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Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.

Adolescent↗

Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian inuit.

In this study, we identified the main hydroxylated polychlorinated biphenyls (OH-PCBs) and other chlorinated phenolic compounds and we determined their relative concentrations in whole blood from 13 male and 17 female Inuit from northern Quebec, Canada, and from a pooled whole blood sample from southern Quebec. We also determined concentrations of polychlorinated biphenyls (PCBs). Total OH-PCB concentrations were variable among the Inuit samples, ranging over 2 orders of magnitude (0.117-11.6 ng/g whole blood wet weight). These concentrations were equal to and up to 70 times those found for the southern Quebec pooled whole blood sample. Geometric mean concentrations of total OH-PCBs were 1.73 and 1.01 ng/g whole blood for Inuit men and women, respectively, and 0.161 ng/g whole blood for the southern population pool. There are limited data available for comparison, but the levels of OH-PCBs in Inuit are higher than those previously reported in the literature for other populations. There was a significant correlation (p < 0.005) between OH-PCBs and PCBs (r = 0.84) and both correlated significantly (p < 0.005) with age (r = 0.68 and 0.78, respectively). The ratio of OH-PCBs to PCBs was lower in Inuit (0.11) than in the southern Quebec pool (0.33). There is no apparent explanation for the difference. There was considerable variability in the congener pattern of the identified OH-PCBs. The main metabolite, 4-OH-CB109 (4-OH-2,3,3',4', 5-pentachlorobiphenyl), constituted 12-62% of the total OH-PCBs in the samples. Pentachlorophenol (PCP) was the dominant phenolic compound in blood, constituting 46% (geometric mean) of the total quantitated chlorinated phenolic compounds. PCP concentrations in Inuit blood ranged from 0.558 to 7.77 ng/g on a wet weight basis. All but two Inuit samples had lower concentrations than the southern Quebec pool (6.29 ng/g). The possible role of OH-PCBs in mediating PCB-induced adverse effects needs to be investigated further.

Adolescent↗

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

Adolescent↗

Activities of an Environmental Analysis Van in the German Federal State Schleswig-Holstein.

A cooperation was started between the Union of Physicians of Schleswig-Holstein (Bad Segeberg, Germany) and an environmental engineer in 1992. A mobile unit for environmental analysis was set up, the Environmental analysis Van (EAV) or mobile umweltambulanz. Inspection of sites and collection of air and dust/material samples for analysis of xenobiotics were performed on request. The results of this cooperation were evaluated to show which sources of indoor pollutants could be particularly relevant to human health impairment. During a 30-month period form July 1993 to December 1995, 1793 site inspections wer conducted. Xenobiotic analysis and subsequent advising was performed in 1318 cases; enhanced concentrations of one or more toxic substances (mainly biocides such a pentachlorophenol, permethrin, and/or hexachlorocyclohexane) were found in 71% of the sites analyzed. Formaldehyde, volatile organic compounds, and contamination by molds were also documented. A follow-up was done on 80 clients of the Environmental Analysis Van, which had detected elevated concentrations of permethrin because of pyrethroid-treated carpeting. The effect of removing all contaminated carpeting on health improvement in comparison with nonremoval was statistically significant (p<0.0001). Pyrethroid-treated carpeting, which was already 5, 7 and 10 years old, revealed permethrin concentrations of 115, 100, and 150 mg/kg dust. This result indicates that indoor contamination of permethrin is highly persistent and may be the cause of adverse health effects.

Air Pollution, Indoor↗

Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men.

We examined the influence of widely varied consumption of fatty fish from the Baltic Sea and of age on plasma concentrations of polychlorinated biphenyls (PCBs), polychlorobiphenylols (OH-PCBs), 2, 2-bis(4-chlorophenyl)-1,1,1-trichloroethane (4,4'-DDT), 2, 2-bis(4-chlorophenyl)-1,1-dichloroethane (4,4'-DDE), 2,2',4, 4'-tetrabromodiphenyl ether (BDE-47), hexachlorobenzene (HCB), and pentachlorophenol (PCP) in Latvian and Swedish men. Both age and fish consumption were significantly correlated with the concentrations of [sigman]PCB, [sigman]OH-PCB, 4,4'-DDE, 4,4'-DDT, and HCB. In the case of BDE-47, no significant relationship with age was observed, and fish consumption had the largest relative effect on plasma concentrations of this contaminant. This relationship may be a result of exposure to BDE-47 having been more recent than that of PCBs and DDE, or because the half-life of BDE-47 may be shorter than that of PCB and DDE. Latvian men demonstrated higher plasma levels of DDE and DDT but lower levels of [sigman]PCB and PCP than did Swedish men. The corresponding levels of HCB and BDE-47 were similar in both countries. The Spearman's rank correlation coefficient obtained by comparing the level of the metabolite 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to the combined levels of its parent compounds, 2,3,3',4, 4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118), was higher than the median correlation coefficient obtained upon comparing the level of this metabolite to all other possible combinations of two PCB levels. No other increased correlation between metabolite and parent PCB concentration was observed.

Adult↗

Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study.

Prenatal pesticide exposures may adversely affect children's health. However, exposure and health research is hampered by the lack of reliable fetal exposure data. No studies have been published that report measurements of commonly used nonpersistent pesticides in human amniotic fluid, although recent studies of pesticides in urine from pregnant women and in meconium indicate that fetuses are exposed to these chemicals. Amniotic fluid collected during amniocentesis is the only medium available to characterize direct fetal exposures early in pregnancy (approximately 18 weeks of gestation). As a first step in validating this exposure biomarker, we collected 100 amniotic fluid samples slated for disposal and evaluated analytical methods to measure organophosphate and carbamate pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and chlorinated phenolic compounds. The following six phenols were detected (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%), carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%), with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L, respectively, for positive values. The organophosphate metabolites diethylphosphate and dimethylphosphate were detected in two (10%) samples, and dimethylthiophosphate was detected in one (5%) sample, with geometric mean concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive values. These levels are low compared with levels reported in urine, blood, and meconium in other studies, but indicate direct exposures to the young fetus, possibly during critical periods of development. Results of this pilot study suggest that amniotic fluid offers a unique opportunity to investigate fetal exposures and health risks.

Adolescent↗

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Adult↗

Environmental fate and biodegradability of benzene derivatives as studied in a model aquatic ecosystem.

A model aquatic ecosystem is devised for studying relatively volatile organic compounds and simulating direct discharge of chemical wastes into aquatic ecosystems. Six simple benzene derivatives (aniline, anisole, benzoic acid, chlorobenzene, nitrobenzene, and phthalic anhydride) and other important specialty chemicals: hexachlorobenzene, pentachlorophenol, 2,6-diethylaniline, and 3,5,6-trichloro-2-pyridinol were also chosen for study of environmental behavior and fate in the model aquatic ecosystem. Quantitative relationships of the intrinsic molecular properties of the environmental micropollutants with biological responses are established, e.g., water solubility, partition coefficient, pi constant, sigma constant, ecological magnification, biodegradability index, and comparative detoxication mechanisms, respectively. Water solubility, pi constant, and sigma constant are the most significant factors and control the biological responses of the food chain members. Water solubility and pi constant control the degree of bioaccumulation, and sigma constant limits the metabolism of the xenobiotics via microsomal detoxication enzymes. These highly significant correlations should be useful for predicting environmental fate of organic chemicals.

Animals↗

Overview of potential mutagenic problems posed by some pesticides and their trace impurities.

This review principally addresses a number of aspects of usage of pesticides as well as populations at potential risk and attempts to highlight categories of pesticides whose structures or those of their metabolites and/or trace impurities, degradation and transformation products suggest an a priori mutagenic and/or carcinogenic risk. The pesticides considered include: DDT, hexachlorobenzene (HCB), 2,4,5-T, pentachlorophenol, and various herbicidal precursors (e.g., carbamates, triazines) of nitrosamines and nitroso derivatives. Structural features of a number of halo-unsaturated pesticides (e.g., dichloropropenes) were also reviewed from a viewpoint of contrasting their potential mutagenicity with that of vinyl chloride and vinylidene chloride. Additionally the mutagenicity of the organophosphorus pesticide Trichlorophon is contrasted with that of its degradation products.

Animals↗

Negative chemical ionization studied of human and food chain contamination with xenobiotic chemicals.

Negative chemical ionization mass spectrometry with a mixture of isobutane, methylene chloride, and oxygen as the reagent gas has been used to explore contamination of environmental substrates with xenobiotic chemicals. The substrates in question, fish tissue, human seminal plasma, and human adipose tissue, were cleaned up by one of the following three cleanup procedures: (1) continuous liquid-liquid extraction steam distillation; (2) gel-permeation chromatography; and (3) adsorption on activated carbon followed by elution with toluene. The third procedure was used only for the examination of planar polychlorinated aromatic hydrocarbons in environmental samples. Using these techniques, we have found evidence for contamination of fish samples with polychloronaphthalenes, polychlorostyrenes, polychlorobiphenyls, polychlorodibenzofurans, and polychlorodibenzodioxins among other chemicals. The polychlorodibenzodioxins appeared only in the spectra of extracts of fish obtained from the Tittabawassee River at Midland Michigan. The polychlorodibenzofuran ions appeared in NCI mass spectra of fish that were significantly contaminated (above 2 ppm) with polychlorobiphenyls. Toxic substances occurring in human seminal plasma included pentachlorophenol, hexachlorobenzene, DDT metabolites, and polychlorobiphenyls. We have investigated toxic substances in human seminal plasma because of the apparent decrease in sperm density in U.S. males over the last 30 years. Results of screening human adipose tissue for contamination with xenobiotic chemicals have been largely coincident with result of the EPA human monitoring program. Polychlorobiphenyls, DDT metabolites, nonachlor, and chlordane have appeared in most samples examined. Detection limits for all of these chemicals were of the order of 1 ppb.

Adipose Tissue↗

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.

Air Pollutants↗

PCDD/PCDF indoor exposure in day-care centers and PCDD/PCDF blood concentrations of female employees.

We determined blood concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in 41 female employees with previous exposure to pentachlorophenol-based wood preservatives from 10 day-care centers in the Hamburg, Germany, area. We compared the blood concentrations with estimated age-dependent reference values and analyzed the correlation between PCDD/PCDF indoor air exposure and blood concentrations. The analyses based on the PCDD congeners 1,2,3,4,7,8-, 1,2,3,6,7,8-, and 1,2,3,7,8,9-hexaCDD (hexaCDD), 1,2,3,4,6,7,8-heptaCDD (heptaCDD), octaCDD, and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents calculated according to the international NATO-CCMS model (I-TEQ). In comparison to the estimated reference values, the blood concentrations of hexaCDD and I-TEQ spread around the mean estimate. Data for octaCDD scattered in some cases distinctly above the upper confidence limit. Reference values for heptaCDD could not be estimated. The correlation between PCDD/PCDF indoor air exposure and PCDD/PCDF blood concentrations was examined by linear multiple regression analysis considering different exposure variables and taking confounders into account. Analyses were carried out with the total study group and with a restricted subgroup. Associations were shown between the PCDD/PCDF indoor air concentrations and blood concentrations for heptaCDD and for the I-TEQ, whereas hexaCDD showed no association. OctaCDD showed a negative association in the total study group and no association in the subgroup analysis. In summary, the analyses showed no clear association between PCDD/PCDF indoor air exposure in day-care centers and PCDD/PCDF blood levels of female employees previously exposed to wood preservatives. By contrast, the results consistently indicated a positive association between PCDD/PCDF blood concentrations and exposure to wood preservatives in private homes.

Adult↗

A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice.

Spontaneously occurring and chemically induced pheochromocytomas are rare in mice. That the mouse pheochromocytoma is a more appropriate animal model than that of the rat for study of human medullary adrenal tumors has been suggested. The expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme responsible for production of epinephrine from norepinephrine, is common to both mouse and human pheochromocytomas. This investigation assessed the expression of the immunohistochemical markers PNMT, tyrosine hydroxylase (TH), and chromogranin A (CGA) in spontaneously occurring and chemically induced pheochromocytomas in the B6C3F1 mouse. Spontaneous tumors were derived from control animals from 10 different studies and the pheochromocytomas from treated groups from 4 different studies. All tumors were positive for maximal TH expression. A highly significant difference in PNMT expression (p < 0.01) occurred between spontaneously occurring pheochromocytomas classified as benign or "malignant" by the criteria of toxicologic pathology. Chemically induced tumors showed intermediate PNMT staining. A marked reduction in CGA expression occurred in pheochromocytomas induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors. These findings suggest that immunohistochemistry is a reliable tool in investigating the functional capabilities of pheochromocytomas in mice. PNMT expression is a tightly regulated component of the chromaffin cell phenotype and appears to be readily lost in mouse pheochromocytomas, particularly those with aggressive characteristics.

Adrenal Gland Neoplasms↗

Properties and biochemical characterization of NADH 5 alpha-reductase from rat liver microsomes.

NADH 5 alpha-reductase is present in microsomes of various rat organs: heart and skeletal muscle, liver, adrenal glands, kidney, testes and prostate. The enzyme from rat liver microsomes utilizes B-hydrogen from the coenzyme NADH for steroid reduction. After solubilization of the enzyme with the nonionic detergent lubrol, phosphatidylcholine is necessary to restore the activity. This reactivation of the enzyme activity is paralleled by a corresponding increase of Vmax for testosterone (17 beta-hydroxy-4-androsten-3-one). Km and Vmax for testosterone change, Km and Vmax for the coenzyme NADH remain constant with an alteration of phosphate concentration in the incubation medium. The NADH 5 alpha-reductase is inhibited by numerous substances: amytal, phenobarbital, mepacrin, thenoyltrifluoracetone, gallic acid propyl ester, dicoumarol, pentachlorophenol, NADP and antibodies against rat liver NADPH ferrihemoprotein reductase. Antibodies against rat liver cytochrome-b5 reductase cause an activation of NADH 5 alpha-reductase.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

The effects of endocrine-disrupting chemicals on thyroid hormone binding to Xenopus laevis transthyretin and thyroid hormone receptor.

We investigated the effects of medical, industrial and agricultural chemicals on 3,3',5-L-[125I]triiodothyronine ([125I]T3) binding to purified recombinant Xenopus laevis (X. laevis) transthyretin (xTTR), a plasma thyroid hormone-binding protein, and to the ligand-binding domain of thyroid hormone receptor-beta (xTR LBD). xTTR derived from X. laevis serum had about 80 times higher affinity for T3 than for L-thyroxine. The xTTR's relative affinities for diethylstilbestrol, pentachlorophenol and ioxynil were 10(-1)- to 10(-2)-fold less than that for T3. However, all chemicals investigated had either a weak or no influence on [125I]T3 binding to xTR LBD. The concentration of diethylstilbestrol, the most potent chemical, required for 50% inhibition of [125I]T3 binding to xTR LBD was 10(4) times greater than that of unlabeled T3. These results indicate the existence of several chemicals that interact with xTTR but not with xTR LBD.

Animals↗

Persistent organochlorine pollutants in children working at a waste-disposal site and in young females with high fish consumption in Managua, Nicaragua.

The aim of this study was to assess persistent organochlorine pollutant (POP) levels in serum collected from children (11-15 years old) working and sometimes also living at the municipal waste-disposal site in Managua, located at the shore of Lake Managua, and in nonworking children living both nearby and also far away from the waste-disposal site. The influence of fish consumption was further evaluated by assessing POPs levels in serum from young women (15-24 years old) with markedly different patterns of fish consumption from Lake Managua. 2,2-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (4,4'-DDT) and 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethene (4,4'-DDE), gamma-hexachlorocyclohexane (gamma-HCH), polychlorinated biphenyls, pentachlorophenol, and polychlorobiphenylols were quantified in all samples. In general, the levels observed were higher than those reported in children from developed countries, such as Germany and United States. Toxaphene, aldrin, dieldrin, and beta-HCH could not be identified in any sample. The children working at the waste-disposal site had higher levels of POPs compared with the nonworking reference groups. In children not working, there were also gradients for several POPs, according to vicinity to the waste-disposal site. Moreover, in children, as well as in young women, there were gradients according to fish consumption. The most abundant component was 4,4'-DDE, but at levels still lower than those reported in children from malarious areas with a history of recent or current application of 4,4'-DDT for vector control.

Adolescent↗

Influence of xenobiotics on rainbow trout liver estrogen receptor and vitellogenin gene expression.

Rainbow trout hepatocyte primary culture was used to test the influence of some xenobiotics on the expression of two genes implicated in reproduction, those for the estrogen implicated in reproduction, those for the estrogen receptor (ER) and vitellogenin (Vg). We showed that chlordecone, nonylphenol, a polychlorobiphenol (PCB) mixture (Aroclor 1245) and lindane were able to induce ER and Vg mRNA accumulation. Antiestrogens, 4-hydroxytamoxifen and ICI 164,384, prevented the effects of the xenobiotics, indicating that the induction of gene expression is mediated by the ER. Among these four xenobiotics, only chlordecone and nonylphenol were able to displace the binding of [3H]estradiol to ER-enriched COS-1 extracts, and to activate an estrogen-dependent reporter gene (ERE-TK-CAT) cotransfected with an expression vector containing ER cDNA. The results suggest that chlordecone and nonylphenol are direct inducers of rainbow trout ER and Vg gene expression, whereas PCBs and lindane act through their hepatic metabolites. Moreover, pentachlorophenol acts as an antagonist of the induction by estradiol of rainbow trout ER and Vg gene expression.

Actins↗

A multivariate biomarker-based model predicting population-level responses of Daphnia magna.

A multivariate model is proposed relating short-term biomarker measurements in Daphnia magna to chronic effects (21-d exposure) occurring at the population level (time to death, mean brood size, mean total young per female, intrinsic rate of natural increase, net reproductive rate, and growth). The results of the short-term exposure (48 h-96 h) to eight model toxicants (cadmium, chromium, mercury, tributyl tin, linear alkylsulfonic acid, sodium pentachlorophenolate, lindane, and 2,4-dichlorophenoxyacetic acid) on the following biomarkers were used for the multivariate model: digestive enzymes (amylase, cellulase, beta-galactosidase, trypsin, and esterase), enzymes of the intermediary metabolism (glycogen phosphorylase, glucose-6-phosphate dehydrogenase, pyruvate kinase, lactate dehydrogenase, and isocitrate dehydrogenase), cellular energy allocation (CEA) (protein, carbohydrate, and lipid content and electron transport activity), and DNA damage and antioxidative stress activity. Using partial least squares to latent structures (PLS), a two-component model was obtained with R2 of 0.68 and a Q2 value of 0.60 based on the combined analysis of a limited number of the 48- and 96-h biomarker responses. For the individual population-level responses, the R2 values varied from 0.66 to 0.77 and the Q2 values from 0.52 to 0.69. Energy-related biomarkers (cellular energy allocation, lipid contents, anaerobic metabolic activity--pyruvate kinase, and lactate dehydrogenase), combined with parameters related to oxidative stress (catalase) and DNA damage measured after 48 and 96 h of exposure, were able to predict long-term effects at higher levels of biological organization.

Animals↗