Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides.

Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), ß-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. "Lower cognitive function" was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of ß-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in prospective studies.

Association of DDT and heptachlor epoxide in human blood with diabetic nephropathy.

Six organochlorine pesticides and pesticide metabolites in human blood were tested to determine their relationships with diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted, n=2992, population estimate=133,088,752). The six chemicals were p,p'-DDT (dichlorodiphenyltrichloroethane), p,p'-DDE (dichlorodiphenyltrichloroethylene), beta-hexachlorocyclohexane, oxychlordane, trans-nonachlor and heptachlor epoxide. In this research, total diabetes included diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥6.5%), and nephropathy was defined as a urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria. The pesticide p,p'-DDT and pesticide metabolite heptachlor epoxide were significantly associated with total diabetes with nephropathy, with odds ratios of 2.08 (95% CI 1.06-4.11) and 1.75 (95% CI 1.05-2.93), respectively. Organochlorine pesticides are thought to act through the constitutive androstane receptor/pregnane X receptor disease pathway, but this is not well established. When p,p'-DDT and heptachlor epoxide were both elevated, the odds ratio for diabetic nephropathy was 2.76 (95% CI 1.31-5.81), and when six of six organochlorine pesticides and pesticide metabolites, were elevated, the odds ratio for diabetic nephropathy was 3.00 (95% CI 1.08-8.36). The differences in the odds ratios for these groups appear to be due to differences in the mean heptachlor epoxide concentration of each category. Organochlorine pesticides and pesticide metabolites are known to have estrogenic, antiestrogenic or antiandrogenic activity. The constitutive androstane receptor/pregnane X receptor pathway is thought to interact with the aryl hydrocarbon receptor pathway, and the associations noted may be due to that interaction.

Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring.

Prenatal exposure to environmental endocrine disrupters has been postulated to cause adverse effects on male reproductive health. Exposure to organochlorine pesticides with anti-androgenic and estrogenic potency has been shown to interfere with the sex-hormone-dependent process of testicular descent in animal models. We examined the relation between serum levels of the pesticides heptachlor epoxide (HCE), hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (beta-HCCH) in pregnant women, and the occurrence of cryptorchidism in their sons. These three pesticides were previously suggested as risk factors for cryptorchidism. In a nested case-control design, we compared serum levels between mothers of cases (n = 219) and controls (n = 564), selected from the Collaborative Perinatal Project, a US birth cohort study of pregnancies in 1959-1966. The offspring of mothers with HCE levels above the 90th percentile compared to those below the 10th percentile had an adjusted odds ratio of cryptorchidism of 1.2 (95% confidence interval 0.6-2.6); for beta-HCCH the odds ratio was 1.6 (0.7-3.6). For HCB the adjusted odds ratio was near one. These results provide little support for an association of cryptorchidism with exposure to low levels of HCE or HCB. For beta-HCCH the findings were somewhat suggestive of an association but were inconclusive.

Xenoestrogens: do they lower survival after thermal injury?

The effect of hormone disruptors on human health is an area of recent concern. The authors measured heptachlor epoxide and oxychlordane--the body storage forms of estrogenic insecticides-in the sera of patients with major burns (i.e., 7 survivors and 10 age- and burn-size-matched nonsurvivors) on days 1, 3, 5, 7, and 11 after they had been burned, as well as in 12 age-matched normal controls. During the hypermetabolic phase, serum concentrations of heptachlor epoxide and oxychlordane were greater in nonsurvivors than in controls, and heptachlor epoxide concentrations in nonsurvivors exceeded those in survivors on postburn day 5. The postburn alterations in heptachlor epoxide and oxychlordane concentrations could not be accounted for by changes in concentrations of circulating lipid. These findings, which indicate that xenoestrogens are released from fat depots after thermal injury, suggest a possible contribution to mortality, especially in older patients.

Heptachlor, heptachlor epoxide, and other chlordane compounds in Finnish plywood workers.

Residue levels of heptachlor, heptachlor epoxide, and other chlordane compounds were determined in sera from 74 Finnish plywood workers and 52 controls. Concentrations of heptachlor epoxide in plywood workers varied from below the detection limit of 0.1 ng/g to 19.2 ng/g serum (conversion factor for SI units = 975 [1 ng/g = 0.98 microgram/l]); the mean and standard deviation were 3.2 and 3.9 ng/g, respectively. Heptachlor expoxide values in controls varied from below the detection limit to 1.2 ng/g serum. The exposure time, i.e., number of years spent working with sizings that contained heptachlor, correlated with the residue levels of heptachlor epoxide that were measured in serum samples taken from employees at two companies (p = .03). The most common chlordane compound (contaminant of heptachlor) found in the sera of plywood workers was trans-nonachlor; also found were high concentrations of heptachlor epoxide. Headache, dizziness, and eye irritation were not related to serum levels of heptachlor or chlordane compounds.

Residues in beef cattle accidentally exposed to commercial heptachlor.

The changes in concentration of heptachlor epoxide (HCE) and oxychlordane (OCD) were studied in the tissues of beef cattle that had previously grazed pasture contaminated with commercial heptachlor. In 25 cows and heifers monitored over 488 days, the mean concentration of HCE decreased from 22.0 to 0.08 mg/kg and of OCD from 5.68 to 0.18 mg/kg. The respective half-lives were estimated to be 66 and 92 days. In a controlled feeding experiment, nine steers were subjected to one of three dietary regimes; a high plane of nutrition for 81 days then a low plane for 140 days; a moderate plane of nutrition for the total period; and a low plane of nutrition for 81 days then a high plane for 140 days. Approximately five months later similar treatments were applied for 101 and 94 days. The rate of decline of HCE and OCD was consistently greatest in animals on the high plane of nutrition and lowest in those on the low plane. Lactation did not appear to have a major effect on the rate of decline in the tissue concentrations of these compounds. No significant (P greater than 0.05) relationships were found between the concentrations of HCE or OCD in the subcutaneous fat and either milk or blood at any stage of the experiment. At slaughter, from 18 to 24 months after the commencement of the experiments, significant correlations (P less than 0.05) were found among concentrations of HCE and OCD in subcutaneous fat, renal fat and fat from the bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between chlordane and its metabolites in blood of pest control operators and spraying conditions.

Chlordane has been widely used to protect soil and house foundations against termite infestation. Pest control operators (PCOs) are occupationally exposed to chlordane. The relationship between chlordane and its metabolites in blood of PCOs and spraying conditions were investigated. Chlordane and its metabolites were detected in the blood of some chlordane-exposed PCOs, but not in that of the controls. Trans-nonachlor and the metabolites oxychlordane and heptachlor epoxide were detected in the blood of PCOs. Total concentration of chlordane and its metabolites in blood (trans-nonachlor + oxychlordane + heptachlor epoxide) was less than 5.6 ppb (mean: 0.89 ppb). The concentration of chlordane and its metabolites in blood of chlordane-exposed PCOs was significantly correlated with the number of spraying days and the amount of chlordane sprayed, particularly with a large correlation coefficient (r = 0.81, P less than 0.001) with the spraying days in the three months prior to the medical examination. The concentration of chlordane and its metabolites in blood is considered to be a useful indicator of biological monitoring for chlordane exposed workers (PCOs).

Residues and metabolites of selected persistent halogenated hydrocarbons in blood specimens from a general population survey.

The National Center for Health Statistics collaborated with the National Human Monitoring Program of the U.S. Environmental Protection Agency (EPA) in a four-year study to assess the exposure of the general population to selected pesticides through analysis of blood serum and urine specimens. Specimens were collected on a national probability half-sample of persons 12-74 years of age from 64 locations across the United States comprising the sample areas in the Second National Health and Examination Survey (NHANES II) and analyzed for selected organochlorine, carbamate, chlorophenoxy and organophosphorus pesticides. Medical, nutritional and pesticide usage data are also available for each sample person. Results of the blood serum analyses indicate that the general population is being exposed to some of these types of pesticides. For selected pesticide residues, the percent quantifiable positives and median serum levels by age group are presented for three regions of the United States. Since 1970, EPA has conducted a national probability sampling of human adipose tissue. Specimens obtained on a survey design representative of the general population were analyzed for selected organochlorine pesticides and toxic chemicals. Findings from the 1979 survey also indicate exposure of the general population to some of these chemicals.

Serum pesticide levels in patients with childhood colorectal carcinoma.

From September 1974 through November 1976, 13 adolescent patients with mucin-producing colorectal adenocarcinoma were treated at a Memphis, Tennessee, pediatric oncology center. Ten of these children were from rural areas of the Mississippi Delta, areas of high pesticide use. None of them had a family history of colorectal cancer, familial polyposis, or ulcerative colitis. Levels of pesticide residues, however, were not generally higher in blood samples from patients and their families than from controls.