Multigeneration Reproduction and Male Developmental Toxicity Studies on Atrazine in Rats

• Published in: Birth defects research. Part B. Developmental and reproductive toxicology 2014-06, Vol.101 (3), p.237-253
• Main Authors: DeSesso, John M., Scialli, Anthony R., White, Tacey E. K., Breckenridge, Charles B.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; atrazine; Atrazine - administration & dosage; Atrazine - toxicity; Body Weight; Dose-Response Relationship, Drug; Endpoint Determination; Epididymis - drug effects; Epididymis - metabolism; Female; gestation; Lactation; Male; male development; Maternal Exposure; multigeneration reproduction; No-Observed-Adverse-Effect Level; Organ Size - drug effects; postcoitum; Pregnancy; rat; Rats; Reproduction - drug effects; Reproductive system; Rodents; Sperm; Spermatozoa - drug effects; Studies; Testosterone; Testosterone - blood; Toxicity
• ISSN: 1542-9733; 1542-9741
• DOI: 10.1002/bdrb.21106

BACKGROUND Reproductive toxicity of Atrazine (ATR) was evaluated in two rat multigenerational studies. Development of male reproductive parameters was evaluated in separate studies after prenatal or postnatal exposure. METHODS In multigenerational studies, rats received dietary concentrations of 0, 10, 50, 100 or 500 ppm ATR. In separate studies in female rats, ATR was administered by gavage at 0, 1, 5, 25 or 125 mg/kg/day during pregnancy (GD6–21) or lactation (LD2–21). Plasma testosterone concentration, testicular and epididymal weights, and sperm counts were measured in male offspring on PND70 and 170. RESULTS In the multigenerational studies, parental systemic toxicity occurred at 500 ppm (38.7 mg/kg/day), but reproductive endpoints were unaffected. In the prenatal study, maternal toxicity and embryo‐fetal mortality occurred at 125 mg/kg/day. In male offspring, testosterone levels and sperm counts were unaffected, although the percentage of abnormal sperm increased at 125 mg/kg/day (PND 70) and 25 mg/kg/day (PND170). In the postnatal study, maternal toxicity and reduced body weights of male offspring occurred at 125 mg/kg/day. Additionally, reduced testicular (PND70, PND170) and epididymal (PND70) weights and increased numbers of abnormal sperm (PND70, PND170) were seen, but no changes in plasma testosterone or sperm counts. CONCLUSIONS Dietary administration of ATR did not affect rat reproduction up to a parentally toxic dose of 38.7 mg/kg/day. Some effects on male reproductive system development occurred after high dose, bolus administration to dams, but doses were much higher than expected under normal use conditions. Thus, oral RfDs for ATR would be protective for reproductive effects