Showing papers by "Gerald L. Kennedy published in 1997"
TL;DR: Hematological and histopathological alterations were judged to be secondary to nutritional and body weight effects in male and/or female rats at 30,000 ppm and mice, and cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females.
Abstract: Twenty-eight day feeding studies were conducted to evaluate the repeated dose toxicity of NMP, a widely used industrial solvent, in Crl:CD BR rats and B6C3F1 mice. Groups of 5 male and 5 female rats each were fed either 0, 2,000, 6,000, 18,000, or 30,000 ppm NMP; similar groups of mice were fed either 0, 500, 2,500, 7,500, or 10,000 ppm. In vivo parameters, hematology and clinical chemistry parameters, and complete pathology evaluations were conducted after approximately 28 days. Decrements in mean body weight gains, reflecting decreases in food consumption and efficiency, were seen in male rats fed 18,000 ppm and in both sexes fed 30,000 ppm. In rats, clinical chemical changes, indicating possible compound-related alterations in lipid, protein, and carbohydrate metabolism, occurred at 18,000 ppm in males and 30,000 ppm in both sexes. No histopathological changes in rats were judged to be directly related to NMP exposure. Hematological (mild to moderate leukopenia) and histopathological alterations (hypocellular bone marrow, testicular degeneration and atrophy, and thymic atrophy) were judged to be secondary to nutritional and body weight effects in male and/or female rats at 30,000 ppm. In mice, cloudy swelling of the epithelia of the distal parts of the renal tubuli was observed in 4 males and 3 females at 10,000 ppm and in 2 male mice at 7,500 ppm. For both rats and mice, abnormal urine coloration was observed (in mice at 2,500 ppm and above, and in rats at 18,000 ppm and above). The discoloration was interpreted as a sign of systemic availability of the test substance, but not as an adverse effect. The NOAEL was 6,000 ppm for male rats and 18,000 ppm for female rats. In mice, the NOAEL was 2,500 ppm based on the kidney histopathology.
33 citations
TL;DR: Testicular damage, consisting of degeneration of seminifierous tubules and oligospermia, occurred in a concentration-dependent manner in mice exposed to DMAC, and was seen in mice from these groups sacrificed after a 14-day recovery period.
Abstract: Two 10-day inhalation toxicity studies were conducted with dimethylacetamide (DMAC, CAS no. 127-19-5). In one study, pubescent Crl:CD-1 mice (35 days old) were exposed to DMAC at 30, 100, 310, 490, or 700 ppm for 6 h/day, 5 days/wk for 10 days. Although well tolerated up to 310 ppm, exposure to 490 ppm or greater caused severe clinical signs and mortality. Hematologic changes in these groups included reduced erythrocyte and platelet counts, reduced hemoglobin concentration, and reduced hematocrit. Relative testes weights were decreased and relative liver weights were increased. In addition, centrilobular hepatocellular necrosis and hypertrophy, lymphoid organ atrophy and necrosis, bone marrow hypoplasia, and cortical adrenal gland necrosis occurred; these pathologic changes were not seen in mice from these groups sacrificed after a 14-day recovery period. Testicular damage, consisting of degeneration of seminifierous tubules and oligospermia, occurred in a concentration-dependent manner in mice exposed to...
6 citations
TL;DR: DMS is not a developmental toxin in the rat following inhalation exposures up to 1.5 ppm during the period of major organogenesis, and none of the reproductive parameters was altered in any of the groups and no statistically significant fetal effects were detected.
Abstract: Dimethyl sulfate (DMS; CAS No. 77–78) is a colorless, oily liquid which is used as a chemical intermediate and as a reactant in producing polyurethane resins. In this study, groups of pregnant Crl:CD®BR rats were exposed, nose-only, to either 0.1, 0.7 or 1.5 ppm DMS by inhalation for 6 hr/day from Days 7 through 16 of gestation (day in which copulation plug was detected was designated Day 1G). A control group of pregnant rats was exposed simultaneously to air only. All female rats were euthanized on Day 22G and the fetuses were examined. A suppression of both food consumption and the rate of body weight gain was seen in the 0.7 and 1.5 ppm groups. No unusual clinical signs were seen in rats exposed to DMS. None of the reproductive parameters was altered in any of the groups and no statistically significant fetal effects were detected. DMS is not a developmental toxin in the rat following inhalation exposures up to 1.5 ppm during the period of major organogenesis.
4 citations