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Key value for chemical safety assessment

Additional information

Genotoxicity in vitro:

Two studies were available: one with relaibilty 1 (GLP study, Hoechst, 1988) and another one with reliability 2 (Haworth, 1983). They were selected as key studies.

In these reverse gene mutation assays in bacteria, strains TA98, TA100, TA1535, TA1537 and TA1538 of S. typhimurium were exposed to paradimethoxybenzene at concentrations of 0 to 5000 µg/plate in the presence and absence of mammalian metabolic activation (rat or hamster liver cells).

Paradimethoxybenzene was tested up to cytotoxic concentrations.

The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence of induced mutant colonies over background in these two studies.

Genotoxicity in vivo:

Only one study (Hoechst, 1996) was available and was selected as key study.

The micronucleus test was performed with Paradimethoxybenzene, according to the OECD 474 guideline under GLP conditions.

The test compound was suspended in starch mucilage and was given once as an orally dose of 2000 mg/kg bw to male and female NMRI mice, based on the results of a preliminary study.

According to the test procedure, the animals were killed 12, 24 or 48 hours after administration.

Endoxan (cyclophosphamide in distilled water) was used as positive control substance and was administered once orally at a dose of 50 mg/kg bw.

The number of polychromatic and normochromatic erythrocytes containing micronuclei was not increased. The ratio of polychromatic/normochromatic erythrocytes in both male and female animals remained unaffected by the treatment with Paradimethoxybenzene and was statistically not different from the control values.

Positive control induced in both males and females a marked statistically significant increase in the number of polychromatic cells with micronuclei, indicating the sensitivity of the test system. The ratio of polychromatic erythrocytes to normocytes was not changed to a significant extent.

Under the test conditions, the results indicate that Paradimethoxybenzene is not mutagenic in the micronucleus test.


Short description of key information:
Negative results in Ames test with and without metabolic activation (Hoechst, 1988; Haworth, 1983).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification