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Description of key information

28-day subacute repeated dose study: oral: LOAEL = 50 mg/kg/day

Key value for chemical safety assessment

Additional information

The objective of this study was to evaluate the potential toxicity of the test substance, 2,6 -dichloro-4 -trifluoromethylaniline (DCPTFMA) when administered daily by oral route to Sprague-Dawley rats for 4 weeks. This study was performed similar to the OECD guideline 407. Three groups of 6 male and 6 female Sprague-Dawley rats received daily the test substance by gavage, at doses of 50, 160 or 500 mg/kg/day. An additional group of 6 males and 6 females received the vehicle alone and acted as a control group. Clinical signs and mortality were recorded daily. Body weight and food consumption were recorded weekly. Haematology, blood biochemistry and urinanalysis were performed on week 4. At the end of the treatment period, all the animals were sacrificed and were submitted to a complete macroscopic examination. Organs were weighed, tissues were preserved and microscopic examination was performed on designated tissues. Ptyalism was observed at all dose levels, with a dose-related latency. No mortality was observed during the treatment period. No effects upon the food consumption were observed during the treatment period. A lower mean body weight gain was observed in males given 500 mg/kg/day when compared to that of respective controls. Concerning the haematology and urinanalysis, no abnormalities of toxicological importance were observed in treated animals. A moderate higher total protein, total cholesterol, triglyceride and aminotransferases (ASAT, ALAT) activities were observed in males and/or females given 500 mg/kg/day. A moderate lower alkaline phosphatase activity was observed in animals of both sexes given 500 mg/kg/day. A dose-related increase in absolute and relative liver weights was noted. Enlarged liver, sometimes associated to an accentuated lobular pattern or punctiform greyish/whitish foci, was noted in animals given 160 or 500 mg/kg/day. A dose-related hepatocellular hypertrophy, sometimes associated to a minimal to moderate focal or multifocal hepatocellular degeneration/necrosis was observed in all the treated groups, and accumulation of acidophilic globules in the cortical tubular epithelium of kidneys was noted with an higher incidence and severity in males given 160 or 500 mg/kg/day.

Because of the liver effects observed in the low dose group, considered to be adverse (interlobular fibrosis in 3/6 males, cholangiofibrosis in 1/6 males, zonal coagulative hepatocellular necrosis in 1/6 males and minimal focal or multifocal hepatocellular degeneration/necrosis in another 1/6 males), the LOAEL is set at the lowest dose, 50 mg/kg bw.

Justification for classification or non-classification

The test substance induced adverse liver effects in the lowest dose tested. As a consequence, 2,6 -dichloro-4 -trifluoromethylaniline has to be classified as Xn; R48 according to Directive 67/548/EEC and with STOT RE cat.2; H373 according to Regulation (EC) No. 1272/2008.