Organohalogen concentrations and a gross and histologic ...

of CYP-450 activity that impact circulating sex hormone levels (e.g. estrogens
and androgens) (e.g AMAP 2002, Birnbaum 1994, Damstra et al. 2002, de
March et al. 1998, Lind et al. 2003, Lind et al. 2004, Navas and Segner 1998).
Such an endocrine modulation by organohalogen compounds has earlier
been demonstrated for polar bears (Ursus maritimus) (e.g. Letcher et al. 1996).
The negative correlation between organohalogen compounds (e.g. 4,4’-DDE)
and BMD have earlier been described in humans (e.g. Beard and Jong 2000;
Glynn et al. 2000).
In conclusion on the skull measurements of FA and BMD, we found a lower
bone mineral density (high stress) and a low FA (low stress) in the skulls
collected 1961-2002 when compared to 1892-1960 and therefore the two
studies do not support each other. The skulls investigated for BMD and FA
were the same and environmental factors such as nutrition status, nutrition
composition, climate oscilliations and pollution did not differ between the
two studies. The different response in FA and BMD parameters over the two
parameters could therefore be due to different sensitivity and/or specificity
of these two variables to reflect stress.
Both renal and liver lesions showed clear relationships to age (increasing) and
for renal lesions these were more frequently observed in old females and
with higher severity which may be a result of a more systemic exposure to
organohalogens due to adipose mobilization and storage dynamics associated
with reproductive cycle periods of fasting and lactation (e.g. Polischuk
et al. 1995, 2002). Other aetiological factors like infectious agents and
food composition may have played a role as well and we could not conclude
whether or not organohalogen pollution or mercury was a co-factor in the
development of the lesions. Concentrations used in the acute toxicity studies
were significantly larger compared to the chronic sublethal exposure of the
polar bear but on the other hand, the polar bears were exposed to a broad
mixture of organohalogens which may have increased the risk for organohalogen
induced histopathological changes.
As depicted in Fig. 10 the hepatic and renal lesions may have a relation to
organohalogens based on the morphology of the histopathological changes.
The hepatic lipid accumulation was not comparable to lipidosis while there
were several similarities between the renal lesions and glomerulonephritis in
humans, laboratory mammals and wildlife. For example chronic nephritis
induced by organic solvents in humans have been proposed to be of autoimmune
origin due to chronic base membrane injury to kidney and/or lung
epithelium. This could theoretically be some of the same mechanisms involved
in the aetiology and pathogenesis of the renal lesions in the present
East Greenland polar bears.
Furthermore, the indications of a difference in BMD between different degrees
of renal lesions could indicate a damage to the proximal kidney due to renal
osteodystrophy (osteoporosis) (Friberg et al. 1986, WHO, 1992). However, the
sample size was low and therefore the result is not reliable but needs a higher
sample size in the future. Whether the significant relation between renal and
hepatic mononuclear cell infiltrations as well as the similarities with earlier
studies of organohalogen induced lesions and the negative correlation between
BMD and organohalogens supports a broader theory of organohalogen
toxicity, remains unanswered. A controlled case-control, dose-response study
is needed to make firm conclusions on these potential relationships
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