Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague–Dawley Rat

Abstract

Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post‐weaning (G/L/PW cohort) to F1 generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen‐primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND 21–133 or from PND 120–133. Slight reductions in fertility and the percentage of F1 generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F1 generation offspring. The onset of puberty was delayed in of the F1 generation G/L/PW females at doses of 25 and 50 mg/kg/day. F1 generation females in the PW high‐dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F1 generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F1 generation females exposed from gestation through to PND 133 or only for two weeks from PND 120–133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults

PBPK Model for Atrazine and Its Chlorotriazine Metabolites in Rat and Human

“…There were no effects on either the LH surge or ovulation when the same dose was given as a temporally distributed dose in feed ( Foradori et al , 2014 ). High bolus doses of ATZ also reduced LH pulse frequency ( Foradori et al , 2013 ), an effect that has been linked to delayed onset of puberty ( Breckenridge et al , 2015 ), as observed in both male ( Stoker et al , 2000 ) and female rats ( Ashby et al , 2002 ; Laws et al , 2000 , 2003 ). The no-observable-adverse-effect levels (NOAELs) for ATZ’s effect on puberty (NOAEL = 6.25 mg/kg/day) and the LH surge (NOAEL = 1.8 mg/kg/day) are used to set 30-day (NOAEL = 6.25 mg/kg/day), 90-day (NOAEL = 1.8 mg/kg/day), and lifetime (NOAEL = 1.8 mg/kg/day) points of departure (PODs) for ATZ and its chlorometabolites ( USEPA, 2006 ).…”

“…The magnitude, frequency, and duration of exposure to chlorotriazines are important determinants of whether adverse effects are observed in animal models ( Breckenridge et al , 2015 ; Foradori et al , 2014 ). This article describes a physiologically based pharmacokinetic (PBPK) model that is capable of converting time-varying concentrations of ATZ, DEA, DIA, and DACT in drinking water into estimates of internal human plasma concentrations for each chemical separately and for calculating total chlorotriazines (TCT) plasma concentrations.…”

Chemical Pesticides and Human Health: The Urgent Need for a New Concept in Agriculture

“…Atrazine is the most known of the triazines, and it is a very widely used herbicide that has been associated with oxidative stress ( 103 ), cytotoxicity ( 105 , 106 ), and dopaminergic effects ( 107 , 108 ). Furthermore, the exposure of experimental animals to atrazine has been associated with reproductive toxicity ( 109 ) and delays in sexual maturation ( 110 ).…”

A Review on Comparative Analytical Approach Towards Chemical Pesticides to Bio Pesticides

“…Atrazine (commonly used), Simazine and Ametryn Endocrine-disrupting effects Reproductive toxicity and delays in sexual maturation, oxidative stress, cytotoxicity and dopaminergic effects . 28,29,30…”