Development of Biomonitoring Equivalents for chlordane and toxaphene with application to the general Canadian population.

Biomonitoring Equivalents (BEs) were developed for chlordane and toxaphene using one-compartment pharmacokinetic models and compared with biomonitoring data from the Canadian Health Measures Survey, Cycle 1 (2007-2009). A secondary objective was to examine the toxicities of the components of technical chlordane in a HEPG2 cell culture experiment. Oral reference doses were identified from national and international regulatory agencies and sources. Pharmacokinetic parameters were obtained from experimental data in rodent models. A set of BEs have been derived for the main chlordane isomers, cis-chlordane, trans-chlordane, cis-nonachlor, and trans-nonachlor, and the chlordane metabolite, oxychlordane. BEs were also derived for the main toxaphene isomers found in biota, Parlar No. 26, 50 and 62. Among the general Canadian population, no exceedances of chlordane or toxaphene BEs were observed. Based on the LC50 from the in vitro study, trans-nonachlor was the most toxic, and the trans-isomers were more toxic than the cis-isomers. The derived BE values can be used as screening guidelines to assess the risk of biomonitoring data in human populations. The results of an in vitro experiment suggest that trans-nonachlor is more toxic than technical chlordane and, therefore, the BE for this compound may need to be further lowered.

Lymphohematopoietic cancers in the United Farm Workers of America (UFW), 1988-2001.

OBJECTIVE: Agricultural risk factors for lymphohematopoietic cancers (LHC) in Hispanic farm workers in California were examined in a nested case-control study embedded in a cohort of 139,000 ever members of a farm worker labor union in California. METHODS: Crop and pesticide exposures were estimated by linking county/month and crop specific job history information from union records with California Department of Pesticide Regulation pesticide use reports during the 20-year period prior to cancer diagnosis. RESULTS: A total of 131 LHC diagnosed in California between 1988 and 2001 were included in the analysis. Analyses were conducted by gender and subtype of non-Hodgkins lymphoma (nodal, extra nodal) and by leukemia histology (lymphocytic, granulocytic). Odds ratios were calculated by stratification and by unconditional logistic regression. Risk for all LHC was elevated in workers cultivating vegetables (OR = 1.67, 95% CI = 1.12-2.48). Risk of leukemia was associated with exposure to the pesticides mancozeb (OR = 2.35, 95% CI = 1.12-4.95) and toxaphene (OR = 2.20, 95% CI = 1.04-4.65) while NHL risk was increased in association with 2,4-D (OR = 3.80, 95% CI=1.85-7.81). Risk of leukemia was particularly elevated among female workers and for granulocytic versus lymphocytic leukemia for several chemicals. No associations were noted for multiple myeloma. CONCLUSIONS: California farm workers employed where mancozeb and toxaphene were used had an increased risk of leukemia compared to farm workers employed elsewhere. Employment in farms using 2,4-D was associated with an increased risk of NHL.

Detection of an estrogen receptor in two nematode species and inhibition of binding and development by environmental chemicals.

The presence of estrogen receptors or binding proteins was demonstrated in the free-living nematode species Panagrellus redivivus and Caenorhabditis elegans by radioimmunoassay. Twenty-five nanomolar concentrations of toxaphene, dieldrin, and dieldrin plus nonylphenol significantly inhibited estrogen binding to the receptor in P. redivivus. Binding was inhibited but not significantly by 25 nM nonylphenol, toxaphene plus dieldrin, or toxaphene plus nonylphenol. The current research supports the hypothesis that dieldrin, nonylphenol, and toxaphene may mimic estrogen, altering the normal pathways of estrogen metabolism. Based on observations of secondary sex structures, estrogenic chemicals had no effect on sex ratios or growth in Panagrellus redivivus, but caused a reduction of fecundity in this nematode.

Arctic indigenous women consume greater than acceptable levels of organochlorines.

Exposure to polychlorinated biphenyls and organochlorine pesticides through traditional food resources was examined for Arctic Indigenous women living in two cultural and environmental areas of the Canadian Arctic--one community representing Baffin Island Inuit in eastern Arctic and two communities representing Sahtú Dene/Métis in western Arctic. Polychlorinated biphenyls, toxaphene, chlorobenzenes, hexachlorocyclohexanes, dichlorodiphenyltrichloroethane, chlordane-related compounds and dieldrin were determined in local food resources as normally prepared and eaten. Quantified dietary recalls taken seasonally reflected normal consumption patterns of these food resources by women in three age groups: 20-40 y, 41-60 y and > or = 61 y. There was wide variation of intake of all organochlorine contaminants in both areas and among age groups for the Sahtú. Fifty percent of the intake recalls collected from the Baffin Inuit exceeded the acceptable daily intake for chlordane-related compounds and toxaphene, and a substantial percentage of the intake records for dieldrin and polychlorinated biphenyls exceeded the acceptable or tolerable daily intake levels. Primary contributing foods to organochlorine contaminants intake for the Baffin Inuit were meat and blubber of ringed seal, blubber of walrus and mattak and blubber of narwal. Important foods contributing organochlorine contaminant to the Sahtú Dene/Métis were caribou, whitefish, inconnu, trout and duck. The superior nutritional benefits and potential health risks of traditional food items are reviewed, as are implications for monitoring organochlorine contaminant contents of food, clinical symptoms and food use.

The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells.

Estrogenic pesticides such as DDT and chlordecone generate deleterious reproductive effects. An "in culture" bioassay was used to assess the estrogenicity of several pesticides. The E-screen test uses human breast estrogen-sensitive MCF7 cells and compares the cell yield achieved after 6 days of culture in medium supplemented with 5% charcoal-dextran stripped human serum in the presence (positive control) or absence (negative control) of estradiol and with diverse concentrations of xenobiotics suspected of being estrogenic. Among the organochlorine pesticides tested, toxaphene, dieldrin, and endosulfan had estrogenic properties comparable to those of DDT and chlordecone; the latter are known to be estrogenic in rodent models. The E-screen test also revealed that estrogenic chemicals may act cumulatively; when mixed together they induce estrogenic responses at concentrations lower than those required when each compound is administered alone.