N-nitro-N-(3-methyl-3,6-dihydro-2H-1,3,5-oxadiazin-4-yl)amine

Endpoint summary

Description of key information

A Klimisch-1-rated 28-days feeding study was conducted with rats in 1997. The study also included a recovery period of one month. At an approximate test substance intake of 85 mg/kg bw/d certain adeverse effects on liver and kidney were being observed. After discussing the observed effects, it is concluded that no classification of CA 2343 as to its repeated dose toxicity effects is necessary.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

85 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

At 5000 ppm test substance in the food (i.e. substance intake ca. 400 mg/kg bw/d), and also in some animals receiving 1000 ppm (ca. 85 mg/kg bw/d), changes to plasma levels of proteins, glucose, bilirubin, cholesterol, and triglycerides were noted and increased activities of liver enzymes were indicative of hepatotoxic and hepatotropic effects. This was confirmed by the major histopathologic findings of hepatocellular hypertrophy and necrosis. At 1000 ppm, slight hepatotropic effects were noted in both sexes. Slight nephrotropic effects in males were typical for an alpha- 2 -microglobulin accumulation. In some males slight hypocellularity of the bone marrow was observed. Reversibility was incomplete for hepatotropic effects, but was generally more pronounced in males than in females.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; urogenital: kidneys

Justification for classification or non-classification

A LOAEL of 85 mg/kg bw/day was being observed for both sexes, based on nominal concentrations. In the OECD-GHS classification system, the test substance basically could get classified as "Specific Target Organ Toxicity, category 2" (i.e. "harmful, R48/22" acc. to the DSD classification system) when during a 28 -d study on rats the result is 30 mg/kg bw/d > LOAEL > 300 mg/kg bw/d. However, the second condition for classification is that "significant organ damage" has to be observed. This is not considered to be the case here, since hypertrophy was the most severe effect reported, which is not assessed being a "significant organ damage". Furthermore these effects were was also partly reversible during the recovery period of one month, so full recovery deems to be possible if a longer recovery period would have been observed during the study. Overall, taking into account all of the arguments discussed above, no classification of test item CA 2343 is suggested as to its specific target organ toxicity.