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

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the highest dose, and food consumption was consistently lower in the group at the highest dose when
compared with controls.
Electrocardiographic changes occurred in dogs at the highest dose and included slight to moderate
increases in heart rate (primarily in males), moderate decreases in height of the P-wave, PR and
QT values. Atrial premature complexes and atrial fibrillation were found in one female.
Haematology data indicated a slight but significant decrease in erythrocyte parameters in males
and an increase in the number of platelets in males and females at 1000 ppm. Treatment-related
changes in clinical chemistry were restricted to dogs at 1000 ppm and included a slight decrease in
total plasma protein and albumin, considered to be secondary to the reduction in food consumption.
Necropsy revealed heart lesions in the group at the highest dose, these consisting of moderate
to severe dilatation of right and/or left atria, and in some dogs, a fluid-filled pericardium and enlarged
heart. In females at the highest dose, there was a treatment-related decrease in absolute heart weight.
Histopathological findings were restricted to the heart in the group at the highest dose and included
myolysis and atrophy of myocardial fibres, and oedema of the heart. These findings correlated with
the clinical symptoms, the electrocardiogram results and with the gross pathology observations.
The NOAEL was 150 ppm, equal to 5 mg/kg bw per day, on the basis of decreased body-weight
gain and cardiac effects at 1000 ppm (O’Connor et al., 1987).
Rabbits
In a short-term study of dermal toxicity, groups of five male and five female New Zealand
White rabbits were given atrazine (purity, 97.6%) at a dose of 0, 10, 100 or 1000 mg/kg bw per day
under semi-occluded conditions to the skin for 6 h per day for at least 25 consecutive days. The study
was conducted in compliance with GLP and US EPA test guidelines.
At 1000 mg/kg bw per day, systemic toxicity (faecal changes, body-weight loss, decrease
in food consumption) was recorded in males and females during treatment, while females at
100 mg/kg bw per day showed a transient decrease in body-weight gain during the first week of treatment.
Also at 1000 mg/kg bw per day, changes in haematology and clinical chemistry parameters
(slight depression of erythrocyte count and haemoglobin concentration with a minimal increase in the
percentage of reticulocytes, decrease in total serum albumin and chloride values) and slight changes
in absolute and relative organ weights were observed. Local effects in females at 1000 mg/kg bw per
day included slight dermal irritation, an increased incidence of minimal to moderate acanthosis and
focal subacute lymphocytic inflammation of the skin.
The NOAEL for systemic toxicity was 100 mg/kg bw per day on the basis of decreased bodyweight
gain and food intake, a slight reduction in erythrocyte parameters and increased spleen weight
at 1000 mg/kg bw per day (Huber et al., 1989).
2.3 Long-term studies of toxicity and carcinogenicity
Mice
In an early study of carcinogenicity, atrazine (from commercial sources, purity not given) was
administered to groups of 18 male and 18 female mice of each of the C57BL/6 × C3H/Anf and
C57BL/6 × AKR strains (a total of 36 males and 36 females). At the beginning of the study, mice
aged 7 days (pre-weanling) were given atrazine at a dose of 21.5 mg/kg bw per day by gavage in 0.5%
gelatin, and were switched at weaning (age 4 weeks) to diet containing atrazine at 82 ppm (cited to be
approximately equivalent to the dose given by gavage, but estimated in review to be approximately
half this dose). Doses were not adjusted for body-weight gain, either when given by gavage or by
dietary administration. The dose was selected as the highest not causing mortality in a pilot screening
ATRAZINE 37–138 JMPR 2007