Evaluation of developmental toxicity of amitraz in Sprague-Dawley rats.
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.
Kim
J C
JC
College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, South Korea. toxkim@chonnam.ac.kr
Shin
J Y
JY
Yang
Y S
YS
Shin
D H
DH
Moon
C J
CJ
Kim
S H
SH
Park
S C
SC
Kim
Y B
YB
Kim
H C
HC
Chung
M K
MK
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005328:Fetal Viability; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000145:classification / Q000633:toxicity*; D014052:Toluidines / Q000633:toxicity*; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects
D007306:Insecticides; D013723:Teratogens; D014052:Toluidines; C014983:amitraz