Combined Actions and Interactions of Chemicals in Mixtures

eaction with sulfhydryl groups). Therefore, the possibility for interactions is
potentially great (Cassarett & Doull, 1986).
Lead, mercury and manganese exhibit interaction with other neurotoxicants, possibly
via kinetic mechanisms. Ethanol may increase the absorption of lead from the
gastrointestinal tract (Barton & Conrad, 1978). Cadmium and lead absorption is
increased in individuals with low iron status (Flanagan et al., 1978, Berglund et al.,
1994, Watson et al., 1980).
The neurotoxicity of toxic metals may be reduced by chelation with chelators as
EDTA, n-acetyl-D-penicillamine, dimercaptosuccinic acid, and 2,3dimercaptopropane
(Goyer et al., 1995).
7.6.6.4 Pesticides and manganese
Many epidemiological investigations demonstrate a relation between exposure to
pesticides and increased incidence for the development of Parkinson’s disease (Ho
et al., 1989; Koller et al., 1990, Semchuk et al., 1992, Gorell et al., 1997, Golbe,
1998, Gorell et al., 1998, Tüchsen & Jensen, 2000, Engel et al., 2001).
Inhalation exposure to manganese is known to induce symptoms of Parkinson’s
disease (Parkinsonism, manganism) (Zayed et al., 1990, Calne et al., 1994, Gorell
et al., 1997). The underlying mechanisms are not known in details (Veldman,
1998), but are proposed to include elements different from those supposed to be
related to Parkinson’s disease (Arlien-Søborg, 2001). Because of the similarity in
effect, a potential for interaction between pesticides and manganese in the
development of symptoms of Parkinson’s disease exists. However, this potential
has not been investigated.
7.6.6.5 PCB
Polychlorinated biphenyl (PCB) is a mixture of compounds, which may possess
individual effects on the nervous system as well as exhibit interaction phenomena.
Developmental neurotoxicity involving cognitive and behavioural disturbances has
been implicated following perinatal exposure to environmental pollutants through
fish. Mainly PCBs have been implicated (Jacobson & Jacobson, 1996). There are
several studies, which show that PCBs produce a wide spectrum of neurochemical
and neuroendocrine effects in animals. Ortho-substituted PCB congeners affect brain
neurochemistry, while non-ortho-substituted PCBs having dioxin-like activity may
have little or no activity in the nervous system (Tilson & Kodavanti, 1997). However,
the fish contains a mixture of methylmercury, arsenic, lead, PCBs, DDT and DDE,
and effects may be the end result of additive or synergistic interaction between these
components (Mergler et al., 1997).
7.6.6.6 γ-diketones
When γ-diketone precursors are co-administered, the neurotoxic effect observed
equals the sum of effects caused by the individual substances.
7.6.6.7 Glutamate agonists
Injection of the glutamate agonist NMDA prior to injection of the causative agent for
shellfish poisoning, domoic acid, which is also a glutamate agonist, potentiates the
acute neurotoxicity of domoic acid in mice by a factor less than two (Tasker & Strain,
1998). This is an example of toxicodynamic interaction at the level of the glutamate
receptor.
7.6.6.8 Physical stimuli
Physical stimuli may interact with the neurotoxicity of chemicals. One example is the
increased hearing loss caused by interaction between organic solvents and noise
(Morata et al., 1993).
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