Biomedical Engineering Reference
In-Depth Information
in frequencies of micronuclei in blood cells, sister-chromatid exchange,
chromosome aberrations of micronuclei in lung cells or of synaptone-
mal complex damage in spermatocytes was noted (Campbell et al.,
1991). Methanol did not induce chromosomal aberration, SCE, or
increase in micronucleus in tests conducted by NEDO (1986). Methanol
was also tested and gave negative results in two human cell line [MCF-
7, HepG2] (Ohno et al., 2005). Urine from mice given 5000mg/kg bw
for 5 days showed no mutagenic activity (Chang et al., 1983).
Micronucleus assay was performed in normal and folate-deficient
mice, 10 per group, following four daily doses of 0, 300, 600, 1200, or
2500mg/kg methanol. No indication of genotoxic potential was
observed in normal and folate-deficient mice (O'Loughlin et al., 1992).
Methanol was positive in mouse in both chromosomal aberration and
micronuclei in erythrocytes assay and in structural chromosome aber-
ration in bone marrow (IPCS, 1997).
Methanol does not appear to be genotoxic based on the majority of in
vitro and in vivo testing reported in the literature. Methanol treatment
does not appear to affect blood formaldehyde levels or the rate of
breakdown of formaldehyde in vivo in animals.
Formaldehyde, the metabolite of methanol is considered a genotoxic
in vitro but is generally not genotoxic in vivo assays.
In a recent elegant study, Lu et al. (2012) has shown that in rats
exposed orally for 5 days to 500mg/kg or 2000mg/kg of labeled
methanol (
13
CD
4
) had a dose-related increase in exogenous labeled
formaldehyde hydroxymethyl DNA adducts, derived from labeled
methanol (
13
CD
4
), in multiple tissues (liver, lung, kidney, spleen,
thymus, bone marrow, and WBC). The level of exogenous hydroxy-
methyl formaldehyde DNA adducts derived from methanol was similar
to the endogenous formaldehyde hydroxymethyl DNA adducts, nor-
mally found in all tissues in the rats dosed at 500mg/kg. However, in the
rats dosed at 2000mg/kg the level of exogenous formaldehyde hydrox-
ymethyl DNA adducts derived from methanol were higher (
two- to
fivefold) than levels found in rats dosed at 500mg/kg. In the bone
marrow, the exogenous formaldehyde hydroxymethyl formaldehyde
DNA adduct level was higher than the endogenous formaldehyde
hydroxymethyl DNA adducts levels. This study suggests that methanol
