RESUMEN
1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.
Asunto(s)
Aberraciones Cromosómicas/efectos de los fármacos , Hidrocarburos Halogenados/toxicidad , Reproducción/efectos de los fármacos , Administración Oral , Animales , Células CHO , Células Cultivadas , Cricetulus , Relación Dosis-Respuesta a Droga , Femenino , Hidrocarburos Halogenados/administración & dosificación , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Ratas , Ratas Sprague-Dawley , Pruebas de ToxicidadRESUMEN
4-Benzylphenol (CAS No. 101-53-1), a structural analog of bisphenol F, has estrogenic activity in vitro and in vivo, as is the case with bisphenol F. 4-Benzylphenol is used in plastics and during organic synthesis. Since its safety is largely unknown, we conducted toxicity tests as part of screening risk assessment in an existing chemical safety survey program. Based on results of the Ames test and the chromosomal aberration test using Chinese hamster lung cells (OECD TG 471 and 473), 4-benzylphenol was determined to be non-genotoxic in vitro. In a 28-day repeated-dose toxicity study, Crl:CD (SD) rats were administrated 4-benzylphenol by gavage at 0, 30, 150, or 750â¯mg/kg/day (OECD TG 407). Consequently, body weight was lower in males at 750â¯mg/kg/day. In the liver, relative organ weights were increased in both sexes at 750â¯mg/kg/day, and centrilobular hepatocellular hypertrophy was observed in males at 150 and 750â¯mg/kg/day. In the forestomach, hyperkeratosis and hyperplasia of squamous cells were observed in males at 150 and 750â¯mg/kg/day, and in females at 750â¯mg/kg/day. Based on these results, we identified the NOAEL for 4-benzylphenol as 30â¯mg/kg/day, with a hazard assessment value (D-value) of 0.05â¯mg/kg/day corresponding to hazard class 3.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Aberraciones Cromosómicas/efectos de los fármacos , Mutágenos/toxicidad , Administración Oral , Animales , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/química , Células CHO , Cricetulus , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Estructura Molecular , Mutágenos/administración & dosificación , Mutágenos/química , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. Therefore, toxicity tests and hazard classification were conducted for screening assessment under the Japanese Chemical Substances Control Law. Benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using Chinese hamster lung cells. However, the combined repeated-dose and reproductive/developmental screening toxicity test, in which male and female rats were administered benzyl salicylate by gavage at 0, 30, 100, or 300â¯mg/kg/day for 42 and 41-46 days, respectively, from 14 days before mating until postnatal Day 4, showed that repeated doses had major effects on the thymus, liver, epididymis, and femur at 100 and/or 300â¯mg/kg/day. Furthermore, although benzyl salicylate had no effect on the estrus cycle, fertility, corpus lutea, or implantation rate, embryonic resorption, offspring mortality, and neural tube defects were observed at 300â¯mg/kg/day, and the offspring had lower body weights at 30 and 100â¯mg/kg/day, suggesting teratogenicity similar to other salicylates. Based on the developmental toxicity, this chemical was classified as hazard class 2, with a lowest observed adverse effect level (LOAEL) of 30â¯mg/kg/day and a D-value of 0.003â¯mg/kg/day.