Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 3-amino-1,2,4-triazole based on the Organization for Economic Co-operation and Development draft protocols.

We performed a uterotrophic assay, the Hershberger assay, and the 28-day repeated-dose toxicity study (enhanced OECD test guideline no. 407) of 3-amino-1,2,4-triazole based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and no changes were observed.

Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 4,4'-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol, based on the OECD draft protocols.

We performed a uterotrophic assay, the Hershberger assay, and a 28-day repeated-dose toxicity study [enhanced Organization for Economic Co-operation and Development (OECD) test guideline No. 407] of 4,4'-butylidenebis(2-tert-butyl-5-methylphenol) and 3-(dibutylamino)phenol, based on the OECD draft protocols. In the uterotrophic assay of 4,4'-butylidenebis(2-tert-butyl-5-methylphenol), female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and no changes were observed.

Subacute oral toxicity study of bisphenol F based on the draft protocol for the "Enhanced OECD Test Guideline no. 407".

Since bisphenol F (4,4'-dihydroxydiphenylmethane) has been reported to exhibit estrogen agonistic properties in the uterotrophic assay, we performed a 28-day repeated-dose toxicity study (enhanced OECD test guideline No. 407) on bisphenol F based on the OECD draft protocols to determine whether it has endocrine-mediated properties. Bisphenol F was orally administered at doses 0, 20, 100 and 500 mg/kg per day for at least 28 days, but no clear endocrine-mediated changes were detected, and it was concluded to have no endocrine-mediated effects in young adult rats.

A two-generation reproductive toxicity study of butyl benzyl phthalate in rats.

A two-generation reproductive toxicity study with extra parameters was performed for Butyl benzyl phthalate (BBP). The compound was administered orally by gavage with the doses of 0, 100, 200, or 400 mg/kg/day to groups of 24 Crj:CD (SD)IGS rats of both sexes to confirm the utility of the protocol for identification of non-steroid chemicals with endocrine activity by ssessing effects on parental animals and offspring. Softening of the testes, diffuse atrophy of testicular seminiferous tubules, decreased spermatozoa and/or residual germ cells in the epididymal lumina were observed in the F1generation after doses more than 100 mg/kg, lowering of the F1 epididymal weights at doses more than 200 mg/kg, along with low F0 epididymal weights, Leydig cell hyperplasia, residual germ cells in the epidimymal lumina, and low seminal vesicle weights, small testes and epididymes, partial aplasia or aplasia of the epididymes, and Leydig cell hyperplasia in the F1 generation with 400 mg/kg.

A two-generation reproductive toxicity study of 4-nitrotoluene in rats.

4-Nitrotoluene (4-NT) was administered orally at doses of 0, 40, 80, or 160 mg/kg/day by gavage to 24 Crj:CD (SD)IGS rats of each sex per group over two successive generations, and the effects on reproductive capacity in the parental animals and growth and development of the offspring were investigated. In the F0 and F1 parents, increased hepatic and/or renal weights were observed at the doses of 40 mg/kg or more in both generations, with lowered body weights in the F1 case and reduced feeding efficiency, histopathological changes in the kidney and spleen at doses of 80 and 160 mg/kg, as well as worsening of clinical signs and death during the perinatal period at 160 mg/kg in both generations. With regard to effects on the reproductive capacity, reduced vaginal opening was observed at 160 mg/kg in the F1 generation.

Subacute oral toxicity study of di(2-ethylhexyl)adipate based on the draft protocol for the "Enhanced OECD Test Guideline no. 407".

We performed a 28-day repeated-dose toxicity study of di(2-ethylhexyl)adipate (DEHA) based on the draft protocol of the "Enhanced OECD Test Guideline 407" to investigate whether it has endocrine-mediated properties according to this assay. DEHA was orally administered to SD rats at doses of 0, 40, 200 and 1,000 mg/kg/day for at least 28 days, and disturbance of the estrous cycle and increased ovarian follicle atresia were detected in the 1,000 mg/kg group.

Subacute oral toxicity study of diethylphthalate based on the draft protocol for "Enhanced OECD Test Guideline no. 407".

We performed a 28-day repeated-dose toxicity study of diethylphthalate based on the draft protocol of the "Enhanced OECD Test Guideline 407" to investigate whether it has endocrine-mediated properties according to this assay. Diethylphthalate was orally administered to SD rats at doses of 0, 40, 200, and 1,000 mg/kg/day for at least 28 days, but no endocrine-mediated effects were detected based on any of the parameters examined, suggesting that diethylphthalate does not possess endocrine properties according to this assay.

Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay.

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone sensitization test for determining the sensitizing potential of chemicals, and it has the advantage of yielding a quantitative endpoint that can be used to predict the sensitization potency of chemicals. The EC3 has been proposed as a parameter for classifying chemicals according to the sensitization potency. We previously developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new procedure to predict the sensitization potency of chemicals based on comparisons with known human contact allergens.

Age-related changes of genital systems in the female Crj:CD (SD) IGS rats during sexual maturation.

The age-related changes of vaginal opening, body weight, the weights of the uterus and ovary, together with histological examination, serum 17beta-estradiol (E2) and progesterone levels were examined in intact female Crj:CD (SD) IGS rats between 21 and 36 days of age to understand the basic biological profile of changes of the female genital system during sexual maturation in the rat for female pubertal assays. With the beginning of the elevation of serum E2 level from 28 days of age, all parameters except body weight started to show drastic change until 31 days of age. The highest incidence of vaginal opening was recorded at 34 days of age.