Assessment of 8-methosypsoralen, lomefloxacin, sparfloxacin, and Pirfenidone phototoxicity in Long-Evans rats.

Phototoxicity has a strong impact on drug development. Although several animal models have been developed to quantitatively assess human risks, none have been validated for standardized use. In this study, we validated an in vivo phototoxicity model using Long-Evans (LE) rats treated with 4 well-known phototoxic drugs, namely 8-methoxypsoralen, lomefloxacin, sparfloxacin, and pirfenidone.

Collaborative work on evaluation of ovarian toxicity. 17) Two- or four-week repeated-dose studies and fertility study of sulpiride in female rats.

To find the appropriate dosing period to detect ovarian toxicity, sulpiride, a D2 antagonist was orally dosed to female rats at dose levels of 1, 10, and 100 mg/kg/day daily for 2 or 4 weeks in repeated-dose toxicity studies. In addition, sulpiride at the same dose levels was given to female rats daily during the pre-mating period, mating period, and Days 0-7 of gestation to assess its effect on fertility. In ovarian histology in the 2-week study, increases in atretic follicle were seen at 1 mg/kg or more and increases in follicular cysts at 10 mg/kg or more.

Spontaneous cerebellar dysplasias in BrlHan: WIST@Jcl rats.

Focal disturbed laminar architecture in cerebellar vermis was observed in 25 out of 100 (25%) males, and 25 out of 100 (25%) females of BrlHan: WIST@Jcl rats. The cortical molecular and granular layers were haphazardly distributed around the primary and/or secondary fissures. The stellate and basket cells positively stained with parvalbumin immunohistochemistry were observed exclusively in the separated molecular layer.

Interlaboratory comparison of short-term carcinogenicity studies using CB6F1-rasH2 transgenic mice.

In order to evaluate a short-term carcinogenicity testing system using CB6F1 -Tg rasH2 (rasH2-Tg) mice carrying a human prototype c-Ha-ras gene, 26-week studies were conducted in 12 different facilities as a part of an International Life Science Institute Health and Environmental Science Institute (ILSI HESI) international collaborative project. In each study N-methyl-N-nitrosourea (MNU) was administered to a separate group of rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. We herein have summarized the mortality, body weight change, and neoplastic and nonneoplastic lesions detected in these positive control groups as representative historical positive control data.

Twenty-six week carcinogenicity study of ampicillin in CB6F1-TgrasH2 mice.

As a part of the ILSI-HESI Alternative to Carcinogenicity Testing (ACT) program, we performed a 26-week carcinogenetic study of nonmutagenic drug, ampicillin (ABPC) in Tg-rasH2 mice. ABPC was given to Tg-rasH2 mice (0, 350, 1000, 3000 mg/kg, p.o.

A novel mutation vf causing abnormal vacuoles in the central nervous system maps on rat chromosome 8.

Body-tremorous rats were found in a colony of WTC-tm rats and a new coisogenic mutant strain void of the tm mutation was established. Histological analysis revealed that these rat mutants had abnormal vacuoles in the red nucleus of the midbrain, the reticular formation in the brain stem, and the white matter of the cerebellum and spinal cord. Electron microscopic observation showed many irregular myelin-bound vacuoles and degenerated oligodendroglia.