Evaluation of developmental toxicity of amitraz in Sprague-Dawley rats

Arch Environ Contam Toxicol. 2007 Jan;52(1):137-44. doi: 10.1007/s00244-006-0021-7. Epub 2006 Nov 2.

Abstract

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo-fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced*
  • Animals
  • Body Weight / drug effects
  • Bone and Bones / abnormalities
  • Bone and Bones / drug effects
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Embryonic Development / drug effects*
  • Female
  • Fetal Viability
  • Insecticides / toxicity*
  • Male
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Specific Pathogen-Free Organisms
  • Teratogens / classification
  • Teratogens / toxicity*
  • Toluidines / toxicity*
  • Toxicity Tests
  • Weight Gain / drug effects

Substances

  • Insecticides
  • Teratogens
  • Toluidines
  • amitraz