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

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75<br />

Table 15. Relevant f<strong>in</strong>d<strong>in</strong>gs <strong>in</strong> a study of prenatal developmental toxicity <strong>in</strong> rats given DEA<br />

by gavage<br />

F<strong>in</strong>d<strong>in</strong>g<br />

Dose (mg/kg bw per day)<br />

0 5 25 100<br />

Food consumption (g/day):<br />

Days 6–11 23 22 21* 16**<br />

Days 11–16 26 25 26 24<br />

Body-weight ga<strong>in</strong> (g):<br />

Days 6–11 26.0 24.3 21.5* 10.7**<br />

Days 11–16 39.7 39.8 37.3 34.5*<br />

Net body-weight change (g) from day 6 37.1 31.9 27.2 29.5<br />

No. of animals pregnant 23 23 22 24<br />

Postimplantatation loss (mean) 0.6 0.8 0.9 1.1<br />

Postimplantation loss (%) 4.0 5.1 6.3 8.8<br />

Mean No. of live fetuses 14.2 14.5 14.2 12.6<br />

Mean fetal weights (g), males/females 5.7/5.3 5.6/5.3 5.8/5.4 5.6/5.3<br />

Skeletal exam<strong>in</strong>ation (No. of fetuses/litters) 168/23 174/23 164/22 158/24<br />

Fused sternebrae 1 and 2 a 2/2 1/1 2/2 32**/14**<br />

Total skeletal anomalies a 5/5 5/5 5/5 41/18**<br />

Poster. digit 5, proximal phalanx; absent ossification a 16/11 23/12 8/6 28*/16<br />

Total skeletal variations a 168/23 173/23 163/22 158/24<br />

From Marty (1992b)<br />

DEA, deethyl-atraz<strong>in</strong>e.<br />

a<br />

No. of fetuses/litters.<br />

* p < 0.05; ** p < 0.01.<br />

s<strong>in</strong>gle dose at 250, 500, 2000, 3500 or 5050 mg/kg bw by gavage. Each group consisted of five males<br />

and five female with the exception of the group at the lowest dose that consisted of five females. The<br />

rats were observed for cl<strong>in</strong>ical signs and mortality for 14 days. The LD 50<br />

s for males, females and both<br />

sexes comb<strong>in</strong>ed were 2290, 810 and 1240 mg/kg, respectively (Kuhn, 1991d).<br />

In a short-term study of oral toxicity, which complied with GLP and the test guidel<strong>in</strong>es of<br />

OECD and US EPA, groups of 10 male and 10 female KFM-WIST rats were fed diets conta<strong>in</strong><strong>in</strong>g DIA<br />

(purity, 97.4%) at a concentration of 0, 50, 500 or 2000 ppm, equal to 0, 4.6, 46.5 and 161.2 mg/kg bw<br />

per day <strong>in</strong> males and 0, 4.6, 49.7 and 164.7 mg/kg bw per day <strong>in</strong> females, for 4 weeks.<br />

There was no mortality. Cl<strong>in</strong>ical signs of restlessness were observed <strong>in</strong> the rats at the highest<br />

dose dur<strong>in</strong>g the fourth week of treatment. At 2000 ppm, <strong>food</strong> consumption was reduced by approximately<br />

60% dur<strong>in</strong>g the first week of treatment and by about 40% over the 4-week treatment period.<br />

Body weights were significantly reduced at 500 ppm from the third week and from the second week<br />

at 2000 ppm; after 4 weeks the body weights at 2000 ppm were reduced by 34% (males) and 28%<br />

(females) when compared with rats <strong>in</strong> the control group. Slight changes <strong>in</strong> haematological and cl<strong>in</strong>ical<br />

biochemistry parameters were observed <strong>in</strong> the groups at the <strong>in</strong>termediate and highest dose, with<br />

<strong>in</strong>dication of a compensated haemolytic anaemia <strong>in</strong> the group at the highest dose. Absolute and relative<br />

thymus weights were reduced at 500 ppm <strong>in</strong> males and at 2000 ppm <strong>in</strong> both sexes. No treatmentrelated<br />

histopathological f<strong>in</strong>d<strong>in</strong>gs were noted <strong>in</strong> the groups at the lowest and <strong>in</strong>termediate dose. At<br />

2000 ppm, m<strong>in</strong>eralized deposits were noted <strong>in</strong> the renal pelvis of four males and two females, and a<br />

m<strong>in</strong>imal erosion of the gastric mucosa was noted <strong>in</strong> one male.<br />

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

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