RESUMO
Ethylbenzene was administered to groups of male and female Wistar rats by gavage for 4 (n = 5/dose/sex) and 13 weeks (n = 10/dose/sex) (OECD 408) at doses of 0 (vehicle control), 75, 250, and 750 mg/kg bodyweight/day (mg/kg bw/day), administered am/pm as half doses. In the 4-week study, > or =250 mg/kg increased serum alanine aminotransferase, total bilirubin and cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and kidney weights; males also had post-dose salivation, increased urinary epithelial cell casts and cells, and hyaline droplet nephropathy. In the 13-week study, > or =250 mg/kg increased water consumption and produced post-dose salivation. Liver-related effects: increased serum alanine aminotransferase, gamma-glutamyltransferase, bilirubin, total protein, albumin and globulins, cholesterol, liver weights and centrilobular hepatocyte hypertrophy, and reduced prothrombin times. Kidney-related effects: increased serum potassium, calcium, magnesium, kidney weights, and (males only) urea and hyaline droplets in renal tubular epithelium, and reduced sodium (females only); creatinine was reduced in 750 mg/kg males. The NOAEL of ethylbenzene in these studies, based on hepatocyte hypertrophy and liver- and kidney-related clinical chemistry changes, was 75 mg/kg bw/day.
Assuntos
Derivados de Benzeno/toxicidade , Testes de Toxicidade/métodos , Administração Oral , Alanina Transaminase/sangue , Animais , Comportamento Animal/efeitos dos fármacos , Derivados de Benzeno/administração & dosagem , Derivados de Benzeno/química , Bilirrubina/sangue , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Índices de Eritrócitos/efeitos dos fármacos , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Salivação/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/patologia , Fatores de Tempo , Testes de Toxicidade/normas , Ureia/sangueRESUMO
Wistar rats continuously received octyl methoxycinnamate (OMC) in the diet through two successive generations at nominal doses of 0, 150, 450 or 1000 mg/kg bw/day. OMC had no adverse effects on estrous cycles, mating behavior, conception, parturition, lactation and weaning, sperm and follicle parameters, macropathology and histopathology of the sexual organs. 1000 mg/kg bw/day reduced parental food consumption and body weight (-14% to -16% in males, -4% to -5% females), increased liver weight, produced hepatic cytoplasmic eosinophilia and erosion/ulceration of glandular stomach mucosa. and led to a slightly decreased implantation rate in the top dose F0 and F1 dams. The high dose F1 and F2 pups had reduced lactation weight gain and organ weights and delayed sexual maturation landmarks. There was no evidence of a selective influence of the test compound on pups' sexual landmarks. The NOAEL (no observed adverse effect level) is 450 mg/kg bw/day for fertility and reproductive performance, for systemic parental and developmental toxicity.