Reaction mass of glycerol and methanol and Fatty acids, vegetable-oil

Endpoint summary

Additional information

Methanol:

In vitro studies:

Methanol has been examined in numerous tests including bacterial, mammalian and fungal test systems. Most studies failed to demonstrate mutagenic activity, with four exceptions: 1) in Salmonella tester strain TA 102, a questionable positive response was observed (DeFlora et al., 1984); 2) in a DNA damage and repair assay with E. coli WP strains (repair proficient and deficient types), the result was considered ambiguous (DeFlora et al. 1984b); 3) in a mouse-lymphoma assay, a significant increase in the mutation rate was reported at 7.9 mg/mL methanol (McGregor et al., 1985); and 4) in a test of mitotic chromosomal segregation in Aspergillus nidulans, a positive result was observed (Crebelli et al., 1989). All other studies produced consistently negative results (Shimizu et al., 1985; DeFlora, 1981; NEDO, 1987; Lasne et al., 1984).

In vivo studies:

The available in vivo assays are negative for mutagenicity and clastogenicity. Some of these assays were conducted under specific stress conditions using folate-deficient mice (Am. Petrol. Inst., 1991; Fu, 1996).

In conclusion, the majority of in vitro and in vivo assays on methanol are negative for mutagenicity and clastogenicity. However a few of the in vitro assays were positive or ambiguous (DeFlora et al., 1984a, 1984b; McGregor et al., 1985; Crebelli et al., 1989). The positive findings can not be evaluated since the available data base is limited.

Potassium hydroxide:

The in vitro genetic toxicity tests indicated no evidence of mutagenic activity. In addition, both the in vitro and the in vivo genetic toxicity tests with the structurally related sodium hydroxide indicated no evidence of mutagenic activity. According to the REACH Regulation, further in vivo mutagenicity studies shall only be considered in case of a positive result in genotoxic (in vitro) studies (column 2, Annexes VII, VIII). Therefore, further in vivo testing for mutagenicity is not relevant for potassium hydroxide.

Moreover, it is technically not feasible to perform genotoxicity tests at physiological pH with KOH.

Overall, the registered is considered to be not genetically toxic.

Short description of key information:
Methanol:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): S. typhimurium negative except TA 102+S9 (ambiguous) (OECD 471)
Gene mutation (Mammalian cell gene mutation assay): V79 negative, L5178Y+S9 positive (both comparable to OECD 476)
Chromosome aberration (in vitro micronucleaus assay): V79 negative
DNA damage (Damage and repair assay in bacteria): E. coli positive
Genome mutation (Mitotic chromosomal segregation assay): A. nidullans positive

In vivo:
Chromosome aberration (Chromosomal aberration): primary lung cells negative
Chromosome aberration (Micronucleus assay): erythrocytes negative (similar OECD 474), primary lung cells negative
Chromosome aberration (Synaptonemal complex): pachytene spermatocytes negative

KOH:
It is impossible to perform the test at physiological pH when KOH is added.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the negative results in the in vivo studies, methanol does not seem to be mutagenic. Furthermore, carcinogenicity studies indicated no evidence of a carcinogenic potential in rats and mice exposed to methanol. No need for classification.