RESUMO
Tridecyl acetate was administered to male and female Sprague-Dawley rats by oral gavage, 5 days per week for 13 weeks (90 days). Treated rats received daily doses of 0.1, 0.5, or 1.0 g/kg/day and control rats received distilled water at a dose of 1.0 g/kg/day. After 45 days an interim termination was made to evaluate potential hematologic or hepatic effects of tridecyl acetate. Blood samples were collected for routine hematology and serum chemistry determinations and liver tissue was obtained for histological examination. After 90 days all animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examination. Treatment-related effects observed in the mid and high dose groups consisted of (1) increased liver weights and/or liver/body weight ratios in both sexes at the interim and 13 week termination, (2) increased kidney weights and/or kidney/body weight ratios in both sexes at the terminal necropsy, (3) histopathologic evidence of hydrocarbon nephropathy in males, and (4) a slight decrease in serum glucose levels in male rats at both the interim and terminal necropsies. The increases in liver weight are believed to be a normal physiological response to a chemical challenge. The nephropathy produced by tridecyl acetate is characteristic of that produced by a diverse group of hydrocarbons and, to date, appears to be limited to male rats. The low dose in this study was a no observed effect level. These results are indicative of an overall low degree of systemic toxicity following subchronic oral administration of tridecyl acetate at doses up to 1 g/kg body weight.
Assuntos
Acetatos/toxicidade , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hemoglobinas/análise , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Relação Estrutura-AtividadeRESUMO
Octyl acetate (CAS RN 108419-32-5) was administered via oral gavage to pregnant Sprague-Dawley rats on Gestation Days 6 through 15 at dose levels of 0, 0.1, 0.5, and 1.0 g/kg. The dams were weighed and observed for clinical signs of toxicity during pregnancy, and food consumption was measured. On Gestation Day 20 the dams were sacrificed and the fetuses were examined for external, visceral, and skeletal malformations and variations. The mid- and high-dose levels resulted in maternal toxicity as evidenced by reductions in body weight gain and food consumption. There were no statistically significant effects on embryo-fetal lethality or fetal growth for any treatment group. The number of litters with at least one malformed fetus and the mean percentage of the litter malformed were significantly (p less than 0.05) elevated in the high-dose group only. The results of the present study demonstrate that octyl acetate produced some evidence of developmental toxicity at a dose (1.0 g/kg) that was maternally toxic. Developmental toxicity was not observed at the maternally toxic 0.5 g/kg dose level or the maternally nontoxic dose level (0.1 g/kg). Therefore, these data indicate that octyl acetate is not a selective developmental toxicant in the rat.
Assuntos
Acetatos/toxicidade , Teratogênicos , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Masculino , Gravidez , Ratos , Ratos EndogâmicosRESUMO
The subchronic toxicity of octyl acetate was assessed following its administration to rats via oral gavage, 5 days per week for 13 weeks. Treated rats received undiluted octyl acetate at doses of 0.1, 0.5, or 1.0 g/kg. Control rats received distilled water at a dose of 1.0 g/kg. An interim termination was made after 45 days of dosing at which time five animals per sex per group were terminated and necropsied. Blood samples were collected and liver tissues were prepared for histological examination. After 13 weeks of dosing all animals were terminated and necropsied. Blood samples were obtained and selected organs were weighed and prepared for subsequent histological examination. Several treatment-related effects were observed in the high-dose group (1.0 g/kg) animals. These effects included slight reductions in body weight and food consumption, increased liver and kidney weights, and evidence of hydrocarbon nephropathy in high-dose males only. The significance of these observations is discussed in the report. With the exception of increased liver weights in the mid-dose group, no other significant treatment-related effects were observed in the mid- or low-dose groups of animals. It is believed that the increases in liver weight which were observed are a compensatory response to an increased metabolic load, and not a reflection of true hepatotoxicity. The results of this study indicated that octyl acetate possessed an overall low degree of systemic toxicity when administered orally to rats for 13 weeks.
Assuntos
Acetatos/toxicidade , Solventes/toxicidade , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Enzimas/sangue , Feminino , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
In general, the carcinogenic potential of petroleum-derived materials is related to the polycyclic aromatic hydrocarbon (PAH) content. Thus it has been assumed that liquids which boil below the PAH distillation range (i.e., below approx. 370 degrees C (700 degrees F) would not be carcinogenic. Several early studies supported this conclusion but were of relatively short duration. Several recent and more rigorous studies have shown that repeated application of certain petroleum-derived materials boiling between approximately 177-370 degrees C (350-700 degrees F) (i.e., middle distillate fuels) can produce tumors in mouse skin. The current studies assessed the tumorigenic potential of a series of middle distillates which varied with respect to boiling range, composition, and source of blending stocks. All of the samples produced evidence of weak tumorigenic activity which was characterized by low tumor yields and long median latencies. However, the majority of the tumor yields were significantly different from the control. There were no apparent differences in response among the samples. Thus the various parameters examined did not substantially influence tumor outcome. In particular, there was no association of tumorigenic activity with aromatic carbon content; this finding, coupled with evidence that PAH levels were low, suggested that the tumorigenic responses were not PAH-dependent. In addition to the tumors, there was evidence of non-neoplastic dermal changes including hyperplasia. These may have contributed to the tumorigenic responses; however, the actual mechanism of tumor induction is unknown.