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EC number: 446-620-9
CAS number: 120983-72-4
JAU 6476-Chlormethylketon was administered in the diet to 6 male and 6 female Wistar rats per dose group in concentrations of 0, 10, 100 and 500 ppm for a period of 8 weeks. The same number of rats received 1000 ppm starting one week later for 7 weeks.
This study was intended as an exploratory feeding study for the dose selection for a 1 generation study.
Investigations on blood samples were performed. Organs and tissues were subjected to gross and histopathological investigations in liver, spleen, kidney and stomach (done in 0, 10, 100 and 500 ppm rats only). Selected organs (liver, spleen, kidneys) were weighed. The test substance was homogeneously distributable in the diet. Based on analytically established instability of test substance in the diet averaged dose levels of maximally 67, 335 and 670 ppm were roughly estimated for the 100, 500 and 1000 ppm concentrations. Consequently the diet as administration route has turned out to be inadequate.
In summary there were no remarkable effects at 10 ppm except the decrease of liver weights in males, which is not considered to reflect an adverse effect as corresponding histopathologically or biochemical findings are lacking. From 100 ppm onwards effects on the kidneys were evident and APh plasma activities were decreased. At 500 ppm and above body weights, blood parameters and liver were affected and clinical findings indicated poor general condition. At 1000 ppm more prounouced toxicity was evident.
As the test substance had turned out to be strongly instable in the diet caused by its high volatility the outcome of this study is limited (especially for the 10 ppm group) and cannot be used for setting a doubtless NOEL or NOAEL. However, following rough estimations of the decrease of the test substance content during a feeding period of 7 days the concentration of about 67 ppm (instead of 100 ppm) corresponding to 35.0 (males) and 36.3 mg/kg body weight per day (females) could be expected to be the LOAEL under the conditions described.
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