Biomedical Engineering Reference
In-Depth Information
Syndrome (FAS). There are specific craniofacial abnormalities that are
commonly associated with FAS, including a smooth philtrum (groove
between nose and upper lip), thin upper lip, and small palpebral fissures,
where the eye width is shortened (Jones and Smith, 1973). Neurological
and functional impairments can also result from fetal EtOH exposure
(Jones, 2011). It is difficult to determine the exact dose of EtOH in
humans that leads to FASD, precluding a direct comparison of drug
potency with MeOH, for which no human developmental effects have
been reported. EtOH, like MeOH, is teratogenic in mice and similarly
exhibits strain differences in teratogenicity (Abel, 1982; Gilliam et al.,
1987; Becker and Randall, 1989; Mattson et al., 2001). Our studies
further investigating species- and strain-specific differences in suscepti-
bility to both EtOH and MeOH are discussed later in Section 7.3.
7.1.3 Carcinogenic Potential
EtOH consumed in alcoholic beverages is regarded as carcinogenic in
humans based on epidemiological evidence (NTP, 2002; IARC, 2006;
AICR, 2007). Mechanistic evidence supporting a causal role of acetal-
dehyde in alcohol-related esophageal cancer comes from studies in
aldehyde dehydrogenase-2 (ALDH2)-deficient individuals who con-
sume large quantities of alcoholic beverages (Baan et al., 2007; Brooks
et al., 2009). However, there is a fundamental difference between EtOH
and MeOH in that the majority of primary exposures to MeOH of
toxicological interest, other than accidental poisonings from oral
ingestion, will occur via exposure to vapors or dermal contact of the
skin. It is important to keep this fundamental difference in mind as the
exposure to EtOH in subsets of the human population will be orders of
magnitude higher than that following environmental and/or industrial
exposure to MeOH, and this factor is central to any assessment of risk
even if these agents share a common potential mechanism of initiation
owing to structural or biochemical similarities. Among other
unappreciated possibilities, MeOH could theoretically cause cancer
either by the covalent binding of its reactive formaldehyde metabolite to
DNA, or via the formation of highly reactive and potentially toxic forms
of oxygen termed reactive oxygen species (ROS) and ROS-initiated
