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

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basophilia, minimal subacute interstitial inflammation) were observed in 7 males and 11 females at
300 ppm.
The NOAEL was 100 ppm, equal to 6.3 and 7.35 mg/kg bw per day in males and females,
respectively, on the basis of kidney toxicity (tubular and interstitial chronic nephropathy) at 300 ppm
and greater (Rudzki et al., 1989).
In a short-term study of oral toxicity, which complied with GLP and US EPA test guidelines,
groups of four male and four female beagle dogs were fed diets containing hydroxyatrazine (purity,
97.1%) at a concentration of 0, 15, 150, 1500, or 6000 ppm, equal to 0, 0.6, 5.8, 59.6, and 247.7 mg/kg
bw per day in males and 0, 0.6, 6.2, 63.9, and 222.1 mg/kg bw per day in females, for 13 weeks.
There were no mortalities. A treatment-related reduction in body-weight gain (−29% in males,
‐31‐37% in females), accompanied by some initial reduction in food consumption was observed at
1500 ppm and greater. Treatment-related clinical chemistry changes were restricted to females at
6000 ppm that displayed increased blood urea nitrogen (BUN) and/or creatinine concentrations. Urine
analysis performed at day 85 revealed an increased urine volume (about twofold) and a decreased
specific gravity at 1500 ppm and greater.
There were no treatment-related effects on organ weights, although at necropsy, pitted or rough
kidneys were observed in three out of four males and one out of four females at 1500 ppm and
four out of four males and two out of four females at 6000 ppm. Treatment-related histopathological
lesions were restricted to the kidneys at 1500 ppm and greater. Minimal to marked multifocal,
chronic nephropathy characterized by tubular dilation, atrophy and basophilia was observed, often
in the presence of a prominent chronic interstitial fibrosis and lymphocytic infiltration. The kidney
lesions appeared predominantly in the cortex, while medullary areas were occasionally involved.
Intratubular crystalline casts were observed in the renal papilla in all males at 1500 ppm and greater
and in three out of four females in each group at 1500 and 6000 ppm.
The NOAEL was 150 ppm, equal to 5.8 and 6.2 mg/kg bw per day in males and females,
respectively, on the basis of decreased body-weight gain and kidney toxicity (tubular and interstitial
chronic nephropathy) at 1500 ppm and greater (Chau et al., 1990).
In a combined long-term study of toxicity and carcinogenicity, which complied with GLP
and the test guidelines of OECD and US EPA, groups of 80 male and 80 female (control and highest
dose) or 70 male and 70 female (all other groups) Crl:CD(SD)BR rats were fed diets containing
hydroxyatrazine (purity, 97.1%) at a concentration of 0, 10, 25, 200, or 400 ppm, equal to 0, 0.388,
0.962, 7.75 and 17.4 mg/kg bw per day in males and 0, 0.475, 1.17, 9.53 and 22.3 mg/kg bw per day
in females, for 24 months. Ten males and 10 females (intermediate dose) or 20 males and 20 females
(control and highest dose) were scheduled for interim kill at 12 months.
Mortality attributable to severe renal failure was markedly increased at 400 ppm (survival
rate by week 52, 96%, 94%, 94%, 94% and 75% in males; 98%, 97%, 97%, 97%, and 76% in
females at 0, 10, 25, 200 and 400 ppm, respectively) and, thus, rats at the highest dose were killed
after 18 months. Treatment-related clinical signs were limited to the group at 400 ppm and included
emaciation, polyuria, general pallor, piloerection and tremors. Body weight and body-weight gain
were significantly decreased at 400 ppm throughout the study. Food consumption was decreased at
200 ppm and greater, while food efficiency was decreased only at 400 ppm. Water consumption was
increased at 200 ppm and greater, but only for the first year.
Treatment-related changes in haematology parameters (decreases in erythrocyte count,
haemoglobin concentration, erythrocyte volume fraction), clinical chemistry parameters
(increased calcium, phosphorus, gamma-glutamyl transferase, BUN and creatinine concentrations;
decreased glucose, total protein and albumin plasma concentrations) and urine analysis
ATRAZINE 37–138 JMPR 2007