The influence of zinc on apical uptake of cadmium in the gills and cadmium influx to the circulatory system in zebrafish (Danio rerio).

Zn (0-16 microM) effects on apical Cd uptake from the water into the branchial epithelium and influx of Cd from the water to the circulatory system in zebrafish (Danio rerio) were studied in three experiments. Apical Cd uptake was decreased by Zn in all three experiments. In fish exposed to 1-600 nM Cd (experiment 1), apical Cd uptake showed saturation kinetics at 2 and 4 microM Zn, and a competitive interaction was indicated. At 16 microMZn, Cd uptake increased linearly. Cadmium influx did not show saturation kinetics, but was inhibited by 16 microM Zn at low Cd exposure concentrations. In fish exposed to 0.1-600 nM Cd (experiment 2), Cd uptake was inhibited by 16 microM Zn, whereas at 30 nM Cd uptake was inhibited by 2 microM Zn. Similarly, 2 microM Zn did not influence Cd uptake in fish exposed to 0.1-2 nM Cd (experiment 3), whereas 2 microM Zn inhibited uptake at 8-30 nM Cd. Zinc also inhibited Cd influx at higher Cd concentrations. However, at lower Cd exposures, a Zn-induced increased influx was indicated. Zinc influences the Cd uptake and influx processes at several sites in the branchial epithelial cells, indicating that influx of Zn2+ and Cd2+ occurs through common pathways.

Influence of aluminium on the immune system--an experimental study on volunteers.

The purpose of this study was to examine whether oral exposure to aluminum (Al) can affect the human immune system. Eighteen healthy volunteers (mean age 42, 28-57 yr) were divided into a test group (9 females, 4 males) and a referent group (3 females, 2 males). Over 6 weeks, the test subjects ingested 10 ml of antacid (aluminum hydroxide, 59 mg Al/ml) three times daily. Aluminum was analyzed in urine before and during the exposure period (ICP-MS). Blood samples were used for analysis of lymphocyte subpopulations, mitogen-induced lymphocyte proliferation and in vitro production and circulating plasma concentrations of immunoglobulin (Ig) A, IgG, IgM, interleukin (IL) -2 and IL-4. Urinary Al concentration in the test subjects was approximately 10- to 20-fold higher than in the referent group during exposure. This indicates that ingestion of an Al-containing antacid is associated with an Al absorption far above that originating from food and drinking water. In both referents and test subjects the lymphocyte subpopulations, lymphocyte proliferation and the in vitro Ig and IL production showed similar, time-dependent changes before as well as during the exposure period. No major differences were seen between the referent and test groups regarding the immune parameters, except for a slightly smaller CD8+CD45R0+ population (primed cytotoxic T-cells), in the exposed individuals as compared to the referents. The results also show that subjects on antacid therapy may constitute a suitable population for studying biological effects of high-dose oral exposure to Al.

Redistribution of accumulated 2,3,7,8-tetrachlorodibenzo-p-dioxin during coxsackievirus B3 infection in the mouse.

The tissue redistribution of accumulated 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during infection was studied in adult male A/J mice using a common human virus coxsackievirus B3. Before infection (day 1), all mice were injected intraperitoneally (i.p.) with 1 microCi 3H-TCDD, corresponding to 0.5 microg TCDD kg(-1). One group was sacrificed before virus inoculation (day 0). Of the remaining mice, one subgroup was inoculated i.p. with CB3 virus while the other subgroup served as a noninfected control. On days 0, 4 and 7, the spleen, thymus, heart, pancreas, liver, white and brown adipose tissue, skeletal muscle, lung, kidney, brain, adrenals, thyroid, testes, epididymis and blood were sampled from infected and noninfected groups. Liquid scintillation was used to determine the 3H-TCDD-content of the tissues. The results showed that the accumulated TCDD was redistributed due to infection. The major changes occurred in the organs involved in the infectious process. In the target organs for coxsackievirus B3 (the pancreas and heart), the TCDD concentration peaked in relation to noninfected control values, concurrent with the development of inflammatory lesions (P<0.001 and 0.01, respectively for the heart and pancreas). The TCDD levels in the thymus increased three-fold during the infection to an estimated 0.5 pmol g(-1) tissue on day 7 of the infection, whereas the levels in noninfected mice did not change markedly (P<0.001). In the brain of infected mice, the TCDD concentration increased significantly with time, at day 7 reaching two-fold levels in comparison with noninfected controls (P<0.001). The findings suggest that a common infection causes redistribution of a previously accumulated environmental pollutant, resulting in increased concentrations and potentially increased toxicity in selected target tissues.

Organochlorines and endometrial cancer risk.

There is concern that persistent environmental pollutants such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) increase breast cancer risk, at least partially through estrogenic effects. Because the endometrium is more sensitive to estrogenic stimulation than the breast, such a carcinogenic effect should be more pronounced in the endometrium than the breast. In a population-based case-control study in Sweden, we measured serum concentrations of 10 chlorinated pesticides and 10 PCB congeners in 154 endometrial cancer cases and 205 population controls. Information on potential confounders was obtained by mailed questionnaires. We used logistic regression to calculate odds ratios (ORs) as measures of relative risk. We performed analyses for lipid-adjusted concentrations of each individual substance and after grouping substances according to putative hormonal effects. We found no significant associations of increasing levels of pesticide or PCB exposure with endometrial cancer risk. The multivariate OR was 1.0 (95% confidence interval, 0.6-2.0; P for trend, 0.78) for the highest compared with the lowest quartile of dichlorodiphenyldichloroethylene (DDE), the predominant dichlorodiphenyltrichloroethane metabolite. Corresponding ORs were 1.0 for hexachlorobenzene, 0.9 for beta-hexachlorocyclohexane, 1.4 for oxychlordane, and 1.2 for trans-nonachlor. Analyses of substances grouped by putative hormonal effect also showed no associations with endometrial cancer risk. For all estrogenic compounds, the OR for the highest compared with the lowest quartile was 1.1 (95% confidence interval, 0.6-2.2; P for trend, 0.90). Our data do not support the hypothesis that the organochlorine exposure studied increases the risk for endometrial cancer.

Non-ortho PCB levels in various fish species from the east and west coast of Sweden.

Non-ortho (coplanar) PCBs 77, 126 and 169 were determined in a number of fish species from the Swedish coastal environment, using either supercritical fluid extraction (SFE) or the traditional liquid/liquid extraction followed by HPLC separation on porous graphitic carbon (PGC) column prior to GC/MS analysis. While PCB 77 showed the highest concentration level, the TEQ value for PCB 126 was dominant in virtually all the samples analysed. The toxic equivalents, however, indicated some differences in analytical data between 1990 and 1992/93 but these are not significant probably owing to the short period in between.

The involvement of metallothionein in the intestinal absorption of cadmium in mice.

Female mice were exposed to a single dose of 0.005 to 5 microg Cd/kg body wt., in order to test the hypothesis that once the Cd-binding capacity of intestinal metallothionein is saturated. Cd becomes more readily available for transfer from the mucosa to the circulatory system, causing an increase in Cd absorption. In this case the binding of Cd to MT would act as a barrier against Cd absorption, thus protecting the organism from accumulation and toxic effects of Cd in target organs such as the kidney. In mice the fractional Cd uptake (% of dose) in the duodenum, which was the main site of Cd uptake in the intestine, was not influenced by the Cd dose 6 h after dosage. However, the percentage of cytosolic Cd associated to MT in the duodenum decreased when the Cd dosage increased from 0.005 or 0.025 microg/kg to 5 microg/kg. Concomitantly, the percentage bound to low-molecular-weight (LMW) ligands increased, indicating saturation of the Cd-binding capacity of MT. Nevertheless, the fractional absorption was not dosage dependent in the dosage interval studied. Moreover, there was no statistically significant correlation between the percentage of cytosolic Cd bound to MT and the percentage of Cd absorbed. Thus, our results do not support the hypothesis that the intestinal Cd absorption is increased when the Cd-binding capacity of intestinal MT is saturated.

Survey of consumption fish from Swedish waters for chlorinated pesticides and polychlorinated biphenyls.

In this survey eighty-seven samples of consumption fish comprising mainly of salmon, pike, eel, herring, whitefish, sea-trout, perch, pike-perch, mackerel, cod, flounder, plaice and sole collected between 1992-1993 have been analysed for the levels of chlorinated pesticides and polychlorinated biphenyls (PCBs). Considering the diversity in the sizes and assortment, locations, and time of catch, the samples are deemed to represent the normal fish variety available to the local people at various seasons of the year. Virtually all the samples contained CB-153 levels below the new established maximum limit of 0.1 mg/kg fresh weight. Results are compared with those obtained between 1985 and 1993. Neither the total PCB (on fat weight basis) nor CB 153 as a marker showed any clear trend for most of the fish species analysed, particularly for the short period 1991-1993. The pesticides, on the other hand, showed a rather good downward trend up till 1991; some of them seem to have virtually attained a steady state after 1991.

Bioavailability of cadmium from crab hepatopancreas and mushroom in relation to inorganic cadmium: a 9-week feeding study in mice.

The bioavailability of Cd from boiled crab hepatopancreas and dried mushroom was studied in relation to that of inorganic Cd (CdCl2). Female Balb/c mice were fed with diets containing 0.4 ppm Cd from either boiled crab (Cancer pagurus) hepatopancreas or dried mushroom (Agaricus augustus), or as inorganic Cd (CdCl2). A control group received low Cd (< 0.007 ppm) feed, and did not accumulate detectable levels of Cd during 9 wk of exposure. Using Cd accumulation in the liver and kidney as a measure of Cd absorption, it was indicated that the bioavailability of Cd from boiled crab hepatopancreas is slightly lower than that of Cd from mushroom and inorganic Cd. Fractionation of Cd in boiled crab hepatopancreas and mushroom indicated that Cd in crab hepatopancreas mainly is associated with denaturated proteins with low solubility, whereas a large fraction of Cd in dried mushroom is associated with soluble ligands. This difference in speciation of Cd may be a reason for the lower bioavailability of crab Cd than that of mushroom Cd. The difference in bioavailability is, however, low and as a safety measure it is recommended that human consumption of both crab hepatopancreas and wild mushrooms with high Cd levels should be restricted.

Bioavailability of labile aluminium in acidic drinking water: a study in the rat.

The bioavailability of labile Al (Allab; Al3+, and monomeric hydroxo and sulfato complexes) in drinking water was studied in the rat. The hypothesis was that Allab in drinking water is more available for absorption in the gastro-intestinal tract than Al complexed in the rat feed. Male Sprague-Dawley rats were exposed to 4 mg Al/litre in acidic drinking water (pH 4-5) and 5 mg Al/kg in the feed for 10 wk. The Al intake of these rats was about twice that in a control group of rats that received Al only in the feed. Both a theoretical speciation calculation and a speciation analysis of the water in a flow injection system showed that more than 98% of the Al in the water was present as Allab. However, intake of this water did not result in increased levels of Al in the bone, liver or brain tissue of the rats. Al speciation in a simulated rat stomach indicated that Allab in drinking water is rapidly complexed by feed constituents as the water enters the acidic milieu of the stomach, resulting in a very low concentration of Allab. The concentration of dissolved Al was also low in comparison to the added amount of labile Al. The possibility of complex formation between Allab and feed components in the gastro-intestinal tract should be taken into account in further studies of the bioavailability of drinking water Al in experimental animals and in humans.