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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Magnesium methanolate rapidly hydrolyzes in aqueous environments. Toxicity is mediated by its degradation products MeOH and Mg(OH)2 and assessed for these products.

MeOH

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

Mg(OH)2

Three key studies were carried out on magnesium hydroxide: gene mutation in bacteria, cytogenicity in mammalian cells and gene mutation in mammalian cells. The results of all these studies were negative.

Genetic toxicity in vivo

Description of key information

Magnesium methanolate rapidly hydrolyzes in aqueous environments. Toxicity is mediated by its degradation products MeOH and Mg(OH)2 and assessed for these products.

MeOH

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

Mg(OH)2

Magnesium hydroxidedoes not have any mutagenic effects in vitro. Therefore, further testing for mutagenicity in vivo is not warranted.

Additional information

MeOH

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.

Mg(OH)2

Magnesium hydroxide does not have any mutagenic effects in vitro. Therefore, further testing for mutagenicity in vivo is not warranted.

Justification for classification or non-classification

Magnesium methanolate

Magnesium methanolate rapidly hydrolyzes in aqueous environments. Toxicity is mediated by its degradation products MeOH and Mg(OH)2 and assessed for these products.

Both hydrolysis products should not be classified for genetic toxicity. Based on the available information, magnesium methanolate thus does not have to be classified and has no obligatory labelling requirement for

genetic toxicity.

MeOH

Based on the negative results in the in vivo studies, methanol does not appear to be mutagenic. No need for classification.

Mg(OH)2

Three studies were carried out on magnesium hydroxide according to current guidelines and under GLP: a bacteria reverse mutation study, an in vitro gene mutation assay in mammalian cells, and an in vitro chromosome aberration test. The results of all of these studies were negative. No need for classification.