title: Four-week intravenous repeated dose toxicity study of L-cysteine in male rats.
abstract: A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this compound and to determine the dose level at which these toxic effects are observed following repeated intravenous administration. Male rats were randomly allocated to 4 groups to receive L-Cys by intravenous administration at dosages of 0, 100, 300, and 1,000 mg/kg body weight/day. Body weight gain was significantly suppressed throughout the study period in the 1,000-mg/kg group, although food consumption was reduced only on study day 3. A decrease in spontaneous activity, salivation, stereotypy, ptosis, and tremor were observed in the 1,000-mg/kg group. Mild anemia characterized by decreases in hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and an increase in the reticulocyte count was also noted in the 1,000-mg/kg group. Histopathological examination showed sperm granulomas in the epididymis and necrosis of the Purkinje cells and granular layer in the cerebellum in the 1,000-mg/kg group. Slight tubular basophilia with blood or hyaline casts was observed in the kidney in the 300-mg/kg and 1,000-mg/kg groups, associated with proteinuria or occult blood in urinalysis. Additional studies are needed to clarify the causes for these toxicological findings by excess of L-Cys.
authors.affiliation: Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., 115 Kuguhara, Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Sawamoto
authors.forename: Sadakatsu
authors.initials: S
authors.lastname: Kyo
authors.forename: Shinya
authors.initials: S
authors.lastname: Kaneda
authors.forename: Miwa
authors.initials: M
authors.lastname: Harada
authors.forename: Sanae
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Koshitani
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Kurisu
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D003545:Cysteine / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D004435:Eating / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003545:Cysteine