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E-M:/ Synergism of PCB's and methylmercury

------------------------------------------------------------------------- Enviro-Mich message from Tracey Easthope -------------------------------------------------------------------------
A new study in Environmental Health Perspectives finds synergistic effects in laboratory animals exposed to both PCB's and methylmercury. The authors conclude: "The synergism between these contaminants suggests that future revisions of fish- consumption guidelines should consider contaminant interactions."
This study raises questions about the adequacy of current advisories in Michigan.
Apparently another study by Dr. Stewart at SUNY Oswego (New York) which is attempting to confirm the Jacobsen results finds the same synergistic effect.

Jeffrey C. Bemis and Richard F. Seegal. Polychlorinated Biphenyls
and Methylmercury Act Synergistically to Reduce Rat Brain
Dopamine Content in Vitro. Environmental Health Perspectives
Volume 107, Number 11, November 1999, pages 879-885.

Consumption of contaminated Great Lakes fish by pregnant women
is associated with decreased birth weight and deficits in cognitive
function in their infants and children. These fish contain many
known and suspected anthropogenic neurotoxicants, making it
difficult to determine which contaminant(s) are responsible for the
observed deficits. We have undertaken a series of experiments to
determine the relevant toxicants by comparing the neurotoxic
effects of two of these contaminants--polychlorinated biphenyls
(PCBs) and methylmercury (MeHg)--both of which are recognized
neurotoxicants. Striatal punches obtained from adult rat brain were
exposed to PCBs only, MeHg only, or the two in combination, and
tissue and media concentrations of dopamine (DA) and its
metabolites were determined by high performance liquid
Exposure to PCBs only reduced tissue DA and elevated media DA
in a dose-dependent fashion. Exposure to MeHg only did not
significantly affect either measure. However, when striatal punches
were simultaneously exposed to PCBs and MeHg, there were
significantly greater decreases in tissue DA concentrations and
elevations in media DA than those caused by PCBs only, in the
absence of changes in media lactate dehydrogenase
concentrations. Elevations in both tissue and media 3,4-
dihydroxyphenylacetic acid concentrations were also observed. We
suggest that the significant interactions between these two
toxicants may be due to a common site of action (i.e., toxicant-
induced increases in intracellular calcium and changes in second
messenger systems) that influences DA function. The synergism
between these contaminants suggests that future revisions of fish-
consumption guidelines should consider contaminant interactions.
[Online 7 October 1999]
{ HYPERLINK http://ehpnet1.niehs.nih.gov/docs/1999/107p879-

Discussion [Extract]
This study is part of a larger project to determine the neurologic
(i.e., behavioral and neurochemical) effects of developmental
exposure of laboratory rodents to the toxicants present in Great
Lakes salmon. Although the concentrations of PCBs and MeHg
used in these experiments are higher then those seen in Great
Lakes fish (PCB content ranged from 0.84 to 1.9 ppm, whereas
mercury concentrations were 0.34 ppm) (5,6), the concentrations of
these contaminants are similar to, or lower than, those used in
other in vivo and in vitro studies (18-21). Furthermore, some human
populations consume contaminated pilot whale meat that contains
PCB concentrations as high as 30 ppm and mercury levels in the
range of 3.3 ppm (22), well within our range of doses. As
presented, these results provide the first evidence of a significant
functional interaction between two of the major neurotoxicants
present in contaminated Great Lakes salmon and other freshwater
and marine species--PCBs and MeHg. To understand the potential
mechanisms for the interactions between these contaminants, it
is appropriate to first discuss the mechanisms by which the
individual contaminants alter DA function.
In summary, we have shown that exposure of rat striatal punches
to PCBs and MeHg decreases punch DA content and elevates
media DA levels to a greater extent than exposure to the single
toxicants alone in the absence of significant changes in media LDH
concentrations, which provides a recognized measure of both the
integrity of the plasma membrane and the viability of the striatal
punch. The magnitude of the decrease in punch DA content after
combined exposure to MeHg and PCBs (a 20-50% decrease
depending on the level of the contaminants studied) is not as great
as that seen in rat brain after developmental exposure to the
complex mixture of contaminants found in Great Lakes salmon
(10). Although there are methodologic differences between these
studies (e.g., in vivo vs. in vitro), we suggest that a major difference
is related to the greater number of putative neurotoxicants present
in the contaminated fish as compared to the two neurotoxicants
studied here. Examination of binary pairs of contaminants (e.g.,
MeHg + PCBs) is but a preliminary step in the investigation of the
neurotoxic potential of complex contaminant mixtures. Thus, we
have begun to examine functional interactions between PCBs and
other fish-borne contaminants, including the chlorinated pesticide
chlordane, and we demonstrated similar changes in striatal punch
DA function. Examination of the neurotoxic actions of tertiary and
higher order combinations of toxicants provides a logical next step
toward understanding the actions of complex mixtures of
environmentally relevant toxicants on nervous system function.
Thus, our results warrant examination of the impact of other
environmental mixtures on human health, suggest that future fish-
consumption advisories consider the likelihood that environmental
contaminants may act synergistically, and provide a strong
rationale for examining for possible interaction effects of this and
other contaminant mixtures in the intact developing animal.

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