RESUMEN
This reevaluation of the current U.S. EPA cancer potency factor for toxaphene is based upon a review of toxaphene carcinogenesis bioassays in mice conducted by Litton Bionetics (unpublished report, 1978) and the National Cancer Institute (NCI) (Technical Report Series No. 37, conducted by Gulf South Research Institute, 1979). The mechanistic data available for toxaphene, including consideration of the potential of the compound to induce genotoxicity, was examined with an emphasis on whether this information supports a change in the cancer potency factor. If a quantitative dose-response assessment for toxaphene is to be performed, the data from both the NCI and Litton cancer bioassays should be used. Additionally, liver tumor results from female mice, rather than male mice, should be used for estimating potential human cancer risk because the background rate of liver tumors in females is lower and less variable than that exhibited by males. An ED(10) was estimated as the point of departure. The mechanistic data were not sufficient to fully support a margin of exposure approach. Therefore, we believe that applying a linear extrapolation from the ED(10) to the origin is an appropriate means to estimate risk at low doses. This is a highly conservative approach and, when it is applied, we conclude that the current EPA cancer potency factor should be reduced from 1.1 (mg/kg/day)(-1) to 0.1 (mg/kg/day)(-1).
Asunto(s)
Carcinógenos/toxicidad , Insecticidas/toxicidad , Neoplasias/inducido químicamente , Toxafeno/toxicidad , Animales , Femenino , Humanos , Masculino , Revisión por ParesRESUMEN
Phosphine is a highly toxic gas used as a fumigant, a dopant in semiconductor manufacturing, and in the production of organophosphines. In a chronic toxicity and oncogenicity study of phosphine, 60 male and female F344 rats per group were exposed via whole-body inhalation for 6 h/day, 5 days/wk for up to 104 wk to mean concentrations of 0, 0.3, 1, or 3 ppm phosphine. Three parts per million was considered the maximum exposure level because of lethality seen at higher exposure levels in previous repeat dose studies. Ten rats per sex per group were sacrificed after 52 wk of exposure. Survivors were sacrificed after 104 wk of exposure. There were no phosphine-related effects seen on clinical observations, body weight, food consumption, hematology, clinical chemistry, urinalysis, or ophthalmology. There were no phosphine-related macroscopic findings or effect on absolute or relative organ weights. No histomorphologic alterations attributable to phosphine exposure were seen. In conclusion, under the conditions of this study, there were no treatment-related changes suggestive of a toxic or carcinogenic effect seen in rats following 52 wk or 2 yr of whole-body inhalation exposure to 0.3, 1, or 3 ppm phosphine.
Asunto(s)
Exposición por Inhalación/efectos adversos , Fosfinas/toxicidad , Animales , Cámaras de Exposición Atmosférica , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Fosfinas/administración & dosificación , Ratas , Ratas Endogámicas F344 , Análisis de SupervivenciaAsunto(s)
Fungicidas Industriales/metabolismo , Glutatión/metabolismo , Nitrilos/metabolismo , Administración Oral , Animales , Fungicidas Industriales/administración & dosificación , Fungicidas Industriales/toxicidad , Riñón/anatomía & histología , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Nitrilos/administración & dosificación , Nitrilos/toxicidad , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Estómago/efectos de los fármacos , Compuestos de Sulfhidrilo/orinaRESUMEN
This study was initiated because of a suspected increase in incidence of lung cancer in antimony smelter workers in England. Three groups of 8-mo-old Wistar-derived rats (90 males and 90 females per group) were exposed by inhalation to either Sb2O3 [time-weighted average (TWA) 45 mg/m3], Sb ore concentrate (TWA 36 + 40 mg/m3), or filtered air (controls) for 7 h/d, 5 d/wk, for up to 52 wk and sacrificed 20 wk after terminating exposures. Serial sacrifices (5 rats/sex/group) were performed at 6, 9, and 12 mo. Autopsies and histopathological examinations were performed on all animals. The dusts and animal tissues were analyzed for Sb, arsenic, and other inorganic elements by atomic absorption and proton-induced X-ray emission methods. The most significant findings were the presence of lung neoplasms in 27% of females exposed to Sb2O3 and 25% of females exposed to Sb ore concentrate (p less than 0.01). None of the male rats in any group or the female controls developed lung neoplasms. There were no significant differences in incidences of cancer of other organs between exposed and control rats. These results were compared with other published results, including an animal inhalation study with Sb2O3 in which lung tumors were also induced. Higher concentrations of arsenic were found in tissues from female rats than from male rats. For example, arsenic levels in blood of control males, control females, Sb2O3 males, Sb2O3 females, Sb ore males, and Sb ore females were 60, 123, 115, 230, 71, and 165 micrograms arsenic/g dry blood, respectively, 9 mo after initiating exposures.
Asunto(s)
Antimonio/toxicidad , Carcinógenos , Animales , Cámaras de Exposición Atmosférica , Peso Corporal , Polvo , Femenino , Neoplasias Pulmonares/inducido químicamente , Masculino , Ratas , Ratas Endogámicas , Factores Sexuales , Espectrofotometría Atómica , Distribución TisularRESUMEN
Female Golden Syrian hamsters, F-344 rats, Swiss CD-1 mice, and B6C3F1 hybrid mice were exposed 6 hr/day, 5 days/week to carcinogenic levels of vinyl chloride (VC) for 6, 12, 18, or 24 months (rats and hamsters only). Other groups of rodents were held for 6 or 12 months and then exposed for 6 or 12 months. At the end of the study the incidence of VC-induced neoplasms was compared in each of the groups to assess the effects of duration of exposure and age at the start of exposure on carcinogenicity of VC. In rats, with early initial exposure, hemangiosarcomas, hepatocellular carcinomas, and mammary gland carcinomas occurred with increasing incidence with longer exposure duration. Rats held for 6 months before exposure developed VC-related neoplasms, while rats held 12 months before the start of exposure failed to show a significantly increased incidence of these neoplasms. In hamsters, hemangiosarcomas, mammary gland carcinomas, gastric adenocarcinomas, and skin carcinomas resulted from VC exposure. The highest incidence of malignant neoplasms occurred in hamsters exposed for the first 12 months, whereas exposure begun after 12 months of age did not cause neoplasms. In both strains of mice, VC exposure during the first 6 months of the experiment induced a high incidence of hemangiosarcomas and mammary gland carcinomas. Swiss mice also developed lung carcinomas after only 6 months of exposure. In all three rodent species an initial 12 month exposure to VC was adequate to detect its carcinogenic potential, but the shortened survival of VC exposed mice and hamsters precluded a meaningful comparison with longer periods of exposure. Exposures were most effective when started early in life.
Asunto(s)
Neoplasias Experimentales/inducido químicamente , Factores de Edad , Animales , Cricetinae , Femenino , Hemangiosarcoma/inducido químicamente , Neoplasias Hepáticas/inducido químicamente , Masculino , Neoplasias Mamarias Experimentales/inducido químicamente , Mesocricetus , Ratones , Ratones Endogámicos , Ratas , Ratas Endogámicas F344 , Neoplasias Gástricas/inducido químicamente , Factores de Tiempo , Cloruro de Vinilo/toxicidadAsunto(s)
Carcinógenos , Compuestos de Vinilo/toxicidad , Animales , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Femenino , Gases , Masculino , Neoplasias Experimentales/inducido químicamente , Ratas , Ratas Endogámicas , Factores Sexuales , Factores de Tiempo , Compuestos de Vinilo/análisisRESUMEN
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.
Asunto(s)
Metano/análogos & derivados , Nitrocompuestos/toxicidad , Propano/análogos & derivados , Animales , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Hematócrito , Hemoglobinas/análisis , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Concentración Máxima Admisible , Tamaño de los Órganos/efectos de los fármacos , Conejos , Ratas , RespiraciónRESUMEN
Guinea pigs were exposed inhalation chambers to 25 mg/m3 sulfuric acid mist 6 h/d for 2 d, and the acute respiratory effects were correlated by light and electron microscopy. This concentration of acid was selected since lower concentrations result in only slight effects while higher concentrations result in death. By light microscopy, the most prominent pulmonary lesion at 48 h was segmental alveolar hemorrhage and edema accompanied by proliferation of alveolar macrophages and type 2 pneumocytes. The segmental distribution of the pulmonary lesion was reaffirmed by scanning electron microscopy, while transmission electron microscopy showed injury to the distal airways and changes in the vascular endothelium.
Asunto(s)
Enfermedades Respiratorias/inducido químicamente , Ácidos Sulfúricos/farmacología , Aerosoles , Animales , Femenino , Cobayas , Macrófagos/efectos de los fármacos , Masculino , Alveolos Pulmonares/ultraestructura , Sistema Respiratorio/patología , Sistema Respiratorio/ultraestructuraAsunto(s)
Detergentes/toxicidad , Enzimas/toxicidad , Respiración/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Polvo/análisis , Enzimas/sangre , Enzimas/inmunología , Femenino , Crecimiento/efectos de los fármacos , Haplorrinos , Macaca fascicularis , Masculino , Tamaño de la Partícula , Pruebas de Función Respiratoria , Enfermedades Respiratorias/patologíaRESUMEN
Three groups composed of rats, rabbits, and monkeys were exposed for 26 weeks to 1,2,4-trichlorobenzene (-TCB), and one group of each species was used as a control group. The nominal exposure concentrations of 1,2,4-TCB were 25.0, 50.0, and 100.0 ppm. Pulmonary function and operant behavior tests in monkeys, ophthalmoscopic examinations in rabbits and monkeys, and measurement of body weights and hematologic and serum biochemical determinations in all species were conducted before and during the exposure period. At termination of 1, 3, and 6 months of exposure, microscopic examination of selected rat tissues was performed. Microscopic changes were seen in the parenchymal of livers and kidneys from all groups of rats exposed to 1,2,4-TCB when sacrificed after 4 and 13 weeks of exposure, but no exposure-related abnormalities or other effects were seen after 26 weeks of exposure in any species.
Asunto(s)
Clorobencenos/toxicidad , Animales , Cámaras de Exposición Atmosférica , Conducta Animal/efectos de los fármacos , Exposición a Riesgos Ambientales , Haplorrinos , Masculino , Conejos , Ratas , Pruebas de Función RespiratoriaRESUMEN
Ozone and the oxides of sulfur are common environmental pollutants. The acute pulmonary lesions caused by ozone and sulfuric acid mist in rats and guinea pigs have been characterized. Rats are not affected by sulfuric acid mist in concentrations up to 100 mg/m3 except for reduced body weight at the higher doses. A true alveolitis develops in guinea pigs exposed to more than 20 mg/m3 sulfuric acid mist. The ozone lesion is primarily confined to the terminal bronchioles and proximal alveoli. In combination studies with up to 2 ppm ozone and up to 10 mg/m3 sulfuric acid mist, the pulmonary lesion and lung/body weight data were essentially the same as in exposure to ozone alone, and the number of statistically significant synergistic effects in rats and guinea pigs was about what one would expect to observe by chance alone.
Asunto(s)
Ozono/toxicidad , Ácidos Sulfúricos/toxicidad , Aerosoles , Animales , Peso Corporal/efectos de los fármacos , Sinergismo Farmacológico , Cobayas , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ozono/administración & dosificación , Alveolos Pulmonares/patología , Ratas , Especificidad de la Especie , Ácidos Sulfúricos/administración & dosificación , Factores de TiempoRESUMEN
Groups of cynomolgus monkeys and guinea pigs were exposed to mixtures of sulfur dioxide, fly ash, and sulfuric acid mist. The exposure concentrations varied between 0.1 and 5.0 ppm for sulfur dioxide, 0.1 and 1 mg/cu m for sulfuric acid mist, while a concentration of approximately 0.5 mg/cu m was used for fly ash. The duration of exposure was 52 weeks for guinea-pigs and 78 weeks for monkeys. Pulmonary function tests and serum biochemical and hematological analyses were conducted prior to and periodically during the exposure period. At the termination of exposure, the lungs were examined microscopically. Analysis of the data revealed that in groups exposed to the mixtures of pollutants, sulfuric acid mist was responsible for the effects observed. No synergistic action between the pollutants was detected.