Jc. Eldridge et al., SHORT-TERM EFFECTS OF CHLOROTRIAZINES ON ESTRUS IN FEMALE SPRAGUE-DAWLEY AND FISCHER-344 RATS, Journal of toxicology and environmental health, 43(2), 1994, pp. 155-167
Atrazine or simazine (s-chlorotriazines) was administered by gavage da
ily for 2 wk to female Sprague-Dawley and Fischer 344 rats at oral dos
es of 100 or 300 mg/kg to evaluate effects on body, ovary, uterus, and
adrenal weights, estrous cycle stages, vaginal cytology, and plasma h
ormone (estradiol, progesterone, prolactin, and corticosterone) levels
. Significant reductions in body weights of both Sprague-Dawley and Fi
scher 344 female rats at both dose levels were accompanied by a signif
icant reduction in ovarian and uterine weights, and a decrease in circ
ulating estradiol levels. The magnitudes of the effects were less in F
ischer 344 rats than in Sprague-Dawley rats, and the effects of simazi
ne were less pronounced than those of atrazine at the same dose. A max
imum tolerated dose (MTD: greater than or equal to 10% body weight red
uction) was estimated to be 100 mg/kg for atrazine and 300 mg/kg for s
imazine for both stains. The Sprague-Dawley female rats exhibited a tr
eatment-related lengthening of the estrous cycle and an increased numb
er of days characterized by cornified epithelial cells. This resulted
in a greater percent of the cycle days spent in estrus and reduction i
n the percent of the cycle days spent in diestrus. Atrazine-dosed Fisc
her 344 females also exhibited a significant trend toward cycle length
ening, but this was due to reduction in the percent of cycle spent in
estrus and a concomitant increase in diestrual days. These findings su
ggest that treatment with doses of triazine at or above the MTD may re
sult in prolonged exposure to endogenous estrogen in the Sprague-Dawle
y but not the Fischer 344 rat. These changes may account for the obser
ved earlier onset and/or increased incidence of mammary tumors in chlo
rotriazine-treated female Sprague-Dawley rats. This strain of rat is a
lready known to be prone to a substantial development of mammary tumor
s with advancing age, while the Fischer 344 strain is not as likely to
exhibit this response.