RESUMO
The subchronic inhalation toxicity of ammonium persulfate was characterized using Sprague-Dawley rats (20/sex/group) at respirable dust concentrations of 0, 5.0, 10.3, and 25 mg/m(3). Whole-body exposures were conducted 6 h/day, 5 days/wk for 13 wk. Gravimetric airborne test material samples were taken daily and particle size samples were taken weekly from each exposure chamber for analysis. Ten animals/sex/group were necropsied after 13 wk of exposure, and 5 animals/sex/group were held for 6- and 13-wk recovery periods. Animals were observed for clinical signs. Effects on body weight, food consumption, clinical chemistry and hematology, ophthalmologic parameters, organ weights, gross lesions, and histopathology were evaluated. There were no exposure-related deaths during the study. Rales and increased respiration rate were noted in both males and females in the 25 mg/m(3) group, and in a few animals in the 10.3 mg/m(3) group. The incidence of these clinical signs decreased to zero during the first few weeks of the recovery period. Body weights for both males and females in the 25 mg/m(3) group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m(3) group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchiole was noted microscopically after 13 wk of exposure to 25 mg/m(3). These lesions had recovered by 6 wk postexposure. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) was 10.3 mg/m(3), while the no-observed-effect level (NOEL) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m(3).
Assuntos
Sulfato de Amônio/toxicidade , Sistema Respiratório/patologia , Sulfato de Amônio/administração & dosagem , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Poeira , Ingestão de Alimentos , Feminino , Exposição por Inalação , Masculino , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Sistema Respiratório/efeitos dos fármacosRESUMO
Two inhalation studies were conducted to evaluate the possible subchronic and developmental toxic effects of n-butyl propionate. In the subchronic study, Sprague-Dawley rats (15/sex/group) were exposed to 0, 250, 750, or 1500 ppm vapor for 6 h/d, 5 d/wk for 13 wk. Five of the rats per sex per group were held after the final exposure for an 8-wk recovery period. Standard parameters of subchronic toxicity were measured throughout the study, and at the end of exposure and recovery periods, necropsies were performed, organs weighed, and tissues processed for microscopic examination. Exposure did not produce marked treatment-related deaths or adversely affect clinical signs, hematology, clinical chemistries, organ weights, or the histology of major visceral organs. The only systemic toxic effects were significant decreases in body weight, body weight gain, and feed consumption that occurred in 1500 ppm group rats. Morphologic changes were limited to the nasal cavity as evidenced by a concentration-related increased incidence and severity of olfactory epithelium degeneration in rats of the 750 and 1500 ppm groups. These degenerative microscopic alterations were primarily confined to the olfactory epithelium within the dorsal portion of the medial meatus, with lesser involvement of the olfactory mucosae overlying the tips of some of the adjacent ethmoturbinates. Both the systemic and nasal cavity effects appeared reversible after exposure ceased. In the developmental toxicity study, pregnant Sprague-Dawley rats (24/group) were exposed to 0, 500, 1000, or 2000 ppm vapor for 6 h/d on gestation d 6-15 and sacrificed on gestation d 20. All treatment-group dams exhibited significant reductions in body weight, body weight gain, and feed consumption. Gestational parameters were equivalent across all groups and there were no treatment-related developmental or teratogenic effects. The no-observed-adverse effects levels (NOAELs) determined for nbutyl propionate were 250 ppm for subchronic toxicity (based on the olfactory epithelium degeneration) and 22000 ppm for developmental toxicity (no developmental effects at top dose tested). Under the conditions of this study, a NOAEL was not determined for maternal toxicity.
Assuntos
Propionatos/toxicidade , Reprodução/efeitos dos fármacos , Administração por Inalação , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Anormalidades Congênitas/etiologia , Ingestão de Alimentos/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Crescimento/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Gravidez , Propionatos/administração & dosagem , Ratos , Ratos Sprague-Dawley , SolventesRESUMO
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.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Intoxicação por Arsênico , Arsenicais , Óxidos/toxicidade , Administração por Inalação , Animais , Trióxido de Arsênio , Câmaras de Exposição Atmosférica , Peso Corporal/efeitos dos fármacos , Osso e Ossos/anormalidades , Osso e Ossos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Exposição Ambiental , Feminino , Feto/anormalidades , Feto/efeitos dos fármacos , Masculino , Nível de Efeito Adverso não Observado , Projetos Piloto , Gravidez , Ratos , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Sons Respiratórios/efeitos dos fármacos , Medição de Risco , Testes de ToxicidadeRESUMO
The potential for subacute toxicity and neurotoxicity of a potassium carbonate-based scrubbing solution used in petroleum refineries was evaluated in Sprague-Dawley Crl:CD BR rats. Exposures were to aerosols of a "used" scrubbing solution by wholebody inhalation, 6 h/d, for 21 consecutive days at target concentrations of 0 (filtered air-control), 0.1, 0.2, or 0.4 mg/L (30 animals/sex/group). A functional observation battery (FOB) and locomotor activities tests were conducted and monitored. No apparent adverse effects were noted at any exposure level as determined by clinical observations, food consumption, hematology, serum chemistry, ophthalmologic observations, and gross pathology. Statistically significant increases in lung weights were noted at all treatment levels but returned to control values upon cessation of exposure except for the 0.4 mg/L female group. There were no significant changes in other organ weights. Histopathologic findings were restricted to the respiratory tract and characterized by minimal to moderate epithelial hyperplasia, epithelial necrosis, and cytoplasmic vacuolation at levels I and II of the nasal cavities. Lung bronchiolization and alveolar macrophage infiltration were also observed. The respiratory-tract findings were considered a local response to the high alkalinity of the test material as substantiated by the return to normal upon cessation of exposure. Exposure to scrubbing solution had no adverse effect on FOB endpoints and locomotor activity evaluations, brain weight and size, and neuropathologic examinations. In conclusion, inhalation exposure to a used scrubbing solution aerosol for 21 d did not result in any persistent systemic toxicity or neurotoxicity in either male or female rats.
Assuntos
Carbonatos/toxicidade , Potássio/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Relação Dose-Resposta a Droga , Feminino , Exposição por Inalação , Locomoção/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Exposição Ocupacional , Petróleo , Ratos , Ratos Sprague-DawleyRESUMO
The developmental toxicity potential of a scrubbing solution used extensively in petroleum refineries to remove CO2 from hydrogen gas streams was evaluated via inhalation. Pregnant female CD (Sprague-Dawley) rats were exposed to aerosols of a "used" scrubbing solution at 0.05, 0.1, 0.2, or 0.3 mg/l for 6 h/d on d 6-19 of pregnancy. Control animals were exposed to filtered air under the same exposure conditions. Dams were sacrificed on d 20 of pregnancy and a laparohysterectomy was performed. The mass median aerodynamic diameter of the aerosol revealed that all particles ranged from 1.6 to 2.8 microm, with geometric standard deviations between 2.0 and 2.3 microm. The overall pregnancy rate was high (>95%) and equivalent across all groups. All pregnant dams had live litters, and 22-24 litters were examined in each group. Treatment-related clinical signs consisted of rales, observed at all exposure levels, and gasping noted only at the 0.3 mg/l exposure level. The occurrence of rales was presumably a localized effect on the respiratory tract and likely due to the irritating properties of the scrubbing solution. Maternal toxicity was exhibited in the 0.3 mg/l group, including reduced body weight, weight gain, and food consumption and one possible treatment-related death on gestation d 17. At scheduled necropsy, there were no treatment-related gross pathological observations and no statistically significant reproductive and developmental effects. The incidences of fetuses with skeletal variations involving the sternum were clustered in two litters at the highest exposure level with atypically low term fetal body weights. Under the conditions of this investigation, potassium carbonate scrubbing solution is not a selective developmental toxicant.
Assuntos
Carbonatos/toxicidade , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Potássio/toxicidade , Sabões/toxicidade , Acidentes de Trabalho , Administração por Inalação , Aerossóis , Animais , Câmaras de Exposição Atmosférica , Blastocisto/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carbonatos/administração & dosagem , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Petróleo , Potássio/administração & dosagem , Gravidez , Complicações na Gravidez/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Sons Respiratórios/etiologia , Esterno/anormalidades , Aumento de Peso/efeitos dos fármacosRESUMO
Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide-boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 Aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent also known as High Flash Aromatic Naphtha (HFAN). A program was initiated to assess the toxicological properties of HFAN since there may be human exposure, especially in the workplace. The current study was conducted to assess the potential for neurotoxicity in the rat. Adult male Sprague-Dawley rats of approximately 300 grams body weight, in groups of twenty, were exposed by inhalation to HFAN for 90 days at concentrations of 0, 100, 500, and 1500 ppm. During this period the animals were tested monthly for motor activity and in a functional observation battery. After three months of exposure, for 6 hours/day, 5 days/week, 10 animals/group/sex were sacrificed and selected nervous system tissue was examined histopathologically. No signs of neurotoxicity were seen in any of the evaluated parameters, nor was there evidence of pathologic changes in any of the examined tissues.
Assuntos
Hidrocarbonetos/toxicidade , Sistema Nervoso/efeitos dos fármacos , Administração por Inalação , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Sistema Nervoso/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Previous studies have shown that aerosols of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100) produced an inflammatory response in lungs of rats in short-term repeated exposures at relatively low concentrations. This study was carried out on related polyalkylene glycols (EO/PO copolymers) to determine if similar effects would occur upon short-term repeated exposure. Rats were treated by whole body liquid droplet aerosol exposures of six hours per day, five days per week for two consecutive weeks to each of five EO/PO copolymers. The exposure level for the positive control (UCON 50-HB-5100) was 55 mg/m3, while the remaining 4 test copolymers were evaluated at 100 mg/m3. Each exposure group consisted of ten male albino rats. After three exposures, nine of ten rats exposed to UCON 50-HB-5100, and six of ten rats exposed to UCON 50-HB-2000 had died. At necropsy, congestion, consolidation and red discoloration of the lungs were noted. A moderate to severe alveolitis, characterized by intraalveolar edema, hemorrhage and fibrin deposition, was observed after five days of exposure. At necropsy, these rats exhibited elevated lung weights and similar macroscopic and microscopic lesions. Rats exposed to the other test materials (UCON 75-H-1400, Pluronic L17R1, Pluronic L31, and Pluronic L64) survived with essentially no signs of toxicity through the ten exposure days. Body weights, organ weights, hematological evaluation, pharmacotoxic signs, and macroscopic and microscopic evaluation after necropsy were similar between groups and when compared to the negative control group. Only a slight alveolitis was noted after two weeks of exposure which subsided by two-weeks post exposure.
Assuntos
Compostos de Epóxi/toxicidade , Óxido de Etileno/toxicidade , Pneumopatias/induzido quimicamente , Alvéolos Pulmonares/efeitos dos fármacos , Administração por Inalação , Aerossóis , Análise de Variância , Animais , Compostos de Epóxi/administração & dosagem , Óxido de Etileno/administração & dosagem , Pneumopatias/patologia , Macrófagos Alveolares , Neutrófilos , Polímeros , Alvéolos Pulmonares/patologia , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos , Ratos EndogâmicosRESUMO
Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 (stabilized and unstabilized, respectively) or 25 mg m-3 (stabilized) for 6 h day-1, 5 days week-1 for 2 years. No dust-exposure-related pathological changes were observed, other than lung lesions, in all exposed rats. There were no significant differences in pulmonary response between unstabilized and stabilized CrO2 at the 0.5 mg m-3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg m-3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, six developed keratin cysts and two had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization in the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally-induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of ths type of lung tumor appears to be negligible.
Assuntos
Compostos de Cromo , Cromo/toxicidade , Poeira , Pulmão/patologia , Administração por Inalação , Aerossóis , Animais , Cromo/administração & dosagem , Cromo/urina , Feminino , Pulmão/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The developmental toxicity potential of propylene oxide (PO) was evaluated in Fischer 344 rats following inhalation exposure. Four groups of 25 mated female rats were exposed to 0, 100, 300, and 500 ppm of PO for 6 hr per day on Gestation Days 6 through 15, inclusive. Cesarean sections were performed on all females on Gestation Day 20 and the fetuses removed for morphological evaluation. Exposure to propylene oxide did not adversely affect survival, appearance, or behavior at any of the exposure levels tested. Maternal body weight gain and food consumption were reduced significantly among the females at the 500 ppm level during the exposure period. No exposure-related effects were noted with respect to maternal water consumption, organ weights, cesarean section, or fetal morphological observations with the sole exception of increased frequency of seventh cervical ribs in fetuses at the maternally toxic exposure level of 500 ppm. In summation, the no-observable-adverse-effect level (NOAEL) of propylene oxide, when administered to Fischer 344 rats via whole-body inhalation exposure, was considered to be 300 ppm.
Assuntos
Compostos de Epóxi/toxicidade , Éteres Cíclicos/toxicidade , Teratogênicos , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Compostos de Epóxi/administração & dosagem , Feminino , Feto/efeitos dos fármacos , Masculino , Gravidez , Ratos , Ratos Endogâmicos F344RESUMO
This study was initiated to assess the safety of atmospheres containing maleic anhydride. Accordingly, rats (15/sex/group), hamsters (15/sex/group), and monkeys (3/sex/group) were treated 6 hr a day 5 days a week for 6 months. Atmospheres were generated by subliming maleic anhydride and were monitored using Tenax collection columns and gas chromatography to detect total maleic; i.e., maleic anhydride plus maleic acid. The mean analytical concentrations were 0, 1.1, 3.3, and 9.8 mg/m3 of total maleic. Dose-related signs of nasal and ocular irritation were observed at each test level in all three species; signs included discharge, sneezing, gasping, and coughing. No significant treatment-related mortality was observed in any species. While reduced weight gains were observed only in mid- and high-dose rats, their terminal body weights were greater than 90% of control values. No treatment-related effects were observed in hematology, clinical chemistry, urinalysis, and pulmonary function tests. Although microscopic evaluation of tissue revealed evidence of nasal irritation in all species, there was no evidence of systemic toxicity which was directly attributed to maleic anhydride. While the results of this study support the current ACGIH TLV and OSHA PEL of 1 mg/m3 regarding systemic toxicity, continuous exposure at this level during the day may produce some signs of irritation.
Assuntos
Furanos/toxicidade , Anidridos Maleicos/toxicidade , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Cricetinae , Feminino , Macaca mulatta , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Testes de Função Respiratória , Especificidade da Espécie , Fatores de TempoRESUMO
Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 mg/m3 (stabilized and unstabilized, respectively), or 25 mg/m3 (stabilized) for 6 hr/day, 5 days/week for 2 years. No dust-exposure-related pathological changes other than lung lesions were observed in all exposed rats. There were no significant differences in pulmonary responses between unstabilized and stabilized CrO2 at the 0.5 mg/m3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg/m3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, 6 developed keratin cysts and 2 had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization at the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of this type of lung tumor appears to be negligible.
Assuntos
Compostos de Cromo , Cromo/toxicidade , Poeira/efeitos adversos , Aerossóis , Animais , Peso Corporal/efeitos dos fármacos , Cromo/urina , Feminino , Pulmão/patologia , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Ratos , Ratos EndogâmicosRESUMO
Chlorine (Cl2) gas is a potentially lung-damaging irritant which is used in the chemical, plastics, and paper industries. There are no data published using experimental animals on the chronic inhalation toxicity of chlorine. The purpose of this study was to investigate the chronic effects of Cl2 inhalation in Rhesus monkeys (Macaca mulatta). Rhesus monkeys were exposed to concentrations of 0, 0.1, 0.5, or 2.3 ppm Cl2 for 6 hr per day. 5 days per week for 1 year. Pulmonary physiology (pulmonary diffusing capacity and distribution of ventilation), body weights, urinalysis, electrocardiographs, hematology, and clinical chemistry were evaluated monthly during the study. Blood gas evaluations were performed at 3-month intervals during the study. Histopathologic, ophthalmologic, and neurologic parameters were evaluated after the 1-year exposure period. Monkeys exposed to 2.3 ppm Cl2 exhibited signs of ocular irritation during the daily exposures and a superficial conjunctival irritation was present in the 2.3 ppm group after the 1-year exposure regimen. Treatment-induced lesions revealed by histopathology were confined to the respiratory tract. Lesions associated with the nasal parasite Anatrichosoma spp. were present in the region of squamous epithelium of the nasal vestibule and did not interfere with interpretation of Cl2-induced effects. Treatment-induced histopathologic changes were found in the respiratory epithelium of the nasal passages and trachea and were limited to focal, concentration-related epithelial hyperplasia with loss of cilia and decreased numbers of goblet cells in affected areas. These changes in the nose and trachea were focal and mild in monkeys exposed to 2.3 ppm and were not found in all animals in these exposure groups. Tracheal lesions were confined to the 2.3 ppm group. The lesions observed at 2.3 ppm were not present in all animals. At the lower Cl2 concentrations, similar though less prominent respiratory epithelial lesions were observed. The latter changes were very minimal and were confined to the nasal passages of some treated monkeys and one male control animal. The results of this study indicate that 2.3 ppm chlorine acts as an upper respiratory irritant in monkeys, while 0.5 and 0.1 ppm induce changes of questionable clinical significance. Furthermore, the monkey appears to be less sensitive than the rat to chlorine toxicity.
Assuntos
Cloro/toxicidade , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Cloro/administração & dosagem , Relação Dose-Resposta a Droga , Eletrocardiografia , Olho/efeitos dos fármacos , Feminino , Macaca mulatta , Masculino , Tamanho do Órgão/efeitos dos fármacos , Testes de Função Respiratória , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/patologia , Fatores SexuaisRESUMO
n-Butyl mercaptan (n-BM) is used as a solvent and a chemical intermediate. Pregnant Charles River CD-1 mice and COBS CD rats were randomly assigned to a control group and to three n-BM-exposed groups of 25 rats and 25 mice each. The animals were exposed by whole-body inhalation to mean n-BM concentrations of 10, 68, or 152 ppm on a 6-hr daily exposure schedule. Rats were exposed on Gestation Days 6-19 and mice on Gestation Days 6-16. The control group was exposed to filtered air only on a comparable regimen. Cesarean sections were performed on all surviving mice on Gestation Day 17 and on all rats on Gestation Day 20. Seventeen of the n-BM-treated mice died: 8 at the 68-ppm level and 9 at the 152-ppm level; none of the n-BM-treated rats died. An increased postimplantation loss and increased early resorption occurred in mice exposed at 68 and 152 ppm, indicating embryotoxicity. An increased incidence of cleft palate was observed in mice exposed to 10 or 68 ppm which was not statistically significant. Total fetal abnormalities were statistically significantly different from controls at 68 ppm where maternal lethality was observed when based on the fetal unit although not when based on the litter unit. Rats exposed to 152 ppm or less demonstrated no terata.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Compostos de Sulfidrila/toxicidade , Teratogênicos , Administração por Inalação , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Camundongos , Gravidez , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Compostos de Sulfidrila/administração & dosagemRESUMO
The 4-hr inhalation LC50 was determined for methyl-, ethyl-, n-propyl-, n-butyl-, isobutyl-, and isopentyl nitrite in Sprague-Dawley rats. LC50 values were 176, 160, 300, 420, 777, and 716 ppm, respectively. The dose-mortality curves were characterized by extremely steep slopes. Toxic signs observed during exposure included cyanosis, prostration, and rarely, convulsions. There were no effects of exposure on body weight gain during a 14-day postexposure observation period. Signs of pulmonary hemorrhage were apparent in rats which died during exposure but were much less prominent in rats sacrificed at study termination. No animals died after cessation of exposure, and rapid recovery was apparent after exposure. Concentration X Time (CT) relationships suggested that the actual concentration was more important than the "dose" in determining the lethal effects of inhalation exposure to nitrites. Because of the extremely steep dose-mortality curves, the aliphatic nitrites are more hazardous than the LC50 values would indicate.
Assuntos
Nitritos/toxicidade , Animais , Sistema Cardiovascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Masculino , Metemoglobina/biossíntese , Azul de Metileno/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Sprague-Dawley rats and Cynomolgus monkeys were exposed to dust aerosol concentrations (0, 10.2, and 30.7 mg/m3) of micronized delayed process petroleum coke for 6 hr/day, 5 days/week over 2 years. With the exception of pulmonary effects, particularly in the rats, no significant adverse treatment-related effects were observed. Both dust-exposed groups of both species exhibited a gray to black discoloration of the lung, an observation consistent with pulmonary deposition of the coke dust, as well as increased absolute and/or relative lung weight values. The pulmonary histopathology in the monkeys was limited to the deposition and phagocytosis of the test material by pulmonary macrophages. The rats also exhibited these responses, but with concomitant signs of chronic inflammation and focal areas of fibrosis, bronchiolization, sclerosis, squamous alveolar metaplasia, and keratin cyst formation. No difference in the mortality rate was observed between the control and exposed groups of rats. Lastly, no significant increases in chromosomal aberrations were observed in rodents of the 10.2 or 30.7 mg/m3 exposure groups when examined after 5 days, 12 months, and 22 months of exposure.
Assuntos
Carvão Mineral/efeitos adversos , Coque/efeitos adversos , Pneumopatias/etiologia , Petróleo/toxicidade , Animais , Aberrações Cromossômicas , Poeira/efeitos adversos , Feminino , Pneumopatias/patologia , Macaca fascicularis , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Traqueia/patologiaRESUMO
An animal inhalation study was initiated to study the chronic biological effects of inhalation of short chrysotile asbestos fibers. Rats and monkeys were exposed for 18 months, 7 hr/day, 5 days/week to a specially prepared, chrysotile asbestos aerosol. Based upon daily chamber measurements, the mean concentration of fibers in the chamber air was 1.0 mg/m3. By phase contrast microscopy, the number of fibers greater than 5 micron in length was determined to be 0.79 fiber per cubic centimeter. Rats were autopsied for pathological and histochemical examination at 1, 3, 6, 12, 18, and 24 months after initiating exposures. No significant differences in the histochemical data were seen between the exposed and control groups. Gross and histopathologic examination of exposed and control groups of rats indicated no compound-related lesions, including fibrosis. Open lung biopsies were performed on the chrysotile-exposed and the control monkeys 28 months after initiating exposures. Histopathologic evaluation of the lung biopsy tissue showed the presence of asbestos bodies adjacent to the terminal bronchioles of the asbestos-exposed monkeys. There was no observed fibrosis in pulmonary tissue. All monkeys are being maintained for an indefinite period and observed for signs of latent pulmonary disease.
Assuntos
Amianto/toxicidade , Aerossóis , Animais , Asbestos Serpentinas , Peso Corporal/efeitos dos fármacos , Poeira , Pulmão/ultraestrutura , Pneumopatias/etiologia , Pneumopatias/patologia , Macaca fascicularis , Masculino , Microscopia Eletrônica de Varredura , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Ratos , Ratos Endogâmicos , Silício/sangue , Silício/metabolismo , Especificidade da Espécie , Fatores de TempoRESUMO
There has long been a need to define differences in the amount of aerosol inhaled by group caged rodents as compared to the theoretically ideal individually caged rodent. Therefore, an experiment was designed and conducted to gain insight into this problem. Three groups of animals were evaluated for the degree of pulmonary deposition following a single six hour exposure to a 3 mu aerosol of dodecyl alcohol. One group contained individually caged rats, while the other two groups contained rats caged either in groups of three or seven. Analyzing lungs and trachea for the dodecyl alcohol indicated 25.6 micrograms/g, 27.1 microbrams/g, and 23.1 micrograms/g for rats caged individually, in threes, or in sevens, respectively. There was no statistically significant difference between the amount of dodecyl alcohol found in group caged rat lungs as compared to individually caged rats. Thus group housing does not appear to reduce the amount of aerosol inhaled by rats during a six hour whole body exposure.
Assuntos
Aerossóis , Pulmão/metabolismo , Animais , Dodecanol/metabolismo , Tamanho da Partícula , Ratos , Meio SocialRESUMO
Nitromethane (NM) and 2-nitropropane (2-NP) and versatile compounds employed in a wide variety of industrial applications, thus providing ample opportunity for occupational exposure. The purpose of this study was to determine the subchronic inhalation toxicity of NM and 2-NP in order to recommend acceptable exposure levels in the workplace. Fifty male rats and 15 male rabbits were exposed to either 98 ppm or 745 ppm of NM or 27 or 207 ppm of 2-NP 7 hours/day, 5 days/week, for periods up to 24 weeks. Fifty rats and 15 rabbits were exposed to filtered air for similar lengths of time and served as controls. Ten rats from each exposure and control group were sacrificed following 2 days, 10 days, 1 month, 3 months, and 6 months of exposure. Five rabbits from each exposure or control group were sacrificed at 1, 3, and 6 months of exposure. Effects relatable to exposure to NM were decreased body weight gain in rats following 8 weeks of exposure to 745 ppm, and a thyroid effect evidenced by an increased thyroid weight and decreased serum thyroxin levels, most notable in rabbits. Liver weights were significantly elevated in rats exposed to 207 ppm of 2-NP for 1, 3, and 6 months. No exposure-related gross or microscopic alterations were seen in any of the tissues examined for rats and rabbits exposed to 745 and 98 ppm of NM and 27 ppm of 2-NP or in tissues of rabbits exposed to 207 ppm of 2-NP. Liver neoplasms were seen in all 10 rats killed following 6 months of exposure to 207 ppm of 2-NP, indicating that 2-NP is a potent carcinogen in the rat.
Assuntos
Metano/análogos & derivados , Nitrocompostos/toxicidade , Propano/análogos & derivados , Animais , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Hematócrito , Hemoglobinas/análise , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Concentração Máxima Permitida , Tamanho do Órgão/efeitos dos fármacos , Coelhos , Ratos , RespiraçãoRESUMO
Monkeys and rats were exposed to 11.6, 112.5, and 1152 micrograms Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various evaluations of pulmonary function, electromyographic activity, limb tremor, and tissue manganese levels were conducted. No exposure related effects on pulmonary function, limb tremor, or electromyographic activity were observed. After nine months of exposure Mn levels were elevated in a near dose related manner in kidney, lung, spleen, and blood. However, by six months postexposure there were no differences as compared to the control group in tissue Mn levels which could be attributed to the exposure conditions.
Assuntos
Pulmão/efeitos dos fármacos , Intoxicação por Manganês , Aerossóis , Animais , Eletromiografia , Feminino , Haplorrinos , Rim/análise , Fígado/análise , Pulmão/análise , Masculino , Manganês/análise , Músculos/efeitos dos fármacos , Ratos , Testes de Função Respiratória , Saimiri , Fatores de Tempo , Tremor/induzido quimicamenteRESUMO
Monkeys and rats were exposed to 11.6, 112.5, or 1152 microgram Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various serum biochemical, and hematologic evaluations were conducted on both specie. Body weight gain was accelerated in rats exposed to 1152 microgram Mn/m3. Hemoglobin concentrations were slightly elevated for both sexes and both specie exposed to 1152 microgram Mn/m3; however, the effect may not be directly related to Mn. Some evidence of hypophosphatemia was observed. No exposure related effects were demonstrated by organ weight or histopathologic observations.