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

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50<br />

Table 3. Dermal irritation and sensitization potential of atraz<strong>in</strong>e<br />

Species Stra<strong>in</strong> Sex End-po<strong>in</strong>t (method) Purity (%) Result Reference<br />

Rabbit Himalayan Males &<br />

females<br />

Rabbit Himalayan Males &<br />

females<br />

Gu<strong>in</strong>ea-pig<br />

Gu<strong>in</strong>ea-pig<br />

Pirbright White<br />

(Tif:DHP)<br />

Pirbright White<br />

(Tif:DHP)<br />

Males &<br />

females<br />

Males &<br />

females<br />

Human — NR Repeated-<strong>in</strong>sult<br />

patch test<br />

NR, not reported.<br />

Sk<strong>in</strong> irritation NR Not irritat<strong>in</strong>g Ullmann<br />

(1976b)<br />

Eye irritation NR Not irritat<strong>in</strong>g Ullmann<br />

(1976a)<br />

Sk<strong>in</strong> sensitization 98.2 Sensitiz<strong>in</strong>g Maurer (1983)<br />

(optimization test)<br />

Sk<strong>in</strong> sensitization 98 Sensitiz<strong>in</strong>g Schoch (1985)<br />

(Magnussen &<br />

Kligman test)<br />

Atraz<strong>in</strong>e 80 W<br />

formulation<br />

Not<br />

sensitiz<strong>in</strong>g<br />

Shelanski &<br />

Gittes (1965)<br />

highest dose and the control group to evaluate an additional 4-week recovery period. The study was<br />

conducted <strong>in</strong> compliance with GLP and US EPA and OECD test guidel<strong>in</strong>es.<br />

There were no major treatment-related cl<strong>in</strong>ical signs and no deaths. A statistically significant<br />

decrease <strong>in</strong> body-weight ga<strong>in</strong>, compared with controls, was found <strong>in</strong> males (−15%) and <strong>in</strong> females<br />

(−9%) of the group at 500 ppm. A slight, non-statistically significant decrease (−8%) <strong>in</strong> body-weight<br />

ga<strong>in</strong> was also reported <strong>in</strong> males at 50 ppm. Food consumption was decreased <strong>in</strong> males (−10%) and<br />

females (−5%) of the group at 500 ppm and for males at 50 ppm (−5%). No treatment-related changes<br />

were found for any haematological or cl<strong>in</strong>ical chemistry parameters at any dose. The mean absolute<br />

liver and kidney weights were lower <strong>in</strong> the males at 500 ppm and liver weight relative to body weight<br />

was higher <strong>in</strong> females at 500 ppm than <strong>in</strong> the controls. Histologically, deposition of haemosider<strong>in</strong><br />

pigment <strong>in</strong> the spleen was found at an <strong>in</strong>creased <strong>in</strong>cidence and severity at 500 ppm. In females, this<br />

f<strong>in</strong>d<strong>in</strong>g was still present at a higher <strong>in</strong>cidence after the recovery period.<br />

The NOAEL was 50 ppm, equal to 3.3 mg/kg bw per day, on the basis of decreased body<br />

weight and <strong>in</strong>creased splenic haemosiderosis at 500 ppm (Bachmann, 1994).<br />

Dogs<br />

In a study of oral toxicity <strong>in</strong> beagle dogs, groups of four males and four females (lowest and<br />

<strong>in</strong>termediate dose) or six males and six females (control and highest dose) were fed diets conta<strong>in</strong><strong>in</strong>g<br />

atraz<strong>in</strong>e (purity, 97%) at a concentration of 0, 15, 150 or 1000 ppm, equal to 0, 0.5, 5 and 33.7 mg/kg<br />

bw per day, for 52 weeks. Fixed portions of 400 g of diet were offered dur<strong>in</strong>g a 3-h period each day.<br />

Two males and two females <strong>in</strong> the control group and <strong>in</strong> the group at highest dose were designated to<br />

be placed <strong>in</strong> a recovery group. Investigations <strong>in</strong>cluded cl<strong>in</strong>ical pathology, ophthalmoscopic, auditory<br />

and electrocardiographic exam<strong>in</strong>ations at 3-monthly <strong>in</strong>tervals throughout the study. The study was<br />

conducted <strong>in</strong> compliance with GLP and US EPA and OECD test guidel<strong>in</strong>es.<br />

Two dogs at the highest dose (one male on day 250, one female on day 113) and one male at<br />

the <strong>in</strong>termediate dose (on day 75) were killed <strong>in</strong> a moribund condition dur<strong>in</strong>g the course of the study.<br />

The two dogs found <strong>in</strong> a moribund condition at the highest dose may have been affected by treatmentrelated<br />

cardiac dysfunction s<strong>in</strong>ce compound-related myocardial lesions were observed <strong>in</strong> these animals.<br />

Treatment-related symptoms were restricted to dogs at the highest dose. Cl<strong>in</strong>ical symptoms at<br />

1000 ppm <strong>in</strong>cluded cachexia, ascites and laboured and shallow breath<strong>in</strong>g. The ascites was considered<br />

related to treatment-<strong>in</strong>duced myocardial degeneration, as was the laboured breath<strong>in</strong>g. Marked reduction<br />

<strong>in</strong> body-weight ga<strong>in</strong> (males, 61%; and females, 55% of control values) was recorded <strong>in</strong> dogs at<br />

ATRAZINE 37–138 JMPR <strong>2007</strong>

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