Chlorimuron ethyl

Endpoint summary

Justification for classification or non-classification

Under the criteria of CLP Regulation [EC] No. 1272/2008, STOT RE may be assigned on the basis of a substance demonstrating evidence of significant or severe specific organ toxicity in a 90-day oral study at or below a guidance value of 100 mg/kg bw/day (basis of Category 2). This guidance value is adjusted in accordance with the Haber’s rule for studies of different durations. ‘Significant’ toxicity is taken to mean changes that clearly indicate functional disturbance or morphological changes that are toxicologically relevant. ‘Severe’ toxicity is considered to be more profound or serious and indicates changes that are of a considerably adverse nature with a significant impact on health. There is no evidence for any adverse findings or serious target organ toxicity in 90-day repeat dosing studies in rats, mice or dogs that meet the criteria of CLP Regulation [EC] No. 1272/2008 for STOT RE. The primary effects in these feeding studies were reductions in body weight in rats and dogs. The liver was the only organ affected histologically in rats and mice. Margination of hepatocyte cytoplasmic contents in the centrilobular areas occurred in rats; however, these changes were interpreted to represent a non-degenerative, adaptive response by the liver. In mice, centrilobular hepatocellular hypertrophy was observed. Although compound-related, these changes were not considered to be degenerative, but were interpreted to represent a hepatic metabolic adaptation. In dogs, evidence of a more specific and binary toxic effect was indicated first by a fulminant anemia with clinically evident pale gums and languid posture, erythrocytic changes and enlarged spleens accompanied by extra­medullary hematopoiesis and hyperplastic bone marrow in high-dose animals. The other primary toxic effect appears to be hepatic in nature and was exhibited as clinically icteric animals, hepatomegaly and blood chemistry changes in high-dose animals as well as correlative histopathology changes in mid- and high-dose animals. The dose levels for these findings were above STOT RE guidance value for Category 2. Therefore, the test substance is not classified for STOT RE according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.