Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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Table 18. Relevant findings in a study of prenatal developmental toxicity in rats given DACT by
gavage
Finding
Dose (mg/kg bw per day)
0 2.5 25 75 150
Food consumption (g/day):
Days 6–8 22.95 22.80 20.62 18.48* 11.98*
Days 8–12 22.54 24.73 23.70 21.85 15.63*
Body-weight gain (g):
Days 6–8 11.68 11.39 7.92 −1.64* −11.26*
Days 8–12 21.18 23.00 22.20 17.12 5.70*
No. of pregnant rats 22 23 25 25 23
Mean No. of resorptions 0.77 0.48 1.04 0.84 2.61*
Postimplantatation loss (mean) 0.77 0.48 1.04 0.84 2.70*
Postimplantation loss (%) 5.56 3.59 7.15 6.16 18.86*
Mean No. of live fetuses 13.18 12.61 13.20 13.60 11.26
Mean fetal weights (g), males/females 3.45/3.29 3.45/3.32 3.43/3.29 3.14*/3.03* 2.79*/2.68*
Visceral examination (No. of fetuses/litters) 141/22 140/23 160/25 166/25 126/23
Renal papilla absent (No. of fetuses/litters) 5/3 7/6 8/5 12/8 28*/11*
Kidneys pitted (No. of fetuses/litters) 0 0 0 0 6*/3*
Skeletal examination (No. of fetuses/litters) 149/22 150/23 170/25 174/25 133/23
Hyoid not ossified (No. of fetuses/litters) 7/5 7/5 26*/10* 49*/16* 53*/15*
Interparietal not completely ossified
27/10 28/11 60*/20* 92*/23* 86*/21*
(No. of fetuses/litters)
Parietals not completely ossified (No. of fetuses/litters) 5/3 14/5 18*/10* 20*/10* 20*/8*
From Hummel et al. (1989)
DACT, diaminochlorotriazine.
* p < 0.05; ** p < 0.01;
reduced body-weight gain, increased water consumption, changes in clinical chemistry and urine
analysis parameters as well as macroscopic and microscopic lesions in the kidney, due to the low
solubility of hydroxyatrazine in water resulting in crystal formation and consequent inflammatory
response. The overall NOAEL was 100 ppm, equal to 6.3 mg/kg bw per day. In a 13-week study in
dogs given hydroxyatrazine at dietary concentrations of up to 6000 ppm, effects included reduced
body-weight gain and food consumption, changes in clinical chemistry and urine analysis parameters
and macroscopic and microscopic lesions in the kidney. The NOAEL was 150 ppm, equal to
5.8 mg/kg bw per day. In a 2-year study of toxicity and carcinogenicity in rats given hydroxyatrazine
at dietary concentrations of up to 400 ppm, effects included clinical signs and increased mortality,
reduced body-weight gain and food consumption, increased water consumption, changes in haematological,
clinical chemistry and urine analysis parameters and macroscopic and microscopic lesions
in the kidney. The NOAEL was 25 ppm, equal to 1 mg/kg bw per day. There was no evidence of carcinogenicity.
Hydroxyatrazine was not genotoxic in a battery of tests including assays for point mutation
and DNA repair in vitro and tests for clastogenicity in vivo. In a study of prenatal developmental
toxicity in rats, reduced food consumption and body-weight gain in dams and increased incidences of
incompletely ossified hyoid and interparietal bones and not ossified forepaw metacarpals and proximal
phalanges in fetuses were seen at 125 mg/kg bw per day, and the NOAEL was 25 mg/kg bw per
day for both maternal and developmental toxicity. In a special study on the effects of hydroxyatrazine
ATRAZINE 37–138 JMPR 2007