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

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on pubertal development in female rats, atrazine equimolar doses of up to 200 mg/kg bw per day did
not significantly delay vaginal opening.
In a study of acute oral toxicity, which complied with GLP and the US EPA test guidelines,
a group of five male and five female HSD:(SD) rats received hydroxyatrazine (purity, 97.1%; suspended
in 2% carboxymethyl-cellulose) as a single dose at 5050 mg/kg bw by gavage. The rats were
observed for clinical signs and mortality for 14 days. The oral LD 50
was > 5050 mg/kg bw (Kuhn,
1991e).
In a short-term study of oral toxicity, which complied with GLP and US EPA test guidelines,
groups of 10 male and 10 female Sprague-Dawley rats were fed diets containing hydroxyatrazine
(purity, not reported) at a concentration of 0, 10, 250, 500 or 750 ppm, equal to 0, 0.92, 22.5, 44.4
and 67.3 mg/kg bw per day in males and 0, 1.0, 25.2, 47.3 and 67.4 mg/kg bw per day in females,
for at least 29 days.
No mortalities were observed during the study. An increased incidence of diarrhoea was
observed in males at 250 ppm and greater. Body weight and body-weight gain were decreased in
males at 500 ppm and greater and in females at 750 ppm, and food consumption was reduced in
males at 250 ppm and greater and in females at 500 ppm and greater. Some changes in haematological
and clinical chemistry parameters were observed in both sexes at 500 ppm and greater. At
necropsy, an increased incidence of mottled and rough kidneys was seen in males at 500 ppm and
greater and in females at 750 ppm.
The NOAEL was 10 ppm, equal to 0.9 and 1.0 mg/kg bw per day in males and females, respectively,
on the basis of increased incidence of diarrhoea and reduced food consumption at 250 ppm and
greater (Hazelette & Arthur, 1989a).
In a short-term study of oral toxicity, which complied with GLP and US EPA test guidelines,
groups of 15 male and 15 female Sprague-Dawley (Crl:CD Br) rats were fed diets containing
hydroxyatrazine (purity, 97.1%) at a concentration of 0, 10, 100, 300, or 600 ppm, equal to 0, 0.64,
6.3, 18.89 and 37.47 mg/kg bw per day in males and 0, 0.75, 7.35, 22.73 and 45.64 mg/kg bw per day
in females, for 13 weeks.
No mortality occurred throughout the study and no treatment-related clinical symptoms were
observed. Body-weight gain was decreased by about 12.5% in both sexes at 600 ppm, while food
consumption was slightly decreased in males at 600 ppm. An increase in water consumption was
observed in both sexes at 600 ppm. Slight decreases in erythrocyte parameters (erythrocyte count,
haemoglobin concentration and erythrocyte volume fraction) and increases in serum urea nitrogen,
creatinine, sodium and chloride concentrations were seen at 600 ppm, while increased chloride concentrations
were also observed in females at 300 ppm. Mean urine volume was increased in males at
300 ppm and in both sexes at 600 ppm, and mean specific gravity in urine was decreased in females
at 600 ppm.
At necropsy, mean absolute and relative kidney weights were increased in both sexes at 600 ppm
(absolute weights, +33.7 and +33.2%; relative organ-to-body weights, +44.3 and +45.1% in males
and females, respectively). Rough or pitted kidneys, with or without pale and tan discoloration, were
noted in all males and in 14 out of 15 females at 600 ppm. Similar findings were noted in four males
and two females at 300 ppm. Treatment-related histopathological findings were restricted to the kidneys
at 300 ppm and greater. All rats at the highest dose had marked tubular dilatation and basophilia,
extensive chronic hyperplastic inflammation in the interstices, and cellular casts. Anisotropic
crystals, later identified as hydroxyatrazine, were noted in the papillary tubules of 11 males and 13
females of the group at the highest dose. Less severe lesions (minimal tubular dilatation and tubular
ATRAZINE 37–138 JMPR 2007