STRmix™ collaborative exercise on DNA mixture interpretation.

An intra and inter-laboratory study using the probabilistic genotyping (PG) software STRmix™ is reported. Two complex mixtures from the PROVEDIt set, analysed on an Applied Biosystems™ 3500 Series Genetic Analyzer, were selected. 174 participants responded. For Sample 1 (low template, in the order of 200 rfu for major contributors) five participants described the comparison as inconclusive with respect to the POI or excluded him. Where LRs were assigned, the point estimates ranging from 2 × 104 to 8 × 106. For Sample 2 (in the order of 2000 rfu for major contributors), LRs ranged from 2 × 1028 to 2 × 1029. Where LRs were calculated, the differences between participants can be attributed to (from largest to smallest impact): This study demonstrates a high level of repeatability and reproducibility among the participants. For those results that differed from the mode, the differences in LR were almost always minor or conservative.

Impairment of cellular immunity in west Greenland sledge dogs (Canis familiaris) dietary exposed to polluted minke whale (Balaenoptera acutorostrata) blubber.

Minke whale (Balaenoptera acutorostrata) blubber is rich in organohalogen contaminants, mercury, and n-3 fatty acids. In the present study we show that a daily intake of 50-200 g of minke whale blubber causes an impairment of the nonspecific and specific cellular immune system in the West Greenland sledge dog (Canis familiaris). Immune reactions were measured by mitogen (PHA, Con A) and antigen (KLH) intradermal testing, and as the study used exposure levels similar to those of Inuits and polar bears (Ursus maritimus), it is reasonable to infer that Inuits and polar bears suffer from similar decreased resistance to diseases. It is speculated that food sources are depleted by thinning sea ice due to climate change and that more research should assess the forecasted rise in additive immunopathy effects in polar bears. Additionally, our study suggests that the fatty acid composition may be of importance when investigating combined immunotoxic effects of contaminated food resources in future Inuit and polar bear studies.

Endocrine disruption induced by organochlorines (OCs): field studies and experimental models.

Long-range transport of persistent organic compounds by air and ocean currents from industrialized areas resulted in high levels of these pollutants in food webs in the Svalbard area. With the aim to test if organochlorine (OC) exposure in free-living polar bears from Svalbard affected their plasma steroid hormone concentrations, it was found that polychlorinated biphenyls (PCBs) were associated with increased progesterone levels in females. The sum of pesticides (sigma pesticides) and sigma PCBs contributed significantly negative to the variation of the plasma testosterone in males, and the overall contribution of the OCs to the plasma cortisol variation was negative. A second objective was to study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health as a consequence of effects on endocrine-regulated functions such as reproduction and immunity in a goat model focusing on long-term and low-level exposure during the periods of fetal development and in the neonatal period. Additionally, acute exposure was studied in adult mice. The results indicated that exposure to low doses of PCB 153 in utero and in the suckling period influenced reproductive functions and both PCB 153 and PCB 126 exerted immunomodulatory effects on the offspring, whereas acute exposure of adult mice had minor effects on male reproductive function.

Perinatal exposure to low doses of PCB 153 and PCB 126 affects maternal and neonatal immunity in goat kids.

Pregnant does (10 goats/group) were dosed orally either with polychlorinated biphenyl (PCB) 153 (98 microg/kg body weight/d) or PCB 126 (ng/kg body weight/d) dissolved in corn oil or with corn oil only (control group) from gestation day (GD) 60 until delivery. An additional group (n = 5) of pregnant does received the synthetic estrogen diethylstilbestrol (DES; 0.4 microg/kg body weight/d) by intramuscular injection using the same treatment schedule as for the PCB groups. Blood samples for immune analysis were collected at wk 0, 1, 2, 4, 6, and 8 of age. The effects of perinatal PCB exposure on postnatal humoral immune responses were examined by assessing the levels of total immunoglobulin G (IgG) and immunoglobulins to specific microbes at wk 0, 1, 2, 4, 6, and 8 of age, and immune responses following immunization of kids at 2 wk of age. PCB 153 exposure suppressed maternal and neonatal immunity, as demonstrated by reduced transfer of maternal IgG and specific antibodies to the environmental microbes Arcanobacterium pyogenes, Mannheimia haemolytica, and reovirus (REO-1). Furthermore, PCB 153 reduced the level of maternal antibodies to Mycobacterium avium paratuberculosis and equine influenza virus (EIV-1) in the newborn kids. The antibody response against EIV-1 was significantly higher in PCB 153-exposed kids 2 wk following immunization. PCB 126 exposure reduced the levels of maternal antibodies to REO-1. In contrast, gestational exposure to PCB 126 increased the concentrations of maternal antibodies to tetanus toxoid. No differences from controls in plasma total IgG levels at birth or colostrum IgG concentrations were observed in the PCB 126-treated does. However, a significant reduction in IgG levels from GD 60 until delivery was found in this group. Gestational exposure to DES reduced the concentrations of maternal antibodies against A. pyogenes, M. haemolytica, M. avium Paratuberculosis, and REO-1. These results suggest that perinatal exposure to low doses of PCB 126 and PCB 153 affects the maternal immunity in kids. The difference in responses between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms. The observation that the effects produced by PCB 153 resembled those produced by DES raises the question of whether this congener may modulate immunity by estrogenic mechanisms.

Levels of PCB 126 and PCB 153 in plasma and tissues in goats exposed during gestation and lactation.

The aim of the present study was to gain knowledge about the disposition of the PCB congeners 126 and 153 in a goat model where pregnant does were given oral doses of PCB from day 60 of gestation until delivery. The goat kids were thus exposed to PCB during gestation and lactation. The doses of PCB 153 and PCB 126 were 98 and 49 ng/kg body wt/day, respectively. PCB levels were measured in plasma from the does at day 90 of gestation and at delivery, and in plasma from the kids at birth and four weeks post partum. Concentrations of PCB were analysed in brain, liver and fat tissue from the does six weeks after delivery and in liver and fat tissue from the kids at nine months of age. The ratio of estimated body burden to ingested dose in the does, was 0.95 +/- 0.07 for PCB 153 and 0.41 +/- 0.03 for PCB 126. Approximately 9% of PCB 153 and 6% of PCB 126 was transferred from the mothers to their kids during gestation and lactation. Prenatal exposure contributed to a much lower fraction of the body burden than postnatal PCB intake via milk, due to the fact that almost 100% of the PCB 153 transferred from the does to kids was transferred via milk, and the PCB 126 intake via milk was threefold higher than the calculated body burden. The hepatic PCB 126 concentration in both does and kids was significantly higher than the concentration in fat, in contrast to PCB 153, where the highest concentrations were found in fat. A significant difference in body burden between the does at delivery, the newborn kids, and the kids at four weeks of age, did not influence the plasma concentration of PCB 153 on a fat weight basis, which showed no difference with sampling time. Our results suggest that PCB 126 and PCB 153 have different pharmacokinetic properties. The higher levels of PCB 126 in liver tissue compared to fat tissue confirm the concept of hepatic sequestration. The similar blood concentration of PCB 153 in the does at delivery and their newborn kids despite the considerable difference in body burden, suggests a high degree of placental transfer. This supports previous observations that low molecular weight, lipid-soluble, non-polar chemicals reach the fetus to the greatest possible extent. For PCB 153, the body burden may provide the appropriate dose metric at steady state, but may give a minor underestimation of PCB 126 at low environmental exposure levels due to hepatic sequestration.