Combined repeated dose and reproductive/developmental toxicity screening test of the nitrophenolic herbicide dinoseb, 2-sec-butyl-4,6-dinitrophenol, in rats.
In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2-sec-butyl-4,6-dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44-48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day.
Matsumoto
Mariko
M
Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, 1-1-18 Kamiyoga, Setagaya-ku, Tokyo 185-8501, Japan.
Furuhashi
Tadakazu
T
Poncipe
Carlo
C
Ema
Makoto
M
D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives* / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D008098:Litter Size; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D018812:Paternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013154:Spleen / Q000187:drug effects; D018675:Toxicity Tests
D006540:Herbicides; D019297:2,4-Dinitrophenol; C018527:dinoseb