Guidelines for Metals and Metalloids in Ambient ... - ARCHIVE: Defra

Arsenic
86. Some toxicologists believe that arsenic does not act by direct reaction
with DNA but rather by interfering with DNA synthesis. Inhibition of
DNA replicative mechanisms and effects on repair mechanisms
could explain the chromosomal effects of arsenic and synergism with
DNA-reactive chemicals. Other mechanisms for the carcinogenicity of
arsenic have, on the basis of experimental evidence, been suggested;
they include clastogenicity (chromosomal breakage) and mutagenicity
(changes in the structure of genetic material). No single hypothesis has
attracted universal support.
87. Recent studies have also suggested that DMA, a major metabolite of
ingested inorganic arsenic in mammals, may initiate carcinogenesis in
a number of organs (Yamanaka et al., 2004; Wanibuchi et al., 2004).
The methylation of trivalent arsenic has been associated with DNA
damage and activation of AP-1 dependent gene transcription
(Styblo et al., 2002). However, it is unclear if these metabolites are
present in sufficient quantities or length of time to induce toxicity
(Schoen et al., 2004).
2.3.3.2 Humans
88. Human genotoxic effects, manifest as an increase in risk of
chromosomal abnormalities in peripheral leucocytes, have been
reported from one population, employed in a Swedish copper smelter.
No associated exposure estimates were presented (Beckman et al.,
1977) and it not clear that the effects were attributable to arsenic
exposure. Trivalent arsenic may be more genotoxic to human
lymphocytes than pentavalent arsenic (Nordenson et al., 1981).
89. Close attention has been paid to the carcinogenic effects of inhaled
arsenic in the workplace; and in particular to the risk of lung cancer.
This in part may reflect the relative ease with which secondary
(mortality) data can be collected. Workers exposed to arsenic may also
be exposed to other carcinogens such as tobacco smoking or other
workplace toxins. These need to be accounted for although this is
commonly not the case in published studies.
90. There is some information suggesting that those who lived in the
vicinity of smelters had an increased risk of lung cancer (Pershagen,
1985). When taken together with the studies of developmental defects
mentioned below, these indicate a need to control non-occupational
airborne exposures but the available data on exposure levels would not
be helpful in standard setting.
91. Increased risks of lung cancer attributed to arsenic have been reported
in serial studies of the workforces of two US and one Swedish smelters
(Enterline et al., 1995; Lee-Feldstein, 1986; Jarup et al., 1989); and in
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