toxicity study in rats.

    PubMed

    Cao, Sishuo; Xu, Wentao; Luo, YunBo; He, Xiaoyun; Yuan, Yanfang; Ran, Wenjun; Liang, Lixing; Huang, Kunlun

    2011-07-01

    Rice is one of the most important staple foods in the world. The Cry2A gene was inserted into the rice genome to help the plant combat insects. As the unintended effects of the genetically modified (GM) organisms are the most important barriers to the promotion of GM organisms, we have carried out a useful exploration to establish a new in vivo evaluation model for genetically modified foods by metabonomics methods. In this study, the rats were fed for 90 days with the GM and NON-GM rice diets. The changes in metabolites of the urine were detected using (1)H-NMR. The metabonomics were analyzed to see whether the GM rice can induce the metabolite changes in the rats' urine when compared with the NON-GM rice group. The multivariate analysis and ANOVA were used to determine the differences and the significance of differences respectively, and eventually we concluded that these differences did not have a biological significance. The conclusion of the metabonomics was comparable with that from the traditional method. As a non-invasive and dynamic monitoring method, metabonomics will be a new way of assessing the food safety of GM foods.

  6. A Study on Subchronic Inhalation Toxicity of 1-Chloropropane

    PubMed Central

    Chung, Yong Hyun; Han, Jeong Hee

    2015-01-01

    This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats. PMID:26877841

  7. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    PubMed

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  8. Repeated exposure toxicity of 2-ethyl-1,3-hexanediol by cutaneous applications to the rat for 9 and 90 days.

    PubMed

    Van Miller, J P; Losco, P E; Neptun, D A; Ballantyne, B

    1995-02-01

    2-Ethyl-1,3-hexanediol (EHD; CASRN 94-96-2), an industrial chemical and insect repellent, has a high potential for recurrent skin contact. Short-term (9 d) and subchronic (13 w) repeated epicutaneous contact studies were conducted to determine the potential for cumulative local skin irritation and systemic toxicity in Fischer 344 rats. Doses were 0.5, 2.0 or 4.0 ml/kg/d of undiluted EHD. There were no clinical signs and no treatment-related effects on hematology, clinical chemistry or histology of a large number of organs and tissues including the treated skin. The only effects where slight decreases in body weight gain for the high-dose males in the 9-d study and males and females of the high-dose group in the subchronic study; slight decreases in food consumption for females of all treatment groups in the subchronic study; and slight increases in relative liver weight for high-dose females in the 9-d study and high-dose males in the subchronic study, which is probably a compensatory hypertrophy for the metabolism of EHD. Thus, recurrent epicutaneous applications of undiluted EHD to the rat did not cause any local skin irritation or cumulative or organ-specific toxicity. PMID:7709587

  9. Subacute Inhalation Toxicity of 3-Methylpentane.

    PubMed

    Chung, Yong Hyun; Shin, Seo-Ho; Han, Jeong Hee; Lee, Yong-Hoon

    2016-07-01

    3-Methylpentane (C6H14, CAS No. 96-14-0), isomer of hexane, is a colorless liquid originating naturally from petroleum or natural gas liquids. 3-Methylpentane has been used as a solvent in organic synthesis, as a lubricant, and as a raw material for producing carbon black. There is limited information available on the inhalation toxicity of 3-methylpentane, and the aim of this study was to determine its subacute inhalation toxicity. According to OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study), Sprague Dawley rats were exposed to 0, 284, 1,135, and 4,540 ppm of 3-methylpentane for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, organ weights, and gross and histopathological findings were compared between control and all exposure groups. No mortality or remarkable clinical signs were observed during the study. No gross or histopathological lesions, or adverse effects on body weight, food consumption, hematology, serum chemistry, and organ weights were observed in any male or female rats in all exposure groups, although some statistically significant changes were observed in food consumption, serum chemistry, and organ weights. In conclusion, the results of this study indicate that no observable adverse effect level (NOAEL) for 3-methylpentane above 4,540 ppm/6 hr/day, 5 days/week for rats. PMID:27437092

  10. Subacute Inhalation Toxicity of 3-Methylpentane

    PubMed Central

    Chung, Yong Hyun; Shin, Seo-Ho; Han, Jeong Hee; Lee, Yong-Hoon

    2016-01-01

    3-Methylpentane (C6H14, CAS No. 96-14-0), isomer of hexane, is a colorless liquid originating naturally from petroleum or natural gas liquids. 3-Methylpentane has been used as a solvent in organic synthesis, as a lubricant, and as a raw material for producing carbon black. There is limited information available on the inhalation toxicity of 3-methylpentane, and the aim of this study was to determine its subacute inhalation toxicity. According to OECD Test Guideline 412 (subacute inhalation toxicity: 28-day study), Sprague Dawley rats were exposed to 0, 284, 1,135, and 4,540 ppm of 3-methylpentane for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, organ weights, and gross and histopathological findings were compared between control and all exposure groups. No mortality or remarkable clinical signs were observed during the study. No gross or histopathological lesions, or adverse effects on body weight, food consumption, hematology, serum chemistry, and organ weights were observed in any male or female rats in all exposure groups, although some statistically significant changes were observed in food consumption, serum chemistry, and organ weights. In conclusion, the results of this study indicate that no observable adverse effect level (NOAEL) for 3-methylpentane above 4,540 ppm/6 hr/day, 5 days/week for rats. PMID:27437092

  11. Toxicity of inhaled methyl isocyanate vapor

    SciTech Connect

    Ferguson, J.S.

    1988-01-01

    The toxicity of inhaled isocyanate (MIC) vapor was evaluated using several bioassays designed to investigate the toxicity of airborne chemicals. Two methods which measure changes in respiratory rate and identify characteristic breathing patterns in mice were used to evaluate the potency of MIC as a sensory and pulmonary irritant. Using the CO{sub 2} challenge method in conjunction with the measurement of airflow (V) and tidal volume (VT), the pulmonary effects and subsequent recovery process following a single exposure to MIC were studied in guinea pigs for a period of one year. Flow-volume loops were also obtained by plotting V vs. VT. Measurement of O{sub 2} uptake and CO{sub 2} output were also performed to determine the acute and chronic effects of MIC exposure on gas exchange. Lastly, guinea pigs and mice were exposed to {sup 14}C-MIC in an effort to determine uptake and fate of inhaled MIC.

  12. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (4 males and 4 females) shall be used. (B) If interim sacrifices are planned, the number of animals shall be increased by the number of animals scheduled to be sacrificed before the completion of the... with continuous or repeated exposure to a test substance for a period of 90 days. The test is......

  13. Leadership Transitions and the First 90 Days.

    PubMed

    Shirey, Maria R

    2016-04-01

    This department highlights change management strategies that may be successful in strategically planning and executing organizational change initiatives. In this article, the author discusses leadership role transitions and provides a framework for successfully navigating the crucial 1st 90 days in an executive leadership role. PMID:27011151

  14. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  15. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  16. Toxicological assessment of kretek cigarettes. Part 7: the impact of ingredients added to kretek cigarettes on inhalation toxicity.

    PubMed

    Schramke, H; Roemer, E; Dempsey, R; Hirter, J; Meurrens, K; Berges, A; Weiler, H; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    The biological activity of mainstream smoke from experimental kretek cigarettes with and without three mixes of ingredients was assessed in a 90-day rat inhalation study and in a 4-day in vivo micronucleus assay. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes, were applied at a low and a high target level to test cigarettes with a typical Indonesian blend of tobaccos and cloves. In the 90-day inhalation study, effects commonly seen in rat inhalation studies with mainstream smoke were observed. In general, no ingredients-related histopathological changes were found in the respiratory tract. In the 4-day micronucleus assay exposure of male rats to mainstream smoke from the test cigarettes containing any of the three mixes did not increase the proportions of micronucleated cells in peripheral blood and bone marrow over the proportion of micronucleated cells in the control group. Based on the results of these studies, it can be concluded that the addition of ingredients commonly used in the manufacture of kretek cigarettes did not change the overall in vivo toxicity profile of the mainstream smoke. PMID:25455220

  17. Inhalation toxicity of multiwall carbon nanotubes in rats exposed for 3 months.

    PubMed

    Ma-Hock, Lan; Treumann, Silke; Strauss, Volker; Brill, Sandra; Luizi, Frederic; Mertler, Michael; Wiench, Karin; Gamer, Armin O; van Ravenzwaay, Bennard; Landsiedel, Robert

    2009-12-01

    Carbon nanotubes (CNT) are of great commercial interest. Theoretically, during processing and handling of CNT and in abrasion processes on composites containing CNT, inhalable CNT particles might be set free. For hazard assessment, we performed a 90-day inhalation toxicity study with a multiwall CNT (MWCNT) material (Nanocyl NC 7000) according to Organisation for Economic Co-operation and Development test guideline 413. Wistar rats were head-nose exposed for 6 h/day, 5 days/week, 13 weeks, total 65 exposures, to MWCNT concentrations of 0 (control), 0.1, 0.5, or 2.5 mg/m(3). Highly respirable dust aerosols were produced with a proprietary brush generator which neither damaged the tube structure nor increased reactive oxygen species on the surface. Inhalation exposure to MWCNT produced no systemic toxicity. However, increased lung weights, pronounced multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic inflammation, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5 mg/m(3). These effects were accompanied by slight blood neutrophilia at 2.5 mg/m(3). Incidence and severity of the effects were concentration related. At 0.1 mg/m(3), there was still minimal granulomatous inflammation in the lung and in lung-associated lymph nodes; a no observed effect concentration was therefore not established in this study. The test substance has low dust-forming potential, as demonstrated by dustiness measurements, but nonetheless strict industrial hygiene measures must be taken during handling and processing. Toxicity and dustiness data such as these can be used to compare different MWCNT materials and to select the material with the lowest risk potential for a given application. PMID:19584127

  18. Cadmium inhalation and male reproductive toxicity.

    PubMed

    Ragan, H A; Mast, T J

    1990-01-01

    Cadmium is a highly toxic element that is cumulative and has a long biological half-life in mammals. The severe toxicity of cadmium in man has been known for more than 100 years. Despite the knowledge that cadmium is toxic, only 20 human cases of poisoning via ingestion were recorded prior to 1941, whereas in the ensuing five-year period more than 680 cases of cadmium poisonings from accidental oral ingestion of this metal were documented. Some of the recorded effects of exposure to cadmium in laboratory animals include renal tubular damage, placental and testicular necrosis, structural and functional liver damage, osteomalacia, testicular tumors, teratogenic malformations, anemia, hypertension, pulmonary edema, chronic pulmonary emphysema, and induced deficiencies of iron, copper, and zinc. Some of these effects have also been observed in human after accidental exposures to cadmium oxide fumes and are characteristic of the syndrome described in Japan as Itai Itai disease in which ingestion of cadmium is the inciting chemical.

  19. 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).

  20. Pulmonary toxicity of printer toner following inhalation and intratracheal instillation.

    PubMed

    Morimoto, Yasuo; Oyabu, Takako; Horie, Masanori; Kambara, Tatsunori; Izumi, Hiroto; Kuroda, Etsushi; Creutzenberg, Otto; Bellmann, Bernd; Pohlmann, Gerhard; Schuchardt, Sven; Hansen, Tanja; Ernst, Heinrich

    2013-10-01

    The pulmonary effects of a finished toner were evaluated in intratracheal instillation and inhalation studies, using toners with external additives (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups and persistent neutrophil infiltration in the high-dose groups. There were increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76 µm). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13 weeks, and the rats were sacrificed at 6 days and 91 days after the end of the exposure period. The low and medium concentrations did not induce neutrophil infiltration in the lung of statistical significance, but the high concentration did, and, in addition, upon histopathological examination not only showed findings of inflammation but also of fibrosis in the lung. Taken together, the results of our studies suggest that toners with external additives lead to pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload. The changes observed in the pulmonary responses in this inhalation study indicate that the high concentration (16 mg/m(3)) is an LOAEL and that the medium concentration (4 mg/m(3)) is an NOAEL.

  1. Cadmium inhalation and male reproductive toxicity

    SciTech Connect

    Ragan, H.A.; Mast, T.J. )

    1990-01-01

    Cadmium is a highly toxic element that is cumulative and has a long biological half-life in mammals. The severe toxicity of cadmium in man has been known for more than 100 years. Despite the knowledge that cadmium is toxic, only 20 human cases of poisoning via ingestion were recorded prior to 1941, whereas in the ensuing five-year period more than 680 cases of cadmium poisonings from accidental oral ingestion of this metal were documented. Some of the recorded effects of exposure to cadmium in laboratory animals include renal tubular damage, placental and testicular necrosis, structural and functional liver damage, osteomalacia, testicular tumors, teratogenic malformations, anemia, hypertension, pulmonary edema, chronic pulmonary emphysema, and induced deficiencies of iron, copper, and zinc. Some of these effects have also been observed in human after accidental exposures to cadmium oxide fumes and are characteristic of the syndrome described in Japan as Itai Itai disease in which ingestion of cadmium is the inciting chemical.134 references.

  2. A new methyl bromide gas generator for inhalation toxicity studies.

    PubMed

    Hori, H; Hyakudo, T; Tanaka, I

    1992-09-01

    A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

  3. Inhalation toxicity of chromium from Whetlerite dust in rats.

    PubMed

    Hilaski, R; Katz, S; Salem, H

    1992-08-01

    The acute inhalation toxicity and metabolic fate of chromium and copper from Whetlerite dust in rats were investigated. Groups of male and female, Sprague-Dawley rats were exposed to Whetlerite dust and base carbon dust as outlined in the OECD Limit Test guidelines. At 14, 28 and 180 days post-exposure, rats were evaluated for gross pathological changes and tissues were collected for chromium and copper determination. Four deaths occurred during or post-exposure, but did not appear to be compound related. No gross pathological changes were observed at necropsy in either group. Organ chromium concentrations were below detection limits of 0.5 micrograms Cr/g dry tissue in both exposure groups. According to OECD guidelines, neither Whetlerite dust nor base carbon dust demonstrated an acute inhalation toxicity.

  4. Toxicity of inhaled traffic related particulate matter

    NASA Astrophysics Data System (ADS)

    Gerlofs-Nijland, Miriam E.; Campbell, Arezoo; Miller, Mark R.; Newby, David E.; Cassee, Flemming R.

    2009-02-01

    Traffic generated ultrafine particulates may play a major role in the development of adverse health effects. However, little is known about harmful effects caused by recurring exposure. We hypothesized that repeated exposure to particulate matter results in adverse pulmonary and systemic toxic effects. Exposure to diesel engine exhaust resulted in signs of oxidative stress in the lung, impaired coagulation, and changes in the immune system. Pro-inflammatory cytokine levels were decreased in some regions of the brain but increased in the striatum implying that exposure to diesel engine exhaust may selectively aggravate neurological impairment. Data from these three studies suggest that exposure to traffic related PM can mediate changes in the vasculature and brain of healthy rats. To what extent these changes may contribute to chronic neurodegenerative or vascular diseases is at present unclear.

  5. Toxic smoke compounds and inhalation injury--a review.

    PubMed

    Prien, T; Traber, D L

    1988-12-01

    Although the role of inhalation injury in contributing to the mortality of burn patients has received increasing attention, the available information on the toxic and injurious effects of smoke generated from uncontrolled fires is scarce. This is because each fire generates its own variety of smoke, depending on the nature of the combusting materials and the burning conditions. This review summarizes the actions of the primary smoke components, heat, particulate materials, asphyxiants (carbon monoxide and hydrogen cyanide), and pulmonary irritants, without covering the whole field of smoke toxicity. In addition, emergency measures to counteract carbon monoxide and hydrogen cyanide poisoning are discussed. PMID:2855039

  6. White phosphorus burns and arsenic inhalation: a toxic combination.

    PubMed

    Berndtson, Allison E; Fagin, Alice; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

    2014-01-01

    White phosphorus is a common industrial and military compound, which can cause severe thermal and chemical burns beyond what would be predicted from body surface area alone. The authors present a rare case of a 45-year-old male patient who suffered white phosphorus burns combined with arsenic inhalation because of an industrial accident. The presented case is used to review the history and the toxicities of these chemicals as well as current methods of treatment. A literature review was performed to summarize the current knowledge of white phosphorus burns, as well as arsenic poisoning, and no similar case reports of the two combined were found. The patient ultimately recovered and was discharged, though with significant chronic complications. This case highlights the risk of burns and inhalation injury present in industrial manufacturing jobs, as well as the potential severity of these conditions. The systemic effects of chemicals absorbed across burned skin and via inhalation were the main contributors to our patient's severe illness, and required more intensive treatment than the burns themselves. Arsenic toxicity is rare and could easily have been missed without the appropriate patient history.

  7. Toxicological assessment of kretek cigarettes Part 3: kretek and American-blended cigarettes, inhalation toxicity.

    PubMed

    Piadé, J-J; Roemer, E; Dempsey, R; Weiler, H; Meurrens, K; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    A typical Indonesian kretek cigarette brand and an experimental kretek reference cigarette were compared to the reference cigarette 2R4F in two 90-day inhalation studies. Male and female rats were exposed nose-only to mainstream smoke for 6 hours daily, for 90 consecutive days. Biological endpoints were assessed according to OECD guideline 413, with special emphasis on respiratory tract histopathology and on lung inflammation (broncho-alveolar lavage fluid levels of neutrophils, macrophages and lymphocytes). Histopathological alterations included: in the nose, hyperplasia and squamous metaplasia of the respiratory epithelium and squamous metaplasia and atrophy of the olfactory epithelium; in the larynx, epithelial squamous metaplasia and hyperplasia; in the lungs, accumulation of macrophages in alveoli and goblet cell hyperplasia in bronchial epithelium. The findings were qualitatively consistent with observations from previous similar studies on conventional cigarettes. Compared to 2R4F cigarette, however, kretek smoke exposure was associated with a pronounced attenuation of pulmonary inflammation and less severe histopathological changes in the respiratory tract. Neutrophilic inflammation was also significantly lower (>70%). These results are consistent with the observations made on smoke chemistry and in vitro toxicology. They do not support any increased toxicity of the smoke of kretek cigarettes compared to conventional American-blended cigarettes. PMID:25455226

  8. Toxicological assessment of kretek cigarettes Part 3: kretek and American-blended cigarettes, inhalation toxicity.

    PubMed

    Piadé, J-J; Roemer, E; Dempsey, R; Weiler, H; Meurrens, K; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    A typical Indonesian kretek cigarette brand and an experimental kretek reference cigarette were compared to the reference cigarette 2R4F in two 90-day inhalation studies. Male and female rats were exposed nose-only to mainstream smoke for 6 hours daily, for 90 consecutive days. Biological endpoints were assessed according to OECD guideline 413, with special emphasis on respiratory tract histopathology and on lung inflammation (broncho-alveolar lavage fluid levels of neutrophils, macrophages and lymphocytes). Histopathological alterations included: in the nose, hyperplasia and squamous metaplasia of the respiratory epithelium and squamous metaplasia and atrophy of the olfactory epithelium; in the larynx, epithelial squamous metaplasia and hyperplasia; in the lungs, accumulation of macrophages in alveoli and goblet cell hyperplasia in bronchial epithelium. The findings were qualitatively consistent with observations from previous similar studies on conventional cigarettes. Compared to 2R4F cigarette, however, kretek smoke exposure was associated with a pronounced attenuation of pulmonary inflammation and less severe histopathological changes in the respiratory tract. Neutrophilic inflammation was also significantly lower (>70%). These results are consistent with the observations made on smoke chemistry and in vitro toxicology. They do not support any increased toxicity of the smoke of kretek cigarettes compared to conventional American-blended cigarettes.

  9. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... possible, throughout the duration of the study, and the research sample should be stored under conditions... clinical chemistry examinations must be made on all animals, including controls, of each sex in each group. The hematology and clinical chemistry parameters should be examined at terminal sacrifice at the...

  10. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... triglycerides, hormones, methemoglobin, and cholinesterases. (iii) Optionally, the following...

  11. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements specified under EPA Good Laboratory Practice Standards at 40 CFR part 792, subpart J, the... triglycerides, hormones, methemoglobin, and cholinesterases. (iii) Optionally, the following...

  12. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of this study to humans is valid only to a limited degree. It can, however, provide useful... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the... substance (grams, milligrams), per unit body weight of test animal (milligrams per kilogram), or as...

  13. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... level. (B) If interim sacrifices are planned, the number must be increased by the number of animals... solution of oil and then solution of other vehicles. (ii) One lot of the test substance should be used, if... characterization of the test substance, including the purity......

  14. Inhalation threshold of toxicological concern (TTC) - Structural alerts discriminate high from low repeated-dose inhalation toxicity.

    PubMed

    Schüürmann, Gerrit; Ebert, Ralf-Uwe; Tluczkiewicz, Inga; Escher, Sylvia E; Kühne, Ralph

    2016-03-01

    The threshold of toxicological concern (TTC) of a compound represents an exposure value below which the associated human health risk is considered negligible. As such, this approach offers assessing the risk of potential toxicants when little or no toxicological information is available. For the inhalation repeated-dose TTC, the goal was to derive structural alerts that discriminate between high- and low-toxic compounds. A further aim was to identify physicochemical parameters related to the inhalation-specific bioavailability of the compounds, and to explore their use as predictors of high vs low toxicity. 296 compounds with subacute, subchronic and chronic inhalation toxicity NOEC (no-observed effect concentration) values were subdivided into three almost equal-sized high-, medium- and low-toxic (HTox, MTox, LTox) potency classes. Whereas the derived 14 HTox and 7 LTox structural alerts yield an only moderate discrimination between these three groups, the high-toxic vs low-toxic mis-classification is very low: LTox-predicted compounds are not HTox to 97.5%, and HTox-predicted compounds not LTox to 88.6%. The probability of a compound being HTox vs LTox is triggered further by physicochemical properties encoding the tendency to evaporate from blood. The new structural alerts may aid in the predictive inhalation toxicity assessment of compounds as well as in designing low-toxicity chemicals, and provide a rationale for the chemistry underlying the toxicological outcome that can also be used for scoping targeted experimental studies.

  15. Inhalation threshold of toxicological concern (TTC) - Structural alerts discriminate high from low repeated-dose inhalation toxicity.

    PubMed

    Schüürmann, Gerrit; Ebert, Ralf-Uwe; Tluczkiewicz, Inga; Escher, Sylvia E; Kühne, Ralph

    2016-03-01

    The threshold of toxicological concern (TTC) of a compound represents an exposure value below which the associated human health risk is considered negligible. As such, this approach offers assessing the risk of potential toxicants when little or no toxicological information is available. For the inhalation repeated-dose TTC, the goal was to derive structural alerts that discriminate between high- and low-toxic compounds. A further aim was to identify physicochemical parameters related to the inhalation-specific bioavailability of the compounds, and to explore their use as predictors of high vs low toxicity. 296 compounds with subacute, subchronic and chronic inhalation toxicity NOEC (no-observed effect concentration) values were subdivided into three almost equal-sized high-, medium- and low-toxic (HTox, MTox, LTox) potency classes. Whereas the derived 14 HTox and 7 LTox structural alerts yield an only moderate discrimination between these three groups, the high-toxic vs low-toxic mis-classification is very low: LTox-predicted compounds are not HTox to 97.5%, and HTox-predicted compounds not LTox to 88.6%. The probability of a compound being HTox vs LTox is triggered further by physicochemical properties encoding the tendency to evaporate from blood. The new structural alerts may aid in the predictive inhalation toxicity assessment of compounds as well as in designing low-toxicity chemicals, and provide a rationale for the chemistry underlying the toxicological outcome that can also be used for scoping targeted experimental studies. PMID:26735350

  16. MODELING APPROACHES FOR ESTIMATING THE DOSIMETRY OF INHALED TOXICANTS IN CHILDREN

    EPA Science Inventory

    Risk assessment of inhaled toxicants has typically focused upon adults, with modeling used to extrapolate dosimetry and risks from laboratory animals to humans. However, behavioral factors such as time spent playing outdoors can lead to more exposure to inhaled toxicants in chil...

  17. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials

    PubMed Central

    2014-01-01

    Background A standard short-term inhalation study (STIS) was applied for hazard assessment of 13 metal oxide nanomaterials and micron-scale zinc oxide. Methods Rats were exposed to test material aerosols (ranging from 0.5 to 50 mg/m3) for five consecutive days with 14- or 21-day post-exposure observation. Bronchoalveolar lavage fluid (BALF) and histopathological sections of the entire respiratory tract were examined. Pulmonary deposition and clearance and test material translocation into extra-pulmonary organs were assessed. Results Inhaled nanomaterials were found in the lung, in alveolar macrophages, and in the draining lymph nodes. Polyacrylate-coated silica was also found in the spleen, and both zinc oxides elicited olfactory epithelium necrosis. None of the other nanomaterials was recorded in extra-pulmonary organs. Eight nanomaterials did not elicit pulmonary effects, and their no observed adverse effect concentrations (NOAECs) were at least 10 mg/m3. Five materials (coated nano-TiO2, both ZnO, both CeO2) evoked concentration-dependent transient pulmonary inflammation. Most effects were at least partially reversible during the post-exposure period. Based on the NOAECs that were derived from quantitative parameters, with BALF polymorphonuclear (PMN) neutrophil counts and total protein concentration being most sensitive, or from the severity of histopathological findings, the materials were ranked by increasing toxic potency into 3 grades: lower toxic potency: BaSO4; SiO2.acrylate (by local NOAEC); SiO2.PEG; SiO2.phosphate; SiO2.amino; nano-ZrO2; ZrO2.TODA; ZrO2.acrylate; medium toxic potency: SiO2.naked; higher toxic potency: coated nano-TiO2; nano-CeO2; Al-doped nano-CeO2; micron-scale ZnO; coated nano-ZnO (and SiO2.acrylate by systemic no observed effect concentration (NOEC)). Conclusion The STIS revealed the type of effects of 13 nanomaterials, and micron-scale ZnO, information on their toxic potency, and the location and reversibility of effects

  18. Inhalation toxicity of lithium combustion aerosols in rats

    SciTech Connect

    Greenspan, B.J.; Allen, M.D.; Rebar, A.H.

    1986-01-01

    Studies of the acute inhalation toxicity of lithium combustion aerosols were undertaken to aid in evaluating the health hazards associated with the proposed use of lithium metal in fusion reactors. Male and female F344/Lov rats, 9-12 wk of age, were exposed once for 4 h to concentrations of 2600, 2300, 1400, or 620 mg/m/sup 3/ of aerosol (MMAD = 0.69 ..mu..m, sigma/sub g/ = 1.45) that was approximately 80% lithium carbonate and 20% lithium hydroxide to determine the acute toxic effects. Fourteen-day LC50 values (with 95% confidence limits) of 1700 (1300-2000) mg/m/sup 3/ for the male rats and 2000 (1700-2400) mg/m/sup 3/ for the female rate were calculated. Clinical signs of anorexia, dehydration, respiratory difficulty, and perioral and perinasal encrustation were observed. Body weights were decreased the first day after exposure in relation to the exposure concentration. In animals observed for an additional 2 wk, body weights, organ weights, and clinical signs began to return to pre-exposure values. Histopathologic examination of the respiratory tracts from the animals revealed ulcerative or necrotic laryngitis, focal to segmental ulcerative rhinitis often accompanied by areas of squamous metaplasia, and, in some cases, a suppurative bronchopneumonia or aspiration pneumonia, probably secondary to the laryngeal lesions. The results of these studies indicate the moderate acute toxicity of lithium carbonate aerosols and will aid in the risk analysis of accidental releases of lithium combustion aerosols.

  19. 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.

  20. Assessment of chronic inhalation non-cancer toxicity for diethylamine

    PubMed Central

    Grant, Roberta L.; Taiwo, Samuel O.; McCant, Darrell

    2015-01-01

    Abstract A non-cancer inhalation chronic toxicity assessment for diethylamine (DEA, CAS number 109-89-7) was conducted by the Texas Commission on Environmental Quality. A chronic Reference Value (ReV) was determined based on a high-quality study conducted in mice and rats by the National Toxicology Program. Chronic inhalation ReVs are health-based exposure concentrations used in assessing health risks of long-term (i.e. lifetime) chemical exposure. DEA is used industrially as an organic intermediate to produce corrosion inhibitors, and is widely used in rubber, pharmaceuticals, resins, pesticides, insect repellants, dye processing and as a polymerization inhibitor. Although systemic effects have been noted at higher concentrations, DEA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract. Rats were exposed to 0, 31, 62.5 and 125 ppm DEA and mice to 0, 16, 31 and 62.5 ppm DEA for 6 h/day, 5 days/week for 105 weeks. Mice were slightly more sensitive than rats. The critical effect identified in mice was hyperostosis in the turbinates although DEA caused a number of other non-neoplatic lesions. Dose–response data were suitable to benchmark concentration (BMC) modeling. The human equivalent point of departure (PODHEC) was calculated from the 95% lower limit of the BMC(10) using default duration and animal-to-human dosimetric adjustments. Total uncertainty factors of 90 were applied to the PODHEC to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and database uncertainty. The chronic ReV for DEA is 11 ppb (33 µg/m3). PMID:26671196

  1. Single and 14-day repeated dose inhalation toxicity studies of hexabromocyclododecane in rats.

    PubMed

    Song, Naining; Li, Lei; Li, Haishan; Ai, Wenchao; Xie, Wenping; Yu, Wenlian; Liu, Wei; Wang, Cheng; Shen, Guolin; Zhou, Lili; Wei, Changlei; Li, Dong; Chen, Huiming

    2016-05-01

    Limited toxicological information is available for hexabromocyclododecane (HBCD),a widely used additive brominated flame retardant. Inhalation is a major route of human exposure to HBCD. The aim of this study was to determine the acute inhalation toxicity and potential subchronic inhalation toxicity of HBCD in Sprague-Dawley rats exposed to HBCD only through inhalation. The acute inhalation toxicity of HBCD was determined using the limit test method on five male and five female Sprague-Dawley rats at a HBCD concentration of 5000 mg/m(3). Repeated-dose toxicity tests were also performed, with 20 males and 20 females randomly assigned to four experimental groups (five rats of each sex in each group). There were three treatment groups (exposed to HBCD concentrations of 125,500, and 2000 mg/m(3)) and a blank control group (exposed to fresh air). In the acute inhalation toxicity study, no significant clinical signs were observed either immediately after exposure or during the recovery period. Gross pathology examination revealed no evidence of organ-specific toxicity in any rat. The inhalation LC50(4 h) for HBCD was higher than 5312 ± 278 mg/m3 for both males and females. In the repeated dose inhalation study, daily head/nose-only exposure to HBCD at 132 ± 8.8, 545.8 ± 35.3, and 2166.0 ± 235.9 mg/m(3) for 14 days caused no adverse effects. No treatment-related clinical signs were observed at any of the test doses. The NOAEL for 14-day repeated dose inhalation toxicity study of HBCD is 2000 mg/m(3). PMID:26929994

  2. Inhalants

    MedlinePlus

    ... Drug Facts Chat Day: Inhalants Drug Facts Chat Day: Inhalants Print Can you get high off of ... Cool Order Free Materials National Drugs & Alcohol Chat Day Newsletter Sign up to receive National Drug & Alcohol ...

  3. Towards a 90-Day Monthly Storm Outlook for Alaska

    NASA Astrophysics Data System (ADS)

    Partain, J. L.

    2011-12-01

    In all seasons, storms represent high-impact weather events in Alaska. Alaska's extensive coastline makes the region especially vulnerable to coastal flooding and erosion, particularly where a protective sea ice buffer is absent. There exists a major need for an expanded temporal range of storm outlooks to enable proactive responses by coastal communities and the various industries noted above. The expansion envisioned here is to the 90-day range. The NOAA Climate Prediction Center's (CPC) Storm Tracks website presently includes summaries of storm tracks and accumulated precipitation for the past 10-, 30- and 90-day periods, together with Week-1 and Week-2 forecast storm tracks from the Global Forecast System's (GFS) operational run and the GFS ensemble. Given the limits of deterministic predictability, we will extend the window of the storm outlook to 90 days by drawing upon the present and CPC-predicted states of ENSO, the Pacific Decadal Oscillation, and the Arctic Oscillation -- three large-scale modes of variability known to affect Alaska. In order to link the large-scale modes of variability to storm probabilities in various Alaskan sub-regions, we will explore the use of composites and analog years based on the states of the major teleconnection modes. This presentation will include an end-to-end plan for the development and testing of this product.

  4. Photochemical Reaction Altered Cardiac Toxicity of Diesel Exhaust Inhalation

    EPA Science Inventory

    Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled diesel exhaust and compared with photochemically altered d...

  5. Subchronic inhalation toxicity of benzene in rats and mice.

    PubMed

    Ward, C O; Kuna, R A; Snyder, N K; Alsaker, R D; Coate, W B; Craig, P H

    1985-01-01

    A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion

  6. An interesting case of characteristic methanol toxicity through inhalational exposure

    PubMed Central

    Kumar, Pratyush; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2015-01-01

    Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID:26285665

  7. Safety assessment of meat from transgenic cattle by 90-day feeding study in rats.

    PubMed

    Liu, Shan; Li, Chen-Xi; Feng, Xiao-Lian; Wang, Hui-Ling; Liu, Hai-Bo; Zhi, Yuan; Geng, Gui-Ying; Zhao, Jie; Xu, Hai-Bin

    2013-07-01

    The study was carried out to evaluate the subchronic toxicity of meat derived from human lactoferrin gene-modified cattle in male and female Wistar rats. Rats were fed 5% or 10% transgenic meat diet, 5% or 10% conventional meat diet, or AIN93G diet for 90 days. During the study, body weight and food consumption were weighed weekly and clinical observations were conducted daily. At the end of the study, urinary examination, hematology and blood biochemistry examination, macroscopic and microscopic examinations were performed. There were no biologically significant differences in these factors between the rat groups fed transgenic meat diet and conventional meat diet. Therefore, the present 90-day rodent feeding study suggests that meat derived from the transgenic cattle is equivalent to meat from conventional cattle in use as dietary supplements.

  8. Toxicological assessment of kretek cigarettes Part 5: mechanistic investigations, inhalation toxicity.

    PubMed

    Roemer, E; Dempsey, R; Van Overveld, F J; Berges, A; Pype, J; Weiler, H; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    The biological effects of mainstream smoke (MS) from Indonesian-blended cigarettes with and without added cloves, cloves extracted with hot ethanol, and extracted cloves replenished with eugenol or clove oil were assessed in a 90-day inhalation study in rats. A separate 35-day inhalation study in rats was performed with MS from American-blended cigarettes with 0%, 2.5%, 5% or 10% added eugenol. Effects commonly seen in inhalation studies with MS were observed. These included histopathological changes indicative of irritation in the entire respiratory tract and inflammatory responses in the lung. Adding cloves to American- or Indonesian-blended cigarettes reduced the inflammatory response in the lung but with no difference between the two blend types. When the clove oil was extracted (∼ 75% reduction of eugenol achieved) from cloves, the inflammatory response in the lung was still reduced similarly to whole cloves but the severity of histopathological changes in the upper respiratory tract was less reduced. Add back of clove oil or pure eugenol reduced this response to a level similar to what was seen with whole cloves. When eugenol was added to American-blended cigarettes, similar findings of reduced lung inflammation and severity of histopathological changes in respiratory the tract was confirmed. These studies demonstrate a clear effect of cloves, and in particular eugenol, in explaining these findings. PMID:25455231

  9. Toxicological assessment of kretek cigarettes Part 5: mechanistic investigations, inhalation toxicity.

    PubMed

    Roemer, E; Dempsey, R; Van Overveld, F J; Berges, A; Pype, J; Weiler, H; Vanscheeuwijck, P; Schorp, M K

    2014-12-01

    The biological effects of mainstream smoke (MS) from Indonesian-blended cigarettes with and without added cloves, cloves extracted with hot ethanol, and extracted cloves replenished with eugenol or clove oil were assessed in a 90-day inhalation study in rats. A separate 35-day inhalation study in rats was performed with MS from American-blended cigarettes with 0%, 2.5%, 5% or 10% added eugenol. Effects commonly seen in inhalation studies with MS were observed. These included histopathological changes indicative of irritation in the entire respiratory tract and inflammatory responses in the lung. Adding cloves to American- or Indonesian-blended cigarettes reduced the inflammatory response in the lung but with no difference between the two blend types. When the clove oil was extracted (∼ 75% reduction of eugenol achieved) from cloves, the inflammatory response in the lung was still reduced similarly to whole cloves but the severity of histopathological changes in the upper respiratory tract was less reduced. Add back of clove oil or pure eugenol reduced this response to a level similar to what was seen with whole cloves. When eugenol was added to American-blended cigarettes, similar findings of reduced lung inflammation and severity of histopathological changes in respiratory the tract was confirmed. These studies demonstrate a clear effect of cloves, and in particular eugenol, in explaining these findings.

  10. Clinical expert panel on monitoring potential lung toxicity of inhaled oligonucleotides: consensus points and recommendations.

    PubMed

    Alton, Eric W; Boushey, Homer A; Garn, Holger; Green, Francis H; Hodges, Michael; Martin, Richard J; Murdoch, Robert D; Renz, Harald; Shrewsbury, Stephen B; Seguin, Rosanne; Johnson, Graham; Parry, Joel D; Tepper, Jeff; Renzi, Paolo; Cavagnaro, Joy; Ferrari, Nicolay

    2012-08-01

    Oligonucleotides (ONs) are an emerging class of drugs being developed for the treatment of a wide variety of diseases including the treatment of respiratory diseases by the inhalation route. As a class, their toxicity on human lungs has not been fully characterized, and predictive toxicity biomarkers have not been identified. To that end, identification of sensitive methods and biomarkers that can detect toxicity in humans before any long term and/or irreversible side effects occur would be helpful. In light of the public's greater interests, the Inhalation Subcommittee of the Oligonucleotide Safety Working Group (OSWG) held expert panel discussions focusing on the potential toxicity of inhaled ONs and assessing the strengths and weaknesses of different monitoring techniques for use during the clinical evaluation of inhaled ON candidates. This white paper summarizes the key discussions and captures the panelists' perspectives and recommendations which, we propose, could be used as a framework to guide both industry and regulatory scientists in future clinical research to characterize and monitor the short and long term lung response to inhaled ONs.

  11. Inhalation toxicity of soman vapor in non-anesthetized rats: a preliminary assessment of inhaled bronchodilator or steroid therapy.

    PubMed

    Perkins, Michael W; Wong, Benjamin; Rodriguez, Ashley; Devorak, Jennifer L; Alves, Derron A; Murphy, Gleeson; Sciuto, Alfred M

    2013-12-01

    Respiratory toxicity, injury and treatment following vapor inhalational exposure to the chemical warfare nerve agent (CWNA) soman (GD) were examined in non-anesthetized rats. This study exposed male Sprague-Dawley rats (250-300g) to 520, 560, 600, 825 or 1410mg×min/m(3) of soman in a customized head-out inhalation system. Signs of CWNA-induced cholinergic crises were observed in all soman-exposed animals. The LCt50 of vaporized soman as determined by probit analysis was 593.1mg×min/m(3). All animals exposed to 825 and 1410mg×min/m(3) developed severe convulsions and died within 4-8min post-exposure. Edema measured by wet/dry weight ratio of the left lung lobe increased in a dose-dependent manner in all soman-exposed animals. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase (AChE) activities were inhibited dose-dependently in soman-exposed groups at 24h. A significant increase in total BAL protein was observed in soman-exposed animals at all doses. AChE activity was inhibited in lung and whole brain tissues in all soman-exposed animals. Histopathological analysis of the lungs of animals exposed to 600mg×min/m(3) of soman revealed prominent morphological changes including alveolar histiocytosis, hemorrhage and inflammation consisting of neutrophilic exudate. Exposure of animals to 600mg×min/m(3) of soman followed by treatment with two actuations for 10s of Combivent (21μg of ipratropium bromide and 120μg of albuterol sulfate) and Symbicort (80μg budesonide and 4.5μg formoterol) by inhalation into a modified metered dose inhaler (MDI) 10min post-exposure resulted in increased minute volume, but did not decrease mortality. These results indicate that inhalation exposure to soman vapor causes acute respiratory toxicity and injury in untreated, un-anesthetized rats and that inhalation treatment with Combivent or Symbicort did improve the respiratory outcomes, but did not influence lethality. PMID:23886498

  12. Inhalants

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

  13. Toxicity of inhaled plutonium dioxide in beagle dogs

    SciTech Connect

    Muggenburg, M.A.; Guilmette, R.A.; Mewhinney, J.A.

    1996-03-01

    This study was conducted to determine the biological effects of inhaled {sup 238}PuO{sub 2} over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of {sup 238}PuO{sub 2} to achieve graded levels of initial lung burden (ILB). The aerosols also contained {sup 169}Yb to provide a {gamma}-ray-emitting label for the {sup 238}Pu inhaled by each dog. Excreta were collected periodically over each dog`s life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest {alpha}-particle doses, ranging from 0.16-68 Gy for the liver. At death, all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to {sup 238}PuO{sub 2}. 89 refs., 10 figs., 11 tab.

  14. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    NASA Technical Reports Server (NTRS)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  15. Assessment of Airborne Particles. Fundamentals, Applications, and Implications to Inhalation Toxicity.

    ERIC Educational Resources Information Center

    Mercer, Thomas T., Ed.; And Others

    Concern over chemical and radioactive particulate matter in industry and over rapidly increasing air pollution has stimulated research both on the properties of airborne particles and methods for assessing them and on their biological effects following inhalation. The Third Rochester International Conference on Environmental Toxicity was,…

  16. Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

    PubMed

    Yeager, R Philip; Kushman, Mary; Chemerynski, Susan; Weil, Roxana; Fu, Xin; White, Marcella; Callahan-Lyon, Priscilla; Rosenfeldt, Hans

    2016-06-01

    This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease. PMID:26969371

  17. Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

    PubMed

    Yeager, R Philip; Kushman, Mary; Chemerynski, Susan; Weil, Roxana; Fu, Xin; White, Marcella; Callahan-Lyon, Priscilla; Rosenfeldt, Hans

    2016-06-01

    This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease.

  18. Inhalants

    MedlinePlus

    ... or LSD. But you may not realize the dangers of substances in your own home. Household products such as glues, hair sprays, paints and lighter fluid can be drugs for kids in search of a quick high. Many young people ... need to know the dangers. Even inhaling once can disrupt heart rhythms and ...

  19. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    PubMed Central

    Bakand, Shahnaz; Hayes, Amanda

    2016-01-01

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture. PMID:27314324

  20. Lung deposition analyses of inhaled toxic aerosols in conventional and less harmful cigarette smoke: a review.

    PubMed

    Kleinstreuer, Clement; Feng, Yu

    2013-09-23

    Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions.

  1. Lung Deposition Analyses of Inhaled Toxic Aerosols in Conventional and Less Harmful Cigarette Smoke: A Review

    PubMed Central

    Kleinstreuer, Clement; Feng, Yu

    2013-01-01

    Inhaled toxic aerosols of conventional cigarette smoke may impact not only the health of smokers, but also those exposed to second-stream smoke, especially children. Thus, less harmful cigarettes (LHCs), also called potential reduced exposure products (PREPs), or modified risk tobacco products (MRTP) have been designed by tobacco manufacturers to focus on the reduction of the concentration of carcinogenic components and toxicants in tobacco. However, some studies have pointed out that the new cigarette products may be actually more harmful than the conventional ones due to variations in puffing or post-puffing behavior, different physical and chemical characteristics of inhaled toxic aerosols, and longer exposure conditions. In order to understand the toxicological impact of tobacco smoke, it is essential for scientists, engineers and manufacturers to develop experiments, clinical investigations, and predictive numerical models for tracking the intake and deposition of toxicants of both LHCs and conventional cigarettes. Furthermore, to link inhaled toxicants to lung and other diseases, it is necessary to determine the physical mechanisms and parameters that have significant impacts on droplet/vapor transport and deposition. Complex mechanisms include droplet coagulation, hygroscopic growth, condensation and evaporation, vapor formation and changes in composition. Of interest are also different puffing behavior, smoke inlet conditions, subject geometries, and mass transfer of deposited material into systemic regions. This review article is intended to serve as an overview of contributions mainly published between 2009 and 2013, focusing on the potential health risks of toxicants in cigarette smoke, progress made in different approaches of impact analyses for inhaled toxic aerosols, as well as challenges and future directions. PMID:24065038

  2. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... actual concentration of the test substance shall be measured in the breathing zone. During the exposure... found dead and isolation or sacrifice of weak or moribund animals). (iii) Signs of toxicity shall be... from dead animals if autolysis or where decomposition has occurred. The degree of resorption shall...

  3. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... actual concentration of the test substance shall be measured in the breathing zone. During the exposure... found dead and isolation or sacrifice of weak or moribund animals). (iii) Signs of toxicity shall be... from dead animals if autolysis or where decomposition has occurred. The degree of resorption shall...

  4. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... actual concentration of the test substance shall be measured in the breathing zone. During the exposure... found dead and isolation or sacrifice of weak or moribund animals). (iii) Signs of toxicity shall be... from dead animals if autolysis or where decomposition has occurred. The degree of resorption shall...

  5. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... actual concentration of the test substance shall be measured in the breathing zone. During the exposure... found dead and isolation or sacrifice of weak or moribund animals). (iii) Signs of toxicity shall be... from dead animals if autolysis or where decomposition has occurred. The degree of resorption shall...

  6. Acute inhalation toxicity and sensory irritation of dimethylamine. [Rats, mice

    SciTech Connect

    Steinhagen, W.H.; Swenberg, J.A.; Barrow, C.S.

    1982-06-01

    The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC/sub 50/ for rats exposed to dimetylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The six hour LC/sub 50/ was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

  7. Inhaled toxic agents: An evaluation of dose. Final report

    SciTech Connect

    Hanna, L.M.

    1993-01-01

    A mathematical model was developed for the absorption of gases or vapors in the respiratory tract for use in determining the dose of inhaled gases and vapors to the airways of an individual and to extrapolate doses from animals to human subjects. The physical and chemical properties of the gas or vapor determine its absorption and must be considered in extrapolation between species. The method developed depends on determining the dimensions of the airspace surrounding each turbinate and assumes the airspace is geometrically similar to an annulus or a duct. The method may be used to quantify regional variability in airway dimensions of a population. Casted models of air passages made from cadavers were also studied and found to differ significantly from those of living human subjects. The extrapolations made using these cadaver models may not accurately reveal the flow and deposition rates found in living persons. Measurements which were made from hand traced images of airway dimensions were significantly different from measurements made with an image analyzer in which the digital data containing the scanned images were downloaded to the analyzer.

  8. Cold blast furnace syndrome: a new source of toxic inhalation by nitrogen oxides

    PubMed Central

    Tague, I; Llewellin, P; Burton, K; Buchan, R; Yates, D

    2004-01-01

    Methods: Fourteen workers developed acute respiratory symptoms shortly after exposure to "air blast" from blast furnace tuyeres. These included chest tightness, dyspnoea, rigors, and diaphoresis. Chest radiographs showed pulmonary infiltrates, and lung function a restrictive abnormality. This report includes a description of clinical features of the affected workers and elucidation of the probable cause of the outbreak. Results: Clinical features and occupational hygiene measurements suggested the most likely cause was inhalation of nitrogen oxides at high pressure and temperature. While the task could not be eliminated, engineering controls were implemented to control the hazard. No further cases have occurred. Conclusions: "Cold blast furnace syndrome" represents a previously undescribed hazard of blast furnace work, probably due to inhalation of nitrogen oxides. It should be considered in the differential diagnosis of acute toxic inhalational injuries in blast furnace workers. PMID:15090669

  9. Inhalation toxicity of 316L stainless steel powder in relation to bioaccessibility.

    PubMed

    Stockmann-Juvala, H; Hedberg, Y; Dhinsa, N K; Griffiths, D R; Brooks, P N; Zitting, A; Wallinder, I Odnevall; Santonen, T

    2013-11-01

    The Globally Harmonized System for Classification and Labelling of Chemicals (GHS) considers metallic alloys, such as nickel (Ni)-containing stainless steel (SS), as mixtures of substances, without considering that alloys behave differently compared to their constituent metals. This study presents an approach using metal release, explained by surface compositional data, for the prediction of inhalation toxicity of SS AISI 316L. The release of Ni into synthetic biological fluids is >1000-fold lower from the SS powder than from Ni metal, due to the chromium(III)-rich surface oxide of SS. Thus, it was hypothesized that the inhalation toxicity of SS is significantly lower than what could be predicted based on Ni metal content. A 28-day inhalation study with rats exposed to SS 316L powder (<4 µm, mass median aerodynamic diameter 2.5-3.0 µm) at concentrations up to 1.0 mg/L showed accumulation of metal particles in the lung lobes, but no signs of inflammation, although Ni metal caused lung toxicity in a similar published study at significantly lower concentrations. It was concluded that the bioaccessible (released) fraction, rather than the elemental nominal composition, predicts the toxicity of SS powder. The study provides a basis for an approach for future validation, standardization and risk assessment of metal alloys.

  10. Lung inflammation caused by inhaled toxicants: a review

    PubMed Central

    Wong, John; Magun, Bruce E; Wood, Lisa J

    2016-01-01

    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID:27382275

  11. Lung inflammation caused by inhaled toxicants: a review.

    PubMed

    Wong, John; Magun, Bruce E; Wood, Lisa J

    2016-01-01

    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. PMID:27382275

  12. The toxicity of inhaled particles of sup 238 PuO sub 2 in dogs

    SciTech Connect

    Muggenburg, B.A.; Guilmette, R.A.; Griffith, W.C. Jr.; Hahn, F.F.; Boecker, B.B. . Inhalation Toxicology Research Inst.); Gillett, N.A. )

    1991-01-01

    This study was conducted to determine the toxicity of inhaled {sup 238}PuO{sub 2} in the dog. Inhalation was selected because it is the mostly likely route of human exposure in the event of an accidental airborne release. Of 166 dog in the study, 72 inhaled 1.5{mu}m and 72 inhaled 3.0 {mu}m activity median aerodynamic diameter particles of {sup 238}PuO{sub 2}. Another 24 dogs inhaled the aerosol vector without plutonium. The aerosol exposures resulted in initial pulmonary burdens ranging from 37 to 0.11 and 55.5 to 0.37 kBq of {sup 238}Pu/kg body mass, of 1.5 {mu}m and 3.0 {mu}, particles, respectively. The particles dissolved slowly resulting in translocation of the Pu to liver, bone and other sites. The dogs were observed for biological effects over their life span. Necropsies were performed at death, and tissues were examined microscopically. The principal late-occurring effects were tumors of the lung, skeleton, and liver. Risk factors estimated for these cancers were 2800 lung cancers/10{sup 4} Gy, 800 liver cancers/10{sup 4} Gy, and 6200 bone cancers/10{sup 4} Gy for dogs. The potential hazard from {sup 238}Pu to humans may include tumors of the lung, bone and liver because of the likelihood of similarity of the dose patterns for the two species. 10 refs., 1 fig., 3 tabs.

  13. Toxicity of lunar dust assessed in inhalation-exposed rats

    PubMed Central

    Lam, Chiu-wing; Scully, Robert R.; Zhang, Ye; Renne, Roger A.; Hunter, Robert L.; McCluskey, Richard A.; Chen, Bean T.; Castranova, Vincent; Driscoll, Kevin E.; Gardner, Donald E.; McClellan, Roger O.; Cooper, Bonnie L.; McKay, David S.; Marshall, Linda; James, John T.

    2015-01-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m3. This 4-week exposure study in rats showed that 6.8 mg/m3 was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats. PMID:24102467

  14. Toxicity of lunar dust assessed in inhalation-exposed rats.

    PubMed

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats. PMID:24102467

  15. Toxicity of lunar dust assessed in inhalation-exposed rats.

    PubMed

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  16. Inhalation toxicity and carcinogenicity studies of cobalt sulfate.

    PubMed

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J

    1999-05-01

    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  17. MODULAR APPLICATION OF COMPUTATIONAL MODELS OF INHALED REACTIVE GAS DOSIMETRY FOR RISK ASSESSMENT OF RESPIRATORY TRACT TOXICITY: CHLORINE

    EPA Science Inventory

    Inhaled reactive gases typically cause respiratory tract toxicity with a prominent proximal to distal lesion pattern. This pattern is largely driven by airflow and interspecies differences between rodents and humans result from factors such as airway architecture, ventilation ra...

  18. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing.

  19. An in vitro method for predicting inhalation toxicity of impregnation spray products.

    PubMed

    Sørli, Jorid B; Hansen, Jitka S; Nørgaard, Asger W; Levin, Marcus; Larsen, Søren T

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases are reported frequently. The toxicity appears to be driven by a disruption of the pulmonary surfactant film, which coats the inside of the lungs. Due to the complex chemistry of impregnation spray products, it is impossible to predict if inhalation of an aerosolized product is toxic in vivo. The aim of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film-forming compounds, were identified by mass spectrometry. We used a capillary surfactometry method to assess disruption of pulmonary surfactant function in vitro and a mouse model to evaluate acute respiratory toxicity during inhalation. Concentration-response relationships were successfully determined both in vitro and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing. PMID:25651757

  20. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  1. Emergency planning and the acute toxic potency of inhaled ammonia.

    PubMed

    Michaels, R A

    1999-08-01

    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.

  2. 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

  3. Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2011-07-01

    Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

  4. Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats.

    PubMed

    Holson, J F; Stump, D G; Ulrich, C E; Farr, C H

    1999-09-01

    A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant.

  5. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-01-01

    We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity. PMID:27490535

  6. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

    PubMed

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-01-01

    We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity. PMID:27490535

  7. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    SciTech Connect

    Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Sciuto, Alfred M.; Nambiar, Madhusoodana P.

    2010-06-01

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  8. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

    PubMed

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-08-01

    We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

  9. Acute toxicity of T2 mycotoxin to the guinea-pig by inhalation and subcutaneous routes.

    PubMed Central

    Marrs, T. C.; Edginton, J. A.; Price, P. N.; Upshall, D. G.

    1986-01-01

    The acute inhalation and subcutaneous toxicity of T2 mycotoxin has been investigated in guinea-pigs. The toxicity by the two routes was quantitatively and qualitatively similar. The LCt50 was 5749 mg min m-3 and the subcutaneous LD50 1-2 mg kg-1. Histological changes in the decedents which were similar by both routes of administration were most marked in the lymphoreticular system but also occurred in the gut. Lymphocytolysis and phagocytosis occurred in both the cortex of the thymus and of the lymph nodes. Lymph nodes were more severely affected in the decedents among the animals dosed with T2 by the subcutaneous route. The small intestine exhibited dead and dying cells throughout the lamina propria after T2 by either route. Images Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 2 Fig. 3 PMID:3707855

  10. Carbon monoxide and cyanide toxicity: etiology, pathophysiology and treatment in inhalation injury.

    PubMed

    Huzar, Todd F; George, Tonya; Cross, James M

    2013-04-01

    Inhalation injury is most commonly associated with damage to the mucosal surfaces of the small and large airways after exposure to smoke and other products of incomplete combustion. Yet, there are far deadlier things lurking within the smoke than just the heat and particulate matter: carbon monoxide and cyanide. These two toxic substances are found in varying concentrations within the fire room and are associated with early on-scene death and in-hospital morbidity and mortality. Patients suffering from carbon monoxide and/or cyanide poisoning present with vague symptoms requiring an astute physician to make the diagnosis. Fortunately, the toxic effects related to exposure to these agents can be reversed with readily available antidotes.

  11. Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs.

    PubMed

    Hulet, Stanley W; Sommerville, Douglas R; Miller, Dennis B; Scotto, Jacqueline A; Muse, William T; Burnett, David C

    2014-02-01

    Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.

  12. Improved dispersion method of multi-wall carbon nanotube for inhalation toxicity studies of experimental animals.

    PubMed

    Taquahashi, Yuhji; Ogawa, Yukio; Takagi, Atsuya; Tsuji, Masaki; Morita, Koichi; Kanno, Jun

    2013-01-01

    A multi-wall carbon nanotube (MWCNT) product Mitsui MWNT-7 is a mixture of dispersed single fibers and their agglomerates/aggregates. In rodents, installation of such mixture induces inflammatory lesions triggered predominantly by the aggregates/agglomerates at the level of terminal bronchiole of the lungs. In human, however, pulmonary toxicity induced by dispersed single fibers that reached the lung alveoli is most important to assess. Therefore, a method to generate aerosol predominantly consisting of dispersed single fibers without changing their length and width is needed for inhalation studies. Here, we report a method (designated as Taquann method) to effectively remove the aggregate/agglomerates and enrich the well-dispersed singler fibers in dry state without dispersant and without changing the length and width distribution of the single fibers. This method is base on two major concept; liquid-phase fine filtration and critical point drying to avoid re-aggregation by surface tension. MWNT-7 was suspended in Tert-butyl alcohol, freeze-and-thawed, filtered by a vibrating 25 µm mesh Metallic Sieve, snap-frozen by liquid nitrogen, and vacuum-sublimated (an alternative method to carbon dioxide critical point drying). A newly designed direct injection system generated well-dispersed aerosol in an inhalation chamber. The lung of mice exposed to the aerosol contained single fibers with a length distribution similar to the original and the Taquann-treated sample. Taquann method utilizes inexpensive materials and equipments mostly found in common biological laboratories, and prepares dry powder ready to make well-dispersed aerosol. This method and the chamber with direct injection system would facilitate the inhalation toxicity studies more relevant to human exposure.

  13. Chlorosilane acute inhalation toxicity and development of an LC50 prediction model.

    PubMed

    Jean, Paul A; Gallavan, Robert H; Kolesar, Gary B; Siddiqui, Waheed H; Oxley, Jon A; Meeks, Robert G

    2006-07-01

    The acute inhalation toxicity of 10 chlorosilanes was investigated in Fischer 344 rats using a 1-h whole-body vapor inhalation exposure and a 14-day recovery period. The median lethal concentration (LC50(1)) for each material was calculated from the nominal exposure concentrations and mortality. Experimentally derived LC50(1) values for monochlorosilanes (4257-4478 ppm) were greater than those for dichlorosilanes (1785-2092 ppm), which were greater than those for trichlorosilanes (1257-1611 ppm). Apparent was a strong structure-activity relationship (r2 = .97) between chlorine content and LC50(1) value. Estimated LC50(1) values for mono-, di-, and trichlorosilanes were determined to be 3262, 1639, and 1066 ppm, respectively, utilizing this relationship and the lower limit of the 95% prediction interval. The LC50(1) values determined in this series of studies were greater than that reported for hydrogen chloride (3124 ppm), when expressed on a chlorine equivalence basis (3570-5248 ppm), demonstrating that the acute toxicity of these chlorosilanes is similar to or less than that for hydrogen chloride. The good correlation between chlorine content and LC50(1) provides a sound basis for estimation of LC50(1) for chlorosilanes not already evaluated. The use of structure-activity relationships is consistent with the chemical industry and federal agency initiatives to reduce, refine, and/or replace the use of animals in testing without compromising the quality of health and safety assessments.

  14. Acute inhalation toxicity of smoke of fentanyl and its 1-substituted analogs in Swiss albino mice.

    PubMed

    Yadav, S K; Swami, D; Kumar, P; Meena, M K; Maurya, C K; Gupta, P K; Ganesan, K; Jain, A K; Bhattacharya, R

    2014-01-01

    Fentanyl (N-(1-phenethyl-4-piperidinyl)propionanilide) is a synthetic, potent narcotic analgesic agent. However, it is known to have several side effects, which led to synthesis and evaluation of its new analogs for the management of pain. We have earlier reported the comparative bioassay of fentanyl and its eight 1-substituted analogs (1-8) in mice. Three compounds, viz., N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the comparative acute inhalation toxicity of smoke of fentanyl and its three analogs, viz., 2, 5, and 6 in mice. Animals were exposed to different concentrations of smoke generated by heating the compounds. Exposure was performed in a head only all glass static exposure assembly for 15 min to determine the median lethal concentration (LC50). The breathing pattern and various respiratory parameters of the animals were also monitored online using a polygraph. Out of three compounds tested, analog 5 was found to be most toxic (LC50 = 2820 mg/m3) while 2 was least toxic (LC50 = >8000 mg/m3). All the compounds caused long lasting respiratory depression in a dose-dependent manner, which did not completely resolve even after discontinuation of exposure. Aerodynamic median diameter and geometric standard deviation of smoke particles was determined employing eight-stage Andersen sampler. The particles were found to be within the respirable range. The study, however, concludes that due to possible decomposition of the compounds by heating or its poor absorption by the alveolar surface, the present inhalation technique cannot be employed to generate smoke of fentanyl and its analogs for any medical or surreptitious use. PMID:25208041

  15. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Exception to 90-day rule in special cash... Exception to 90-day rule in special cash account. (a) The Board of Governors has recently interpreted... stock in a special cash account with a member firm on Day 1. On Day 3 customer sold the same stock at...

  16. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  17. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  18. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 3 2013-04-01 2013-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  19. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  20. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 3 2014-04-01 2014-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  1. Household insecticides: evaluation and assessment of inhalation toxicity: a workshop summary.

    PubMed

    Achmadi, U F; Pauluhn, J

    1998-03-01

    from that utilising a daily exposure. 3) In certain instances, inhalation testing of shorter duration, for example 2 or 4 weeks, may be appropriate if the inhalation toxicity of the basic formula has already been characterised or the major constituents contained in the formulation have been examined in extant studies. The duration of study should also depend on actual use and exposure pattern, the accumulation potential and the mode of action of the ingredients of concern. 4) Particularly for mosquito coil smokes, the possible physico-chemical interactions of particulates, potentially irritant water soluble or nonsoluble vapours and aerosol or vapours of the active ingredient(s) are virtually impossible to predict without appropriate inhalation testing. 5) Physiological measurements may be useful for the detection and quantification of the respiratory tract sensory irritation potency. Biochemical endpoints in lung lavage and conventional histopathology of the lungs and extrathoracic airways are considered to be important. 6) It has been agreed that the nose-only exposure technique provides the most cost-effective and controlled means to expose small laboratory animals to well defined atmospheres as long as the limitations of this technique are taken into account.

  2. Per- and polyfluoro toxicity (LC(50) inhalation) study in rat and mouse using QSAR modeling.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2010-03-15

    Fully or partially fluorinated compounds, known as per- and polyfluorinated chemicals are widely distributed in the environment and released because of their use in different household and industrial products. Few of these long chain per- and polyfluorinated chemicals are classified as emerging pollutants, and their environmental and toxicological effects are unveiled in the literature. This has diverted the production of long chain compounds, considered as more toxic, to short chains, but concerns regarding the toxicity of both types of per- and polyfluorinated chemicals are alarming. There are few experimental data available on the environmental behavior and toxicity of these compounds, and moreover, toxicity profiles are found to be different for the types of animals and species used. Quantitative structure-activity relationship (QSAR) is applied to a combination of short and long chain per- and polyfluorinated chemicals, for the first time, to model and predict the toxicity on two species of rodents, rat (Rattus) and mouse (Mus), by modeling inhalation (LC(50)) data. Multiple linear regression (MLR) models using the ordinary-least-squares (OLS) method, based on theoretical molecular descriptors selected by genetic algorithm (GA), were used for QSAR studies. Training and prediction sets were prepared a priori, and these sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the model was verified on a larger set of per- and polyfluorinated chemicals retrieved from different databases and journals. The descriptors involved, the similarities, and the differences observed between models pertaining to the toxicity related to the two species are discussed. Chemometric methods such as principal component analysis (PCA) and multidimensional scaling (MDS) were used to select most toxic compounds from those within the AD of both models, which will be subjected to experimental tests

  3. Lack of selective developmental toxicity of three butanol isomers administered by inhalation to rats.

    PubMed

    Nelson, B K; Brightwell, W S; Khan, A; Burg, J R; Goad, P T

    1989-04-01

    As part of an ongoing study of the developmental toxicology of industrial alcohols, this report presents the results of the teratology assessments of 1-butanol, 2-butanol, and t-butanol administered by inhalation to rats. Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm 1-butanol, 7000, 5000, 3500, or 0 ppm 2-butanol, or 5000, 3500, 2000, or 0 ppm t-butanol for 7 hr/day on Gestation Days 1-19 (sperm = 0). In each case, the highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique. For each butanol isomer examined, the highest concentration (and the intermediate in some cases) was maternally toxic, as manifest by reduced weight gain and feed intake. Even at a maternally toxic dose, and in spite of a dose-dependent reduction in fetal weights for each isomer, the only teratogenicity observed was a slight increase in skeletal malformations (primarily rudimentary cervical ribs), seen with the highest concentration of 1-butanol. Thus, although teratogenicity was observed at 8000 ppm 1-butanol, and developmental toxicity was observed with each of the butyl alcohol isomers studied, concentrations 50 times the current permissible exposure limits for these three butanol isomers do not produce teratogenicity in rats.

  4. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

    PubMed

    Schreiner, C; Lapadula, E; Breglia, R; Bui, Q; Burnett, D; Koschier, F; Podhasky, P; White, R; Mandella, R; Hoffman, G

    1998-10-23

    A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

  5. 4-Phenylcyclohexene: 2-week inhalation toxicity and neurotoxicity studies in Swiss-Webster mice.

    PubMed

    Beekman, M J; Maurissen, J P; Johnson, K A

    1996-09-01

    4-Phenylcyclohexene (4-PCH) is a by-product formed during the polymerization of styrene-butadiene latex used in carpet backing. Limited reports suggest that exposure to very low levels of 4-PCH or other emission products following new carpet installation may result in health complaints. Significantly, it has been claimed that Swiss-Webster mice held in neck restraints and exposed head-only to approximately 0.4 ppm 4-PCH for a few hours suffered severe toxicity including death. A 2-wk inhalation and neurotoxicity study was therefore conducted in Swiss-Webster mice using standard methods of toxicity testing. Groups of 40 mice were exposed to 0, 7, 18 or 71 ppm (near-saturated atmosphere) 4-PCH vapour, 6 hr/day for 9 consecutive days. Data were collected on a wide variety of clinical, neurological and histopathological parameters including extensive neurohistopathology. All animals survived the exposures, and there were no treatment-related effects. Because of the occurrence of spontaneous lesions in two high-dose group mice, 40 additional males were exposed to 0 ppm or a near-saturated atmosphere of 4-PCH under the same exposure regimen. No treatment-related lesions were observed in the follow-up study, confirming the conclusions of the original study. These findings, consistent with the reported lack of toxicity of inhaled 4-PCH in rats, do not suggest a direct, organic, association between low-level 4-PCH exposure and human complaints. Further, the results of this study suggest that positive findings in mice may have been due to methodological problems and not to exposure to 4-PCH.

  6. Evaluation of potential for toxicity from subacute inhalation of tire and road wear particles in rats.

    PubMed

    Kreider, Marisa L; Doyle-Eisele, Melanie; Russell, Robert G; McDonald, Jacob D; Panko, Julie M

    2012-11-01

    Tire and road wear particles (TRWP) are a component of ambient particulate matter (PM) produced from the interaction of tires with the roadway. Inhalation of PM has been associated with cardiopulmonary morbidities and mortalities thought to stem from pulmonary inflammation. To determine whether TRWP may contribute to these events, the effects of subacute inhalation of TRWP were evaluated in rats. TRWP were collected at a road simulator laboratory, aerosolized, and used to expose male and female Sprague-Dawley rats (n = 10/treatment group) at ~10, 40, or 100 μg/m³ TRWP via nose-only inhalation for 6 h/day for 28 days. Particle size distribution of the aerosolized TRWP was found to be within the respirable range for rats. Toxicity was assessed following OECD guidelines (TG 412). No TRWP-related effects were observed on survival, clinical observations, body or organ weights, gross pathology, food consumption, immune system endpoints, serum chemistry, or biochemical markers of inflammation or cytotoxicity. Rare to few focal areas of subacute inflammatory cell infiltration associated with TWRP exposure were observed in the lungs of one mid and four high exposure animals, but not the low-exposure animals. These alterations were minimal, widely scattered and considered insufficient in extent or severity to have an impact on pulmonary function. Furthermore, it is expected that these focal lesions would remain limited and may undergo resolution without long-term or progressive pulmonary alterations. Therefore, from this study we identified a no-observable-adverse-effect-level (NOAEL) of 112 μg/m³ of TRWP in rats for future use in risk assessment of TRWP.

  7. A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats

    PubMed Central

    Singh, Pooja; Chacko, K. Mathai; Aggarwal, M. L.; Bhat, Binu; Khandal, R. K.; Sultana, Sarwat; Kuruvilla, Binu T.

    2012-01-01

    The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt. PMID:23293466

  8. Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation.

    PubMed

    Yang, Young-Su; Kwon, Jung-Taek; Shim, Ilseob; Kim, Hyun-Mi; Kim, Pilje; Kim, Jong-Choon; Lee, Kyuhong

    2015-03-01

    The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.

  9. Odorless inhalant toxic encephalopathy in developing countries household: Gas geyser syndrome

    PubMed Central

    Mehta, Anish; Mahale, Rohan; John, Aju Abraham; Abbas, Masoom Mirza; Javali, Mahendra; Acharya, Purushottam; Rangasetty, Srinivasa

    2016-01-01

    Background: Liquefied petroleum gas geysers are used very frequently for heating water in developing countries such as India. However, these gas geysers emit various toxic gases; one among them is colorless, odorless carbon monoxide (CO). In the past few years, there were reports of unexplained loss of consciousness in the bathroom. However, the exact cause for these episodes has been recognized as toxic encephalopathy due to toxic gases inhalation mainly CO. Objective: To analyze the clinical profile and outcome of patients brought with loss of consciousness in the bathroom while bathing using gas geyser. Materials and Methods: Case records of patients with the diagnosis of gas geyser syndrome from 2013 to 2015 were retrieved and analyzed. Twenty-four cases were identified and included in the study. This was a retrospective, descriptive study. Results: Twenty-four patients were brought to our Emergency Department with loss of consciousness in the bathroom while bathing. Twenty-one cases had loss of consciousness during bathing and recovered spontaneously. Two cases were found dead in the bathroom and were brought to the Department of Forensic Medicine for postmortem. One case was brought in deep altered state of consciousness and succumbed to illness within 1 week. Conclusion: Awareness regarding CO intoxication due to usage of ill-fitted, ill-ventilated gas geyser is necessary as they are entirely preventable conditions. PMID:27114653

  10. Inhaled formaldehyde induces bone marrow toxicity via oxidative stress in exposed mice.

    PubMed

    Yu, Guang-Yan; Song, Xiang-Fu; Liu, Ying; Sun, Zhi-Wei

    2014-01-01

    Formaldehyde (FA) is an economically important chemical, and has been found to cause various types of toxic damage to the body. Formaldehyde-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses, which may increase risk of cancer. Therefore, in the present study, we aimed to investigate the possible toxic mechanism in bone marrow caused by formaldehyde. In accordance with the principle of randomization, the mice were divided into four groups of 6 mice per group. One group was exposed to ambient air and the other three groups were exposed to different concentrations of formaldehyde (20, 40, 80 mg/m3) for 15 days in the respective inhalation chambers, 2h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. Some of those were used for the determination of blood cell numbers, bone marrow karyote numbers, CFU-F, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; others were used for the determination of mitochondrial membrane potential (MMP), cell cycle and Bcl-2, Bax, CytC protein expression. WBC and PLT numbers in median and high dose groups were obvious reduced, but there was no change on RBC numbers. There was also reduced numbers of bone marrow karyotes and CFU-F in the high dose group. SOD activity was decreased, but MDA content was increased. MMP and Bcl-2 expression were decreased with increasing formaldehyde concentration, while expression of Bax and Cyt C was increased. We also observed change in cell cycling, and found that there was S phase arrest in the high dose group. Our study suggested that a certain concentration of formaldehyde could have toxic effects on the hematopoietic system, with oxidative stress as a critical effect.

  11. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles.

    PubMed

    Larsen, Søren T; Jackson, Petra; Poulsen, Steen S; Levin, Marcus; Jensen, Keld A; Wallin, Håkan; Nielsen, Gunnar D; Koponen, Ismo K

    2016-11-01

    Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay. PMID:27323801

  12. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

    PubMed Central

    Larsen, Søren T.; Jackson, Petra; Poulsen, Steen S.; Levin, Marcus; Jensen, Keld A.; Wallin, Håkan; Nielsen, Gunnar D.; Koponen, Ismo K.

    2016-01-01

    Abstract Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay. PMID:27323801

  13. Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3 months.

    PubMed

    Arts, Josje H E; Muijser, Hans; Duistermaat, Evert; Junker, Karin; Kuper, C Frieke

    2007-10-01

    Evidence suggests that short-term animal exposures to synthetic amorphous silicas (SAS) and crystalline silica can provide comparable prediction of toxicity to those of 90-day studies, therefore providing the opportunity to screen these types of substances using short-term rather than 90-day studies. To investigate this hypothesis, the inhalation toxicity of three SAS, precipitated silica Zeosil 45, silica gel Syloid 74, and pyrogenic silica Cab-O-Sil M5 was studied in Wistar rats. Rats were exposed nose-only to concentrations of 1, 5 or 25mg/m(3) of one of the SAS 6h a day for five consecutive days. Positive controls were exposed to 25mg/m(3) crystalline silica (quartz dust), negative controls to clean air. Animals were necropsied the day after the last exposure or 1 or 3 months later. All exposures were tolerated without serious clinical effects, changes in body weight or food intake. Differences in the effects associated with exposure to the three types of SAS were limited and almost exclusively confined to the 1-day post-exposure time point. Silicon levels in tracheobronchial lymph nodes were below the detection limit in all groups at all time points. Silicon was found in the lungs of all high concentration SAS groups 1-day post-exposure, and was cleared 3 months later. Exposure to all three SAS at 25mg/m(3) induced elevations in biomarkers of cytotoxicity in bronchoalveolar lavage fluid (BALf), increases in lung and tracheobronchial lymph node weight and histopathological lung changes 1-day post-exposure. Exposure to all three SAS at 5mg/m(3) induced histopathological changes and changes in BALf only. With all three SAS these effects were transient and, with the exception of slight histopathological lung changes at the higher exposure levels, were reversible during the 3-month recovery period. No adverse changes were observed in animals exposed to any of the SAS at 1mg/m(3). In contrast, with quartz-exposed animals the presence of silicon in the lungs was

  14. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be used throughout the duration of the study and the research sample should be stored under...) Clinical pathology. Hematology and clinical chemistry examinations must be made on all animals, including controls, of each sex in each group. The hematology and clinical chemistry parameters should be examined...

  15. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part 792—Good... include calcium, phosphorus, fasting triglycerides, hormones, methemoglobin, and cholinesterases....

  16. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Practice Standards at 40 CFR part 792, subpart J, the following specific information must be reported: (i... performance of laboratory equipment. The study must be conducted in compliance with 40 CFR Part 792—Good... include calcium, phosphorus, fasting triglycerides, hormones, methemoglobin, and cholinesterases....

  17. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... test at one dose level of at least 1,000 mg/kg body weight (expected human exposure may indicate the...). Extrapolation from the results of this study to humans is valid only to a limited degree. However, it can useful... use in selecting dose levels for chronic studies and for establishing safety criteria for...

  18. 40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... occurring as a result of prolonged action on, or increased concentration of, the administered test substance... sacrifices are planned, the number must be increased by the number of animals scheduled to be sacrificed... oil and then solution in other vehicles. (ii) If possible, one lot of the......

  19. Subchronic (12-week) inhalation toxicity study of methanol-fueled engine exhaust in rats

    SciTech Connect

    Maejima, Kazuhito; Suzuki, Tadao ); Numata, Hiroaki ); Maekawa, Akihiko ); Nagase, Sumi ); Ishinishi, Noburu )

    1994-01-01

    To evaluate the inhalation toxicity to rats of exhaust at low concentration for longer periods, Fischer 344 rats were exposed to 3 concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 6 d/wk for 4, 8, or 12 wk. Concentration- and time-dependent increase carboxyhemoglobin in the erythrocytes and decrease in cytochrome P-450 in the lungs were observed in all treated groups. Furthermore, significant increases in plasma formaldehyde were observed in the group exposed to the highest concentration of exhaust (carbon monoxide, 89.8 ppm; formaldehyde, 2.3 ppm; methanol, 8.1 ppm; nitrogen oxides, 22.9 ppm; nitrogen dioxide, 1.1 ppm) for 8 or 12 wk. No change of plasma folic acid was observed in any group, and no methanol or formic acid was detected in the plasma in any animals. Histopathologically, exposure-related changes were found only in the nasal cavity of the high-concentration group. Slight hyperplasia/squamous metaplasias of the respiratory epithelium lining the nasoturbinate and maxilloturbinate were observed after 4 wk of exposure, and the incidences and degrees of these lesions increased slightly with the exposure time. No changes were found in the olfactory epithelium of the nasal cavity. As judged by optical microscopy, the exhaust concentration with no effect on the nasal cavity under the experimental conditions was concluded to be the medium concentration level containing 0.55 ppm formaldehyde. In the present study, however, concentration- and time-dependent increase of carboxyhemoglobin in the erythrocytes and decrease of the lung P-450 level were observed. Therefore, further study on more long-term inhalation of lower concentrations of exhaust might be needed. 31 refs., 2 figs., 3 tabs.

  20. Rifapentine-Proliposomes for Inhalation: In Vitro and In Vivo Toxicity

    PubMed Central

    Patil-Gadhe, Arpana A.; Kyadarkunte, Abhay Y.; Pereira, Michael; Jejurikar, Gauri; Patole, Milind S.; Risbud, Arun; Pokharkar, Varsha B.

    2014-01-01

    Background: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from the limitation of hepatic metabolism leading insufficient concentration of antitubercular (anti-TB) drugs in alveolar macrophage which harbors Mycobacterium tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is efficient for treating local lung TB infection. Objective: The present study was aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation (RLDPI) for anti-TBactivity and cytotoxicity in vitro. In vivo toxicity study was also undertaken in Wistar rats to determine safe concentration of RLDPI for administration. Materials and Methods: Anti-TB activity of developed RLDPI was assessed using drug susceptibility testing (DST) on Mycobacteria growth indicator tube (MGIT) method. In vitro cytotoxicity was performed in A549 cell lines and IC50 values were used to compare the cytotoxicity of formulation with pure RPT. In vivo repeated dose toxicity study was undertaken using Wistar rats at three different doses for 28-days by intratracheal insufflations method. Results: The results of DST study revealed sensitivity of tubercle bacteria to RLDPI at concentration equivalent to 10 μg/mL of RPT. This study confirmed anti-TB potential of RPT in spray-dried RLDPI, though the spray drying method is reported to reduce activity of drugs. Cytotoxicity study in A549 cells demonstrated that RPT when encapsulated in liposomes as RLDPI was safe to cells as compared to pure RPT. In vivo toxicity study revealed that RPT in the form of RLDPI was safe at 1 and 5 mg/kg dose. However, mortality was seen at higher dose (10 mg/kg), possibly because of liver and kidney damage. Conclusion: Thus, these studies demonstrated safety of RLDPI for the treatment of pulmonary TB. PMID:25948966

  1. A 90-day study of three bruchid-resistant mung bean cultivars in Sprague-Dawley rats.

    PubMed

    Yao, Yang; Cheng, Xuzhen; Ren, Guixing

    2015-02-01

    Mung bean has been traditionally and widely used as an edible and medicinal plant in the South and Southeast Asia. Bruchid resistance mung bean has more potential in commercial use, but scarcely been evaluated for safety through standard in vivo toxicological studies. In the present study, subchronic oral toxicity studies of bruchid-resistant mung bean were designed and conducted in Sprague-Dawley (SD) rats for 90 days. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, macroscopic findings, organ weights and histopathological examination were noted in animal administered diet containing bruchid-resistant mung bean. These results demonstrated that bruchid resistant mung bean is as safe as conventional mung bean.

  2. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  3. Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice.

    PubMed

    Oyama, Tsunehiro; Isse, Toyohi; Ogawa, Masanori; Muto, Manabu; Uchiyama, Iwao; Kawamoto, Toshihiro

    2007-01-01

    In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method. Male C57BL/6 (Aldh2 +/+) mice and Aldh -/- mice were exposed to atmospheres containing acetaldehyde at levels of 0, 125, and 500 ppm for 24 h/day during 14 days. Although the average blood acetaldehyde concentration of Aldh -/- mice was higher than that of Aldh2 +/+ mice in the acetaldehyde exposure group, observable effects by the acetaldehyde exposure on the lung and liver were not different between wild type and ALDH2 null mice. In Aldh2 -/- mice, the levels of 1) erosion of respiratory epithelium and the subepithelial hemorrhage in nose, 2) hemorrhage in nasal cavity, 3) degeneration of respiratory epithelium in larynx, pharynx and trachea, and 4) degeneration of dorsal skin were higher compared with Aldh2 +/+ mice, indicating that Aldh2 -/- mice are more acetaldehyde-sensitive than Aldh2 +/+ mice. This is the first example for studying pathological effects of Aldh2 deficiency using Aldh -/- mice exposed to a low level of acetaldehyde. PMID:17127431

  4. Design and operation of a batch-feed fluidizing bed aerosol generator for inhalation toxicity studies

    SciTech Connect

    Shiotsuka, R.N.; Peck, R.W. Jr.; Drew, R.T.

    1985-02-01

    A fluidizing bed aerosol generator (FBG), designed for inhalation toxicity studies, was constructed and tested. A key design feature contributing to its operational stability was the partial masking of the screen supporting the bronze beads. This caused 20-80% of the bed to fluidize under normal operating conditions. The non-fluidizing areas functioned as reservoirs to feed the fluidizing areas. Using a bed volume of 1000 cc of bronze beads and 20 g of MnO/sub 2/ dust, the mass output rate ranged from 0.1 to 1.0 mg/min when operated at plenum pressures of 1.04 x 10/sup 2/ to 2.42 x 10/sup 2/ kPa (minimum fluidization pressure was approximately 82.8 kPa). During daily operation at three different output rates, the FBG produced aerosols with little change in particle size distributions or concentration when operated six hours/day for five days. Furthermore, when the FBG was operated at a fixed output rate for 15 days with two recharges of MnO/sub 2/ dust, the particle size distribution did not show any cumulative increase. Thus, long-term operation of this FBG should result in a reproducible range of concentration and particle size distribution.

  5. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    PubMed

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone. PMID:25020274

  6. Health assessment of gasoline and fuel oxygenate vapors: subchronic inhalation toxicity.

    PubMed

    Clark, Charles R; Schreiner, Ceinwen A; Parker, Craig M; Gray, Thomas M; Hoffman, Gary M

    2014-11-01

    Sprague Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess whether their use in gasoline influences the hazard of evaporative emissions. Test substances included vapor condensates prepared from an EPA described "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/m(3) and exposures were for 6h/day, 5days/week for 13weeks. A portion of the animals were maintained for a four week recovery period to determine the reversibility of potential adverse effects. Increased kidney weight and light hydrocarbon nephropathy (LHN) were observed in treated male rats in all studies which were reversible or nearly reversible after 4weeks recovery. LHN is unique to male rats and is not relevant to human toxicity. The no observed effect level (NOAEL) in all studies was 10,000mg/m(3), except for G/MTBE (<2000) and G/TBA (2000). The results provide evidence that use of the studied oxygenates are unlikely to increase the hazard of evaporative emissions during refueling, compared to those from gasoline alone.

  7. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats.

    PubMed

    Schrøder, Malene; Poulsen, Morten; Wilcks, Andrea; Kroghsbo, Stine; Miller, Andreas; Frenzel, Thomas; Danier, Jürgen; Rychlik, Michael; Emami, Kaveh; Gatehouse, Angharad; Shu, Qingyao; Engel, Karl-Heinz; Altosaar, Illimar; Knudsen, Ib

    2007-03-01

    An animal model for safety assessment of genetically modified foods was tested as part of the SAFOTEST project. In a 90-day feeding study on Wistar rats, the transgenic KMD1 rice expressing Cry1Ab protein was compared to its non-transgenic parental wild type, Xiushui 11. The KMD1 rice contained 15mg Bt toxin/kg and based on the average feed consumption the daily intake was 0.54mg Bt toxin/kg body weight. No adverse effects on animal behaviour or weight gain were observed during the study. Blood samples collected one week prior to sacrifice were analyzed and compared for standard haematological and biochemical parameters. A few parameters were significantly different, but all within the normal reference intervals for rats of this breed and age and not in relation to any other findings, thus not considered treatment related. Upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. The aim of the study was to use a known animal model in performance of safety assessment of a GM crop, in this case KMD1 rice. The results show no adverse or toxic effects of KMD1 rice when tested in the design used in this 90-day study. Nevertheless the experiences from this study lead to the overall conclusion that safety assessment for unintended effects of a GM crop cannot be done without additional test group(s).

  8. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  9. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  10. A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

    PubMed Central

    Johnson, Todd J.; Clark, Meredith R.; Albright, Theodore H.; Nebeker, Joel S.; Tuitupou, Anthony L.; Clark, Justin T.; Fabian, Judit; McCabe, R. Tyler; Chandra, Neelima; Doncel, Gustavo F.; Friend, David R.

    2012-01-01

    A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 104 ng/g, 106 ng/g, and 101 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. PMID:23006751

  11. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the language and intent of the above-quoted exception in § 220.4(c)(8), until it has been honored by... substantially the same as language found in section 4(f) of Regulation T as originally promulgated in 1934. The language of the subject exception to the 90-day rule of § 220.4(c)(8), i.e., the exception based...

  12. Carbon capture and sequestration: an exploratory inhalation toxicity assessment of amine-trapping solvents and their degradation products.

    PubMed

    McDonald, Jacob D; Kracko, Dean; Doyle-Eisele, Melanie; Garner, C Edwin; Wegerski, Chris; Senft, Al; Knipping, Eladio; Shaw, Stephanie; Rohr, Annette

    2014-09-16

    Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days. C57bl/6N mice were exposed for 7 days by inhalation of 25 ppm neat amine or equivalant concentration in the degraded mixture. The aqueous solutions were nebulized to create the inhalation atmospheres. Pulmonary response was measured by changes in inflammatory cells in bronchoalveolar lavage fluid and cytokine expression in lung tissue. Ames mutagenicity and CHO-K1 micronucleus assays were applied to assess genotoxicity. Chemical analysis of the test atmosphere and liquid revealed complex mixtures, including acids, aldehydes, and other compounds. Exposure to oxidatively degraded MEA increased (p < 0.05) total cells, neutrophils, and lymphocytes compared to control mice and caused inflammatory cytokine expression (statistical increase at p < 0.05). MEA and CO2-degraded MEA were the only atmospheres to show statistical (p < 0.05) increase in oxidative stress. CO2 degradation resulted in a different composition, less degradation, and lower observed toxicity (less magnitude and number of effects) with no genotoxicity. Overall, oxidative degradation of the amines studied resulted in enhanced toxicity (increased magnitude and number of effects) compared to the neat chemicals.

  13. Bioaccumulation and locomotor effects of manganese sulfate in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    SciTech Connect

    Tapin, Danielle; Kennedy, Greg; Lambert, Jean; Zayed, Joseph . E-mail: joseph.zayed@umontreal.ca

    2006-03-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic compound that was introduced as an antiknock additive to replace lead in unleaded fuel. The combustion of MMT results in the emission of fine Mn particulates mainly in the form of manganese sulfate and manganese phosphate. The objective of this study is to determine the effects of subchronic exposure to Mn sulfate in different tissues, on locomotor activity, on neuropathology, and on blood serum biochemical parameters. A control group and three groups of 30 male Sprague-Dawley rats were exposed 6-h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 {mu}g/m{sup 3} Mn sulfate. Locomotor activity was measured during 36 h using an Auto-Track System. Blood and the following tissues were collected and analyzed for manganese content by neutron activation analysis: olfactory bulb, globus pallidus, caudate/putamen, cerebellum, frontal cortex, liver, lung, testis, and kidney. Neuronal cell counts were obtained for the caudate/putamen and the globus pallidus and clinical biochemistry was assessed. Manganese concentrations were increased in blood, kidney, lung, and testis and in all brain regions in the 3000 {mu}g/m{sup 3} exposure group. Significant differences were also noted in the 300 {mu}g/m{sup 3} exposure group. Neuronal cell counts for the globus pallidus were significantly different between the two highest exposed groups and the controls. Locomotor activity for all exposure concentrations and resting time for the middle and highest concentrations for the two night resting periods were significantly increased. Total ambulatory count was decreased significantly for all exposure concentrations. Biochemical profiles also presented significant differences. No body weight loss was observed between all groups. These results suggest that neurotoxicity could occur at low exposure levels of Mn sulfate, one of the main combustion products of MMT.

  14. A chronic inhalation toxicity/oncogenicity study of methylethylketoxime in rats and mice.

    PubMed

    Newton, P E; Wooding, W L; Bolte, H F; Derelanko, M J; Hardisty, J F; Rinehart, W E

    2001-12-01

    To evaluate the oncogenic potential of methylethylketoxime (MEKO), CD-1 mice (50/sex/group) and F-344 rats (50/sex/group) were coexposed 6 h/day, 5 days/wk for 18 mo (mice) or 26 mo (rats) via whole-body inhalation exposures to target vapor concentrations of 0, 15, 75, and 375 ppm (actual concentrations of 0, 15 +/- 1, 75 +/- 2, or 374 +/- 10 ppm). Satellite groups of rats and mice (10/sex/group/interval) were exposed for 12 mo (mice) and 3, 12, or 18 mo (rats) to evaluate chronic toxicity. Methyl ethyl ketone (MEK), a possible hydrolysis product of MEKO, was present at less than 1%. Treatment-related effects included increased body weight (male rats only), methemoglobin formation, hematology and clinical chemistry changes, increased liver weight, and increased spleen and testes weights (rats only). A high incidence of cataracts and corneal dystrophy occurred in both control and MEKO-exposed rats, with an earlier appearance and slightly higher incidence for these ocular lesions in MEKO-exposed animals compared to controls. Degenerative and reparative changes of the olfactory epithelium in the nasal turbinates, primarily limited to the dorsal meatus, occurred in both rats (75 and 374 ppm) and mice (15, 75, and 374 ppm). In addition, in the mice, liver changes included increased incidences of pigment in reticuloendothelial cells, centilobular hypertrophy, granulomatous inflammation, and a slightly increased incidence of necrosis (75 and 374 ppm). An increase in hepatocellular carcinomas occurred in male mice at 374 ppm. Additional MEKO-related findings in the rat included congestion of the spleen with pigment in reticuloendothelial cells and extramedullary hematopoiesis and a decreased incidence of lymphoreticular mononuclear cell leukemia. Effects observed in the liver of the rats included decreases in the incidence of both peribiliary fibrosis and hyperplasia/proliferation of the biliary duct, an increase of spongiosis hepatis in males, and an increase in the

  15. The impact of 90-day prescriptions on adherence at workplace pharmacies compared to traditional mail order.

    PubMed

    Patwardhan, Avinash; Davis, Jeffery; Murphy, Patricia; Khandelwal, Nikhil; Sherman, Bruce; Manfred, James

    2011-12-01

    This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De-identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail-order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist-patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members. PMID:22092153

  16. Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol--I. Introduction, experimental design, and aerosol generation methods.

    PubMed

    Ulrich, C E; Rinehart, W; Busey, W

    1979-03-01

    A brief literature review on manganese toxicity is presented; as related to designing a chronic inhalation study for evaluating methylcyclopentadienyl manganese tricarbonyl when utilized as a motor fuel additive. The experimental design of this study is described. The generation system utilized to simulate the manganese aerosol produced by an internal combustion engine is described in detail. This generation system operated twenty-four hours per day, seven days per week producing aerosols at 11.6, 112.5, and 1152 micrograms Mn/m3 with an aerodynamic diameter of approximately 0.11 micron.

  17. Identification of the appropriate dose metric for pulmonary inflammation of silver nanoparticles in an inhalation toxicity study.

    PubMed

    Braakhuis, Hedwig M; Cassee, Flemming R; Fokkens, Paul H B; de la Fonteyne, Liset J J; Oomen, Agnes G; Krystek, Petra; de Jong, Wim H; van Loveren, Henk; Park, Margriet V D Z

    2016-01-01

    A number of studies have shown that induction of pulmonary toxicity by nanoparticles of the same chemical composition depends on particle size, which is likely in part due to differences in lung deposition. Particle size mostly determines whether nanoparticles reach the alveoli, and where they might induce toxicity. For the risk assessment of nanomaterials, there is need for a suitable dose metric that accounts for differences in effects between different sized nanoparticles of the same chemical composition. The aim of the present study is to determine the most suitable dose metric to describe the effects of silver nanoparticles after short-term inhalation. Rats were exposed to different concentrations (ranging from 41 to 1105 µg silver/m(3) air) of 18, 34, 60 and 160 nm silver particles for four consecutive days and sacrificed at 24 h and 7 days after exposure. We observed a concentration-dependent increase in pulmonary toxicity parameters like cell counts and pro-inflammatory cytokines in the bronchoalveolar lavage fluid. All results were analysed using the measured exposure concentrations in air, the measured internal dose in the lung and the estimated alveolar dose. In addition, we analysed the results based on mass, particle number and particle surface area. Our study indicates that using the particle surface area as a dose metric in the alveoli, the dose-response effects of the different silver particle sizes overlap for most pulmonary toxicity parameters. We conclude that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation.

  18. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    PubMed

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing. PMID:25490426

  19. Effects of depletion of ascorbic acid or nonprotein sulfhydryls on the acute inhalation toxicity of nitrogen dioxide, ozone, and phosgene

    SciTech Connect

    Slade, R.; Highfill, J.W.; Hatch, G.E.

    1989-01-01

    The effect of depleting lung ascorbic acid (AH{sub 2}) and nonprotein sulfhydryls (NPSH) on the acute inhalation toxicity of nitrogen dioxide (NO{sub 2}), ozone (O{sub 3}), and phosgene (COCl{sub 2}) was investigated in guinea pigs. The increase in bronchoalveolar lavage (BAL) fluid protein (an indicator of alveolar-capillary damage leading to increased permeability) was measured 16 to 18 hr following a 4 hr exposure to the gas in animals deficient in (AH{sub 2}) or NPSH. Gas concentrations were chosen which produced low but significant increases in BAL protein. Lung (AH{sub 2}) was lowered to about 20% of control by feeding rabbit chow for 2 weeks. Lung NPSH was lowered to about 50% of control by injecting a mixture of buthionine S,R-sulfoximine (BSO) and diethylmaleate (DEM) (2.7 and 1.2 mmol/kg respectively). BSO/DEM did not affect the lung concentrations of (AH{sub 2}) or alpha-tocopherol. AH{sub 2} depletion caused a 6 fold and a 3 fold enhancement in the toxicity of 5 ppm and 10 ppm (NO{sub 2}), and a 6 fold enhancement in the toxicity of 0.5 ppm (O{sub 3}), but did not affect toxicity of 1.0 ppm (O{sub 3}). AH{sub 2} depletion did not affect phosgene toxicity (at 0.25 ppm and 0.5 ppm).

  20. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.

    EPA Science Inventory

    The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with mult...

  1. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: OXIDATIVE STRESS MARKERS IN BRAIN.

    EPA Science Inventory

    The effects of long-term exposure to volatile organic compounds (VOCs), which is of concern to the EPA, are poorly understood, primarily due to insufficient information about human exposure and unreliable animal models. A sub-chronic inhalation study with multiple endpoints was c...

  2. CATEGORICAL REGRESSION ANALYSIS OF ACUTE INHALATION TOXICITY DATA FOR HYDROGEN SULFIDE

    EPA Science Inventory

    Categorical regression is one of the tools offered by the U.S. EPA for derivation of acute reference exposures (AREs), which are dose-response assessments for acute exposures to inhaled chemicals. Categorical regression is used as a meta-analytical technique to calculate probabi...

  3. Program operational summary: Operational 90 day manned test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    Jackson, J. K.; Wamsley, J. R.; Bonura, M. S.; Seeman, J. S.

    1972-01-01

    An operational 90-day manned test of a regenerative life support system was successfully completed. This test was performed with a crew of four carefully selected and trained men in a space station simulator (SSS) which had a two gas atmosphere maintained at a total pressure of 68.9, 10 psia, and composed of oxygen at a partial pressure of 3.05 psia with nitrogen as the diluent. The test was planned to provide data on regenerative life support subsystems and on integrated system operations in a closed ecology, similar to that of a space station. All crew equipment and expendables were stored onboard at the start of the mission to eliminate the need for pass-in operations. The significant accomplishments of the test, some of the pertinent test results, some of the problem areas, and conclusions are presented.

  4. Ultrastructural response of rat lung to 90 days' exposure to oxygen at 450 mm Hg

    NASA Technical Reports Server (NTRS)

    Harrison, G. A.

    1974-01-01

    Young Sprague-Dawley rats were exposed to 100% oxygen at 450 mm Hg in constant environment capsules for 90 days. Lung tissue examined by electron microscopy revealed a number of changes, many similar to those observed after exposure to oxygen at 760 mm Hg for shorter periods of time. Alterations in vesicle size and number and in mitochondrial matrix and cristae appear in both the endothelial and epithelial cells. Blebbing and rarefication of cytoplasm occur in both cell layers of the alveolo-capillary wall. Also seen are fluid in the basement membrane, platelets in the capillaries, and alveolar fluid and debris. All of these alterations occur at 1 atm exposure. However, after exposure to 450 mm Hg the changes are not as widespread nor as destructive as they are at the higher pressure.

  5. Training plan for the 1164 {lt}90-day non-radioactive hazardous waste storage building

    SciTech Connect

    Demarest, J.L., Westinghouse Hanford

    1996-07-01

    In accordance with Washington Administrative Code (WAC), Chapter 173- 303, `Dangerous Waste Regulations,` a written training plan is required for a {lt}90-day accumulation area. WAC 173-303-200, `Accumulating Dangerous Waste On-site,` requires compliance with WAC- 173-303-330, Personnel Training. This training plan complies with WAC 173-303-330. This training plan, including the names of personnel in Table 1, may be given to a regulatory agency inspector upon request provided that this plan is cleared for public release. Training records associated with personnel identified in this plan are not be given to an outside regulatory agency inspector unless prior approval by the specific individual is obtained. Training records requests by regulatory agency inspectors without the individual`s approval are to be processed via a Freedom of Information Act request through the U.S. Department of Energy, Richland Operations Office.

  6. Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations.

    PubMed

    Roberts, Christopher M; Stone, Robert A; Lowe, Derek; Pursey, Nancy A; Buckingham, Rhona J

    2011-10-01

    COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV1 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV1 and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis. PMID:21864116

  7. Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

  8. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

    PubMed

    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice.

  9. Pulmonary toxicity of well-dispersed multi-wall carbon nanotubes following inhalation and intratracheal instillation.

    PubMed

    Morimoto, Yasuo; Hirohashi, Masami; Ogami, Akira; Oyabu, Takako; Myojo, Toshihiko; Todoroki, Motoi; Yamamoto, Makoto; Hashiba, Masayoshi; Mizuguchi, Yohei; Lee, Byeong Woo; Kuroda, Etsushi; Shimada, Manabu; Wang, Wei-Ning; Yamamoto, Kazuhiro; Fujita, Katsuhide; Endoh, Shigehisa; Uchida, Kunio; Kobayashi, Norihiro; Mizuno, Kohei; Inada, Masaharu; Tao, Hiroaki; Nakazato, Tetsuya; Nakanishi, Junko; Tanaka, Isamu

    2012-09-01

    Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.

  10. A 90-day safety study of genetically modified rice expressing rhIGF-1 protein in C57BL/6J rats.

    PubMed

    Tang, Maoxue; Xie, Tingting; Cheng, Wenke; Qian, Lili; Yang, Shulin; Yang, Daichang; Cui, Wentao; Li, Kui

    2012-06-01

    Genetically modified plants expressing disease resistance traits offer new treatment strategies for human diseases, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of transgenic rice expressing the recombinant human insulin-like growth factor-1 (rhIGF-1) compared to its parental wild rice. Male and female C57BL/6J rats were given a nutritionally balanced purified diet with 20% transgenic rhIGF-1 rice or 20% parental rice for 90 days. This corresponds to a mean daily rhIGF-1 protein intake of approximately 217.6 mg/kg body weight based on the average feed consumption. In the animal study a range of biological, biochemical, clinical, microbiological and pathological parameters were examined and several significant differences were observed between groups, but none of the effects were considered to be adverse. In conclusion, no adverse or toxic effects on C57BL/6J rats were observed in the design used in this 90-day study. These results will provide valuable information for the safety assessment of genetically modified food crops.

  11. The design, construction, and operation of a whole-body inhalation chamber for use in avian toxicity studies.

    PubMed

    Olsgard, Mandy L; Smits, Judit E G

    2008-01-01

    Environmental risk assessments are broadening to include evaluations of avian species exposed to gaseous and particulate materials (Mineau, 2002b; Irvine, 2004; Carmalt, 2005). Since the avian respiratory tract is fundamentally different from the respiratory tract of rodents, the effects of gaseous materials on birds cannot validly be extrapolated from data derived from rodent exposure studies (Briant & Driver, 1992; Brown et al., 1997). To address the lack of avian-specific lowest observable effect levels used to calculate reference concentrations for airborne pollutants, a system was designed to facilitate research on inhalation toxicology in small birds. Birds have long been used as early indicators of poor air quality (Brown et al., 1997), and various chambers have been designed for head only exposures of larger birds (Briant & Driver, 1992). Smaller birds with short tracheal lengths and hooked beaks however require less restrictive exposure apparatus, thus warranting the proposed design. The chamber described in this article was designed to accommodate a small falcon, the American kestrel, a species frequently used in toxicological risk assessments (Wiemeyer & Lincer, 1987a; Smits & Bortolotti, 2001; Bortolotti et al., 2003; Fisher et al., 2006). To accomplish this, a 41-L closed inhalation system capable of exposing 12 adult American kestrels was constructed primarily of galvanized steel, polyvinyl chloride, and copper tubing. Humidified air was passed over the birds and subsequently decontaminated by an activated carbon filter and released to a HEPA filtration system. The proposed inhalation chamber was successfully used in 2005 and 2006 to expose a total of 55 male American kestrels to benzene and toluene. Measurements of various biochemical endpoints associated with benzene and toluene toxicity allowed us to study the effects of airborne pollutants on small nondomesticated birds in a controlled laboratory setting.

  12. The design, construction, and operation of a whole-body inhalation chamber for use in avian toxicity studies.

    PubMed

    Olsgard, Mandy L; Smits, Judit E G

    2008-01-01

    Environmental risk assessments are broadening to include evaluations of avian species exposed to gaseous and particulate materials (Mineau, 2002b; Irvine, 2004; Carmalt, 2005). Since the avian respiratory tract is fundamentally different from the respiratory tract of rodents, the effects of gaseous materials on birds cannot validly be extrapolated from data derived from rodent exposure studies (Briant & Driver, 1992; Brown et al., 1997). To address the lack of avian-specific lowest observable effect levels used to calculate reference concentrations for airborne pollutants, a system was designed to facilitate research on inhalation toxicology in small birds. Birds have long been used as early indicators of poor air quality (Brown et al., 1997), and various chambers have been designed for head only exposures of larger birds (Briant & Driver, 1992). Smaller birds with short tracheal lengths and hooked beaks however require less restrictive exposure apparatus, thus warranting the proposed design. The chamber described in this article was designed to accommodate a small falcon, the American kestrel, a species frequently used in toxicological risk assessments (Wiemeyer & Lincer, 1987a; Smits & Bortolotti, 2001; Bortolotti et al., 2003; Fisher et al., 2006). To accomplish this, a 41-L closed inhalation system capable of exposing 12 adult American kestrels was constructed primarily of galvanized steel, polyvinyl chloride, and copper tubing. Humidified air was passed over the birds and subsequently decontaminated by an activated carbon filter and released to a HEPA filtration system. The proposed inhalation chamber was successfully used in 2005 and 2006 to expose a total of 55 male American kestrels to benzene and toluene. Measurements of various biochemical endpoints associated with benzene and toluene toxicity allowed us to study the effects of airborne pollutants on small nondomesticated birds in a controlled laboratory setting. PMID:18236233

  13. Toxicity of chronic benzene inhalation: CD-1 mice exposed to 300 ppm

    SciTech Connect

    Snyder, C.A.; Goldstein, B.D.; Sellakumar, A.; Bromberg, I.; Laskin, S.; Albert, R.E.

    1982-10-01

    Male, six-week old mice were exposed to benzene in an inhalation chamber for 6 hr/day, 5 days/wk. Red cell, white cell and white cell differential counts were performed. Tissues routinely sectioned at autopsy included lung, liver, spleen, bone marrow and kidney, as well as abnormally appearing organs. Hemototoxic responses observed include immediate depression of peripheral lymphocytes and red blood cells, and an increase in circulating granulocytes. Exposed animals dying with bone hypoplasia survived about 75 fewer days than mice dying with bone hyperplasia. The appearance of hemosiderin pigments in the spleens is evidence for benzene-induced hemolysis. (JMT)

  14. Embracing a weight-of-evidence approach for establishing NOAELs for nanoparticle inhalation toxicity studies.

    PubMed

    Warheit, David B; Reed, Kenneth L; DeLorme, Michael P

    2013-02-01

    The goal of this article is to evaluate a recently published subchronic inhalation study with carbon nanofibers in rats and discuss the importance of a weight-of-evidence (WOE) framework for determining no adverse effect levels (NOAELs). In this Organization for Economic Cooperation and Development (OECD) 413 guideline inhalation study with VGCF-H carbon nanofibers (CNFs), rats were exposed to 0, 0.54, 2.5 or 25 mg/m(3) CNF for 13 weeks. The standard toxicology experimental design was supplemented with bronchoalveolar lavage (BAL) and respiratory cell proliferation (CP) endpoints. BAL fluid (BALF) recovery of inflammatory cells and mediators (i.e., BALF- lactate dehydrogenase [LDH], microprotein [MTP], and alkaline phosphatase [ALKP] levels) were increased only at 25 mg/m(3), 1 day after exposure. No differences versus control values in were measured at 0.54 or 2.5 mg/m(3) exposure concentrations for any BAL fluid endpoints. Approximately 90% (2.5 and 25 mg/m(3)) of the BAL-recovered macrophages contained CNF. CP indices at 25 mg/m(3) were increased in the airways, lung parenchyma, and subpleural regions, but no increases in CP versus controls were measured at 0.54 or 2.5 mg/m(3). Based upon histopathology criteria, the NOAEL was set at 0.54 mg/m(3), because at 2.5 mg/m(3), "minimal cellular inflammation" of the airways/lung parenchyma was noted by the study pathologist; while the 25 mg/m(3) exposure concentration produced slight inflammation and occasional interstitial thickening. In contrast, none of the more sensitive pulmonary biomarkers such as BAL fluid inflammation/cytotoxicity biomarkers or CP turnover results at 2.5 mg/m(3) were different from air-exposed controls. Given the absence of convergence of the histopathological observations versus more quantitative measures at 2.5 mg/m(3), it is recommended that more comprehensive guidance measures be implemented for setting adverse effect levels in (nano)particulate, subchronic inhalation studies including a

  15. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  16. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine.

    PubMed

    Clewell, Amy; Hirka, Gábor; Glávits, Róbert; Palmer, Philip A; Endres, John R; Murbach, Timothy S; Marx, Tennille; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals. PMID:27635133

  17. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  18. Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.

    PubMed Central

    Owen, P E; Glaister, J R

    1990-01-01

    A 2-year inhalation study was conducted in Sprague-Dawley rats with 1,3-butadiene. Groups of 110 male and 110 female rats inhaled 1,3-butadiene at 0, 1000, or 8000 ppm for 6hr/day, 5 days/week. Interim clinical pathology, neuromuscular, and histopathology investigations were carried out. The study terminated at 20 to 25% survival (105 weeks for females, 111 weeks for males). Following exposure to 1,3-butadiene there were no effects on hematology, blood chemistry, urine analysis, and neuromuscular function that definitely could be associated with treatment. Treatment was associated with changes in clinical condition, suppression of body weight gain, reduced survival, and increases in certain organ weights and in both common and uncommon tumor types. Although the biological interpretation of the significance of some of the tumor types is equivocal, the evidence suggests that the test article is an oncogen to the rat under the conditions of exposure used in this study, and the mechanism is more likely to be an indirect effect through the endocrine system, rather than a direct effect through the production of reactive metabolites. PMID:2401255

  19. A 26-Week Toxicity Assessment of AIR001 (Sodium Nitrite) by Inhalation Exposure in Rats and by Intravenous Administration in Dogs.

    PubMed

    Tepper, Jeffrey; Ochoa, Ricardo; Rix, Peter; Elliott, Gary; Hoglen, Niel; Poulin, Dominic; Parsley, Ed; Masamune, Hiroko

    2014-05-01

    Historically, nitrogen oxides (NOx) in food, drinking water, as well as in the atmosphere have been believed to be associated with adverse health consequences. More recently, NOx have been implicated in normal homeostatic regulation, and exogenous administration has been associated with health benefits. One such potential health benefit is the prospect that inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation administration in rats and by intravenous infusion in dogs. The studies revealed that methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels less than 40% were well tolerated in both species, while levels greater than 50% methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated pharmacological effects occurred daily throughout the 26-week treatment period. Chronic exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in additional toxicity or compensatory responses. Based on the exposure levels that produced these pharmacodynamic responses in animals, relative to those measured in early clinical studies, it appears that an adequate margin of safety exists to support the continued clinical development of inhaled AIR001.

  20. Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity

    PubMed Central

    Paffett, Michael L.; Zychowski, Katherine E.; Sheppard, Lianne; Robertson, Sarah; Weaver, John M.; Lucas, Selita N.; Campen, Matthew J.

    2015-01-01

    Ambient ozone (O3) levels are associated with cardiovascular morbidity and mortality, but the underlying pathophysiological mechanisms driving extrapulmonary toxicity remain unclear. This study examined the coronary vascular bed of rats in terms of constrictive and dilatory responses to known agonists following a single O3 inhalation exposure. In addition, serum from exposed rats was used in ex vivo preparations to examine whether bioactivity and toxic effects of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels exhibited greater basal tone and constricted to a greater degree to serotonin stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in coronary arteries from O3-exposed rats, compared with filtered air-exposed controls. Dilation to ACh was restored by combined superoxide dismutase and catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum from exposed rats was perfused into the lumen of coronary arteries from unexposed, naïve rats, the O3-induced reduction in vasodilatory response to ACh was partially recapitulated. Furthermore, following O3 inhalation, serum exhibited a nitric oxide scavenging capacity, which may partially explain blunted ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures may be due to compositional changes of the circulation. These studies shed light on possible mechanisms of action that may explain O3-associated cardiac morbidity and mortality in humans. PMID:25962394

  1. Petroleum prices and profits in the 90 days following the invasion of Kuwait

    SciTech Connect

    Not Available

    1990-11-01

    For the third in the past 20 years the world has experienced an interruption in the flow of oil from the Persian Gulf. The Iraqi invasion of Kuwait on August 2, 1990, and shut down of Kuwait oil production capacity followed by the United Nations boycott of Iraqi oil removed 8 percent of the world's oil supply. The result was a sharp increase in the process of crude oil and petroleum products. These events raised numerous questions about the performance of energy markets and energy firms. This report supplies a first answer for some of those questions. At the time this report was prepared the invasion has been in effect for 90 days. Not all the data is available to fully answer every question. Some issues can only be completely resolved after more time has passed in which the invasion and its effects have had an opportunity to be fully assimilated. This report was specifically requested by W. Henson Moore, Deputy Secretary of Energy as a way of supplying the American public with what could be said about the current situation. Rumors abound and mixconceptions have proliferated. This report strives to give a proper perspective on some of the more vexing issues which the invasion produced. The Energy Information Administration (EIA) has addressed many questions in this report. By the way of summary these are the 10 most most frequently asked questions and EIA's quick answers. The page references tell the reader where to look in the report for further explanation. These are not the only issues addressed and EIA hopes that readers will be able to satisfy their curiosity about their own questions within the pages of this report.

  2. Inhalation Toxicity of Ground Lunar Dust Prepared from Apollo-14 Soil

    NASA Technical Reports Server (NTRS)

    James, John T.; Lam, Chiu-wing; Scully, Robert R.; Cooper, Bonnie L.

    2011-01-01

    Within the decade one or more space-faring nations intend to return humans to the moon for more in depth exploration of the lunar surface and subsurface than was conducted during the Apollo days. The lunar surface is blanketed with fine dust, much of it in the respirable size range (<10 micron). Eventually, there is likely to be a habitable base and rovers available to reach distant targets for sample acquisition. Despite designs that could minimize the entry of dust into habitats and rovers, it is reasonable to expect lunar dust to pollute both as operations progress. Apollo astronauts were exposed briefly to dust at nuisance levels, but stays of up to 6 months on the lunar surface are envisioned. Will repeated episodic exposures to lunar dust present a health hazard to those engaged in lunar exploration? Using rats exposed to lunar dust by nose-only inhalation, we set out to investigate that question.

  3. Inhaled albuterol does not protect against ozone toxicity in nonasthmatic athletes.

    PubMed

    Gong, H; Bedi, J F; Horvath, S M

    1988-01-01

    We evaluated the acute prophylactic efficacy of albuterol aerosol in protecting nonasthmatic athletes from the untoward effects of 0.21 ppm ozone (O3) on symptoms, pulmonary function, exercise performance, and post-exposure histamine bronchoprovocation. Fifteen trained competitive cyclists participated in a randomized crossover study consisting of double-blinded inhalations of albuterol (180 micrograms) and placebo approximately 30 min prior to heavy continuous exercise (minute ventilation, [VE] greater than or equal to 80 L/min) for 60 min, followed by a maximal sprint (peak VE greater than 140 L/min) until exhaustion. Each subject was exposed randomly to either 0.21 ppm O3 or filtered air (FA) during the four single-blinded exposure sessions. Albuterol pretreatment resulted in modest but significant bronchodilation as compared to placebo. However, albuterol did not prevent O3-induced respiratory symptoms, decrements in forced vital capacity (FVC), forced expired volume in one second (FEV1.0), and maximum midexpiratory flow rate (FEF25-75%), and positive histamine challenges as compared to that with placebo/O3. There were no statistically significant differences in the metabolic data or ride times across all drugs and exposures, although the peak VE was significantly lower with O3 than FA (142.3 vs. 150.7 L/min, respectively) regardless of drug. The results indicate that acute pretreatment with inhaled albuterol is unable to prevent or ameliorate O3-induced symptoms and alterations in pulmonary function and exercise performance. The contribution of beta-adrenergic mechanisms in the acute airway responses to O3 appears to be minimal.

  4. Inhaled albuterol does not protect against ozone toxicity in nonasthmatic athletes

    SciTech Connect

    Gong, H. Jr.; Bedi, J.F.; Horvath, S.M.

    1988-01-01

    We evaluated the acute prophylactic efficacy of albuterol aerosol in protecting nonasthmatic athletes from the untoward effects of 0.21 ppm ozone (O/sub 3/) on symptoms, pulmonary function, exercise performance, and post-exposure histamine bronchoprovocation. Fifteen trained competitive cyclists participated in a randomized crossover study consisting of double-blinded inhalations of albuterol (180 micrograms) and placebo approximately 30 min prior to heavy continuous exercise (minute ventilation, (VE) greater than or equal to 80 L/min) for 60 min, followed by a maximal sprint (peak VE greater than 140 L/min) until exhaustion. Each subject was exposed randomly to either 0.21 ppm O/sub 3/ or filtered air (FA) during the four single-blinded exposure sessions. Albuterol pretreatment resulted in modest but significant bronchodilation as compared to placebo. However, albuterol did not prevent O/sub 3/-induced respiratory symptoms, decrements in forced vital capacity (FVC), forced expired volume in one second (FEV1.0), and maximum midexpiratory flow rate (FEF25-75%), and positive histamine challenges as compared to that with placebo/O/sub 3/. There were no statistically significant differences in the metabolic data or ride times across all drugs and exposures, although the peak VE was significantly lower with O/sub 3/ than FA (142.3 vs. 150.7 L/min, respectively) regardless of drug. The results indicate that acute pretreatment with inhaled albuterol is unable to prevent or ameliorate O/sub 3/-induced symptoms and alterations in pulmonary function and exercise performance. The contribution of beta-adrenergic mechanisms in the acute airway responses to O/sub 3/ appears to be minimal.

  5. Acute toxicity when concentration varies with time: A case study with carbon monoxide inhalation by rats.

    PubMed

    Sweeney, Lisa M; Sommerville, Douglas R; Goodwin, Michelle R; James, R Arden; Channel, Stephen R

    2016-10-01

    Exposure to time-varying concentrations of toxic compounds is the norm in both occupational settings and daily human life, but little has been done to investigate the impact of variations in concentration on toxic outcomes; this case study with carbon monoxide helps fill that gap. Median acute lethality of 10-, 20-, 40-, and 60-min continuous exposures of rats to carbon monoxide was well described by the toxic load model (k = C(n) × t; k is constant, C = test concentration, n = toxic load exponent, and t = exposure duration) with n = 1.74. Dose response-relationships for 1-h exposures including a recovery period between 10- or 20-min pulses showed greater similarity (in both median lethality and steepness of dose-response curve) to continuous exposures with equivalent pulse duration and concentration, rather than a 60-min exposure with equivalent time-weighted average concentrations or toxic load. When pulses were of unequal concentration (3:1 ratio), only the high concentration pulse contributed to lethality. These findings show that fluctuations or interruptions in exposure over a short time scale (60 min or less) can have a substantial impact on outcomes (when n > 1), and thus high-resolution monitoring data are needed to aid interpretation of resulting outcomes.

  6. Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells.

    PubMed

    Büch, Thomas Robert Heinrich; Schäfer, Eva Anna Maria; Demmel, Maria-Theresia; Boekhoff, Ingrid; Thiermann, Horst; Gudermann, Thomas; Steinritz, Dirk; Schmidt, Annette

    2013-12-01

    The cation channel TRPA1 functions as a chemosensory protein and is directly activated by a number of noxious inhalants. A pulmonary expression of TRPA1 has been described in sensory nerve endings and its stimulation leads to the acceleration of inflammatory responses in the lung. Whereas the function of TRPA1 in neuronal cells is well defined, only few reports exist suggesting a role in epithelial cells. The aim of the present study was therefore (1) to evaluate the expression of TRPA1 in pulmonary epithelial cell lines, (2) to characterize TRPA1-promoted signaling in these cells, and (3) to study the extra-neuronal expression of this channel in lung tissue sections. Our results revealed that the widely used alveolar type II cell line A549 expresses TRPA1 at the mRNA and protein level. Furthermore, stimulating A549 cells with known TRPA1 activators (i.e., allyl isothiocyanate) led to an increase in intracellular calcium levels, which was sensitive to the TRPA1 blocker ruthenium red. Investigating TRPA1 coupled downstream signaling cascades it was found that TRPA1 activation elicited a stimulation of ERK1/2 whereas other MAP kinases were not affected. Finally, using epithelial as well as neuronal markers in immunohistochemical approaches, a non-neuronal TRPA1 protein expression was detected in distal parts of the porcine lung epithelium, which was also found examining human lung sections. TRPA1-positive staining co-localized with both epithelial and neuronal markers underlining the observed epithelial expression pattern. Our findings of a functional expression of TRPA1 in pulmonary epithelial cells provide causal evidence for a non-neuronal TRPA1-mediated control of inflammatory responses elicited upon TRPA1-mediated registration of toxic inhalants in vivo. PMID:23994502

  7. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

    PubMed Central

    Gosens, Ilse; Cassee, Flemming R.; Zanella, Michela; Manodori, Laura; Brunelli, Andrea; Costa, Anna Luisa; Bokkers, Bas G. H.; de Jong, Wim H.; Brown, David; Hristozov, Danail; Stone, Vicki

    2016-01-01

    Abstract Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m3 CuO NPs, with a primary particle size of 10 9.2–14 nm and an MMAD of 1.5 μm. Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m3. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m3. The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m3, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period. PMID:27132941

  8. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    PubMed

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J

    2010-01-01

    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  9. Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

    NASA Technical Reports Server (NTRS)

    Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

    2011-01-01

    INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

  10. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... exposure and to characterize toxicologic response following acute high exposures. The latter is of... pulmonary toxicity by examining biochemical and cytologic endpoints of material from the lungs of animals... additional functional and morphological evaluations may be necessary to assess completely the...

  11. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... exposure and to characterize toxicologic response following acute high exposures. The latter is of... pulmonary toxicity by examining biochemical and cytologic endpoints of material from the lungs of animals... additional functional and morphological evaluations may be necessary to assess completely the...

  12. 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.

  13. 40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of... detailed microscopic examination to identify adverse effects of chemical substances on this organ system... histopathologic lesions, body weight changes, effects on mortality, and any other toxic effects. These acute...

  14. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    SciTech Connect

    Nambiar, Madhusoodana P.; Doctor, Bhupendra P.

    2007-03-15

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  15. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.

    PubMed

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  16. A clinical pathologic study of four adult cases of acute mercury inhalation toxicity

    SciTech Connect

    Kanluen, S.; Gottlieb, C.A. )

    1991-01-01

    We report four cases of fatal mercury vapor inhalation, a rare occurrence. The mercury vapor was released at a private home, where one of the occupants was smelting silver from dental amalgam containing an unknown amount of mercury. Within 24 hours of the incident, all occupants began having shortness of breath necessitating hospital admission. The clinical courses are briefly detailed; however, all included rapid deterioration with respiratory failure. Chest roentgenograms in all four cases were consistent with adult respiratory distress syndrome. All patients were treated with dimercaprol, a mercury chelator, but all died, with survival varying from 9 to 23 days postexposure. Autopsies were performed on all four patients. The lungs in all cases were heavy, firm, and airless. Histologic examination revealed severe diffuse alveolar damage, with variable amounts of fibrosis, conforming with acute lung injury in various stages of organization. Additional postmortem findings included acute proximal renal tubular necrosis, vacuolar hepatoxicity, and a spectrum of central nervous system alterations including multifocal ischemic necrosis, gliosis, and vasculitis.

  17. Pulmonary toxicity of well-dispersed single-wall carbon nanotubes after inhalation.

    PubMed

    Morimoto, Yasuo; Hirohashi, Masami; Kobayashi, Norihiro; Ogami, Akira; Horie, Masanori; Oyabu, Takako; Myojo, Toshihiko; Hashiba, Masayoshi; Mizuguchi, Yohei; Kambara, Tatsunori; Lee, Byeong Woo; Kuroda, Etsushi; Shimada, Manabu; Wang, Wei-Ning; Mizuno, Kohei; Yamamoto, Kazuhiro; Fujita, Katsuhide; Nakanishi, Junko; Tanaka, Isamu

    2012-11-01

    Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed SWCNT (diameter of bundle: 0.2 μm; length of bundle: 0.7 μm) for 4 weeks. The low and high mass concentrations of SWCNTs were 0.03 ± 0.003 and 0.13 ± 0.03 mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. There were no increases of total cell or neutrophil counts in the bronchoalveolar lavage fluid (BALF), or the concentration of cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high and low concentration-exposed groups. Pulmonary infiltration of neutrophils was not observed in either exposed group throughout the observation period. Well-dispersed SWCNT did not induce neutrophil inflammation in the lung under the conditions in the present study.

  18. Comparative safety testing of genetically modified foods in a 90-day rat feeding study design allowing the distinction between primary and secondary effects of the new genetic event.

    PubMed

    Knudsen, Ib; Poulsen, Morten

    2007-10-01

    This article discusses the wider experiences regarding the usefulness of the 90-day rat feeding study for the testing of whole foods from genetically modified (GM) plant based on data from a recent EU-project [Poulsen, M., Schrøder, M., Wilcks, A., Kroghsbo, S., Lindecrona, R.H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Taylor, M., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007a. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design. Food Chem. Toxicol. 45, 364-377; Poulsen, M., Kroghsbo, S., Schrøder, M., Wilcks, A., Jacobsen, H., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Shu, Q., Emami, K., Sudhakar, D., Gatehouse, A., Engel, K.-H., Knudsen, I., 2007b. A 90-day safety in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA). Food Chem. Toxicol. 45, 350-363; Schrøder, M., Poulsen, M., Wilcks, A., Kroghsbo, S., Miller, A., Frenzel, T., Danier, J., Rychlik, M., Emami, K., Gatehouse, A., Shu, Q., Engel, K.-H., Knudsen, I., 2007. A 90-day safety study of genetically modified rice expressing Cry1Ab protein (Bacillus thuringiensis toxin) in Wistar rats. Food Chem. Toxicol. 45, 339-349]. The overall objective of the project has been to develop and validate the scientific methodology necessary for assessing the safety of foods from genetically modified plants in accordance with the present EU regulation. The safety assessment in the project is combining the results of the 90-day rat feeding study on the GM food with and without spiking with the pure novel gene product, with the knowledge about the identity of the genetic change, the compositional data of the GM food, the results from in-vitro/ex-vivo studies as well as the results from the preceding 28-day toxicity study with the novel gene product, before the hazard characterisation is concluded. The results demonstrated the ability of the 90-day rat feeding study to detect the biological/toxicological effects of the

  19. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  20. Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats

    NASA Technical Reports Server (NTRS)

    Dodd, D. E.; Stuart, B. O.; Rothenberg, S. J.; Kershaw, M.; Mann, P. C.; James, J. T.; Lam, C. W.

    1994-01-01

    Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced

  1. Cross-fostering inhalation toxicity study with HCFC-123 in lactating Sprague-Dawley rats.

    PubMed

    Buschmann, J; Bartsch, W; Dasenbrock, C; Fuhst, R; Pohlmann, G; Preiss, A; Berger-Preiss, E

    2001-08-01

    A study was performed in Sprague-Dawley rats (Crl:CD BR) to differentiate between effects of hydrofluorocarbon 123 (HCFC-123) on the lactating dam or on the fetus using fostering and cross-fostering of the offspring. Pregnant and/or lactating dams without the pups present were exposed to the test substance (1000 ppm) or clean air by whole-body inhalation for 6 h/day from day 6 to 19 post conceptionem (p.c.) and from day 5 to 21 post partum (p.p.). Pups were cross-fostered to new dams within the first 2 days after birth. Treatment of the mothers with HCFC-123 led to decreases in serum glucose, cholesterol, and triglycerides and increases in absolute and relative maternal liver weights. Decreased litter and individual pup weight and decreased serum triglycerides were observed in the pups of treated foster mothers. Treatment of the mothers with HCFC-123 did not influence milk production based on the body weight difference of the dam before suckling and 60 min after beginning of suckling using 12-pup "standard litters" of untreated dams. Total fat, glucose, and protein contents in the milk were also not influenced by the treatment. Trifluoroacetic acid (TFA), a main metabolite of HCFC-123, was observed in urine samples of standard litters that had been nursed by treated dams. In conclusion, the effects on offspring due to HCFC-123 treatment consisted of decreased pup weight and decreased serum triglycerides at weaning. All effects were due to treatment of the lactating dams, as no prenatally induced effects were found. Since milk production and nutritional constituents of the milk were not influenced, but significant amounts of the main metabolite were found in pup urine, an effect of HCFC-123 or its metabolite on the pups via maternal milk is considered to be a possible cause for their decreased weight gain. PMID:11498800

  2. Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats

    SciTech Connect

    Nitschke, K.D.; Burek, J.D.; Bell, T.J.; Kociba, R.J.; Rampy, L.W.; McKenna, M.J.

    1988-07-01

    Male and female Sprague-Dawley rats were exposed to 0, 50, 200, or 500 ppm methylene chloride for 6 hr/day, 5 days/week for 2 years. Blood carboxyhemoglobin levels were elevated in a dose-dependent (less than linear) manner in rats exposed to 50-500 ppm methylene chloride. Histopathologic lesions related to methylene chloride exposure were confined to the liver and mammary tissue of rats. An increased incidence of hepatocellular vacuolization was observed in male and female rats exposed to 500 ppm methylene chloride. Female rats exposed to 500 ppm methylene chloride also had an increased incidence of multinucleated hepatocytes and number of spontaneous benign mammary tumors/tumor-bearing rat (adenomas, fibromas, and fibroadenomas with no progression toward malignancy); the incidence of benign mammary tumors in female rats exposed to 50 or 200 ppm methylene chloride was comparable to historical control values. No increase in the number of any malignant tumor type was observed in rats exposed to concentrations as high as 500 ppm methylene chloride. Additional groups of female rats were exposed to 500 ppm methylene chloride for the first 12 months or the last 12 months of the 24-month study. The response observed in female rats exposed to 500 ppm for the first 12 months was the same as that observed in female rats exposed to 500 ppm for 2 years. Conversely, the response observed in female rats exposed to 500 ppm during the last 12 months of the study was similar to that observed in control animals. Based upon the results of this study, the no-adverse-effect level for chronic inhalation exposure of Sprague-Dawley rats was judged to be 200 ppm methylene chloride.

  3. Effects of exercise exposure on toxic interactions between inhaled oxidant and aldehyde air pollutants

    SciTech Connect

    Mautz, W.J.; Kleinman, M.T.; Phalen, R.F.; Crocker, T.T.

    1988-01-01

    Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO2) and of O3 and formaldehyde (HCHO) was studied in Sprague-Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium-labeled thymidine. Mixtures of O3 (0.35 or 0.6 ppm) with NO2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O3 (0.6 ppm) resulted in reduced lung injury compared to O3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O3 was present in a mixture. Mixtures of O3 and NO2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO3) vapor. Chemical interactions among the oxidants, HNO3, and other reaction products (N2O5 and nitrate radical) and lung tissue may be the basis for the O3-NO2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O3-HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions.

  4. Evaluating the validity and applicable domain of the toxic load model: impact of concentration vs. time profile on inhalation lethality of hydrogen cyanide.

    PubMed

    Sweeney, Lisa M; Sommerville, Douglas R; Channel, Stephen R; Sharits, Brian C; Gargas, Nathan M; Gut, Chester P

    2015-04-01

    The ten Berge model (or "toxic load" model) is often used to estimate the acute toxicity for varying combinations of inhaled concentration and duration. Expressed as C(n) × t = toxic load (TL), TLs are assumed constant for various combinations of concentration (C) and time (t). Experimental data in a recent acute inhalation study of rats exposed to time-varying concentrations of hydrogen cyanide (HCN) supported the validity of the toxic load model except under very brief, discontinuous, high concentration exposures. In the present investigation, experiments were conducted to extend the evaluation of the applicable domain of the model for acute lethality of HCN in the rat (cumulative exposure range of 2900-11,000 ppm min). The lethality of HCN over very short (< 5 min) durations of high concentrations did not conform to the toxic load model. A value of n=1.57 was determined for uninterrupted exposures ⩾ 5 min. For 30-min exposures, the presence or absence of a gap between two exposure pulses of different concentrations, the relative duration, relative height, and the ordering of the pulses (low then high, vs. high then low) did not appear to have a meaningful impact on the toxic load required for median lethality.

  5. Subacute inhalation toxicity of mineral oils, C sub 15 -C sub 20 alkylbenzenes, and polybutene in male rats

    SciTech Connect

    Skyberg, K.; Skaug, V.; Gylseth, B.; Pedersen, J.R.; Iversen, O.H. Univ. of Oslo )

    1990-10-01

    Male Wistar rats were exposed to mist and vapor of two mineral oils, two C{sub 15}-C{sub 20} alkylbenzenes, and one polybutene at aerosol concentrations of 70 mg {center dot} m{sup {minus}3} and 700 mg {center dot} m{sup {minus}3} for 2 weeks. Of oil mist particles, 82-97 wt% were respirable (<4.7 {mu}m). High-level exposure to polybutene was lethal to three of four animals, due to pulmonary edema. Elevated numbers of pulmonary macrophages and increased macrophage vacuolization were observed after exposure to the polybutene, both mineral oils, and one alkylbenzene. The same alkylbenzene produced body weight loss. Deposition analysis was performed for one mineral oil. No oil was detected in brain tissue, while retroperitoneal fat tissue contained 541 (401-702) {mu}g oil/g tissue, half of this still present after an exposure-free period of 2 weeks. It is concluded that inhalation of the polybutene and one of the mineral cable oils tested here produces toxic effects in lung. In light of the respiratory diseases found in oil mist-exposed cable workers, the experiment was designed to give detailed information on histopathological changes in the respiratory tract.

  6. 78 FR 46322 - Endangered and Threatened Species; 90-Day Finding on Petition To Delist the Southern Oregon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... artificially produced hatchery stocks (70 FR 37160; June 28, 2005). The SCWUA has previously submitted several... be warranted. Negative 90-day findings were published for these petitions on October 7, 2011 (76 FR 62375), January 11, 2012 (77 FR 1668), and September 10, 2012 (77 FR 55458). SCWUA Petition In this...

  7. 76 FR 36053 - Endangered and Threatened Wildlife and Plants; Revised 90-Day Finding on a Petition To Reclassify...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ...-day finding published on February 21, 2007 (72 FR 7843), constituted our compliance with the... Columbia vacated and remanded our February 21, 2007, not- substantial 90-day finding (72 FR 7843) back to... endangered species on June 4, 1973 (38 FR 14678), pursuant to the Endangered Species Conservation Act of...

  8. 75 FR 19925 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List a Distinct...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Biodiversity Project, and others requesting that the Pacific fisher (Martes pennanti pacifica) be listed as an... 90-day finding (56 FR 1159) indicating that the fisher in the Pacific States is a distinct population... habitat needs, population size and trends, and demographic parameters (56 FR 1159). On December 29,...

  9. 75 FR 52928 - Endangered and Threatened Wildlife and Plants; Notice of 90-Day Finding for a Petition to List...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... rockfish and tiger rockfish) was insubstantial and we therefore did not conduct status reviews (64 FR 33037... segments of Puget Sound/Georgia Basin distinct population segments of rockfish, 75 FR 22276 (April 28, 2010...; Notice of 90-Day Finding for a Petition to List Georgia Basin Populations of China Rockfish and...

  10. 75 FR 42059 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Giant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... that listing the GPE may be warranted (72 FR 57273). On January 24, 2008, the petitioners filed a... presented a threat (72 FR 57273). The 2009 petition includes a letter of support from Samuel W. James... educational purposes as a potential threat to the GPE. In our October 9, 2007, 90-day finding (72 FR 57273)...

  11. 77 FR 43799 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Gila...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... for feeding, breeding, and sheltering; (b) Genetics and taxonomy; (c) Historical and current range... Regional Office. On December 16, 2009 (74 FR 66866), we published a partial 90-day finding on the petition... from dog and horse waste, manipulation and alteration of streamflow by swimmers, and the trampling...

  12. 76 FR 10299 - Endangered and Threatened Wildlife and Plants: 90-Day Finding on a Petition To List the Wild...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... completed a 90-day finding on August 15, 2007 (72 FR 45717). Based upon the information available at that... FR 54707), for the Arctic grayling (Thymallus arcticus) and a 12-month finding published on September 22, 2010, for the plant Agave eggersiana (75 FR 57720), we have focused on wild populations in...

  13. 78 FR 23533 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To Delist the Wood Bison

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... February 8, 2011 (76 FR ] 6734). Please refer to that document for the complete listing history. Here we... Wildlife, which was published in the Federal Register on June 2, 1970 (35 FR 8491). In 1974, the first list... of Wild Fauna and Flora (CITES). In a 90-day finding published on November 25, 1998 (63 FR 65164),...

  14. 76 FR 60431 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the American...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ..., 2005, the Service issued a 90-day finding (70 FR 38849), which found that the petition presented... threatened or ] endangered was not warranted (72 FR 4967). Species Information This section is a summary of the species information presented in the Service's 2007 12-month finding (72 FR 4967),...

  15. 77 FR 21920 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... a notice of a 90-day finding for the petition in the Federal Register on July 22, 1994 (59 FR 37439... warranted but precluded by other higher priority actions (60 FR 15281). At that time, a listing priority..., 2005 (70 FR 24870). On October 7, 2002, as part of an agreement regarding multiple species, the...

  16. 75 FR 23654 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List Hermes Copper...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... finding (71 FR 44966, August 8, 2006) is limited to Marschalek and Deutschman's (2008) study of the effect... previous 90-day finding published in the Federal Register on August 8, 2006 (71 FR 44966). Previous Federal... Hermes copper (71 FR 44966) or Thorne's hairstreak butterflies (71 FR 44980) was warranted. (For...

  17. 75 FR 18782 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's Hairstreak Butterfly as Endangered Correction In Federal...

  18. 76 FR 23256 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Arapahoe...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... assertion in the petition that mountain biking can cause soil erosion and compaction, degraded water quality... the western United States have been well documented, and include increased soil erosion, sedimentation... published two 90-day findings, on January 6, 2009 (74 FR 419), and February 5, 2009 (74 FR 6122)....

  19. 78 FR 13614 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List the Humphead Wrasse as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ..., delisting, and reclassifying a species under the ESA (``DPS Policy''; 61 FR 4722; February 7, 1996). A... publications, copies of reports or letters from authorities, and maps (50 CFR 424.14(b)(2)). At the 90-day..., including parts of Fiji, southwestern Indian Ocean and the South China Sea (Sadovy et al., 2003). Threats...

  20. 77 FR 55458 - Endangered and Threatened Species; 90-Day Finding on Petition To Delist the Southern Oregon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ... these petitions was published on October 7, 2011 (76 FR 62375) and a second negative 90-day finding for the fourth petition was published on January 11, 2012 (77 FR 1668). The new petition largely..., and drought) rather than man-made factors are responsible for the decline in coho salmon...

  1. 90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol.

    PubMed

    Biegel, L B; Flaws, J A; Hirshfield, A N; O'Connor, J C; Elliott, G S; Ladics, G S; Silbergeld, E K; Van Pelt, C S; Hurtt, M E; Cook, J C; Frame, S R

    1998-08-01

    Over the past several years, there has been increasing concern that chemicals and pesticides found in the environment may mimic endogenous estrogens, potentially producing adverse effects in wildlife and human populations. Because estrogenicity is one of the primary concerns, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to set dose levels for future multigenerational reproduction and combined chronic toxicity/oncogenicity studies. The purpose of these studies is to evaluate the significance of a range of responses as well as to provide benchmark data for a risk assessment for chemicals with estrogen-like activities. This 90-day/one-generation reproduction study was conducted in male and female Crl:CD BR rats using dietary concentrations of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In addition, several mechanistic/biochemical endpoints were evaluated for their usefulness in follow-up studies. In the P1 generation, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced dose-dependent decreases in body weight, body weight gain, food consumption, and food efficiency. At 10 and 50 ppm 17 beta-estradiol, minimal to mild nonregenerative anemia, lymphopenia, decreased serum cholesterol (50 ppm only), and altered splenic lymphocyte subtypes were also observed in the P1 generation. Additionally, at these concentrations, there were changes in the weights of several organs. Evidence of ovarian malfunction, characterized by reduced numbers of corpora lutea and large antral follicles, was observed at 2.5 ppm 17 beta-estradiol and above. Other pathologic changes in males and females fed 10 and 50 ppm 17 beta-estradiol included centrilobular hepatocellular hypertrophy; diffuse hyperplasia of the pituitary gland; feminization of the male mammary glands; mammary gland hyperplasia in females; increased number of cystic follicles in the ovary

  2. Subchronic inhalation of diethylamine vapor in Fischer-344 rats: organ system toxicity.

    PubMed

    Lynch, D W; Moorman, W J; Stober, P; Lewis, T R; Iverson, W O

    1986-04-01

    Male and female Fischer 344 (F-344) rats were exposed at 0,25 or 250 ppm diethylamine (DEA) vapor, 6.5 hr per day, 5 days per week, for 24 weeks in order to assess cardiac and other organ system toxicity. Scheduled sacrifices were performed following 30, 60, and 120 days of exposure. During the first 2 weeks of exposure, the rats exposed at 250 ppm DEA did not gain weight. After 2 weeks, however, the rate of weight gain of these rats was greater than that of controls. Nevertheless, mean body weights for both sexes of rats exposed at 250 ppm DEA remained depressed compared to controls throughout the study. Sneezing, tearing, and reddened noses were seen in rats exposed at 250 ppm DEA. Histopathologic examinations revealed lesions of the nasal mucosa of rats exposed at 250 ppm DEA (rats exposed at 25 ppm were not evaluated). These lesions of the respiratory epithelium consisted of squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia. There were no pronounced treatment-related effects on organ weights, hematology, or clinical chemistry indices except for blood urea nitrogen which was evaluated in rats of both sexes exposed at 250 ppm DEA for 24 weeks. In contrast to the high-dose animals, no treatment-related effects were observed in rats intermittently exposed at 25 ppm DEA for up to 24 weeks. No evidence of cardiotoxicity was seen in rats exposed to either DEA concentration for up to 24 weeks. PMID:3699339

  3. Inhalation of mercury vapor can cause the toxic effects on rat kidney.

    PubMed

    Akgül, Nilgün; Altunkaynak, Berrin Zuhal; Altunkaynak, Muhammed Eyüp; Deniz, Ömür Gülsüm; Ünal, Deniz; Akgül, Hayati Murat

    2016-01-01

    Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Atatürk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model.

  4. A global initiative to refine acute inhalation studies through the use of 'evident toxicity' as an endpoint: Towards adoption of the fixed concentration procedure.

    PubMed

    Sewell, Fiona; Ragan, Ian; Marczylo, Tim; Anderson, Brian; Braun, Anne; Casey, Warren; Dennison, Ngaire; Griffiths, David; Guest, Robert; Holmes, Tom; van Huygevoort, Ton; Indans, Ian; Kenny, Terry; Kojima, Hajime; Lee, Kyuhong; Prieto, Pilar; Smith, Paul; Smedley, Jason; Stokes, William S; Wnorowski, Gary; Horgan, Graham

    2015-12-01

    Acute inhalation studies are conducted in animals as part of chemical hazard identification and characterisation, including for classification and labelling purposes. Current accepted methods use death as an endpoint (OECD TG403 and TG436), whereas the fixed concentration procedure (FCP) (draft OECD TG433) uses fewer animals and replaces lethality as an endpoint with 'evident toxicity.' Evident toxicity is defined as clear signs of toxicity that predict exposure to the next highest concentration will cause severe toxicity or death in most animals. A global initiative including 20 organisations, led by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has shared data on the clinical signs recorded during acute inhalation studies for 172 substances (primarily dusts or mists) with the aim of making evident toxicity more objective and transferable between laboratories. Pairs of studies (5 male or 5 female rats) with at least a two-fold change in concentration were analysed to determine if there are any signs at the lower dose that could have predicted severe toxicity or death at the higher concentration. The results show that signs such as body weight loss (>10% pre-dosing weight), irregular respiration, tremors and hypoactivity, seen at least once in at least one animal after the day of dosing are highly predictive (positive predictive value > 90%) of severe toxicity or death at the next highest concentration. The working group has used these data to propose changes to TG433 that incorporate a clear indication of the clinical signs that define evident toxicity.

  5. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments

    PubMed Central

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-01-01

    Abstract Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m3 as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  6. Toxicity of divinylbenzene-55 for B6C3F1 mice in a two-week inhalation study.

    PubMed

    Morgan, D L; Mahler, J F; Wilson, R E; Moorman, M P; Price, H C; O'connor, R W

    1997-10-01

    Divinylbenzene (DVB) is a crosslinking monomer used primarily for copolymerization with styrene to produce ion-exchange resins. The toxicity of inhaled DVB was investigated because of the potential for worker exposure and the structural similarity of DVB to styrene, a potential carcinogen. Male and female B6C3F1 mice were exposed to 0, 25, 50, or 75 ppm DVB for 6 hr/day, 5 days/week for up to 2 weeks. Six mice/sex/dose group were killed after 3, 5, and 10 exposures and six mice/sex in the 75 ppm group were killed 7 days after 10 exposures. The most severe effects occurred in the nasal cavity and liver, with less severe effects occurring in the kidneys. In the nasal cavity olfactory epithelium acute necrosis and inflammation were present at early time points followed by regeneration, architectural reorganization, and focal respiratory metaplasia by 7 days after the last exposure. Olfactory epithelial changes were concentration-dependent with extensive involvement at 75 ppm and peripheral sparing at 25 ppm. There was also necrosis and regeneration of olfactory-associated Bowman's glands as well as the lateral nasal (Steno's) glands. Hepatocellular centrilobular (CL) necrosis was observed only in the 75 ppm dose group and was similar to that caused by styrene. A time-dependent progression was observed, characterized by CL degeneration after 1 exposure, necrosis after 3 and 5 exposures, and chronic inflammation with CL karyomegaly after 10 exposures and 7 days after the 10th exposure. Hepatic GSH levels were decreased in a dose-dependent manner. In the kidneys, transient tubular damage was observed in some male mice exposed to 75 ppm, and appeared to be a response to DVB-induced tubular epithelial injury.

  7. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments.

    PubMed

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert

    2016-08-01

    Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m(3) as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  8. Visual-motor response of crewmen during a simulated 90-day space mission as measured by the critical task battery

    NASA Technical Reports Server (NTRS)

    Allen, R. W.; Jex, H. R.

    1973-01-01

    In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in a space station simulator for 90 days and administered a tracking test battery. The battery included a clinical test (Critical Instability Task) designed to measure a subject's dynamic time delay, and a more conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The levels of each parameter span the range observed with professional pilots and astronaut candidates tested previously. The chamber environment caused no significant decrement on the average crewman's dynamic response behavior, and the subjects continued to improve slightly in their tracking skills during the 90-day confinement period.

  9. 76 FR 9309 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Sand...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ...We, the U.S. Fish and Wildlife Service, announce a 90-day finding on a petition to list the sand verbena moth, Copablepharon fuscum, as endangered or threatened under the Endangered Species Act of 1973, as amended. Based on our review, we find the petition presents substantial information indicating that listing the sand verbena moth may be warranted. Therefore, with the publication of this......

  10. Chronic kidney disease is associated with a higher 90-day mortality than other chronic medical conditions in patients with sepsis

    PubMed Central

    Mansur, Ashham; Mulwande, Evelyn; Steinau, Maximilian; Bergmann, Ingo; Frederik Popov, Aron; Ghadimi, Michael; Beissbarth, Tim; Bauer, Martin; Hinz, José

    2015-01-01

    According to previous studies, the clinical course of sepsis could be affected by preexisting medical conditions, which are very common among patients with sepsis. This observational study aimed at investigating whether common chronic medical conditions affect the 90-day mortality risk in adult Caucasian patients with sepsis. A total of 482 patients with sepsis were enrolled in this study. The ninety-day mortality was the primary outcome; organ failure was the secondary outcome. Sepsis-related organ failure assessment (SOFA) scores and the requirements for organ support were evaluated to assess organ failure. A multivariate Cox regression model for the association between the 90-day mortality risk and chronic preexisting medical conditions adjusted for all relevant confounders and mortality predictors revealed the highest hazard ratio for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46-3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without CKD (8.9 ± 4.0 and 6.5 ± 3.4, respectively; p < 0.0001). Additionally, an analysis of organ-specific SOFA scores revealed higher scores in three organ systems (kidney, cardiovascular and coagulation). Patients with CKD have the highest 90-day mortality risk compared with patients without CKD or with other chronic medical conditions. PMID:25995131

  11. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic cracked naphtha distillate in rats.

    PubMed

    Lapin, C; Bui, Q; Breglia, R; Koschier, F; Podhasky, P; Lapadula, E; Roth, R; Schreiner, C; White, R; Clark, C; Mandella, R; Hoffman, G

    2001-01-01

    A 15-week, whole-body inhalation study of the vapors of a distillate (LCCN-D) of light catalytic cracked naphtha (CAS no. 64741-55-5, LCCN) was conducted with Sprague-Dawley rats. Target exposure concentrations were 0, 750, 2500, and 7500 ppm for 6 hours/day, 5 days/week. Over the course of the study, animals received at least 65 exposures. For a portion of the control and 7500-ppm groups, a 4-week postexposure period was included in the study. Subchronic toxicity was evaluated using standard parameters. During life, neurotoxicity was evaluated by motor activity assessment and a functional observational battery. Selected tissues from animals in all exposure groups were examined microscopically. Neuropathologic examination of selected neuronal tissues from animals in the control and high-exposure groups was also conducted. No compound-related effects were seen on survival, clinical chemistry, food consumption, or physical signs. No evidence of neurotoxicity was seen at any exposure level. Slight decreases in hematocrit and hemoglobin concentrations were seen in male rats at the end of exposure to 7500 ppm LCCN-D. However, values were within normal physiological ranges and recovery occurred. Slight decreases in mean body weights and body weight gain were observed in high-exposure females during the first 7 weeks of exposure, but this decrease was not seen during the second half of the study. Male rat nephropathy involving hyaline droplet formation and alpha-2micro-globulin accumulation was seen in mid- and high-exposure males, an effect not relevant to humans. The incidence and severity of goblet cell hypertrophy/hyperplasia and respiratory epithelium hyperplasia in nasoturbinal tissues were greater in high-exposure animals, but recovery occurred. None of the effects observed were considered toxicologically significant. The no-observable-adverse-effect level (NOAEL) for subchronic and neurotoxicity of LCCN-D was > or = 7500 ppm.

  12. Direct measurement of toxicants inhaled by water pipe users in the natural environment using a real-time in situ sampling technique.

    PubMed

    Katurji, M; Daher, N; Sheheitli, H; Saleh, R; Shihadeh, A

    2010-11-01

    While narghile water pipe smoking has become a global phenomenon, knowledge regarding its toxicant content and delivery, addictive properties, and health consequences is sorely lagging. One challenge in measuring toxicant content of the smoke in the laboratory is the large number of simplifying assumptions that must be made to model a "typical" smoking session using a smoking machine, resulting in uncertainty over the obtained toxicant yields. In this study, we develop an alternative approach in which smoke generated by a human water pipe user is sampled directly during the smoking session. The method, dubbed real-time in situ sampling (RINS), required developing a self-powered portable instrument capable of automatically sampling a fixed fraction of the smoke generated by the user. Instrument performance was validated in the laboratory, and the instrument was deployed in a field study involving 43 ad libitum water pipe use sessions in Beirut area cafés in which we measured inhaled nicotine, carbon monoxide (CO), and water pipe ma'ssel-derived "tar." We found that users drew a mean of 119 L of smoke containing 150 mg of CO, 4 mg of nicotine, and 602 mg of ma'ssel-derived "tar" during a single use session (mean duration = 61 min). These first direct measurements of toxicant delivery demonstrate that ordinary water pipe use involves inhaling large quantities of CO, nicotine, and dry particulate matter. Results are compared with those obtained using the Beirut method smoking machine protocol. PMID:21062108

  13. Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light catalytic reformed naphtha distillate in rats.

    PubMed

    Schreiner, C; Bui, Q; Breglia, R; Burnett, D; Koschier, F; Lapadula, E; Podhasky, P; White, R

    2000-08-11

    A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on

  14. Compositional and toxicological analysis of a GM potato line with reduced α-solanine content--a 90-day feeding study in the Syrian Golden hamster.

    PubMed

    Langkilde, Søren; Schrøder, Malene; Frank, Thomas; Shepherd, Louise V T; Conner, Sean; Davies, Howard V; Meyer, Otto; Danier, Jürgen; Rychlik, Michael; Belknap, William R; McCue, Kent F; Engel, Karl-Heinz; Stewart, Derek; Knudsen, Ib; Poulsen, Morten

    2012-10-01

    Steroidal glycoalkaloids (GAs) are toxins, produced by plants of the Solanaceae family. The potato plant (Solanum tuberosum L.) and its tubers predominantly contain the two GAs α-chaconine and α-solanine. These compounds are believed to act in synergy, and the degree of toxicity may therefore depend on their ratio in the potato. To determine the influence of α-solanine: α-chaconine ratio in potatoes on toxicity, a GM potato line (SGT 9-2) with reduced α-solanine content, and the parental control line (Desirée wild-type) having a traditional α-solanine: α-chaconine ratio were (1) studied for compositional similarity by analysing for a range of potato constituents, and (2) used in a 90-day feeding trial with the Syrian Golden hamster to study differential toxicity. The animal feeding study used diets with up to 60% freeze-dried potato powder from either line. Whilst data indicated some compositional differences between the GM line and its wildtype control these did not raise concerns related to nutritional value or safety. Results of the feeding trials showed a low number of significant differences between potato lines with different α-solanine: α-chaconine ratio but none were considered to raise safety concerns with regard to human (or animal) consumption.

  15. Multiple-dose chronic inhalation toxicity study of size-separated kaolin refractory ceramic fiber in male Fischer 344 rats.

    PubMed

    Mast, R W; McConnell, E E; Hesterberg, T W; Chevalier, J; Kotin, P; Thevenaz, P; Bernstein, D M; Glass, L R; Miiller, W; Anderson, R

    1995-01-01

    Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure an in an effort to define the dose-response, as a follow up to a maximum tolerated dose [30 mg/m(3)] study in rats (Mast et al., 1995), a multiple dose chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Four groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 3, 9, or 16 mg/m(3)(approximately 36, 91, and 162 fibers/cm(3)) of kaolin-based "size-selected" RCF fibers (approximately 1 µm in diameter and approximately 20 µm in length) for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and sacrificed (30 mo). Croups of 3-6 animals were sacrificed at 3, 6, 12, 18, and 24 mo to follow the progression of pulmonary lesions and to determine fiber lung burdens. Additional groups of 3-6 rats were removed from exposure at 3, 6, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. A dose-related increase in fiber lung burden was observed. Lung burdens at 24 mo ranged from 5.6 × 10(4) to 27.8 × 10(4) fibers/mg dry lung tissue. Significant increases in lung weights and lung to body weight ratios were seen in the high-dose group. Treatment-related lesions were restricted to the lungs. To some extent, all doses of RCF resulted in minimal to mild macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 12 mo of exposure. Interstitial fibrosis was observed at 12 mo in the 9 and 16 mg/m(3) groups but not in the low-dose group at any time point. A minimal amount of focal pleural fibrosis was first observed at 12 mo in the 9 and 76 mg/m(3) dose groups and progressed to a mild severity in the high

  16. Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats.

    PubMed

    Mast, R W; McConnell, E E; Anderson, R; Chevalier, J; Kotin, P; Bernstein, D M; Thevenaz, P; Glass, L R; Miiller, W C; Hesterberg, T W

    1995-01-01

    Abstract Refractory ceramic fibers (RCF) are man-made vitreous fibers used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of their increasing use and potential for human exposure, a chronic toxicity/carcinogenicity inhalation study was conducted in Fischer 344 (F344) rats. Five groups of 140 weanling male F344 rats were exposed via noseonly inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m(3) (approximately 220 fibers/cm(3)) of three types [kaolin-based, high-purity, and aluminum zirconia silica (AZS)] of "size-selected" RCF fibers (approximately 1µ in diameter and approximately 20 um in length) and an "after-service" heat-treated (2400°F for 24 h) kaolin-based fiber for 6 h/day, 5 days/wk for 24 mo. They were then held unexposed until approximately 20% survival and then sacrificed at 30 mo. A positive control group of 80 F344 rats was exposed to 10 mg/m(3) chrysotile asbestos. Croups of 3-6 animals were sacrificed at 3, 6, 9, 12, 15, 18, and 24 mo to follow the progression of lesions and to determine fiber lung burdens. Additional groups of 3 rats were removed from exposure at 3, 6, 9, 12, and 18 mo and were held until sacrificed at 24 mo (recovery groups) for similar determinations. Lung burdens increased rapidly for all RCFs, appearing to plateau by about 12 mo. By 24 mo, lung burdens ranged from 2.6 to 9.6 × 10(5) fiberslmg of dry lung tissue for the RCFs tested. Treatment-related lesions were restricted to the lungs. To some extent all types of RCF resulted in macrophage infiltration, bronchiolization of proximal alveoli, and microgranuloma formation by 3 mo of exposure. Interstitial fibrosis was observed at 6 mo for all types of RCF, except the "after-service" fiber where fibrosis was not seen until 12 mo. The lesions progressed in severity until 12-15 mo, after which they plateaued. A minimal amount of focal pleural fibrosis was first observed at 9 mo and progressed to a

  17. First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

    PubMed Central

    Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

    2015-01-01

    Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

  18. Subchronic inhalation toxicity of iron oxide (magnetite, Fe(3) O(4) ) in rats: pulmonary toxicity is determined by the particle kinetics typical of poorly soluble particles.

    PubMed

    Pauluhn, Jürgen

    2012-07-01

    Wistar rats were nose-only exposed to pigment-sized iron oxide dust (Fe(3) O(4) , magnetite) in a subchronic 13-week inhalation study according to the OECD testing guidelines TG#413 and GD#39. A 4 week pilot study with a 6 month post exposure period served as basis for validating the kinetic modeling approaches utilized to design the subchronic study. Kinetic analyses made during this post exposure period demonstrated that a diminution in particle clearance and lung inflammation occurred at cumulative exposure levels exceeding the lung overload threshold. Animals were exposed 6 h per day, five days per week for 13 consecutive weeks at actual concentrations of 0, 4.7, 16.6 and 52.1 mg m(-3) (mass median aerodynamic diameter ≈1.3 μm, geometric standard deviation = 2). The exposure to iron oxide dust was tolerated without mortality, consistent changes in body weights, food and water consumption or systemic toxicity. While general clinical pathology and urinalysis were unobtrusive, hematology revealed changes of unclear toxicological significance (minimally increased differential neutrophil counts in peripheral blood). Elevations of neutrophils in bronchoalveolar lavage (BAL) appeared to be the most sensitive endpoint of study. Histopathology demonstrated responses to particle deposition in the upper respiratory tract (goblet cell hyper- and/or metaplasia, intraepithelial eosinophilic globules in the nasal passages) and the lower respiratory tract (inflammatory changes in the bronchiolo-alveolar region). Consistent changes suggestive of pulmonary inflammation were evidenced by BAL, histopathology, increased lung and lung-associated-lymph node (LALN) weights at 16.6 and 52.1 mg m(-3) . Increased septal collagenous fibers were observed at 52.1 mg m(-3) . Particle translocation into LALN occurred at exposure levels causing pulmonary inflammation. In summary, the retention kinetics iron oxide reflected that of poorly soluble particles. The empirical

  19. Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system in male rats.

    PubMed

    Wang, Er Hui; Yu, Zhou; Hu, Jing; Xu, Hai Bin

    2013-12-01

    Rice is a staple food crop; however, the threat of pests leads to a serious decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice MingHui63 to produce insect-resistant rice TT51. This study was undertaken to investigate potential unintended effects of TT51 on the reproductive system in male rats. Male rats were treated with diets containing 60% of either TT51 or MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An additional negative control group of rats were fed with a rice-based AIN93G diet. Body weights, food intake, hematology, serum chemistry, serum hormone levels, sperm parameters and relative organ/body weights were measured, and gross as well as microscopic pathology were examined. No diet-related significant differences in the values of response variables were observed between rats that were fed with diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding study. In addition, necropsy and histopathology examination indicated no treatment-related changes. The results from the present study indicated that TT51 does not appear to exert any effect on the reproductive system in male rats compared with MingHui63 or the control.

  20. The development and succession of microbial communities in 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Sun, Yi; Liu, Hong; Fu, Yuming; Liu, Bojie; Su, Qiang; Xie, Beizhen; Qin, Youcai; Dong, Chen; Liu, Guanghui

    Lunar Palace 1, as an integrative experiment facility for permanent astrobase life-support artificial closed ecosystem, is an artificial ecosystem which consists of plant cultivation, animal breeding and waste treatment units. It has been used to carry out a 90-day bioregenerative life support experiment with three crew members. Apparently, it’s hard to prevent the growth of microorganisms in such closed ecosystem for their strong adaptive capacity. Original microorganisms in the cabin, microbes in the course of loads delivery and the autologous microorganism by crew members and animals themselves are all the main source of the interior microorganisms, which may grow and regenerate in air, water and plants. Therefore, if these microorganisms could not be effectively monitored and controlled, it may cause microbial contamination and even lead to the unsteadiness of the whole closed ecosystem. In this study, the development and succession of the microbial communities of air, water system, plant system, and key facilities surfaces in Lunar Palace 1 were continuously monitored and analyzed by using plate counting method and molecular biological method during the 90-day experiment. The results were quite useful for the controlling of internal microorganisms and the safe operation of the whole system, and could also reveal the succession rules of microorganisms in an artificial closed ecosystem.

  1. 90-Day Cycle: Exploration of Math Intensives as a Strategy to Move More Community College Students out of Developmental Math Courses

    ERIC Educational Resources Information Center

    Sherer, Jennifer Zoltners; Grunow, Alicia

    2010-01-01

    The authors prepared this report after exploring programs using a 90-day cycle process borrowed from the Institute for Healthcare Improvement (IHI). The IHI 90-day cycle scans activity in the field as a "quick way to research innovative ideas and assess their potential for advancing quality improvement". The goal was to "get under the hood" of…

  2. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain

    EPA Science Inventory

    The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute an...

  3. Analysis of Air Toxics From NOAA WP-3 Aircraft Measurements During the TexAQS 2006 Campaign: Comparison With Emission Inventories and Additive Inhalation Risk Factors

    NASA Astrophysics Data System (ADS)

    Del Negro, L. A.; Warneke, C.; de Gouw, J. A.; Atlas, E.; Lueb, R.; Zhu, X.; Pope, L.; Schauffler, S.; Hendershot, R.; Washenfelder, R.; Fried, A.; Richter, D.; Walega, J. G.; Weibring, P.

    2007-12-01

    Benzene and nine other air toxics classified as human carcinogens by the International Agency for Research on Cancer (IARC) were measured from the NOAA WP-3 aircraft during the TexAQS 2006 campaign. In-situ measurements of benzene, measured with a PTR-MS instrument, are used to estimate emission fluxes for comparison with point source emission inventories developed by the Texas Commission on Environmental Quality. Mean and median mixing ratios for benzene, acetaldehyde, formaldehyde, 1,3-butadiene, carbon tetrachloride, chloroform, 1,2-dichloroethane, dibromoethane, dichloromethane, and vinyl chloride, encountered over the city of Houston during the campaign, are combined with inhalation unit risk factor values developed by the California Environmental Protection Agency and the United States Environmental Protection Agency to estimate the additive inhalation risk factor. This additive risk factor represents the risk associated with lifetime (70 year) exposure at the levels measured and should not be used as an absolute indicator of risk to individuals. However, the results are useful for assessments of changing relative risk over time, and for identifying dominant contributions to the overall air toxic risk.

  4. Overview of inhalation toxicology.

    PubMed Central

    Dorato, M A

    1990-01-01

    The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres of a wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals. Images FIGURE 1. FIGURE 3. FIGURE 7. FIGURE 8. PMID:2200660

  5. Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

    A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

  6. A 90-day safety study in Wistar rats fed genetically modified rice expressing snowdrop lectin Galanthus nivalis (GNA).

    PubMed

    Poulsen, Morten; Kroghsbo, Stine; Schrøder, Malene; Wilcks, Andrea; Jacobsen, Helene; Miller, Andreas; Frenzel, Thomas; Danier, Jürgen; Rychlik, Michael; Shu, Qingyao; Emami, Kaveh; Sudhakar, Duraialagraja; Gatehouse, Angharad; Engel, Karl-Heinz; Knudsen, Ib

    2007-03-01

    Genetically modified plants expressing insecticidal traits offer a new strategy for crop protection, but at the same time present a challenge in terms of food safety assessment. The present 90-day feeding study was designed to assess the safety of a rice variety expressing the snowdrop Galanthus nivalis lectin (GNA lectin), and forms part of a EU-funded project where the objective has been to develop and validate sensitive and specific methods to assess the safety of genetically modified foods. Male and female Wistar rats were given a purified diet containing either 60% genetically modified or parental rice for 90 days. This corresponds to a mean daily GNA lectin intake of approximately 58 and 67mg/kg body weight for males and females, respectively. Prior to the animal study comprehensive analytical characterization of both rice materials was performed. The chemical analyses showed a number of statistically significant differences, with the majority being within the ranges reported in the literature. In the animal study a range of clinical, biological, immunological, microbiological and pathological parameters were examined. A number of significant differences were seen between groups fed the two diets, but none of them were considered to be adverse. In conclusion, the design of the present animal study did not enable us to conclude on the safety of the GM food. Additional group(s) where the expressed gene products have been spiked to the diet should be included in order to be able to distinguish whether the observed effects were due to the GNA lectin per se or to secondary changes in the GM rice.

  7. A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

    PubMed Central

    Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

  8. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    PubMed

    Bai, Hai; Wang, Zhixian; Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals.

  9. Physico-chemical properties of a novel (-)-hydroxycitric acid extract and its effect on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological changes over a period of 90 days.

    PubMed

    Shara, Michael; Ohia, Sunny E; Schmidt, Robert E; Yasmin, Taharat; Zardetto-Smith, Andrea; Kincaid, Anthony; Bagchi, Manashi; Chatterjee, Archana; Bagchi, Debasis; Stohs, Sidney J

    2004-05-01

    Garcinia cambogia-derived (-)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia (HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control

  10. Developmental toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose-response modeling for estimation of benchmark doses

    SciTech Connect

    Rogers, J.M.; Mole, M.L.; Chernoff, N.; Barbee, B.D.; Turner, C.I.

    1993-01-01

    Pregnant CD-1 mice were exposed to 1,000, 2,000, 5,000, 7,500, 10,000, or 15,000 ppm on methanol for 7 hr/day on days 6-15 of gestation. On day 17 of gestation, remaining mice were weighed, killed and the gravid uterus was removed. Numbers of implantation sites, live and dead fetuses and resorptions were counted, and fetuses were examined externally and weighed as a litter. Significant increases in the incidence of exencephaly and cleft palate were observed at 5,000 ppm and above, increased postimplantation mortality at 7,500 ppm and above (including an increasing incidence of full-litter resorption), and reduced fetal weight at 10,000 ppm and above. A dose-related increase in cervical ribs or ossification sites lateral to the seventh cervical vertebra was significant at 2,000 ppm and above. Thus, the NOAEL for the developmental toxicity in this study is 1,000 ppm. The results of this study indicate that inhaled methanol is developmentally toxic in the mouse at exposure levels which were not maternally toxic. Litters of pregnant mice gavaged orally with 4 g methanol/kg displayed developmental toxic effects similar to those seen in the 10,000 ppm methanol exposure group. (Copyright (c) 1993 Wiley-Liss, Inc.)

  11. Pulmonary toxicity studies in rats with triethoxyoctylsilane (OTES)-coated, pigment-grade titanium dioxide particles: bridging studies to predict inhalation hazard.

    PubMed

    Warheit, D B; Reed, K L; Webb, T R

    2003-12-01

    The aim of this study was to assess and compare the acute lung toxicities of intratracheally instilled hydrophobic relative to hydrophilic surface-coated titanium dioxide (TiO(2)) particles using a pulmonary bridging methodology. In addition, the results of these instillation studies were bridged with data previously generated from inhalation studies with hydrophilic, pigment-grade (base) TiO(2) particles, using the base, pigment-grade TiO(2) particles as the inhalation/instillation bridge material. To conduct toxicity comparisons, the surface coatings of base pigment-grade TiO(2) particles were made hydrophobic by application of triethoxyoctylsilane (OTES), a commercial product used in plastics applications. For the bioassay experimental design, rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO(2) particle-types: (1) base (hydrophilic) TiO(2) particles; (2) TiO(2) with OTES surface coating; (3) base TiO(2) with Tween 80; or (4) OTES TiO(2) with Tween 80. Saline instilled rats served as controls. Following exposures, the lungs of sham- and TiO(2)-exposed rats were assessed both using bronchoalveolar lavage (BAL) biomarkers and by histopathology of lung tissue at 24 hours, 1 week, 1 month, and 3 months post exposure. The results demonstrated that only the base, high-dose (10 mg/kg) pigment-grade TiO(2) particles and those with particle-types containing Tween 80 produced a transient pulmonary inflammatory response, and this was reversible within 1 week postexposure. The authors conclude that the OTES hydrophobic coating on the pigment-grade TiO(2) particle does not cause significant pulmonary toxicity.

  12. Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863).

    PubMed

    Doull, J; Gaylor, D; Greim, H A; Lovell, D P; Lynch, B; Munro, I C

    2007-11-01

    MON 863, a genetically engineered corn variety that contains the gene for modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm, was tested in a 90-day toxicity study as part of the process to gain regulatory approval. This study was reanalyzed by Séralini et al. who contended that the study showed possible hepatorenal effects of MON 863. An Expert Panel was convened to assess the original study results as analyzed by the Monsanto Company and the reanalysis conducted by Séralini et al. The Expert Panel concludes that the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was associated with adverse effects in the 90-day rat study. In each case, statistical findings reported by both Monsanto and Séralini et al. were considered to be unrelated to treatment or of no biological or clinical importance because they failed to demonstrate a dose-response relationship, reproducibility over time, association with other relevant changes (e.g., histopathology), occurrence in both sexes, difference outside the normal range of variation, or biological plausibility with respect to cause-and-effect. The Séralini et al. reanalysis does not advance any new scientific data to indicate that MON 863 caused adverse effects in the 90-day rat study.

  13. Subacute inhalation toxicity of a medium-boiling coal liquefaction product (154-378 degrees C) in the rat [Part III].

    PubMed

    Chu, I; Rinehart, W; Hoffman, G; Villeneuve, D C; Otson, R; Valli, V E

    1989-01-01

    The short-term inhalation toxicity of a medium-boiling coal liquefaction product (CLP) was investigated in the rat. Groups of 5 male and 5 female Sprague-Dawley rats were exposed to CLP aerosols at 25 mg/m3 (low dose) or 100 mg/m3 (high dose) 6 h/d, 5 d/w, for 4 wk. The control group was exposed to filtered air while the positive control received diesel fuel aerosols at 100 mg/m3. Male rats exposed to high-dose CLP aerosols exhibited growth depression and increased hepatic aminopyrine demethylase activity compared to control animals. High-dose females had decreased hemoglobin content and hematocrit values. These biochemical and hematological effects were not observed in animals of either sex treated with the diesel fuel. No other biochemical and hematological changes were observed. Mild histological changes occurred in the liver and thyroid of rats treated with CLP and diesel fuel aerosols. Based on the data presented, inhalation of CLP aerosols resulted in toxicological effects that were similar to those caused by dermal exposure.

  14. Anatomical sector analysis of load-bearing tibial bone structure during 90-day bed rest and 1-year recovery.

    PubMed

    Cervinka, Tomas; Rittweger, Jörn; Hyttinen, Jari; Felsenberg, Dieter; Sievänen, Harri

    2011-07-01

    The aim of this study was to investigate whether the bone response to long bed rest-related immobility and during subsequent recovery differed at anatomically different sectors of tibial epiphysis and diaphysis. For this study, peripheral quantitative tomographic (pQCT) scans obtained from a previous 90-day 'Long Term Bed Rest' intervention were preprocessed with a new method based on statistical approach and re-analysed sector-wise. The pQCT was performed on 25 young healthy males twice before the bed rest, after the bed rest and after 1-year follow-up. All men underwent a strict bed rest intervention, and in addition, seven of them received pamidronate treatment and nine did flywheel exercises as countermeasures against disuse-related bone loss. Clearly, 3-9% sector-specific losses in trabecular density were observed at the tibial epiphysis on average. Similarly, cortical density decreased in a sector-specific way being the largest at the anterior sector of tibial diaphysis. During recovery, the bed rest-induced bone losses were practically restored and no consistent sector-specific modulation was observed in any subgroup. It is concluded that the sector-specific analysis of bone cross-sections has potential to reveal skeletal responses to various interventions that cannot be inferred from the average analysis of the whole bone cross-section. This approach is considered also useful for evaluating the bone responses from the biomechanical point of view. PMID:21672131

  15. Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn.

    PubMed

    Hammond, B; Lemen, J; Dudek, R; Ward, D; Jiang, C; Nemeth, M; Burns, J

    2006-02-01

    The results of a 90-day rat feeding study with YieldGard (YieldGard Rootworm Corn is a registered trademark of Monsanto Technology, LLC.) Rootworm corn (MON 863) grain that is protected against feeding damage caused by corn rootworm larvae are presented. Corn rootworm-protection was accomplished through the introduction of a cry3Bb1 coding sequence into the corn genome for in planta production of a modified Cry3Bb1 protein from Bacillus thuringiensis. Grain from MON 863 and its near isogenic control were separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. Additionally, six groups of rats were fed diets containing grain from different conventional (non-biotechnology-derived) reference varieties. The responses of rats fed diets containing MON 863 were compared to those of rats fed grain from conventional corn varieties. All diets were nutritionally balanced and conformed to Purina Mills, Inc. specifications for Certified LabDiet 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. Overall health, body weight gain, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 863 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 863 grain, confirming that it is as safe and nutritious as existing conventional corn varieties.

  16. A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley rats.

    PubMed

    Zhou, Xing Hua; Dong, Ying; Xiao, Xiang; Wang, Yun; Xu, Yong; Xu, Bin; Shi, Wei Dong; Zhang, Yi; Zhu, Li Jia; Liu, Qiao Quan

    2011-12-01

    A transgenic rice line (TRS) with high amylose level has been developed by antisense RNA inhibition of starch branching enzymes. Compositional analysis of TRS demonstrated that the content of resistant starch (RS) was significantly higher compared to conventional non-transgenic rice. High level of RS is an important raw material in food industry and has various physiological effects for human health. In order to provide the reliable theory basis for field release of TRS rice, we evaluated the potential health effects of long-term consumption of the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley rats fed with diets containing 70% of either TRS rice flour, its near-isogenic rice flour or the control diet. The clinical performance variables (body weight, body weight gain and food consumption) were measured and pathological responses (hematological parameters and serum chemistry at the midterm and the completion of the experiment, urinalysis profile and serum sex hormone response at the completion of the experiment) were performed. Besides, clinical signs, relative organ weights and microscopic observations were also compared between TRS group and its near-isogenic rice group. The combined data indicates that high-amylose TRS grain is as safe as the conventional non-transgenic rice for rat consumption.

  17. A 90-day toxicology study of transgenic lysine-rich maize grain (Y642) in Sprague-Dawley rats.

    PubMed

    He, Xiao Yun; Tang, Mao Zhi; Luo, Yun Bo; Li, Xin; Cao, Si Shuo; Yu, Jing Juan; Delaney, Bryan; Huang, Kun Lun

    2009-02-01

    The gene for a lysine-rich protein (sb401) obtained from potatoes (Solanum berthaultii) was inserted into maize seed to produce Y642 transgenic maize. Compositional analysis of Y642 grain demonstrated that the concentrations of lysine and total protein were higher than those observed in maize grain from a near-isogenic non-genetically modified (non-GM) commercially available control quality protein maize (Nongda 108). The safety of Y642 maize grain was assessed by comparison of toxicology response variables in Sprague-Dawley (SD) rats consuming diets containing Y642 maize grain with those containing Nongda 108 maize grain. Maize grains from Y642 or Nongda 108 were incorporated into rodent diets at low (30%) or high concentrations (76%) and administered to SD rats (n=10/sex/group) for 90 days. An additional group of negative control group of rats (n=10/sex/group) were fed AIN93G diets. No adverse diet-related differences in body weights, feed consumption/utilization, clinical chemistry, hematology, absolute and relative organ weights were observed. Further, no differences in gross or microscopic pathology were observed between rats consuming diets with Y642 maize grain compared with rats consuming diets containing Nongda 108 maize grain. These results demonstrated that Y642 lysine-rich maize is as safe and nutritious as conventional quality protein maize.

  18. Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn.

    PubMed

    Hammond, B G; Dudek, R; Lemen, J K; Nemeth, M A

    2006-07-01

    The results of a 90-day rat feeding study with grain from MON 810 corn (YieldGard Cornborer -- YieldGard Cornborer is a registered trademark of Monsanto Technology, LLC) that is protected against feeding damage from corn and stalk boring lepidopteran insects are presented. Corn borer protection was accomplished through the introduction of cry1Ab coding sequences into the corn genome for in planta production of a bioactive form of Cry1Ab protein. Grain from MON 810 and its near-isogenic control was separately formulated into rodent diets at levels of 11% and 33% (w/w) by Purina Mills, Inc. (PMI). All diets were nutritionally balanced and conformed to PMI specifications for Certified LabDiet (PMI Certified LabDiet 5002 is a registered trademark of Purina Mills, Inc.) 5002. There were a total of 400 rats in the study divided into 10 groups of 20 rats/sex/group. The responses of rats fed diets containing MON 810 were compared to those of rats fed grain from conventional corn varieties. Overall health, body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis), organ weights, and gross and microscopic appearance of tissues were comparable between groups fed diets containing MON 810 and conventional corn varieties. This study complements extensive agronomic, compositional and farm animal feeding studies with MON 810 grain, confirming that it is as safe and nutritious as grain from existing commercial corn varieties.

  19. Toxic Hazards Research Unit annual report, 1990. Annual report No. 27 (Final), 1 Oct 89-15 Nov 90

    SciTech Connect

    Wall, H.G.; Vinegar, A.; Kinkead, E.R.

    1990-12-01

    This report presents a review of the activities of the Toxic Hazards Research Unit for the period of 1 October 1989 through 15 November 1990. Research activities focused on toxicity evaluations of aerospace and naval chemicals to include aircraft fuels and rocket fuels, hydraulic fluids, ground water contaminants, and chemical defense simulants. There was increased utilization of multidisciplinary efforts for quantitative toxicology studies and the development and validation of physiologically based pharmacokinetic models for predicting toxicity responses. The General Toxicology Laboratory conducted acute studies, toxicokinetic studies, repeated-dose studies, and subchronic inhalation studies to include a 90-day continuous inhalation study using the Thomas Domes. The development and characterization of a unique high pressure aerosol generator was a significant adjunct benefitting the study conducted in the Thomas Domes.

  20. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

    PubMed Central

    2012-01-01

    Introduction Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. Methods We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. Results We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. Conclusions Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments. PMID:23075459

  1. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats.

    PubMed

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-12-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  2. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats.

    PubMed

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-12-02

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control.

  3. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

    PubMed Central

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-01-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  4. Development of a short-term model of decalin inhalation nephrotoxicity in the male rat.

    PubMed

    Stone, L C; McCracken, M S; Kanerva, R L; Alden, C L

    1987-01-01

    Fischer 344 male rats and C57BL/6 male mice were exposed 'continuously' (22 hr/day, 7 days/wk) for 20, 28 or 35 days to a model compound, decalin, at 0, 25, 62.5 or 125 ppm. Fischer 344 female rats were exposed 'continuously' to decalin at 0 or 125 ppm for 28 days. No histopathological changes were observed in selected organs of female rats or male mice exposed to up to 125 ppm decalin for 28 or 35 days, respectively. However, kidney lesions were observed in all three test groups of male rats after 20, 28 and 35 days' exposure. The nephrotoxicity was characterized by the formation of hyaline droplets in the cytoplasm of proximal convoluted tubule epithelial cells, by the presence of granular casts at the outer zone of the medulla, and by chronic nephrosis. These changes were time and dose dependent and were identical to the renal toxicity that has been reported to occur in male rats following 90 days of continuous exposure to decalin by inhalation. No histopathological effects were observed in the heart, liver, lung or nasal turbinates of male rats. Our results indicate a sex and species specificity for the kidney toxicity. This leads to questions with regard to the appropriateness of using the male rat to assess the potential inhalation toxicity of volatile hydrocarbons. By producing nephrotoxicity in less than 90 days, decalin may now be used to examine, in a well-defined manner, the effect on nephrotoxicity of variables such as dose, exposure regimen, sex, species, and route of exposure. Data from these studies can be used to ascertain whether or not the male rat is an appropriate test animal for predicting potential human nephrotoxic responses to volatile chemicals such as perfumes and perfume raw materials.

  5. Inhalation exposure methodology.

    PubMed Central

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.). PMID:6383799

  6. Acute inhalation toxicity evaluation of a 93:7 mixture of perfluoro-2-butene and 1-bromopropane, a replacement candidate for ozone depleting substances. Interim report, July--August 1997

    SciTech Connect

    Feldmann, M.L.; Leahy, H.F.; Vinegar, A.

    1997-10-01

    The DoD requires the development of toxicity profiles for chemical substitute candidates proposed to replace ozone depleting substances such as chloro- and fluorocarbons and halons. A 93:7 mixture of perfluoro-2-butene and 1-bromopropane was identified as a possible replacement candidate for ozone-depleting fire extinguishants. An acute inhalation toxicity test utilizing male and female Fischer 344 rats was performed on this test material. No deaths occurred in any of the rats exposed to 5.3 mg/L of the 93:7 perfluoro-2-butene and 1-bromopropane mixture. Body weights of male and female rats during the subsequent 14-day observation period were unaffected by treatment. The test material did not produce acute toxicity via the inhalation route.

  7. Acute inhalation toxicity of carbon monoxide and hydrogen cyanide revisited: Comparison of models to disentangle the concentration × time conundrum of lethality and incapacitation.

    PubMed

    Pauluhn, Juergen

    2016-10-01

    Contemporary emergency response planning guidelines are stratified to consider the threshold for serious toxicity and/or impairment of escape, relative to the potentially lethal level above this threshold and the lower level at which individuals should not experience or develop effects more serious than mild irritation. While harmonized testing guidelines and risk assessment paradigms are available for the quantification of thresholds for lethality or establishing no adverse effect levels, the quantification of 'impairment of escape' appears to be a more elusive goal. Approaches were explored in context with CO and HCN in past experimental combustion toxicology studies to estimate the time available for escape. This point of departure (POD) was compared with the non-lethal threshold (LC01) and one third thereof from published recent acute inhalation studies in rats examining the Cxt-matrix of both CO and HCN. The findings from this analysis suggest that the rat delivers the most consistent data. However, it remains challenging yet to bridge the behavioral variables of human behavior typical of escape to any surrogate animal model. For the asphyxiant gases examined, the PODs characterizing 'impairment of escape' were difficult to distinguish from those indicative of impending death. No specific modeled carboxyhemoglobin (COHb) level could be linked to onset of incapacitation. In summary, the higher ventilation of rats (kg body weight adjusted) renders this species even more susceptible than heavy breathing humans. LCt01 × 1/3 values derived from the comprehensive Cxt matrix of rat inhalation studies are considered to be most suitable and robust to estimate the human equivalent threshold (POD) of 'impairment of escape'. PMID:27346845

  8. Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

    PubMed Central

    Pott, F; Roller, M; Kamino, K; Bellmann, B

    1994-01-01

    At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882919

  9. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A®) Following Acute Repeated Inhalation Exposure

    PubMed Central

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution

  10. FURTHER REFINEMENTS AND TESTING OF APEX3.0: EPA'S POPULATION EXPOSURE MODEL FOR CRITERIA AND AIR TOXIC INHALATION

    EPA Science Inventory

    The Air Pollutants Exposure Model (APEX(3.0)) is a PC-based model that was derived from the probabilistic NAAQS Exposure Model for carbon monoxide (pNEM/CO). APEX will be one of the tools used to estimate human population exposure for criteria and air toxic pollutants as part ...

  11. Alternative acute inhalation toxicity testing by determination of the concentration-time-mortality relationship: experimental comparison with standard LC50 testing

    SciTech Connect

    Zwart, A.; Arts, J.H.; Ten Berge, W.F.; Appelman, L.M. )

    1992-06-01

    A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a concentration-time-mortality relationship, enabling calculation of LC50 (50% mortality exposure concentration) values. By exposing pairs of rats for different periods of time to about four different test concentrations in a nose-only exposure unit, LT50 (50% mortality exposure time) values were obtained for five pairs of animals per concentration. The mortality data of the approximate 20 time-concentration combinations were used to calculate the probit relationship. Estimated mortality responses from these probit relations were compared with mortality figures obtained by exposing groups of five male rats and five female rats whole-body according to conventional toxicity testing. In general, there was good correspondence between the estimated and the observed mortality response. In this study, the determination of the concentration-time-mortality relationship takes about the same number of animals (40-50) as the conventional LC50 procedure according to the OECD guideline 403. However, the new method has several additional advantages such as: (A) LC50 values are obtained over a 10-fold range in time, with the potential of decreasing the number of animals used when regulations require acute toxicity data for different periods of exposure. (B) The obtained relationship contains considerably more valuable information for risk assessment than the LC50 value.

  12. Short-term inhalation toxicity of polyisocyanate aerosols in rats: comparative assessment of irritant-threshold concentrations by bronchoalveolar lavage.

    PubMed

    Pauluhn, Jürgen

    2002-03-01

    The object of this study was to compare the relative potency of respirable aerosols of the aliphatic hexamethylene 1,6-diisocyanate homopolymer of the isocyanurate type (HDI-IC) and the aromatic polymeric methylenediphenyl-4,4'-diisocyanate (pMDI) to elicit early changes in bronchoalveolar lavage fluid (BALF). The validity of the concentration x time (C x t) concept was addressed in rats exposed to concentrations from 3.4 to 58.1 mg pMDI/m3 and exposure durations of 6 h to 23 min, respectively (C x t approximately 1200 mg/m3-min). One additional group of rats was exposed to 2.7 mg MDA/m3 for 1 x 6 h, a putative product of hydrolysis of pMDI. In rats repeatedly exposed to 12.9 mg pMDI/m3 (6 h/day, 5 days/wk for 14 days), cumulative exposure-related changes were examined. Results show that total protein and angiotensin-converting enzyme (ACE) in BALF were among the most sensitive endpoints to probe early effects caused by exposure to irritant polyisocyanate aerosols. In the repeated-exposure study, BALF protein was maximal after the first exposure day. Based on these most sensitive endpoints in BALF, a benchmark no-effect threshold concentration of 0.5 and 3 mg/m3 was estimated for the pMDI and HDI-IC aerosol, respectively. The slope of the concentration-effect curve was steeper following exposure to HDI-IC than to pMDI. These estimated acute no-observed-effect levels (NOELs) were almost identical to those observed in longer term inhalation studies using conventional endpoints. It is concluded that pulmonary irritation caused by polyisocyanate aerosols can readily be quantified in an acute rat bioassay by the analysis of total protein in BALF.

  13. Inhaled matters of the heart

    PubMed Central

    Zaky, Ahmed; Ahmad, Aftab; Dell’Italia, Louis J; Jahromi, Leila; Reisenberg, Lee Ann; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Inhalations of atmospheric pollutants, especially particulate matters, are known to cause severe cardiac effects and to exacerbate preexisting heart disease. Heart failure is an important sequellae of gaseous inhalation such as that of carbon monoxide. Similarly, other gases such as sulphur dioxide are known to cause detrimental cardiovascular events. However, mechanisms of these cardiac toxicities are so far unknown. Increased susceptibility of the heart to oxidative stress may play a role. Low levels of antioxidants in the heart as compared to other organs and high levels of reactive oxygen species produced due to the high energetic demand and metabolic rate in cardiac muscle are important in rendering this susceptibility. Acute inhalation of high concentrations of halogen gases is often fatal. Severe respiratory injury and distress occurs upon inhalation of halogens gases, such as chlorine and bromine; however, studies on their cardiac effects are scant. We have demonstrated that inhalation of high concentrations of halogen gases cause significant cardiac injury, dysfunction, and failure that can be critical in causing mortalities following exposures. Our studies also demonstrated that cardiac dysfunction occurs as a result of a direct insult independent of coexisting hypoxia, since it is not fully reversed by oxygen supplementation. Therefore, studies on offsite organ effects of inhaled toxic gases can impact development of treatment strategies upon accidental or deliberate exposures to these agents. Here we summarize the knowledge of cardiovascular effects of common inhaled toxic gases with the intent to highlight the importance of consideration of cardiac symptoms while treating the victims. PMID:26665179

  14. A CHRONIC INHALATION STUDY OF METHYL BROMIDE TOXICITY IN B6C3F1 MICE. (FINAL REPORT TO THE NATIONAL TOXICOLOGY PROGRAM)

    SciTech Connect

    HABER, S.B.

    1987-06-26

    This report provides a detailed account of a two year chronic inhalation study of methyl bromide toxicity in B6C3Fl mice conducted for the National Toxicology Program. Mice were randomized into three dose groups (10, 33 and 100 ppm methyl bromide) and one control group (0 ppm) per sex and exposed 5 days/week, 6 hours/day, for a total of 103 weeks. Endpoints included body weight; clinical signs and mortality, and at 6, 15 and 24 months of exposure, animals were sacrificed for organ weights, hematology and histopathology. In addition, a subgroup of animals in each dosage group was monitored for neurobehavioral and neuropathological changes. After only 20 weeks of exposure, 48% of the males and 12% of the females in the 100 ppm group had died. Exposures were terminated in that group and the surviving mice were observed for the duration of the study. Exposure of B6C3Fl mice to methyl bromide, even for only 20 weeks, produced significant changes in growth rate, mortality, organ weights and neurobehavioral functioning. These changes occurred in both males and females, but were more pronounced in males.

  15. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS DIRECT LOAN SERVICING-SPECIAL Loan...

  16. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke

    PubMed Central

    Almasi, Mostafa; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named “ABCD2F” and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days. PMID:27642521

  17. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke.

    PubMed

    Almasi, Mostafa; Hodjati Firoozabadi, Nader; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named "ABCD2F" and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days. PMID:27642521

  18. The Value of ABCD2F Scoring System (ABCD2 Combined with Atrial Fibrillation) to Predict 90-Day Recurrent Brain Stroke

    PubMed Central

    Almasi, Mostafa; Ghasemi, Faeze; Chardoli, Mojtaba

    2016-01-01

    Background. The ABCD2 score is now identified as a useful clinical prediction rule to determine the risk for stroke in the days following brain ischemic attacks. Aim. The present study aimed to introduce a new scoring system named “ABCD2F” and compare its value with the previous ABCD2 system to predict recurrent ischemic stroke within 90 days of the initial cerebrovascular accident (CVA). Methods. 138 consecutive patients with the final diagnosis of ischemic CVA or TIAs who referred to emergency ward of Rasoul-e-Akram general hospital in Tehran from September 2012 to December 2013 were eligible. By adding a new score in the presence of atrial fibrillation to ABCD2 system, the new scoring system as ABCD2F was introduced and the risk stratification was done again on this new system. Results. The area under the curve for ABCD2 was 0.434 and for ABCD2F it was 0.452 indicating low value of both systems for assessing recurrence of stroke within 90 days of primary event. Multivariable logistic regression analysis showed that none of the baseline factors could predict 90-day recurrent stroke. Conclusion. ABCD2 and/or atrial fibrillation are not good scoring candidates for assessing the risk of recurrent stroke within first 90 days.

  19. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  20. 41 CFR 302-7.9 - What are some reasons that would justify the additional storage beyond the initial 90-day limit?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... that would justify the additional storage beyond the initial 90-day limit? 302-7.9 Section 302-7.9 Public Contracts and Property Management Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND...

  1. Inhalant Abuse

    MedlinePlus

    ... risk of being hurt in a fall, a fire or a car crash (for example, if your child tries to drive while he or she is high on an inhalant). Inhalants block oxygen flow to the brain and every other organ ...

  2. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  3. The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada

    PubMed Central

    Renfrew, Paul Douglas; Quan, Hude; Doig, Christopher James; Dixon, Elijah; Molinari, Michele

    2011-01-01

    OBJECTIVE: To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models’ estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) – consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow χ2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT. PMID:21876856

  4. Rheumatoid arthritis is associated with higher 90-day Hospital Readmission Rates Compared to Osteoarthritis after Hip or Knee arthroplasty: A cohort study

    PubMed Central

    Singh, Jasvinder A.; Inacio, Maria C.S.; Namba, Robert S.; Paxton, Elizabeth W.

    2014-01-01

    Objective To examine if an underlying diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA) impacts the 90-day readmission rates after total hip or knee arthroplasty (THA or TKA). Methods Prospectively collected data from an integrated healthcare system Total Joint Replacement Registry of adults with RA or OA undergoing unilateral primary THA or TKA during 2009-2011 were analyzed. Adjusted logistic regression models for 90-day readmission were fit. Odds ratios with 95% confidence intervals (CI) were calculated. Study year was an effect modifier for the outcome, therefore separate analyses were conducted for each of the three study years. Results Of the 34,311 patients, 496 had RA and 33,815 had OA. Comparing RA and OA, there were: 73% and 61% women; 45% and 70% Caucasians; and the mean age was lower, 61 vs. 67 years (p<0.001). Respective crude 90-day readmission rates were 8.5% and 6.7%. The adjusted odds of 90-day readmission increased from year to year for RA compared to OA patients, from 0.89 (95% CI, 0.46-1.71) in 2009 to 1.34 (95% CI, 0.69-2.61) in 2010 to 1.74 (95% CI, 1.16-2.60) in 2011. The two most common readmission reasons were: joint prosthesis infection (10.2%) and septicemia (10.2%) in RA; joint prosthesis infection (5.7%) and other postoperative infection (5.1%) in OA. Conclusions RA is a risk factor for 90-day readmission after primary TKA or THA. An increasing risk of readmissions noted in RA in 2011 is concerning and indicates further studies should examine the reasons for this increasing trend. PMID:25302697

  5. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement.

    PubMed

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health.

  6. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

    PubMed Central

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  7. Evaluation of exposure to water aerosol or air by nose-only or whole-body inhalation procedures for CD-1 mice in developmental toxicity studies.

    PubMed

    Tyl, R W; Ballantyne, B; Fisher, L C; Fait, D L; Savine, T A; Pritts, I M; Dodd, D E

    1994-08-01

    This study was performed to evaluate the effects of nose-only restraint versus whole-body exposure procedures in the absence of test chemical, and to determine the appropriate control environment (water aerosol or air) for subsequent developmental toxicity studies of test materials administered as aerosols. Timed-pregnant CD-1 mice, 30/group, were exposed to high concentrations of water aerosol or to air by whole-body or nose-only inhalation procedures on Gestational Days (GD) 6 through 15 for 6 hr per day. The group exposed to air by whole-body procedures was designated as the control group. Clinical observations and maternal body weights were recorded throughout gestation. At scheduled necropsy on GD 18, maternal animals were evaluated for body weight, gravid uterine weight, liver weight, number of ovarian corpora lutea, and status of uterine implantation sites. Fetuses were counted, weighed, and sexed and were examined for external, visceral (including craniofacial), and skeletal alterations. Indices of maternal toxicity were affected in both nose-only groups. Maternal body weights were reduced during and after the exposure period; maternal weight gain was reduced during the exposure period. Clinical signs observed, from animals struggling during restraint, were resolved by GD 18. At sacrifice on GD 18, maternal body weights and maternal gestational weight gains (both corrected for gravid uterine weights) and absolute liver weights were reduced in both nose-only groups. Four females died (13.3%, all pregnant) in the air nose-only group, and maternal liver weight (relative to body weight) was reduced in the aerosol nose-only group. Gestational parameters were unaffected by any of the treatments. There were no statistically significant differences in the incidences of any individual malformations or malformations by category (external, visceral, or skeletal) or of total malformations. However, exencephaly, low set ears, cleft palate and ventricular septal defect

  8. Asthma Inhalers

    MedlinePlus

    ... reduce the release of chlorofluorocarbons (CFCs) into the atmosphere when taking certain asthma medications. Until recently, most ... hydrofluoroalkane (HFA) inhalers, that do not rob the atmosphere of ozone. “The FDA [Food and Drug Administration] ...

  9. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    PubMed

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury.

  10. Prior statin use and 90-day mortality in Gram-negative and Gram-positive bloodstream infection: a prospective observational study.

    PubMed

    Mehl, A; Harthug, S; Lydersen, S; Paulsen, J; Åsvold, B O; Solligård, E; Damås, J K; Edna, T-H

    2015-03-01

    In several studies on patients with bloodstream infection (BSI), prior use of statins has been associated with improved survival. Gram-positive and Gram-negative bacteria alert the innate immune system in different ways. We, therefore, studied whether the relation between prior statin use and 90-day total mortality differed between Gram-positive and Gram-negative BSI. We conducted a prospective observational cohort study of 1,408 adults with BSI admitted to Levanger Hospital between January 1, 2002, and December 31, 2011. Data on the use of statins and other medications at admission, comorbidities, functional status, treatment, and outcome were obtained from the patients' hospital records. The relation of statin use with 90-day mortality differed between Gram-negative and Gram-positive BSI (p-value for interaction 0.01). Among patients with Gram-negative BSI, statin users had significantly lower 90-day total mortality [odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.23-0.75, p = 0.003]. The association remained essentially unchanged after adjusting for the effect of sex, age, functional status before the infection, and underlying diseases that were considered confounders (adjusted OR 0.38, 95 % CI 0.20-0.72, p = 0.003). A similar analysis of patients with Gram-positive BSI showed no association of statin use with mortality (adjusted OR 1.22, 95 % CI 0.69-2.17, p = 0.49). The present study suggests that prior statin use is associated with a lower 90-day total mortality in Gram-negative BSI, but not in Gram-positive BSI.

  11. Influence of CO2 change during 90-day experiment on growth characteristics and photosynthetic activity in vegetables grown in Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Shao, Lingzhi; Liu, Hong; Wang, Minjuan; Fu, Yuming; Dong, Chen; Liu, Guanghui

    To establish bioregenerative life support system (BLSS) on lunar or Mars bases in the future, it is necessary to firstly conduct manned simulation experiments on the ground. For this purpose, Lunar palace 1 as an integrative experimental facility for permanent astrobase life support artificial closed ecosystem was set up, and 90-day experiment was carried out in this system. Vegtables as one of the important plant units, provide various nutrient content for crews in the system, such as vitamin, antioxidants and so on. However, it is not clear yet that how the CO _{2} change during 90-day experiment to affect on growth characteristics and photosynthetic activity in vegtables grown in the system. In this study, red lettuce, red rape, romaine lettuce, and bibb lettuce grown in the system were chosen as the subject investigated. Growth, expressed as dry weight, length of shoot and root, leaf area, was mearsured, and photosynthesis,expressed as net photosynthetic rate, intercellular CO _{2} concentration, chlorophyll contents and fluorescence was analyzed to detemind influence of CO _{2} change during 90-day experiment on growth in vegtables grown in the system.

  12. A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

    PubMed

    Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

    2011-10-01

    Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

  13. Reduced toxicological activity of cigarette smoke by the addition of ammonia magnesium phosphate to the paper of an electrically heated cigarette: subchronic inhalation toxicology.

    PubMed

    Moennikes, O; Vanscheeuwijck, P M; Friedrichs, B; Anskeit, E; Patskan, G J

    2008-05-01

    Cigarette smoke is a complex chemical mixture that causes a variety of diseases, such as lung cancer. With the electrically heated cigarette smoking system (EHCSS), temperatures are applied to the tobacco below those found in conventional cigarettes, resulting in less combustion, reduced yields of some smoke constituents, and decreased activity in some standard toxicological tests. The first generation of electrically heated cigarettes (EHC) also resulted in increased formaldehyde yields; therefore, a second generation of EHC was developed with ammonium magnesium phosphate (AMP) in the cigarette paper in part to address this increase. The toxicological activity of mainstream smoke from these two generations of EHC and of a conventional reference cigarette was investigated in two studies in rats: a standard 90-day inhalation toxicity study and a 35-day inhalation study focusing on lung inflammation. Many of the typical smoke exposure-related changes were found to be less pronounced after exposure to smoke from the second-generation EHC with AMP than to smoke from the first-generation EHC or the conventional reference cigarette, when compared on a particulate matter or nicotine basis. Differences between the EHC without AMP and the conventional reference cigarette were not as prominent. Overall, AMP incorporated in the EHC cigarette paper reduced the inhalation toxicity of the EHCSS more than expected based on the observed reduction in aldehyde yields. PMID:18464053

  14. Indacaterol Oral Inhalation

    MedlinePlus

    ... as a powder-filled capsule to inhale by mouth using a special inhaler. It is usually inhaled ... stop the pieces of capsule from reaching your mouth as you inhale the medication. Very tiny pieces ...

  15. Inhaled Asthma Medications

    MedlinePlus

    ... metered – dose inhaler (MDI), which uses a chemical propellant to push the medication out of the inhaler. ... powder inhalers (DPIs) deliver medication without using chemical propellants, but they require a strong and fast inhalation. ...

  16. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    SciTech Connect

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  17. STS-90 Day 14 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fourteenth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk focus on the efforts of Neurolab's Neuronal Plasticity Team to better understand how the adult nervous system adapts to the new environment of space. Columbia's science crew -- Mission Specialists Rick Linnehan and Dave Williams and Payload Specialists Jay Buckey and Jim Pawelczyk -- perform the second and final in-flight dissections of the adult male rats on board. The crew euthanizes and dissects nine rats and remove the vestibular or balance organs of the inner ear; the cerebellum, the part of the brain critical for maintaining balance and for processing information from the limbs so they can be moved smoothly; and the cerebrum, one part of which controls automatic functions such as body temperature regulation and the body's internal clock, and the cortical region that controls cognitive functions such as thinking. The first dissection, which was performed on the second day of the flight, went extremely well, according to Neurolab scientists.

  18. STS-90 Day 01 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this first day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk, can be seen performing pre-launch activities such as eating the traditional breakfast, crew suit-up, and the ride out to the launch pad. Also, included are various panoramic views of the shuttle on the pad. The crew is readied in the white room' for their mission. After the closing of the hatch and arm retraction, launch activities are shown including countdown, engine ignition, launch, and the separation of the Solid Rocket Boosters. The shuttle's payload bay doors are then opened in anticipation of the 16-day scientific mission. The astronauts then are seen readying the Spacelab module for various experiments.

  19. STS-90 Day 05 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fifth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk perform tests associated with the STS-90 Neurolab Vestibular Team's efforts to gain insight into the balance organs in the ear and all the connections that system has to the eyes, brain, and muscles in adapting to the weightless condition in space and then readapts to the gravity environment found on Earth.

  20. Past, present and emerging toxicity issues for jet fuel

    SciTech Connect

    Mattie, David R.

    2011-07-15

    The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.

  1. A 90-day subchronic feeding study of genetically modified maize expressing Cry1Ac-M protein in Sprague-Dawley rats.

    PubMed

    Liu, Pengfei; He, Xiaoyun; Chen, Delong; Luo, Yunbo; Cao, Sishuo; Song, Huan; Liu, Ting; Huang, Kunlun; Xu, Wentao

    2012-09-01

    The cry1Ac-M gene, coding one of Bacillus thuringiensis (Bt) crystal proteins, was introduced into maize H99 × Hi IIB genome to produce insect-resistant GM maize BT-38. The food safety assessment of the BT-38 maize was conducted in Sprague-Dawley rats by a 90-days feeding study. We incorporated maize grains from BT-38 and H99 × Hi IIB into rodent diets at three concentrations (12.5%, 25%, 50%) and administered to Sprague-Dawley rats (n=10/sex/group) for 90 days. A commercialized rodent diet was fed to an additional group as control group. Body weight, feed consumption and toxicological response variables were measured, and gross as well as microscopic pathology were examined. Moreover, detection of residual Cry1Ac-M protein in the serum of rats fed with GM maize was conducted. No death or adverse effects were observed in the current feeding study. No adverse differences in the values of the response variables were observed between rats that consumed diets containing GM maize BT-38 and non-GM maize H99 × Hi IIB. No detectable Cry1Ac-M protein was found in the serum of rats after feeding diets containing GM maize for 3 months. The results demonstrated that BT-38 maize is as safe as conventional non-GM maize.

  2. A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in Sprague-Dawley rats.

    PubMed

    Zhu, Yaxi; He, Xiaoyun; Luo, Yunbo; Zou, Shiying; Zhou, Xin; Huang, Kunlun; Xu, Wentao

    2013-01-01

    Maize is not only a staple food crop but also an important raw material for feed and industry; however, the threat of weeds leads to a serious decline in its output and quality. The G2-aroA gene confers glyphosate herbicide tolerance to crops. In this study, the food safety of genetically modified (GM), glyphosate-tolerant maize with the G2-aroA gene was evaluated in a 90-day feeding study in Sprague-Dawley (SD) rats. Maize grain from GM or non-GM isogenic control lines were separately formulated into rodent diets at concentrations of 12.5% (low level), 25% (middle level), and 50% (high level). An additional group of rats were fed a commercialized diet as a control. The toxicological response variables, including body weights, food consumption, serum biochemistry, hematology, and absolute and relative organ weights, were compared between rats fed GM maize and those fed non-GM maize after consumption of test diets for 90days. In addition, gross and microscopic pathology were conducted among treatment groups. No adverse effects related to the consumption of GM maize were detected in the subchronic feeding study. These results indicated that the GM glyphosate-tolerant maize was as safe and nutritious as conventional maize.

  3. Inhaled Corticosteroids

    PubMed Central

    Barnes, Peter J.

    2010-01-01

    Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and control asthma symptoms. ICS are now first-line therapy for all patients with persistent asthma, controlling asthma symptoms and preventing exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers, which improve compliance and control asthma at lower doses of corticosteroids. By contrast, ICS provide much less clinical benefit in COPD and the inflammation is resistant to the action of corticosteroids. This appears to be due to a reduction in HDAC2 activity and expression as a result of oxidative stress. ICS are added to bronchodilators in patients with severe COPD to reduce exacerbations. ICS, which are absorbed from the lungs into the systemic circulation, have negligible systemic side effects at the doses most patients require, although the high doses used in COPD has some systemic side effects and increases the risk of developing pneumonia.

  4. Vertical jump performance after 90 days bed rest with and without flywheel resistive exercise, including a 180 days follow-up.

    PubMed

    Rittweger, Jörn; Felsenberg, Dieter; Maganaris, Constantinos; Ferretti, José Luis

    2007-07-01

    Muscle atrophy and neuromuscular de-conditioning occur in response to space flight and bed-rest. In this study, we investigated the efficacy of flywheel training to conserve jumping power and height during 90 days bed rest. Twenty-four young healthy men underwent strict bed-rest (-6 degrees head down tilt) for 90 days. Eight participants were assigned to a flywheel group (FW) and 16 to a control group (Ctrl). The ground reaction force was measured during vertical jump tests twice during baseline data collection, and on day 4, 7, 14, 90 and 180 of recovery. In half of the participants, jump tests were also performed within minutes after re-ambulation and on four more occasions during the first 2 days of recovery. Jump height was reduced from 40.6 cm (SD 6.1 cm) during the first baseline measurement to 27.6 cm (SD 5.6 cm) on day 4 of recovery in Ctrl, but only from 38.6 cm (SD 3.9 cm) to 34.4 cm (SD 6.5 cm) in FW (P < 0.001). At the same time, peak power was reduced from 47.4 W/kg (SD 8.0 W/kg) to 34.5 W/kg in Ctrl, but only from 46.2 W/kg (6.0 W/kg) to 42.2 W/kg SD 4.6 W/kg) in FW (P < 0.001). Jump height and peak power were completely recovered after 163 and 140 days in Ctrl, respectively, and after 72 and 18 days in FW (regression analysis). In conclusion, flywheel exercise could effectively offset neuromuscular de-conditioning during bed-rest, and led to full recovery at an earlier stage. These findings nourish the hope that adequate training paradigms can fully sustain neuromuscular function under microgravity conditions. PMID:17406887

  5. Inhalation exposure technology, dosimetry, and regulatory issues.

    PubMed

    Dorato, M A; Wolff, R K

    1991-01-01

    Inhalation toxicology technology has provided the scientific community with important advances in studies of inhaled toxicants. These advances include new and more efficient exposure systems (e.g., flow-past nose-only exposure systems), and improved approaches to inhalation chamber environmental control (e.g., temperature, humidity, air quality). Practical problems and approaches to testing and operating inhalation exposure systems and the advantages and disadvantages of the major inhalation exposure types (e.g., whole-body, nose-only) are discussed. Important aspects of study design, such as high level particulate exposures resulting in large lung burdens (e.g., greater than or equal to 2 mg/g of lung), slowed pulmonary clearance rates, and nonspecific toxicity are considered, along with practical issues of comparative dosimetry. Regulatory guidelines have continued to present challenges in designing and conducting acute, subchronic, and chronic inhalation studies. The important regulatory issue of performing acute inhalation toxicity studies at high aerosol concentrations and "respirable" particle size distribution is discussed. PMID:1813983

  6. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  7. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  8. Zinc toxicology following particulate inhalation.

    PubMed

    Cooper, Ross G

    2008-04-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl(2) inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection.

  9. Zinc toxicology following particulate inhalation

    PubMed Central

    Cooper, Ross G.

    2008-01-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl2 inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection. PMID:20040991

  10. Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

    PubMed Central

    Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per; Stål, Per; Langberg, Henning

    2015-01-01

    Summary Introduction spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. Purpose the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise. Methods an explorative analysis was completed based on data from a randomized, controlled trial. The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline (pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle. Results the collagen content of VL was similar between pre and post in the BRE group (−3.8 μg collagen/mg protein [95% CI: −22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: −0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: −6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (−9.3 μg collagen/mg protein [95% CI: −24.9; 6.4], p=0.25) or in the BRE group (−6.5 μg collagen/mg protein [95% CI: −25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference −2.78 μg collagen

  11. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study

    PubMed Central

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis®). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist’s armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  12. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development. PMID:18804141

  13. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    PubMed

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein. PMID:25822065

  14. Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

    PubMed Central

    Egger, Michael E; Ohlendorf, Joanna M; Scoggins, Charles R; McMasters, Kelly M; Martin, Robert C G

    2015-01-01

    Background The aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature. Methods Medline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis. Results Fifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes. Conclusion Quality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery. PMID:26228262

  15. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.

    PubMed

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis(®)). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist's armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  16. A 90 day safety assessment of genetically modified rice expressing Cry1Ab/1Ac protein using an aquatic animal model.

    PubMed

    Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Wang, Jia-Mei; Ding, Jia-Tong; Chen, Xiu-Ping; Peng, Yu-Fa

    2015-04-15

    In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.

  17. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  18. Inhalational anthrax.

    PubMed

    Cuneo, Brian M

    2004-03-01

    Anthrax remains a real threat. In a spore form, it is highly infectious and dispersible. The initial symptoms are similar to those of influenza, and the early stage of inhalational anthrax may not be recognized. Early antibiotic treatment is important to achieving a good outcome. Contrary to historical experience. many patients with even advanced anthrax can be saved with aggressive medical care. Prevention of anthrax infections requires vigilant infection control methods as well as a rational prophylactic plan. All health care providers should be familiar with the symptoms and treatment of this disease. It is hoped that future research will clarify tests for early diagnosis, the best methods of prophylaxis, and the most effective treatments. Unfortunately the threat of bioterrorism, and anthrax in particular, is unlikely to go away. PMID:15062228

  19. NTP technical report on the toxicity studies of Formic Acid (CAS No. 64-18-6) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.

    PubMed

    Thompson, Morrow

    1992-07-01

    Formic acid occurs in a variety of plants and fruits, mammalian tissues, and insect venoms. It is used industrially in preparing a variety of drugs, dyes, and chemicals; as a decalcifier; and in leather tanning. Formic acid also is an environmental contaminant of air and water and has been identified as the toxic intermediate (formate) in methanol poisoning. Two- and 13-week toxicity studies of formic acid were conducted in male and female F344/N rats and B6C3F1 mice by whole body inhalation exposure to formic acid vapors. In addition, in vitro genetic toxicity studies were performed with Salmonella typhimurium, with or without metabolic activation. Formic acid was not mutagenic in this assay. In 2-week studies, groups of 5 F344/N rats and 5 B6C3F1 mice of each sex were exposed to formic acid for 6 hours a day, 5 days a week, at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm. Deaths occurred in animals exposed to 500 ppm (rats and mice) and 250 ppm (1 female mouse). Microscopic lesions in the respiratory and olfactory epithelia occurred in rats and mice exposed to 62.5 ppm and higher concentrations, with the severity related to the exposure concentration. The lesions consisted of squamous metaplasia, necrosis, and inflammation. Exposures had minimal or no effects on coagulation times, blood pH and electrolytes, or on concentrations and activities of urine analytes in rats during the 2-week studies. In 13-week studies, groups of 10 animals of each species and sex were exposed to formic acid at concentrations of 0, 8, 16, 32, 64, and 128 ppm for 6 hours a day, 5 days a week. Two mice, 1 male and 1 female, died in the 128 ppm groups. Body weight gains were significantly decreased in mice exposed to 64 and 128 ppm formic acid. Microscopic changes in rats and mice ranged from minimal to mild in severity and generally were limited to animals in the 128 ppm groups. Lesions related to exposure to formic acid consisted of squamous metaplasia and degeneration of the

  20. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice

    SciTech Connect

    Evans, M.V.; Caldwell, J.C.

    2010-05-01

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools for calculation of internal and target organ doses of parent compound and metabolites. PBPK models, coupled with in vivo inhalation gas-uptake data, can be useful to estimate total metabolism. Previously, such an approach was used to make predictions regarding the metabolism and to make subsequent inferences of DCM's mode of action for toxicity. However, current evidence warrants re-examination of this approach. The goal of this work was to examine two different hypotheses for DCM metabolism in mice. One hypothesis describes two metabolic pathways: one involving cytochrome P450 2E1 (CYP2E1) and a second glutathione (GSH). The second metabolic hypothesis describes only one pathway mediated by CYP2E1 that includes multiple binding sites. The results of our analysis show that the in vivo gas-uptake data fit both hypotheses well and the traditional analysis of the chamber concentration data is not sufficient to distinguish between them. Gas-uptake data were re-analyzed by construction of a velocity plot as a function of increasing DCM initial concentration. The velocity (slope) analysis revealed that there are two substantially different phases in velocity, one rate for lower exposures and a different rate for higher exposures. The concept of a 'metabolic switch,' namely that due to conformational changes in the enzyme after one site is occupied - a different metabolic rate is seen - is also consistent with the experimental data. Our analyses raise questions concerning the importance of GSH metabolism for DCM. Recent research results also question the importance of this pathway in the toxicity of DCM. GSH-related DNA adducts were not formed after in vivo DCM exposure in mice and DCM-induced DNA damage has

  1. Mometasone Oral Inhalation

    MedlinePlus

    ... or she watches.The dose counter on the base of your mometasone inhaler tells you how many ... Hold the inhaler straight up with the colored base on the bottom. Twist the white cap counterclockwise ...

  2. Budesonide Oral Inhalation

    MedlinePlus

    ... 6 years of age and older. Budesonide suspension (liquid) for oral inhalation (Pulmicort Respules) is used in ... of inhalations even if it still contains some liquid and continues to release a spray when it ...

  3. Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

    PubMed

    Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

    2014-03-01

    The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

  4. Oxidative Stress, Inflammatory Biomarkers, and Toxicity in Mouse Lung and Liver After Inhalation Exposure to 100% Biodiesel or Petroleum Diesel Emissions

    PubMed Central

    Shvedova, Anna A.; Yanamala, Naveena; Murray, Ashley R.; Kisin, Elena R.; Khaliullin, Timur; Hatfield, Meghan K.; Tkach, Alexey V.; Krantz, Q. T.; Nash, David; King, Charly; Gilmour, M. Ian; Gavett, Stephen H.

    2015-01-01

    Over the past decade, soy biodiesel (BD) has become a first alternative energy source that is economically viable and meets requirements of the Clean Air Act. Due to lower mass emissions and reduced hazardous compounds compared to diesel combustion emissions (CE), BD exposure is proposed to produce fewer adverse health effects. However, considering the broad use of BD and its blends in different industries, this assertion needs to be supported and validated by mechanistic and toxicological data. Here, adverse effects were compared in lungs and liver of BALB/cJ mice after inhalation exposure (0, 50, 150, or 500 μg/m3; 4 h/d, 5 d/wk, for 4 wk) to CE from 100% biodiesel (B100) and diesel (D100). Compared to D100, B100 CE produced a significant accumulation of oxidatively modified proteins (carbonyls), an increase in 4-hydroxynonenal (4-HNE), a reduction of protein thiols, a depletion of antioxidant gluthatione (GSH), a dose-related rise in the levels of biomarkers of tissue damage (lactate dehydrogenase, LDH) in lungs, and inflammation (myeloperoxidase, MPO) in both lungs and liver. Significant differences in the levels of inflammatory cytokines interleukin (IL)-6, IL-10, IL-12p70, monocyte chemoattractant protein (MCP)-1, interferon (IFN) γ, and tumor necrosis factor (TNF)-α were detected in lungs and liver upon B100 and D100 CE exposures. Overall, the tissue damage, oxidative stress, inflammation, and cytokine response were more pronounced in mice exposed to BD CE. Further studies are required to understand what combustion products in BD CE accelerate oxidative and inflammatory responses. PMID:24156694

  5. Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

    PubMed

    Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A

    2011-07-15

    Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

  6. Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats

    SciTech Connect

    Whittaker, Margaret H.; Wang, Gensheng; Chen Xueqing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A.

    2011-07-15

    Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.

  7. Beclomethasone Oral Inhalation

    MedlinePlus

    ... with water and spit. Do not swallow the water. Keep the inhaler clean and dry with the cover tightly in place ... all times. To clean your inhaler, use a clean, dry tissue or cloth. Do not wash or put any part of your inhaler in water.

  8. NTP technical report on the toxicity studies of 1,6-Hexanediamine Dihydrochloride (CAS No. 6055-52-3) Administered by Drinking Water and Inhalation to F344/N Rats and B6C3F1 Mice.

    PubMed

    Hebert, Charles

    1993-03-01

    1,6-Hexanediamine (HDA) is an aliphatic amine that is produced in large volumes in the United States. HDA is widely used as a corrosion inhibitor in lubricants and as an intermediate in the industrial synthesis of paints, resins, inks, and textiles. Toxicity studies of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and whole-body inhalation routes (2-week and 13-week studies). Animals were evaluated for histopathology, clinical chemistry, hematology, and reproductive toxicity. In addition, the genetic toxicity of HDA was assessed in Salmonella typhimurium and in Chinese hamster ovary cells in vitro; HDDC was evaluated in the mouse micronucleus assay in vivo. In the 2-week drinking water studies, groups of 5 rats of each sex received HDDC at doses of 0.75 to 6.7 mg/mL, and groups of 5 mice of each sex received doses of 0.2 to 3.0 mg/mL for 14 or 15 days. All animals survived to the end of the studies. No gross or microscopic pathologic changes and no clinical abnormalities related to HDDC consumption were seen in any dose group. The only statistically significant change was a slight decrease in absolute and/or relative liver weights of female rats in the 1.7, 5.0, and 6.7-mg/mL treatment groups, in male rats in the 3.0 mg/mL treatment group, and in female mice in the 0.8 mg/mL treatment group. Because there was no significant toxicity in these studies, 13-week drinking water studies were not conducted. In the 2-week inhalation studies, 5 rats and 5 mice of each sex were exposed to 0, 10, 30, 89, 267, or 800 mg HDDC/m(3) for 6-hours per day for 12 days. In the highest exposure group (800 mg/m(3)), all male and female rats, all female mice, and 2 male mice died before the end of the studies. In the remaining groups, there was a dose-dependent depression in body weight gain in male and female mice, but not in rats. Clinical signs were primarily related to upper

  9. A 90-day subchronic study of rats fed lean pork from genetically modified pigs with muscle-specific expression of recombinant follistatin.

    PubMed

    Zou, Shiying; Tang, Min; He, Xiaoyun; Cao, Yuan; Zhao, Jie; Xu, Wentao; Liang, Zhihong; Huang, Kunlun

    2015-11-01

    Because cardiovascular disease incidence has rapidly increased in recent years, people are choosing relatively healthier diets with low animal fat. A transgenic pig with low fat and a high percentage of lean meat was created in 2011; this pig overexpresses the follistatin (FST) gene. To evaluate the safety of lean pork derived from genetically modified (GM) pigs, a subchronic oral toxicity study was conducted using Sprague-Dawley rats. GM pork and non-GM pork were incorporated into the diet at levels of 3.75%, 7.5%, and 15% (w/w), and the main nutrients of the various diets were subsequently balanced. The safety of GM pork was assessed by comparison of the toxicology response variables in Sprague-Dawley rats consuming diets containing GM pork with those consuming non-GM pork. No treatment-related adverse or toxic effects were observed based on an examination of the daily clinical signs, body weight, food consumption, hematology, serum biochemistry, and organ weight or based on gross and histopathological examination. The results demonstrate that GM pork is as safe for consumption as conventional pork.

  10. Comparative acute inhalation toxicity of a saline suspension and an ethanol solution of t-2 mycotoxin in mice. (Reannouncement with new availability information)

    SciTech Connect

    Creasia, D.A.; Thurman, J.D.

    1993-12-31

    We compared retention, distribution, toxicity, and histopathological change in mice after exposure to aerosols of T-2 suspended in saline or dissolved in ethanol. We found that the LC50 for mice exposed for 10 min to an aerosol of a saline suspension of T-2 was 0.035 plus or minus 0.02 T-2 per liter of air, which was lower than the LC50 (0.380 plus or minus 0.08 mg T-2 per liter air) for an aerosol of T-2 dissolved in ethanol. However, within about 15 min postexposure, most of the T-2 deposited in the respiratory tract was translocated from the respiratory tract regardless of whether the T-2 aerosol was from a saline suspension or ethanol solution. Also, although T-2 is an inflammatory agent to dermis and gastrointestinal epithelium, T-2 from either aerosol did not produce any histological evidence of inflammation in the respiratory tract.

  11. TOXICITY OF TETRYL (N-METHYL-N,2,4,6-TETRANITROANILINE) IN F344 RATS

    EPA Science Inventory

    The toxicity of tetryl (N-methyl-N,2,4,6-tetranitroaniline) in male and female F344 rats was evaluated after adminstration in the diet for 14 or 90 days. The 14-day study diet concentrations used were 0, 500, 1250, 2000, 2500, and 5000 ppm; the 90-day study diet concentrations we...

  12. Inhalation Toxicity of Humidifier Disinfectants as a Risk Factor of Children’s Interstitial Lung Disease in Korea: A Case-Control Study

    PubMed Central

    Yu, Jinho; Lee, Eun; Jung, Young-Ho; Kim, Hyung-Young; Seo, Ju-Hee; Kwon, Geun-Yong; Park, Ji-Hyuk; Gwack, Jin; Youn, Seung-Ki; Kwon, Jun-Wook; Jun, Byung-Yool; Kim, Kyung Won; Ahn, Kangmo; Lee, Soo-Young; Park, June-Dong; Kwon, Ji-Won; Kim, Byoung-Ju; Lee, Moo-Song; Do, Kyung-Hyun; Jang, Se-Jin; Pyun, Bok-Yang; Hong, Soo-Jong

    2013-01-01

    Background The occurrence of numerous cases of interstitial lung disease in children (chILD) every spring in Korea starting in 2006 raised suspicion about a causal relationship with the use of humidifier disinfectants (HDs). The aim of this study was to evaluate the association between HD use and the risk of chILD. Methods This retrospective, 1∶3 matched case-control study consisted of 16 cases of chILD that had developed between 2010 and 2011. The three groups of parallel controls (patients with acute lobar pneumonia, asthma, and healthy children) were matched by age, gender, and index date. Indoor/outdoor environmental risk factors, including HD use, were investigated by asking the guardians to complete a questionnaire. Results The median age of the affected children (43.8% male) was 26 months (18.25–36.25). The chILD group did not differ significantly from the control groups with respect to socio-demographic and clinical variables. Indoor and outdoor environmental factors were not associated with a risk of chILD. However, the previous use of HDs (OR; 2.73. 95% CI; 1.41–5.90, P = 0.00) were independently associated with an increased risk. Conclusions This study showed that HDs, which are widely used in South Korea in the winter season, independently increased the risk of chILD in spring. Therefore, continuous monitoring and, if needed, changes in policy are essential to prevent and control pediatric diseases caused by toxic chemicals. PMID:23755124

  13. [Inhaled therapy in asthma].

    PubMed

    Plaza Moral, Vicente; Giner Donaire, Jordi

    2016-04-01

    Because of its advantages, inhaled administration of aerosolized drugs is the administration route of choice for the treatment of asthma and COPD. Numerous technological advances in the devices used in inhaled therapy in recent decades have boosted the appearance of multiple inhalers and aerosolized drugs. However, this variety also requires that the prescribing physician is aware of their characteristics. The main objective of the present review is to summarize the current state of knowledge on inhalers and inhaled drugs commonly used in the treatment of asthma. The review ranges from theoretical aspects (fundamentals and available devices and drugs) to practical and relevant aspects for asthma care in the clinical setting (therapeutic strategies, education, and adherence to inhalers). PMID:26683076

  14. Effect of an 11. 5-hr/day exposure schedule on the distribution and toxicity of inhaled carbon tetrachloride in the rat

    SciTech Connect

    Paustenbach, D.J.; Christian, J.E.; Carlson, G.P.; Born, G.S.

    1986-04-01

    This study evaluated the differences in toxicity and tissue distribution for 16 groups of male rats repeatedly exposed to 100 ppm of /sup 14/CCl/sub 4/ vapors for 8 or 11.5 hr/day for periods of 1 to 10 days. Serum sorbitol dehydrogenase (SDH) was also evaluated for its sensitivity at detecting CCl/sub 4/-induced hepatotoxicity. Following 1, 2, 3, 4, 5, 7, 11, and 14 days, one group of rats from each exposure schedule was sacrificed and /sup 14/C activity in seven tissues and serum SDH levels were measured. To compare the effects of CCl/sub 4/ on the liver and kidney following repeated exposure to the two schedules, one group of rats was exposed for 8 hr/day for 10 of 12 consecutive days and another for 11.5 hr/day for 7 of 12 consecutive days so that each group received essentially the same dose (8000 ppm-hr) of CCl/sub 4/. The 11.5-hr/day exposure schedule, compared to rats exposed 8-hr/day, produced minor changes in the distribution and concentration of /sup 14/C (CCl/sub 4/ equivalents) in various tissues. Following 1 and 2 weeks of exposure to either schedule, the fat, liver, lungs, and adrenals had the highest concentration of CCl/sub 4/ equivalents. There were no significant differences in CCl/sub 4/-induced hepatotoxicity or nephrotoxicity between rats exposed to the two schedules following either 1 or 2 weeks of exposure as measured by histopathology. In contrast, rats exposed 11.5 hr/day had significantly higher SDH levels than those exposed to the 8-hr/day schedule; thus suggesting that the 11.5-hr schedule did produce a measurably greater degree of hepatotoxicity, although it was too subtle to detect pathologically. Rats exposed for a fourth and fifth day during the second week of the 11.5-hr schedule had a significantly greater concentration of /sup 14/C activity in the fat than rats exposed to the 8-hr/day schedule.

  15. Inhalant Abuse and Dextromethorphan.

    PubMed

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. PMID:27338970

  16. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. Howeve...

  17. Inhalants in Peru.

    PubMed

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  18. Inhalation exposure systems: design, methods and operation.

    PubMed

    Wong, Brian A

    2007-01-01

    The respiratory system, the major route for entry of oxygen into the body, provides entry for external compounds, including pharmaceutic and toxic materials. These compounds (that might be inhaled under environmental, occupational, medical, or other situations) can be administered under controlled conditions during laboratory inhalation studies. Inhalation study results may be controlled or adversely affected by variability in four key factors: animal environment; exposure atmosphere; inhaled dose; and individual animal biological response. Three of these four factors can be managed through engineering processes. Variability in the animal environment is reduced by engineering control of temperature, humidity, oxygen content, waste gas content, and noise in the exposure facility. Exposure atmospheres are monitored and adjusted to assure a consistent and known exposure for each animal dose group. The inhaled dose, affected by changes in respiration physiology, may be controlled by exposure-specific monitoring of respiration. Selection of techniques and methods for the three factors affected by engineering allows the toxicologic pathologist to study the reproducibility of the fourth factor, the biological response of the animal. PMID:17325967

  19. Pulmonary toxicity of inhaled and intravenous talc.

    PubMed

    Hollinger, M A

    1990-07-01

    Talc (magnesium silicate) is a widely used, generally considered benign substance. It is principally used as an inert filler material in drug tablets or as a drying ingredient in baby powders. However, in both cases inappropriate use can lead to severe pulmonary toxicological responses. On the one hand, intravenous injection of 'solubilized', CNS active pills can produce microemboli in small pulmonary vessels. This can lead to various degrees of granuloma formation, compromised pulmonary function, or death. Overzealous application of baby powder can also produce severe pulmonary complications if the infant inspires the powder. Although the data are relatively scarce, a number of reports suggest the existence of a chronic problem in this area.

  20. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of the test substance shall be measured in the breathing zone. During the exposure period the actual... the study (e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of... Practice Standards, 40 CFR part 792, subpart J, the following specific information shall be reported:...

  1. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of the test substance shall be measured in the breathing zone. During the exposure period the actual... the study (e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of... Practice Standards, 40 CFR part 792, subpart J, the following specific information shall be reported:...

  2. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of the test substance shall be measured in the breathing zone. During the exposure period the actual... the study (e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of... Practice Standards, 40 CFR part 792, subpart J, the following specific information shall be reported:...

  3. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of the test substance shall be measured in the breathing zone. During the exposure period the actual... the study (e.g., necropsy or refrigeration of those animals found dead and isolation or sacrifice of... Practice Standards, 40 CFR part 792, subpart J, the following specific information shall be reported:...

  4. Prolonged asthma after smoke inhalation: A report of three cases and a review of previous reports

    SciTech Connect

    Moisan, T.C. )

    1991-04-01

    The development of prolonged obstructive airways disease after smoke inhalation is of concern to fire victims and fire fighters. Three cases of asthma that developed following the inhalation of pyrolysis products are presented along with a review of previous reports of airway injury from smoke inhalation. Polyvinyl chloride pyrolysis products seem to pose a high risk, but other toxic inhalants are also implicated. There is substantial evidence that prolonged airway hyper-responsiveness and asthma may follow numerous inflammatory insults including smoke inhalation. Studies to identify specific individual risk factors and asthmagenic pyrolysis products are needed. Early, postexposure anti-inflammatory treatment may modify the outcome. 42 refs.

  5. [Ventricular fibrillation following deodorant spray inhalation].

    PubMed

    Girard, F; Le Tacon, S; Maria, M; Pierrard, O; Monin, P

    2008-01-01

    We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

  6. Levalbuterol Oral Inhalation

    MedlinePlus

    ... inhaler or nebulizer. Ask your doctor, pharmacist, or respiratory therapist to show you how to use it. ... propranolol (Inderal); digoxin (Digitek, Lanoxin); diuretics ('water pills'); epinephrine (Epipen, Primatene Mist); medications for colds; and other ...

  7. Albuterol Oral Inhalation

    MedlinePlus

    ... on the bottom and the inhaler pointing upwards, load the dose by opening the protective dust cap ... or face mask. Connect the nebulizer to the compressor. Place the mouthpiece in your mouth or put ...

  8. Substance use - inhalants

    MedlinePlus

    ... it has been sprayed or put into a paper or plastic bag Ballooning. Inhaling a gas from ... empty soda cans, empty perfume bottles, and toilet paper tubes stuffed with rags or toilet paper soaked ...

  9. Formoterol Oral Inhalation

    MedlinePlus

    ... shortness of breath, and breathing difficulties caused by chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder ...

  10. Olodaterol Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, which includes chronic bronchitis and emphysema). Olodaterol oral inhalation is in ...

  11. Umeclidinium Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, that includes chronic bronchitis and emphysema). Umeclidinium inhalation is in a ...

  12. Cromolyn Oral Inhalation

    MedlinePlus

    ... difficulties (bronchospasm) caused by exercise, cold and dry air, or by inhaling substances such as pet dander, ... of substances that cause inflammation (swelling) in the air passages of the lungs.

  13. Fluticasone Oral Inhalation

    MedlinePlus

    ... you are near an open flame or a heat source. The inhaler may explode if it is ... Nizoral); clarithromycin (Biaxin); HIV protease inhibitors such as atazanavir (Reyataz, in Evotaz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir ( ...

  14. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  15. Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

    PubMed

    Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

    2012-06-01

    Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. PMID:22265940

  16. Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

    PubMed

    Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

    2012-06-01

    Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet.

  17. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    SciTech Connect

    Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.; Proctor, Deborah M.; Harris, Mark A.; Haws, Laurie C.; Thompson, Chad M.

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

  18. Behavioral changes in mice following benzene inhalation.

    PubMed

    Evans, H L; Dempster, A M; Snyder, C A

    1981-01-01

    Although benzene is an important occupational health hazard and a carcinogen, the possibility that behavioral changes may forewarn of the later-occurring hematological changes has not been investigated. A time-sampling protocol was used to quantify the occurrence of 7 categories of behavior in the homecage following daily 6-hr exposures to two strains of adult mice (CD1 and C57BL/6J). The behavioral categories were stereotypic behavior, sleeping, resting, eating, grooming, locomotion, and fighting. The inhalation exposures were designed to reflect occupational exposure. Dynamic vapor exposure techniques in standard inhalation chambers were employed. Exposure to 300 or 900 ppm benzene increased the occurrence of eating and grooming and reduced the number of mice that were sleeping or resting. The responses to benzene of both the CD1 and the C57 strains were similar. The positive findings with benzene inhalation indicate the utility of behavioral investigations into the toxicology of inhaled organic solvents. The methods described herein illustrate an objective observation of animal behavior that is capable of documenting toxicity and of guiding detailed follow-up studies aimed at mechanism of action.

  19. Inhaled antibiotics in mechanically ventilated patients.

    PubMed

    Michalopoulos, A S; Falagas, M E

    2014-02-01

    During the last decade, inhaled antibiotics, especially colistin, has been widely used worldwide as a therapeutic option, supplementary to conventional intravenous antibiotics, for the treatment of multidrug-resistant (MDR) Gram-negative nosocomial and ventilator-associated pneumonia (VAP). Antimicrobial aerosols are commonly used in mechanically ventilated patients with VAP, although information regarding their efficacy and optimal technique of administration has been limited. Recent studies showed that the administration of inhaled antibiotics in addition to systemic antibiotics provided encouraging results associated with low toxicity for the management of VAP mainly due to MDR Gram negative bacteria. Although the theory behind aerosolized administration of antibiotics seems to be sound, there are limited data available to support the routine use of this modality since very few randomized controlled trials (RCTs) have still examined the efficacy of this approach in patients with VAP. Additionally, this route of antibiotic delivery has not been approved until now neither by the FDA nor by the European Medicines Agency (EMEA) in patients with VAP. However, since the problem of VAP due to MDR bacteria has been increased worldwide RCTs are urgently needed in order to prove the safety, efficiency and efficacy of inhaled antimicrobial agents administered alone or in conjunction with parenteral antibiotics for the management of VAP in critically ill patients. Indeed, more data are needed to establish the appropriate role of inhaled antibiotics for the treatment of VAP.

  20. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90days of exposure to hexavalent chromium in drinking water.

    PubMed

    Kopec, Anna K; Kim, Suntae; Forgacs, Agnes L; Zacharewski, Timothy R; Proctor, Deborah M; Harris, Mark A; Haws, Laurie C; Thompson, Chad M

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90days of exposure to 0, 0.3, 4, 14, 60, 170 or 520mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose-response modeling identified >80% of the differentially expressed genes exhibited sigmoidal dose-response curves with EC(50) values ranging from 10 to 100mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC(50) values <10mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation.

  1. [Inhalational or intravenous anesthesia?].

    PubMed

    Dahan, A; Aarts, L P H J

    2016-01-01

    The debate continues whether there is a difference in patient outcome following inhalational versus intravenous anesthesia. A recent meta-analysis showed improved outcome following inhalational anesthesia in patients undergoing cardiac surgery but not in patients undergoing non-cardiac procedures. In this article we discuss the meta-analysis and its caveats, taking into account additional comparative studies. Our overall conclusion is that it is too early to definitively claim that one anesthesia technique results in a better outcome than the other. PMID:27650024

  2. INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    Inhalation toxicology studies are being conducted to inform the risk assessment ofLibby amphibole. The overall purpose of these studies is to compare the toxicity of inhaled Libby amphibole fibers to a positive control fiber sample (UICC amosite). A 2-week study was conducted to ...

  3. MODELING DEPOSITION OF INHALED PARTICLES

    EPA Science Inventory

    Modeling Deposition of Inhaled Particles: ABSTRACT

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

  4. Interspecies modeling of inhaled particle deposition patterns

    SciTech Connect

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    To evaluate the potential toxic effects of ambient contaminants or therapeutic effects of airborne drugs, inhalation exposure experiments can be performed with surrogate laboratory animals. Herein, an interspecies particle deposition theory is presented for physiologically based pharmacokinetic modeling. It is derived to improve animal testing protocols. The computer code describes the behavior and fate of particles in the lungs of human subjects and a selected surrogate, the laboratory rat. In the simulations CO2 is integrated with exposure chamber atmospheres, and its concentrations regulated to produce rat breathing profiles corresponding to selected levels of human physical activity. The dosimetric model is used to calculate total, compartmental (i.e., tracheobronchial and pulmonary), and localized distribution patterns of inhaled particles in rats and humans for comparable ventilatory conditions. It is demonstrated that the model can be used to predetermine the exposure conditions necessary to produce deposition patterns in rats that are equivalent to those in humans at prescribed physical activities.

  5. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  6. Inhalants. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about inhalant abuse. Article 1 presents findings on the psychophysiological effects related to the use of amyl or butyl nitrate as a "recreational drug." Article 2 suggests a strong association between chronic sniffing of the solvent toulene and irreversible brain damage. Article 3 warns about the…

  7. NATIONAL-SCALE ASSESSMENT OF AIR TOXICS RISKS

    EPA Science Inventory

    The national-scale assessment of air toxics risks is a modeling assessment which combines emission inventory development, atmospheric fate and transport modeling, exposure modeling, and risk assessment to characterize the risk associated with inhaling air toxics from outdoor sour...

  8. Wildlife ecological screening levels for inhalation of volatile organic chemicals.

    PubMed

    Gallegos, Patricia; Lutz, Jill; Markwiese, James; Ryti, Randall; Mirenda, Rich

    2007-06-01

    For most chemicals, evaluation of ecological risk typically does not address inhalation because ingestion dominates exposure. However, burrowing ecological receptors have an increased exposure potential from inhalation at sites contaminated with volatile chemicals in the subsurface. Evaluation of ecological risk from contaminants like volatile organic chemicals (VOCs) is constrained by a lack of relevant ecological screening levels (ESLs). To address this need, inhalation ESLs were developed for 16 VOCs: Acetone, benzene, carbon tetrachloride, chloroform, chloromethane, dichlorodifluoromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,1-dichloroethene, methylene chloride, tetrachloroethene, toluene, 1,1,1-trichloroethane, trichloroethene, trichlorofluoromethane, and total xylene. These ESLs are based on Botta's pocket gopher (Thomomys bottae) as a representative fossorial receptor. The ESLs are presented with an emphasis on the process for developing inhalation toxicity reference values to illustrate the selection of suitable toxicity data and effect levels from the literature. The resulting ESLs provide a quantitative method for evaluating ecological risk of VOCs through comparison to relevant exposure data such as direct burrow-air measurements. The toxicity reference value development and ESL calculation processes and assumptions detailed here are provided as bases from which risk assessors can use or refine to suit site-specific needs with respect to toxicity and exposure inputs.

  9. Generation and characterization of aerosols and vapors for inhalation experiments.

    PubMed Central

    Tillery, M I; Wood, G O; Ettinger, H J

    1976-01-01

    Control of aerosol and vapor characteristics that affect the toxicity of inhaled contaminants often determines the methods of generating exposure atmospheres. Generation methods for aerosols and vapors are presented. The characteristics of the resulting exposure atmosphere and the limitations of the various generation methods are discussed. Methods and instruments for measuring the airborne contaminant with respect to various charcteristics are also described. PMID:797565

  10. IS IT THE EXCEPTION OR THE RULE? DAILY CO-OCCURRENCE OF PHYSICAL, SEXUAL, AND PSYCHOLOGICAL PARTNER VIOLENCE IN A 90-DAY STUDY OF SUBSTANCE-USING, COMMUNITY WOMEN

    PubMed Central

    Sullivan, Tami P.; McPartland, Tara; Armeli, Stephen; Jaquier, Véronique; Tennen, Howard

    2013-01-01

    Objective This study aims to describe the daily co-occurrence of physical, sexual, and psychological intimate partner violence (IPV) among substance-using, community-based women currently experiencing IPV. Methods A micro-longitudinal study design was used to collect data daily from 49 women for 90 days. Results On the majority of days (62%), no IPV occurred; 27% of days were characterized by psychological IPV alone, followed by the co-occurrence of psychological and physical IPV (6% of IPV days). Results of person-level analyses showed comparable sized correlations between the proportion of days with physical and sexual IPV and the proportion of days with physical and psychological IPV. However, results of day-level analyses revealed that the association between physical and psychological IPV was much stronger than the association between physical and sexual IPV; Physical IPV was 64 times more likely to occur on days when psychological IPV occurred. Conclusions Results revealed new information about physical, sexual, and psychological IPV experiences and demonstrate the utility of a micro-longitudinal design among this high risk population. Implications for practice, future research, and the development of preventive interventions are noted, underscoring the importance of psychological IPV and the range of IPV experiences among women. PMID:24349863

  11. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  12. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity. PMID:26613951

  13. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison.

  14. Effects of CO2 inhalation exposure on mice vomeronasal epithelium.

    PubMed

    Hacquemand, Romain; Buron, Gaelle; Pourié, Gregory; Karrer, Melanie; Jacquot, Laurence; Brand, Gerard

    2010-08-01

    Nasal epitheliums are the first sites of the respiratory tract in contact with the external environment and may therefore be susceptible to damage from exposure to many toxic volatile substances (i.e., volatile organic components, vapors, and gases). In the field of inhalation toxicology, a number of studies have considered the main olfactory epithelium, but few have dealt with the epithelium of the vomeronasal organ (VNO). However, in several species such as in rodents, the VNO (an organ of pheromone detection) plays an important role in social interactions, and alterations of this organ are known to induce adaptative behavioral disturbances. Among volatile toxicants, health effects of inhaled gases have been thoroughly investigated, especially during CO(2) inhalation because of its increasing atmospheric concentration. Therefore, this work was designed to examine the effects of 3% CO(2) inhalation on VNO in two different exposure conditions (5 h/day and 12 h/day) in mice. Behavioral sensitivity tests to urine of congener and histological measurements of VNO were conducted before, during (weeks 1-4), and after (weeks 5-8) CO(2) inhalation exposures. Results showed no significant modifications of behavioral responses to urine, but there were significant changes of both cell number and thickness of the VNO epithelium. Moreover, the findings indicated a selectively dose-dependent effect of CO(2), and further research could use other gases in the same manner for comparison. PMID:19924548

  15. Inhalant abuse among adolescents: neurobiological considerations.

    PubMed

    Lubman, D I; Yücel, M; Lawrence, A J

    2008-05-01

    Experimentation with volatile substances (inhalants) is common during early adolescence, yet limited work has been conducted examining the neurobiological impact of regular binge use during this key stage of development. Human studies consistently demonstrate that chronic use is associated with significant toxic effects, including neurological and neuropsychological impairment, as well as diffuse and subtle changes in white matter. However, most preclinical research has tended to focus on acute exposure, with limited work examining the neuropharmacological or toxicological mechanisms underpinning these changes or their potential reversibility with abstinence. Nevertheless, there is growing evidence that commonly abused inhalants share common cellular mechanisms, and have similar actions to other drugs of abuse. Indeed, the majority of acute behavioural effects appear to be underpinned by changes in receptor and/or ion channel activity (for example, GABA(A), glycine and 5HT(3) receptor activation, NMDA receptor inhibition), although nonspecific interactions can also arise at high concentrations. Recent studies examining the effects of toluene exposure during the early postnatal period are suggestive of long-term alterations in the function of NMDA and GABA(A) receptors, although limited work has been conducted investigating exposure during adolescence. Given the critical role of neurotransmitter systems in cognitive, emotional and brain development, future studies will need to take account of the substantial neuromaturational changes that are known to occur in the brain during childhood and adolescence, and to specifically investigate the neuropharmacological and toxicological profile of inhalant exposure during this period of development. PMID:18332858

  16. Toxicity test of a dental commercial composite

    PubMed Central

    Ponce-Bravo, Santa; Martínez-Rivera, José-Luis; Garcés-Ortíz, Maricela

    2015-01-01

    Background International rules must be followed for testing biosecurity in dental materials. A new brand of restorative material appeared in the market and regulations indicated that it should be tested for toxicity. Objectives The aim of this study was to determine the 90-day sub chronic toxicity of one triethylene glycol dimethacrylate containing composite (MEDENTAL Light-Cure Composite™) orally administered to rats according to Organization for Economic Co-Operation and Development no. 48 guidelines and the requirements specified in the ISO 10993-11. Material and Methods Wistar rats ate the polymerized composite during 90 days and were observed to determine changes in their behavior, eye and skin signs and other attitudes such as aggressiveness, posture, walking and response to handling. After 90 days were sacrificed to ascertain blood alterations, we did special hematological tests and assessed microscopic slides from 33 different organs. Results We recorded no significant changes in clinical behavior of the animals. Microscopic review of the H&E stained slides obtained from the analyzed organs showed no abnormal inflammatory or cytological changes and all hematological special tests were within normal limits. Conclusions Results of this study show that under our experimental conditions the MEDENTAL Light-Cure Composite™ does not produce inflammatory or cytological changes suggestive of toxicity. Key words:Dental materials, composite resin, toxicity, inflammation, TEGDMA. PMID:26155348

  17. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... methods really work, and people who use these methods may continue to use their inhalers after the inhalers are empty.Some inhalers come with a counter that shows the number of sprays that remain in the inhaler. If your inhaler ...

  18. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic (PBPK) modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice *

    EPA Science Inventory

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools used for cal...

  19. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance

    PubMed Central

    Rao, Krishnasree; Matulevicius, Susan

    2016-01-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis. PMID:27303242

  20. Cyanide poisoning by fire smoke inhalation: a European expert consensus.

    PubMed

    Anseeuw, Kurt; Delvau, Nicolas; Burillo-Putze, Guillermo; De Iaco, Fabio; Geldner, Götz; Holmström, Peter; Lambert, Yves; Sabbe, Marc

    2013-02-01

    Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.

  1. Inhaled Amikacin for Treatment of Refractory Pulmonary Nontuberculous Mycobacterial Disease

    PubMed Central

    Shaw, Pamela A.; Glaser, Tanya S.; Bhattacharyya, Darshana; Fleshner, Michelle; Brewer, Carmen C.; Zalewski, Christopher K.; Folio, Les R.; Siegelman, Jenifer R.; Shallom, Shamira; Park, In Kwon; Sampaio, Elizabeth P.; Zelazny, Adrian M.; Holland, Steven M.; Prevots, D. Rebecca

    2014-01-01

    Rationale: Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. Objectives: We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Methods: Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. Measurements and Main Results: The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. Conclusions: In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted. PMID:24460437

  2. About Steroids (Inhaled and Oral Corticosteroids)

    MedlinePlus

    ... dose-inhalers ( inhaled steroids ), oral forms (pills or syrups) , injections (shots) and intravenous (IV) solutions. Healthcare providers ... slowly decreased. Inhaled steroids and steroid pills and syrups are often prescribed for people with a chronic ...

  3. Parent's Guide to Preventing Inhalant Abuse

    MedlinePlus

    ... conditioning coolants. How can you tell if a young person is an inhalant abuser? If someone is ... youths involved with inhalant abuse. How does a young person who abuses inhalants die? There are many ...

  4. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  5. Asymptomatic inhaled foreign body

    PubMed Central

    Salim, Muhammad U.; Asghar, Asif; Tareen, Irum; Azhar, Muhammad

    2016-01-01

    It is very rare to have a big foreign body in the lungs without any complications or symptoms for 2 years. A 14-year-old male with episodes of minor hemoptysis for 4 weeks had a history of inhalation of a bullet 2 years earlier. He had asymptomatic for lung complications for 2 years. The bullet was removed by right thoracotomy and non-anatomical wedge stapled resection, and he followed an uneventful recovery. An aspirated foreign body although big can remain asymptomatic for a long time, especially if it has migrated to the periphery. PMID:27652366

  6. Insulin inhalation: NN 1998.

    PubMed

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  7. Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?

    PubMed

    Hamad, Eike; Babu, Kavita; Bebarta, Vikhyat S

    2016-06-01

    Cyanide toxicity is common after significant smoke inhalation. Two cases are presented that provide framework for the discussion of epidemiology, pathogenesis, presenting signs and symptoms, and treatment options of inhalational cyanide poisoning. An evidence-based algorithm is proposed that utilizes point-of-care testing to help physicians identify patients who benefit most from antidotal therapy.

  8. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    SciTech Connect

    Clewell, H.J. Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  9. Ntp report on the toxicity studies of ethylbenzene in f344/n rats and b6c3f1 mice (inhalation studies). Report for 29 March-30 June 1988

    SciTech Connect

    Chan, P.

    1992-03-01

    Inhalation toxicology studies of ethylbenzene (99% pure) were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to ethylbenzene vapor at chamber concentrations of 0 to 1000 ppm, 6 hours per day, 5 days per week for 13 weeks. No rats or mice died during the 13-week exposure. Body weight gains were slightly lower in the high dose groups of male and female rats, but the differences were not statistically significant. Absolute and relative kidney, liver, and lung weights were increased in the exposed rats, while weight increases occurred only in the livers of exposed mice. No changes were observed in the evaluation of sperm or vaginal cytology in rats or mice. Ethylbenzene was not mutagenic in Salmonella and did not induce chromosomal aberrations or sister chromatid exchanges in Chinese hamster ovary (CHO) cells in vitro, though it did induce trifluorothymidine resistance in mouse lymphoma cells at the highest concentration tested. Micronuclei assays in peripheral blood of mice were negative.

  10. Inhalation delivery of asthma drugs.

    PubMed

    Matthys, H

    1990-01-01

    In the immediate future, metered-dose inhalers (MDIs) with spacers remain the aerosol application of choice for topical steroids, mainly to reduce side effects. For beta 2-agonist, anticholinergics and prophylactic drugs, MDI (with or without demand valve), dry powder inhalers (multidose inhalers), ultrasonic or jet aerosol generators (with or without mechanical breathing assistance [IPPB]) are chosen according to the preference or the ability of the patients to perform the necessary breathing maneuvers as well as the availability of different products in different countries.

  11. Deposition, retention, and clearance of inhaled particles.

    PubMed

    Lippmann, M; Yeates, D B; Albert, R E

    1980-11-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  12. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  13. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde.

    PubMed

    Kosmider, Leon; Sobczak, Andrzej; Prokopowicz, Adam; Kurek, Jolanta; Zaciera, Marzena; Knysak, Jakub; Smith, Danielle; Goniewicz, Maciej L

    2016-04-01

    Many non-cigarette tobacco products, including e-cigarettes, contain various flavourings, such as fruit flavours. Although many flavourings used in e-cigarettes are generally recognised as safe when used in food products, concerns have been raised about the potential inhalation toxicity of these chemicals. Benzaldehyde, which is a key ingredient in natural fruit flavours, has been shown to cause irritation of respiratory airways in animal and occupational exposure studies. Given the potential inhalation toxicity of this compound, we measured benzaldehyde in aerosol generated in a laboratory setting from flavoured e-cigarettes purchased online and detected benzaldehyde in 108 out of 145 products. The highest levels of benzaldehyde were detected in cherry-flavoured products. The benzaldehyde doses inhaled with 30 puffs from flavoured e-cigarettes were often higher than doses inhaled from a conventional cigarette. Levels in cherry-flavoured products were >1000 times lower than doses inhaled in the workplace. While e-cigarettes seem to be a promising harm reduction tool for smokers, findings indicate that using these products could result in repeated inhalation of benzaldehyde, with long-term users risking regular exposure to the substance. Given the uncertainty surrounding adverse health effects stemming from long-term inhalation of flavouring ingredients such as benzaldehyde, clinicians need to be aware of this emerging risk and ask their patients about use of flavoured e-cigarettes.

  14. Reduction of hydrogen cyanide concentrations and acute inhalation toxicity from flexible polyurethane foam combustion products by the addition of copper compounds. Part 3. The effect of copper additives on the flammability characteristics of flexible polyurethane foam

    SciTech Connect

    Levin, B.C.; Braun, E.; Shields, J.R.; Lowe, D.

    1990-10-01

    The report addresses the issue of whether the addition of a copper compound to a flexible polyurethane foam would affect the flammability characteristics of the foam. The following properties were examined: (1) ignitability in three systems (the NBS Toxicity Test Method, the Cone Calorimeter, and Lateral Ignition and Flame Spread Test (LIFT)), (2) heat release rate under small-scale (Cone Calorimeter) and medium-scale (furniture calorimeter), (3) smoke obscuration (Cone Calorimeter), and (4) rate of flame spread (LIFT). In all cases, no differences in flammability characteristics between the treated and untreated foam were observed.

  15. Potent Inhalational Anesthetics for Dentistry.

    PubMed

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

  16. Potent Inhalational Anesthetics for Dentistry.

    PubMed

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings.

  17. Potent Inhalational Anesthetics for Dentistry

    PubMed Central

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

  18. [Inhaled insulin, new perspective for insulin therapy].

    PubMed

    Radermecker, R P; Sélam, J L

    2005-01-01

    Since the discovery of insulin and its use in diabetes care, patients, physicians and nurses dream of another way of insulin administration than the subcutaneous injections actually used. Different types of insulin administration have been evaluated and, particularly, that using the pulmonary route. The use of this alternative method to deliver insulin may result in improved patient compliance, facilitate intensified therapies and avoid the delay of initiating insulin administration because patient's reluctance. The different insulin pulmonary delivering devices actually studied will be presented. Preliminary data comparing this way of administration and the subcutaneous injection of human regular insulin are good, but sufficient data comparing inhaled insulin with the new short-acting insulin analogues are not yet available. Among various difficulties of the pulmonary insulin delivery, the finding of an effective promoter, capable of increasing the bioavailability of insulin, is a crucial issue. The cost of such insulin administration might also be a problem. Finally, careful studies concerning the safety of this kind of administration, particularly potential long-term pulmonary toxicity, are mandatory. Nevertheless, inhaled insulin is an attractive topic in which most important pharmaceutical companies are currently involved.

  19. [Inhaled antibiotic therapy in cystic fibrosis].

    PubMed

    Girón Moreno, Rosa M; Salcedo Posadas, Antonio; Mar Gómez-Punter, Rosa

    2011-06-01

    Cystic fibrosis is the most frequent fatal genetically-transmitted disease among Caucasians. Chronic bronchial infection, especially by Pseudomonas aeruginosa, is the main cause of morbidity and mortality in this disease. Aerosolized antibiotic therapy achieves high drug concentrations in the airway with low toxicity, allowing chronic use. Currently, two antibiotics have been approved for inhalation therapy, tobramycin inhalation solution and colistimethate sodium aerosol. There is less evidence from clinical trials for the latter. The main indication for these drugs is chronic bronchial colonization by P. aeruginosa, although there is increasing evidence of the importance of the primary infection by this bacterium, whether treated by oral or intravenous antibiotics or not. More controversial is the use of aerosolized antibiotic therapy in bacterial prophylaxis or respiratory exacerbations. For many years, intravenous formulations of distinct antibiotics for aerosolized use have been employed, which are in distinct phases of research for use in nebulizer therapy. In addition to being used to treat P. aeruginosa infection, aerosolized antibiotics have been used to treat other pathogens such as methicillin-resistant Staphylococus aureus, Mycobacterium abscessus and Aspergillus fumigatus. PMID:21703474

  20. Facial injury and airway threat from inhalant abuse: a case report.

    PubMed

    Kurbat, R S; Pollack, C V

    1998-01-01

    Fluorinated hydrocarbons cause toxicity in humans via their dysrhythmogenic potential and their local physical effects on the skin and mucous membranes. The former is generally the more life-threatening toxic consequence. We present a case of fluorinated hydrocarbon injury resulting from an intentional inhalation exposure that created facial frostbite, which threatened the patient's airway. The clinical range and management of these tissue-toxic effects are reviewed.

  1. Toxicological outcomes in rats exposed to inhaled ethanol during gestation.

    PubMed

    Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Rogers, John M; Copeland, Carey B; Bushnell, Philip J

    2014-01-01

    Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is typically blended with gasoline in the United States at concentrations up to 10%, with allowances for concentrations up to 85% for some vehicles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol, and the lack of information about its toxicity by inhalation prompted the present work on its potential developmental effects in a rat model. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or ethanol vapor at concentrations of 5000, 10,000, or 21,000 ppm, which resulted in estimated peak blood ethanol concentrations (BECs) of 2.3, 6.7, and 192 mg/dL, respectively. No overt toxicity in the dams was observed. Ethanol did not affect litter size or weight, or postnatal weight gain in the pups. Motor activity was normal in offspring through postnatal day (PND) 29. On PND 62, the 5000 and 21,000 ppm groups were more active than controls. On PND 29 and 62, offspring were tested with a functional observational battery, which revealed small changes in the neuromuscular and sensorimotor domains that were not systematically related to dose. Cell-mediated and humoral immunity were not affected by ethanol exposure in 6-week-old offspring. Systolic blood pressure was increased by 10,000 ppm ethanol in males at PND 90 but not at PND 180. No differences in lipoprotein profile, liver function, or kidney function were observed. In summary, prenatal exposure to inhaled ethanol caused some mild changes in physiological and behavioral development in offspring that were not clearly related to inhaled concentration or BEC, and did not produce detectable changes in immune function. This low toxicity of inhaled ethanol may result from the slow

  2. Toxicological outcomes in rats exposed to inhaled ethanol during gestation.

    PubMed

    Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Rogers, John M; Copeland, Carey B; Bushnell, Philip J

    2014-01-01

    Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is typically blended with gasoline in the United States at concentrations up to 10%, with allowances for concentrations up to 85% for some vehicles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol, and the lack of information about its toxicity by inhalation prompted the present work on its potential developmental effects in a rat model. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or ethanol vapor at concentrations of 5000, 10,000, or 21,000 ppm, which resulted in estimated peak blood ethanol concentrations (BECs) of 2.3, 6.7, and 192 mg/dL, respectively. No overt toxicity in the dams was observed. Ethanol did not affect litter size or weight, or postnatal weight gain in the pups. Motor activity was normal in offspring through postnatal day (PND) 29. On PND 62, the 5000 and 21,000 ppm groups were more active than controls. On PND 29 and 62, offspring were tested with a functional observational battery, which revealed small changes in the neuromuscular and sensorimotor domains that were not systematically related to dose. Cell-mediated and humoral immunity were not affected by ethanol exposure in 6-week-old offspring. Systolic blood pressure was increased by 10,000 ppm ethanol in males at PND 90 but not at PND 180. No differences in lipoprotein profile, liver function, or kidney function were observed. In summary, prenatal exposure to inhaled ethanol caused some mild changes in physiological and behavioral development in offspring that were not clearly related to inhaled concentration or BEC, and did not produce detectable changes in immune function. This low toxicity of inhaled ethanol may result from the slow

  3. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.

  4. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds. PMID:26775187

  5. Inhalation of titanium dioxide induces endoplasmic reticulum stress-mediated autophagy and inflammation in mice.

    PubMed

    Yu, Kyeong-Nam; Sung, Jae Hyuck; Lee, Somin; Kim, Ji-Eun; Kim, Sanghwa; Cho, Won-Young; Lee, Ah Young; Park, Soo Jin; Lim, Joohyun; Park, Changhoon; Chae, Chanhee; Lee, Jin Kyu; Lee, Jinkyu; Kim, Jun-Sung; Cho, Myung-Haing

    2015-11-01

    Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreen, electronics, drug delivery systems, and diverse bio-application fields. In the workplace, the primary exposure route for TiO2 nanoparticles is inhalation through the respiratory system. Because TiO2 nanoparticles have different physiological properties, in terms of size and bioactivity, their toxic effects in the respiratory system must be determined. In this study, to determine the toxic effect of inhaled TiO2 nanoparticles in the lung and the underlying mechanism, we used a whole-body chamber inhalation system to expose A/J mice to TiO2 nanoparticles for 28 days. During the experiments, the inhaled TiO2 nanoparticles were characterized using a cascade impactor and transmission electron microscopy. After inhalation of the TiO2 nanoparticles, hyperplasia and inflammation were observed in a TiO2 dose-dependent manner. To determine the biological mechanism of the toxic response in the lung, we examined endoplasmic reticulum (ER) and mitochondria in lung. The ER and mitochondria were disrupted and dysfunctional in the TiO2-exposed lung leading to abnormal autophagy. In summary, we assessed the potential risk of TiO2 nanoparticles in the respiratory system, which contributed to our understanding of the mechanism underlining TiO2 nanoparticle toxicity in the lung.

  6. Pneumoconiosis after sericite inhalation

    PubMed Central

    Algranti, E; Handar, A; Dumortier, P; Mendonca, E; Rodrigues, G; Santos, A; Mauad, T; Dolhnikoff, M; De Vuyst, P; Saldiva, P; Bussacos, M

    2005-01-01

    Aims: To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust. Methods: The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chest x ray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area. Results: Respirable dust contained 4.5–10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23–55%) with a mean diameter of <0.5 µm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices and x ray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung. Conclusion: Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis. PMID:15723874

  7. Anaphylaxis induced by lentil inhalation.

    PubMed

    Ayşenur, Kaya; Akan, Ayşegül; Mustafa, Erkoçoğlu; Müge, Toyran; Kocabaş, Can Naci

    2012-06-01

    Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. Foods are the most common allergens leading to anaphylaxis especially for childhood. Most of the food-induced anaphylactic reactions take place after ingestion of the allergic food and only a few cases exist with anaphylactic reactions induced by inhalation of foods such as peanut, soybean and lupine. The case we present is unusual in that an 8 1/2-year-old boy developed anaphylaxis with the inhalation of steam from boiling lentils.

  8. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    SciTech Connect

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-11-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  9. SUBCHRONIC TOXICITY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    The subchronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats was evaluated by feeding a powdered certified laboratory diet containing 0, 66.7, 400 and 800 mg TNB/kg diet for 90 days. The calculated average TNB intake was 4.29, 24.70, and 49.28 mg/kg...

  10. Blood and liver acetaldehyde concentration in rats following acetaldehyde inhalation and intravenous and intragastric ethanol administration

    SciTech Connect

    Watanabe, A.; Hobara, N.; Nagashima, H.

    1986-10-01

    Ethanol is metabolized to acetaldehyde, a highly reactive product of ethanol oxidation. Ethanol might be blended with gasoline and used as a fuel in the future; biohazard of acetaldehyde inhalation must be discussed. Recent improvements in our ability to measure acetaldehyde levels in blood and various tissues have made the assessment of acetaldehyde's role in alcoholic organ intoxication possible. Blood and liver acetaldehyde concentrations in rats were reported as being linearly correlated following intragastric ethanol administration. Acetaldehyde was administered by inhalation to study its toxicity. However, liver concentrations following the inhalation was not investigated. The present communication describes the relationship between blood and liver acetaldehyde concentrations in rats following acetaldehyde inhalation and different routes of ethanol administration.

  11. Nanotechnology-based inhalation treatments for lung cancer: state of the art

    PubMed Central

    Ahmad, Javed; Akhter, Sohail; Rizwanullah, Md; Amin, Saima; Rahman, Mahfoozur; Ahmad, Mohammad Zaki; Rizvi, Moshahid Alam; Kamal, Mohammad A; Ahmad, Farhan Jalees

    2015-01-01

    Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP) carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed. PMID:26640374

  12. Toxic Hazards Research Unit annual technical report, 1972

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1972-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1971 through May 1972 are reviewed in this report. Acute inhalation toxicity experiments were conducted on hydrogen chloride (HCl) gas and aerosol, ethyl bromide (C2H5Br), hydrogen bromide (HBr), hydrogen sulfide (H2S), ammonia (NH3), chlorine (CL2), and silane (SiH4). Subacute toxicity studies were conducted on chlorine pentafluoride (ClF5), dichloromethane (CH2Cl2) and coal tar volatiles. Further toxicity studies of subacute and chronic responses to inhaled monomethylhydrazine (MMH) are also described.

  13. Toxicity of nanomaterials

    PubMed Central

    Sharifi, Shahriar; Behzadi, Shahed; Laurent, Sophie; Forrest, M. Laird; Stroeve, Pieter

    2015-01-01

    Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan’s Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product’s life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity. PMID:22170510

  14. Late-onset respiratory distress after inhalation of laundry detergent.

    PubMed

    Wheeler, Derek S; Bonny, Andrea E; Ruddy, Richard M; Jacobs, Brian R

    2003-04-01

    Accidental poisoning with household cleaning products can pose significant risks to children. Exposure to granular laundry detergents accounts for a number of calls each year to poison control centers, though few of these exposures result in hospitalization. While caustic gastrointestinal injury resulting from ingestion of these highly alkaline cleaning agents is well-recognized, few reports address the potential damage to the respiratory tract that can occur following ingestion or inhalation of granular laundry detergent. We present a previously healthy 1-year-old who presented to the emergency department with Late-onset stridor and increased work of breathing following presumed inhalation of granular laundry detergent. Parents, primary care providers, and emergency department physicians need to be aware of the potential toxicity of these widely used household products.

  15. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  16. Inhalant Use in Florida Youth

    ERIC Educational Resources Information Center

    Siqueira, Lorena; Crandall, Lee A.

    2006-01-01

    Purpose: To determine (1) the prevalence of use, (2) risk and protective factors for use of inhalants in Florida youth. Methods: The Florida Youth Substance Abuse Survey 2004 is a comprehensive assessment of youth substance abuse attitudes and practices obtained by sampling youth from sixty-five counties. Results: The sample consisted of 60,345…

  17. Parental Influence on Inhalant Use

    ERIC Educational Resources Information Center

    Baltazar, Alina; Hopkins, Gary; McBride, Duane; Vanderwaal, Curt; Pepper, Sara; Mackey, Sarah

    2013-01-01

    The purpose of this article is to examine the dynamics of the relationship between parents and their adolescent children and their association with lifetime and past-month inhalant usage. The population studied was seventh- through ninth-grade students in rural Idaho (N = 570). The authors found a small, but consistent, significant inverse…

  18. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  19. Synthetic vitreous fibers--inhalation studies.

    PubMed

    McConnell, E E

    1994-12-01

    Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous fibers," are a class of materials that have their major uses for insulation against heat and sound. The original fibers are produced by melting various types of rock, clay, etc. and then blowing or extruding them into fibers of particular properties. During production and use small fractions of airborne fibers can be generated. Because of this a series of state-of-the-art inhalation studies was initiated to study the possible health hazards presented by the four major types of vitreous materials [two types of insulation glass wool, rock wool, slag wool, and four types of refractory ceramic fibers (RCF)] found in the workplace or to which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6 hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for lifetime observation (until approximately 20% survival) to study the chronic toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile or crocidolite asbestos served as positive controls. All of the fibers stimulated an inflammatory response characterized by an increase in the number of pulmonary macrophages at the level of the terminal bronchioles and proximal alveoli. RCF produced interstitial fibrosis in the walls of the proximal alveoli as early as 3 months and rock wool by 12 months. The only fiber which showed carcinogenic activity was RCF which produced a dose-related increase in both primary lung neoplasms (rats only) and mesotheliomas (rats and hamsters). PMID:7724853

  20. Inhalation toxicology methods: the generation and characterization of exposure atmospheres and inhalational exposures.

    PubMed

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this unit, the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study are outlined. The following methods are described: (1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; (2) the delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; (3) options for on-line functional assays during and between exposures; and (4) options for serial non-invasive assays of response. In doing so, a description beyond exposures to single agents and simple mixtures is presented, and included are methods for evaluating biological responses to complex environmental mixtures. It is also emphasized that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  1. INHALATION TOXICOLOGY METHODS: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

    PubMed Central

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  2. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  3. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis.

    PubMed

    Cilfone, N A; Pienaar, E; Thurber, G M; Kirschner, D E; Linderman, J J

    2015-03-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  4. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  5. Pressurised aerosol inhalers: the cost of misuse.

    PubMed

    King, D; Earnshaw, S M; Delaney, J C

    1991-01-01

    Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique.

  6. Toxic leucoencephalopathy after 'chasing the dragon'.

    PubMed

    Singh, Rajinder; Saini, Monica

    2015-06-01

    Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

  7. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    EPA Science Inventory

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  8. Inhalation therapy in mechanical ventilation

    PubMed Central

    Maccari, Juçara Gasparetto; Teixeira, Cassiano; Gazzana, Marcelo Basso; Savi, Augusto; Dexheimer-Neto, Felippe Leopoldo; Knorst, Marli Maria

    2015-01-01

    Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients. PMID:26578139

  9. Suicidal carbon monoxide inhalation of exhaust fumes. Investigation of cases

    SciTech Connect

    Tsunenari, S.; Yonemitsu, K.; Kanda, M.; Yoshida, S.

    1985-09-01

    The inhalation of automobile exhaust gases is a relatively frequent suicidal method. Two such cases of special interest to forensic pathology and toxicology have been introduced. In case 1, a suicide note disclosed the victim's mental state, the inside conditions of the car, and toxic effects of automobile exhaust. In case 2, a reconstruction experiment has revealed important factors for the investigation of the scene, such as the size of a vinyl hose, the conditions of connecting site of the hose with the exhaust pipe, etc.

  10. Recognition and prevention of inhalant abuse.

    PubMed

    Anderson, Carrie E; Loomis, Glenn A

    2003-09-01

    Inhalant abuse is a prevalent and often overlooked form of substance abuse in adolescents. Survey results consistently show that nearly 20 percent of children in middle school and high school have experimented with inhaled substances. The method of delivery is inhalation of a solvent from its container, a soaked rag, or a bag. Solvents include almost any household cleaning agent or propellant, paint thinner, glue, and lighter fluid. Inhalant abuse typically can cause a euphoric feeling and can become addictive. Acute effects include sudden sniffing death syndrome, asphyxia, and serious injuries (e.g., falls, burns, frostbite). Chronic inhalant abuse can damage cardiac, renal, hepatic, and neurologic systems. Inhalant abuse during pregnancy can cause fetal abnormalities. Diagnosis of inhalant abuse is difficult and relies almost entirely on a thorough history and a high index of suspicion. No specific laboratory tests confirm solvent inhalation. Treatment is generally supportive, because there are no reversal agents for inhalant intoxication. Education of young persons and their parents is essential to decrease experimentation with inhalants. PMID:13678134

  11. 75 FR 5261 - Waybill Data Reporting for Toxic Inhalation Hazards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-02

    ... little as 1% of carloads on a waybill. The proposed amendment, set forth below, would expand the carload... requirements. For the reasons set forth in the preamble, the Surface Transportation Board proposes to...

  12. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals are... period. (3) The actual concentrations of the test substance must be measured in the breathing...

  13. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals are... period. (3) The actual concentrations of the test substance must be measured in the breathing...

  14. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals are... period. (3) The actual concentrations of the test substance must be measured in the breathing...

  15. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals are... period. (3) The actual concentrations of the test substance must be measured in the breathing...

  16. 40 CFR 799.9130 - TSCA acute inhalation toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Definitions. The definitions in section 3 of TSCA and the definitions in 40 CFR Part 792—Good Laboratory... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals are... period. (3) The actual concentrations of the test substance must be measured in the breathing...

  17. Target cell toxicity of inhaled spermidine in rat lungs.

    PubMed Central

    Foster, J. R.; Smith, L. L.; Hext, P. M.; Brammer, A.; Soames, A. R.; Wyatt, I.

    1990-01-01

    Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days. Images Fig. 4 p624-a Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:2206983

  18. Oscillometry complements spirometry in evaluation of subjects following toxic inhalation

    PubMed Central

    Berger, Kenneth I.; Turetz, Meredith; Liu, Mengling; Shao, Yongzhao; Kazeros, Angeliki; Parsia, Sam; Caplan-Shaw, Caralee; Friedman, Stephen M.; Maslow, Carey B.; Marmor, Michael; Goldring, Roberta M.

    2015-01-01

    The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5−20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5−20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa·L−1·s−1, p<0.001; R5−20 0.075 (0.085) versus 0.004 (0.042) kPa·L−1·s−1, p<0.0001). In symptomatic subjects, R5 and R5−20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5–20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms. PMID:27730155

  19. 40 CFR 798.4350 - Inhalation developmental toxicity study.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of the test substance. It is used to compare particles of different sizes, shapes, and densities and... substance given daily per unit volume of air. (c) Principle of the test method. The test substance is... physical or chemical properties of the test substance, the maximum attainable......

  20. Inhalation of Talc Induces Infiltration of Macrophages and Upregulation of Manganese Superoxide Dismutase in Rats.

    PubMed

    Shim, Ilseob; Kim, Hyun-Mi; Yang, Sangyoung; Choi, Min; Seo, Gyun-Baek; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee

    2015-01-01

    Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m(3) for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m(3) of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m(3) talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.

  1. Inhalation of Talc Induces Infiltration of Macrophages and Upregulation of Manganese Superoxide Dismutase in Rats.

    PubMed

    Shim, Ilseob; Kim, Hyun-Mi; Yang, Sangyoung; Choi, Min; Seo, Gyun-Baek; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee

    2015-01-01

    Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m(3) for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m(3) of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m(3) talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung. PMID:26482432

  2. Another Alternative: A 90-Day Contractual Detoxification Treatment Program

    ERIC Educational Resources Information Center

    Kahn, Robert B.; And Others

    1978-01-01

    In May 1974, Fresno County's Narcotic Abuse Treatment Program began a 21-day outpatient methadone detoxification treatment modality. The purpose of this paper is to examine this alternative treatment modality, its characteristics, its therapeutic outcomes and the rationale for its use. (Author)

  3. Inhalation therapy: technological milestones in asthma treatment.

    PubMed

    Dalby, Richard; Suman, Julie

    2003-07-18

    The humble origins of the propellant driven metered dose inhaler, as a response to a child's enquiry, initiated an industry which supplies approximately a half billion inhalers globally for the treatment of asthma. These inhalers fall into three major groups: nebulizers; propellant driven metered dose inhalers and dry powder inhalers. Each requires drug formulation, metering and device technology to be successful. In recent years there have been several new developments in the field including auxiliary systems to improve drug delivery from the device to the patient and new categories of device, notably single breath aqueous systems. As device technology improves and our understanding of the disease leads to new drugs the only barrier to therapy is the patient. Patient training and compliance will continue to be important factors in the success, or failure, of inhaled therapy and the role of health care professionals will depend on who sponsors their intervention.

  4. Overview of inhalation exposure techniques: strengths and weaknesses.

    PubMed

    Pauluhn, Jürgen

    2005-07-01

    The vast majority of toxicity studies and risk evaluations deal with single chemicals. Due to the growing interest in potential human health risks originating from exposure to environmental pollutants or lifestyle-related complex chemical mixtures, well thought-out tailor-made mechanistic inhalation toxicity studies have been performed. In contrast to the complex mixtures potentially encountered from hazardous waste sites, drinking water disinfection by-products, natural flavoring complexes or the cumulative intake of food additives and pesticide residues, the scientific evaluation of complex airborne mixtures, such as acid aerosols, atmospheres produced by combustion or thermolysis, e.g. residual oil fly ash (ROFA), diesel and gasoline exhaust, and tobacco smoke, or volatile organic chemicals (VOCs) in residential areas, to mention but a few, is a daunting challenge for experimental toxicologists. These challenges include the controlled in situ generation of exposure atmospheres, the compositions of which are often process-determined and metastable. This means that volatile agents may partition with liquid aerosols or be adsorbed onto surfaces of solid aerosols. Similarly, the nature and composition of test atmospheres might change continuously through oxidation and aging of constituents or coagulation of particles. This, in turn, poses additional challenges to the analytical characterization of such complex test atmospheres, including the identification of potential experimental artifacts. Accordingly, highly standardized and controlled inhalation studies are required for hazard identification of complex mixtures and the results of inhalation studies have to be analyzed judiciously due to the great number of experimental variables. These variables may be related to technical issues or to the specific features of the animal model. Although inhalation exposure of animals mimics human exposure best, not all results obtained under such rigorous test conditions might

  5. Incinerator air emissions: Inhalation exposure perspectives

    SciTech Connect

    Rogers, H.W.

    1995-12-01

    Incineration is often proposed as the treatment of choice for processing diverse wastes, particularly hazardous wastes. Where such treatment is proposed, people are often fearful that it will adversely affect their health. Unfortunately, information presented to the public about incinerators often does not include any criteria or benchmarks for evaluating such facilities. This article describes a review of air emission data from regulatory trial burns in a large prototype incinerator, operated at design capacity by the US Army to destroy chemical warfare materials. It uses several sets of criteria to gauge the threat that these emissions pose to public health. Incinerator air emission levels are evaluated with respect to various toxicity screening levels and ambient air levels of the same pollutants. Also, emission levels of chlorinated dioxins and furans are compared with emission levels of two common combustion sources. Such comparisons can add to a community`s understanding of health risks associated with an incinerator. This article focuses only on the air exposure/inhalation pathway as related to human health. It does not address other potential human exposure pathways or the possible effects of emissions on the local ecology, both of which should also be examined during a complete analysis of any major new facility.

  6. EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (External Review Draft)

    EPA Science Inventory

  1. Tips for Teens: The Truth about Inhalants

    MedlinePlus

    ... site at www. whitehousedrugpolicy. gov. No.Even though household products like glue and air freshener have legal,useful ... A. A. Q.Since inhalants are found in household products,aren’t they safe? Q.Can inhalants make ...

  2. Investigation of inhalation anthrax case, United States.

    PubMed

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  3. Ataxia with Parkinsonism and dystonia after intentional inhalation of liquefied petroleum gas.

    PubMed

    Godani, Massimiliano; Canavese, Francesca; Migliorini, Sonia; Del Sette, Massimo

    2015-01-01

    The practice of inhaling liquefied petroleum gas (LPG) to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication. PMID:26005350

  4. Principles and Procedures for Evaluating the Toxicity of Household Substances. Revised.

    ERIC Educational Resources Information Center

    National Academy of Sciences - National Research Council, Washington, DC. Assembly of Life Sciences.

    This report was prepared for use by the professional toxicologist. It contains chapters on ingestion exposure, dermal and dye toxicity tests, inhalation exposure, chronic toxicity and carcinogenicity tests, mutagenicity tests, reproduction and teratogenicity tests, and behavioral toxicity tests. In addition, regulations under the Federal Hazardous…

  5. [Dry powder inhalers in cystic fibrosis].

    PubMed

    Steinkamp, G

    2014-06-01

    Inhaled medications play an important role in the daily treatment of patients with cystic fibrosis (CF). The classic route of administration was nebulisation via jet nebulisers. Respiratory delivery of fluid particles should loosen the viscid respiratory secretions, making airway clearance via cough or physiotherapy more efficient. Until recently, only jet nebulisers allowed to administer high doses of aerosolised antipseudomonal antibiotics. Powder inhalers for the treatment of cystic fibrosis have recently been made available. The newly developed powders and inhalers differ considerably from conventional dry powder inhalers used for the treatment of chronic obstructive airway disease. The present article will review two inhaled antibiotics, i. e. tobramycin and colistin, and the hyperosmotic agent mannitol, which increases the hydration of the airways. Topics are particle engineering, efficacy and tolerability results from clinical trials, as well as functional and practical aspects related to these new drugs. PMID:24664997

  6. The ozone layer and metered dose inhalers.

    PubMed

    Boulet, L P

    1998-01-01

    The stratospheric ozone layer plays a crucial role in protecting living organisms against ultraviolet radiation. Chlorofluorocarbons (CFC) contained in metered-dose inhalers (MDIs) contribute to ozone depletion and in accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer established 10 years ago, phase-out strageies have been developed worldwide for this category of agents. Alternatives to CFC-containing inhalers have been developed, such as powder inhalers and those using hydrofluoroalkanes (HFAs) as propellants, which have been shown to be as safe and effective as CFC-containing inhalers and even offer interesting advantages over older inhalers. The transition to non-CFC MDIs requires a major effort to make the new products available and to ensure adequate comparision with the previous ones. It also requires a harmonization of actions taken by industry, government, licencing bodies and patients or health professional associations to ensure adequate information and education to the public and respiratory care providers.

  7. Subchronic inhalation exposure study of an airborne polychlorinated biphenyl (PCB) mixture resembling the Chicago ambient air congener profile

    PubMed Central

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Hu, Dingfei; Hornbuckle, Keri; Thorne, Peter S

    2013-01-01

    Although inhalation of atmospheric PCBs is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago Air Mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 hr/day via nose-only inhalation for 4 wks, 520±10 μg/m3. Congener-specific quantification in tissue and air samples was performed by GC/MS/MS. In contrast to the lower-chlorinated congener enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues, and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of endpoints to catalog the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity and histopathologic abnormalities. GSSG/GSH ratio was increased in blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose estimated at 134 μg/rat. PMID:22846166

  8. Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide.

    PubMed

    Sweeney, Lisa M; Sommerville, Douglas R; Channel, Stephen R

    2014-03-01

    The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C) and duration (t), with TL equaling C(n) × t being a typical form. Hypothetically, any combination of concentration and time that yields the same "toxic load" will give a constant biological response. These formulas have been developed and tested using controlled, constant concentration animal studies, but the validity of applying these assumptions to time-varying concentration profiles has not been tested. Experiments were designed to test the validity of the model under conditions of non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus t profiles was used to evaluate the ability of the model to adequately describe the lethality of HCN under the conditions of non-constant inhalation exposure. The model was found to be applicable under the tested conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.

  9. Inhalation and Dietary Exposure to PCBs in Urban and Rural Cohorts via Congener-Specific Measurements

    PubMed Central

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr–1) and children (12.0 (1.2) μg yr–1) than for rural mothers (2.4 (0.4) μg yr–1) and children (8.9 (0.3) μg yr–1). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children’s inhalation exposure. PMID:25510359

  10. Inhalation of uranium nanoparticles: respiratory tract deposition and translocation to secondary target organs in rats.

    PubMed

    Petitot, Fabrice; Lestaevel, Philippe; Tourlonias, Elie; Mazzucco, Charline; Jacquinot, Sébastien; Dhieux, Bernadette; Delissen, Olivia; Tournier, Benjamin B; Gensdarmes, François; Beaunier, Patricia; Dublineau, Isabelle

    2013-03-13

    Uranium nanoparticles (<100 nm) can be released into the atmosphere during industrial stages of the nuclear fuel cycle and during remediation and decommissioning of nuclear facilities. Explosions and fires in nuclear reactors and the use of ammunition containing depleted uranium can also produce such aerosols. The risk of accidental inhalation of uranium nanoparticles by nuclear workers, military personnel or civilian populations must therefore be taken into account. In order to address this issue, the absorption rate of inhaled uranium nanoparticles needs to be characterised experimentally. For this purpose, rats were exposed to an aerosol containing 10⁷ particles of uranium per cm³ (CMD=38 nm) for 1h in a nose-only inhalation exposure system. Uranium concentrations deposited in the respiratory tract, blood, brain, skeleton and kidneys were determined by ICP-MS. Twenty-seven percent of the inhaled mass of uranium nanoparticles was deposited in the respiratory tract. One-fifth of UO₂ nanoparticles were rapidly cleared from lung (T(½)=2.4 h) and translocated to extrathoracic organs. However, the majority of the particles were cleared slowly (T(½)=141.5 d). Future long-term experimental studies concerning uranium nanoparticles should focus on the potential lung toxicity of the large fraction of particles cleared slowly from the respiratory tract after inhalation exposure. PMID:23296105

  11. Naphthalene toxicity and antioxidant nutrients.

    PubMed

    Stohs, Sidney J; Ohia, Sunny; Bagchi, Debasis

    2002-10-30

    Naphthalene is a bicyclic aromatic compound that has wide industrial and commercial applications. It is used as the starting material for the synthesis of other compounds, as a moth repellent, soil fumigant and lavatory deodorant. Most exposure occurs through low dose chronic inhalation, dermal contact or ingestion through the food chain. The lungs and eyes appear to be most susceptible to toxicity, although biochemical markers of toxicity can be demonstrated in other tissues, such as the kidney, brain and liver. In addition to lens opacification (cataracts) and histological changes associated with pneumotoxicity, other biomarkers of toxic effects include glutathione depletion, lipid peroxidation, DNA fragmentation and the production of the active oxygen species as superoxide anion and hydroxyl radical. In addition, the urinary excretion of lipid metabolites occurs. A role for the tumor suppressor gene p53 has been demonstrated. Toxic manifestations of naphthalene are associated with its oxidative metabolism to various products including quinones. The ability to protect against the toxic effects of naphthalene by using various antioxidants and free radical scavengers has been demonstrated. Studies have been conducted with vitamin E, vitamin E succinate, melatonin, curcumin, various L-cysteine prodrugs, several aldose reductase inhibitors and spin-trapping agents. The ability to prevent the toxic manifestations of naphthalene is dependent on the pharmacokinetic properties of the agents, which have been studied. The appropriate selection of chemoprotectants can be useful in preventing naphthalene toxicity.

  12. Cadmium as a respiratory toxicant

    SciTech Connect

    Grose, E.C.; Graham, J.A.

    1987-01-01

    Cadmium is a major respiratory toxicant as evidenced by numerous human and animal studies. Controlled animal inhalation studies provide supporting evidence to the associations observed in epidemiological studies that Cd has the potential to cause lung fibrosis, emphysema, cancer, and kidney disease after prolonged exposure. Shorter-term exposure studies indicate that mechanisms thought to be involved in several of these chronic disease states (especially fibrosis and emphysema) are acutely activated. The evidence of toxicity is sufficiently clear that a TLV has been set and the International Agency for Research on Cancer has named Cd as a Group B1 substance (probable human carcinogen). The risk to Cd exposure is enhanced by its chemical and physical properties that result in bioaccumulation. Thus, even a low-level exposure over long periods of time would be expected to reach doses that could be toxic.

  13. Emerging inhaled bronchodilators: an update.

    PubMed

    Cazzola, M; Matera, M G

    2009-09-01

    Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field. The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients. A variety of beta(2)-agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development. The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.

  14. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome.

  15. Dynamics of airflow in a short inhalation

    PubMed Central

    Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

    2015-01-01

    During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147

  16. Toxic material advisory report - 2-mercaptoethanol

    SciTech Connect

    Bernholc, N. M.; White, O. Jr.; Baloyi, R. S.; Silverstein, B. D.

    1983-03-01

    A review of the animal toxicity data for 2-ME is presented. The results revealed that chronic inhalation exposures at a concentration of 6 mg/m/sup 3/ produced decreased oxygen consumption, lymphopenia, and neutrophilia. Comparison of acute toxicity data for 2-ME with data of structurally similar compounds suggests that 2-ME may be 2.3 times more toxic than butanethiol (TLV = 0.5 ppM), 6.5 times more toxic than ethanethiol, and 6 times more toxic than propanethiol (TLV = 0.5 ppM) via oral administration but may be comparable to propanethiol and less toxic than butanethiol and ethanethiol by the inhalation route of exposure. The TLVs for ethanethiol, methanethiol, and butanethiol were based on discomfort to human volunteers rather than toxicity. Since 2-ME has many effects similar to those of the thiols discussed and its odor threshold falls in the range of other thiols, by analogy the exposure limit for 2-ME should be comparable to the TLVs for butanethiol and ethanethiol. An interim exposure limit (IEL) of 0.5 ppM for a time-weighted average concentration during an 8-hour work shift is recommended. As with other thiols, a nuisance problem due to 2-ME odors and complaints of odor may serve as a primary reason for controlling workplace concentrations.

  17. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.; Taylor, Larry

    2008-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be

  18. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  19. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  20. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...