Analysis of serum levels of organochlorine pesticides and related factors in Parkinson's disease.

BACKGROUND: There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides. METHODS: In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD. RESULTS: Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein. CONCLUSIONS: This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD.

Levels of organochlorine pesticides in the blood of people living in areas of intensive pesticide use in Sudan.

Ninety-six human blood samples were collected from six locations that represent areas of intensive pesticide use in Sudan, which included irrigated cotton schemes (Wad Medani, Hasaheesa, Elmanagil, and Elfaw) and sugarcane schemes (Kenana and Gunaid). Blood samples were analyzed for organochlorine pesticide residues by gas liquid chromatography (GLC) equipped with an electron capture detector (ECD). Residues of p,p'-dichlorodiphenyldichloroethylene (DDE), heptachlor epoxide, γ-HCH, and dieldrin were detected in blood from all locations surveyed. Aldrin was not detected in any of the samples analyzed, probably due to its conversion to dieldrin. The levels of total organochlorine burden detected were higher in the blood from people in the irrigated cotton schemes (mean 261 ng ml(-1), range 38-641 ng ml(-1)) than in the blood of people from the irrigated sugarcane schemes (mean 204 ng ml(-1), range 59-365 ng ml(-1)). The highest levels of heptachlor epoxide (170 ng ml(-1)) and γ-HCH (92 ng ml(-1)) were observed in blood samples from Hasaheesa, while the highest levels of DDE (618 ng ml(-1)) and dieldrin (82 ng ml(-1)) were observed in blood samples from Wad Medani and Kenana, respectively. The organochlorine levels in blood samples seemed to decrease with increasing distance from the old irrigated cotton schemes (Wad Medani, Hasaheesa, and Elmanagil) where the heavy application of these pesticides took place historically.

Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population.

OBJECTIVES: It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. METHODS: This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. RESULTS: We found a statistically significant association between AD and high levels of ß-hexachlorocyclohexane (ß-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION: This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with ß-HCH, dieldrin, and copper to influence the risk of AD.

Gene-environment interaction in Alzheimer's disease.

OBJECTIVES: The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer's disease (AD). METHODS: A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCRrestriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC). RESULTS: APOE ∈4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, ß- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE ∈4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively. CONCLUSION: GxE interactions exist with APOE ∈4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.

Maternal and cord blood levels of aldrin and dieldrin in Delhi population.

Aldrin and dieldrin, structurally similar organochlorine pesticides belong to cyclodiene family and were widely used for agriculture and public health program in India. Although the manufacturing, use and import of aldrin and dieldrin have been banned in India since 2003, these pesticides are still persistent in environment and may be associated with adverse neurological and reproductive effects. The aim of this study is to assess the recent exposure level of aldrin and dieldrin and their placental transfer to fetus in normal healthy full-term pregnant women belonging to north Indian population undergoing normal delivery at Obstetrics and Gynecology department of UCMS and GTB hospital, Delhi. Quantitative analysis of aldrin and dieldrin residues in maternal and cord blood samples were carried out by gas chromatography system equipped with electron capture detector. The results of our study clearly revealed that maternal and cord blood levels of aldrin and dieldrin of pregnant women are age and dietary habit dependent. The aldrin level in maternal blood and dieldrin level in cord blood are higher in women in the age group 25-30 years than in women in age group of 19-24 years. Similarly, aldrin level in maternal blood is significantly higher in women with non-vegetarian dietary habit than in women with vegetarian dietary habit. No significant association is found for maternal and cord blood level. The results of the present study clearly demonstrate prenatal uptake of aldrin and dieldrin and provide recent information on the subsequent transplacental transfer.

Persistent organochlorine pesticides in serum and risk of Parkinson disease.

BACKGROUND: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. METHODS: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. RESULTS: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97-1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. CONCLUSIONS: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.

Associations of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in U.S. adults.

BACKGROUND: Organochlorine (OC) pesticides are a group of environmental endocrine disruptors that may be associated with an increased risk for hormone-related cancers including cancers of the breast and prostate. However, epidemiologic evidence is limited and inconsistent. OBJECTIVES AND METHODS: We used 1999-2004 National Health and Nutrition Examination Survey data to examine associations between serum concentrations of OC pesticides and prostate and breast cancers. RESULTS: After adjustment for other covariates, serum concentrations of beta-hexachlorocyclohexane (HCH) (p for trend = 0.02), trans-nonachlor (p for trend = 0.002), and dieldrin (p for trend = 0.04) were significantly associated with the risk of prevalent prostate cancer. Adjusted odds ratios for the second and third tertiles of detectable values were 1.46 [95% confidence interval (CI), 0.52-4.13] and 3.36 (95% CI, 1.24-9.10) for beta-HCH; 5.84 (95% CI, 1.06-32.2) and 14.1 (95% CI, 2.55-77.9) for trans-nonachlor; and 1.06 (95% CI, 0.30-3.73) and 2.74 (95% CI, 1.01-7.49) for dieldrin compared with concentrations in the lowest tertile or below the limit of detection. However, there was no positive association between serum concentrations of OC pesticides and breast cancer prevalence. CONCLUSION: Although further study is necessary to confirm these findings, these results suggest that OC pesticide exposures may have a significant effect on cancer risk. Efforts to reduce worldwide OC use are warranted.

Evaluation of endocrine disruptor levels in Kafue Lechwe (Kobus leche kafuensis) samples from the Blue Lagoon National Park of Zambia.

The concentrations of endocrine disruptors were determined in 36 liver tissue, serum and whole blood sample extracts drawn from 15 Blue Lagoon National Park Kafue lechwe. Out of 10 analytes evaluated, 89% of the sample extracts showed very high dieldrin concentrations of between 0.08­100 µg/mL in serum, 0.08­24.8 µg/mL in whole blood and 0.08­4.6 µg/g wet weight in liver tissue extracts. pp-DDE was detected in 83% of the sample extracts at 0.006­5.1 µg/mL in serum, 0.006­8.5 µg/mL in whole blood and 0.006­0.12 µg/g wet weight in liver tissue extracts. There was strong correlation between pp-DDE and dieldrin in all the three matrices. Deltamethrin and endosulfan detected at 50% frequency each. Percent recoveries in spiked laboratory blanks ranged between 60­100% while calculated detection limits ranged from 0.004 to 0.21 µg/mL for all the endocrine disruptors evaluated.

Cancer mortality in workers exposed to dieldrin and aldrin: over 50 years of follow up.

OBJECTIVE: Dieldrin and aldrin, pesticides widely used until the 1970s, have been under suspicion of being carcinogenic. In this study, overall and cause-specific mortality was assessed in a cohort of 570 employees occupationally exposed to the pesticides dieldrin and aldrin to investigate the long-term health effects, in particular carcinogenic effects. METHODS: All of the employees worked in the production plants between January 1954 and January 1970 and were followed for cause-specific mortality until 30 April 2006. Based on dieldrin levels in blood samples taken from 343 workers during the exposure period, the total intake of dieldrin was estimated for each individual subjects in the cohort. The estimated total intake ranged from 11 to 7,755 mg of dieldrin, with an average of 737 mg. RESULTS: Two hundred and twenty-six workers had died before 30 April 2006 compared with an expected number of 327.3, giving a standardized mortality ratio (SMR) of 69.0 (95% confidence interval (CI): 60.3-78.7). Overall cancer mortality was also significantly lower than expected (SMR: 76.4, 95% CI: 60.8-94.9). Also, none of the specific cancer sites showed a significant excess mortality and no association between exposure level and cancer mortality was found. CONCLUSION: The results from this study support findings from other epidemiological and recent animal studies concluding that dieldrin and aldrin are not likely human carcinogens.

Developmental and lactational exposure to environmentally relevant concentrations of dieldrin does not alter pregnancy outcome and mammary gland morphology in BALB/c mice.

The objectives of this study were to: (1) determine the dosing range necessary to produce serum levels of dieldrin in mice representative of human body burdens; and (2) define the effect of developmental exposure to environmentally relevant concentrations of dieldrin on mammary gland development. Sexually mature female BALB/c mice (n=140) were randomly assigned to receive vehicle, 0.45, 2.25, 4.5, and 22.5 microg dieldrin/g body weight (BW)/day. Serum levels of dieldrin were quantified by gas chromatography in pooled samples (n=4/treatment group). Target levels of 10-30 ng/ml were achieved in 0.45 and 2.25 microg/g dose groups by the end of 2 weeks of treatment. Vehicle or dieldrin (0.45, 2.25, and 4.5 microg/g BW) was administered weekly to sexually mature female BALB/c mice (n=48) throughout mating, pregnancy, and lactation. Treatments had no effect on fertility parameters in dams or mammary gland morphology at sexual maturity. Developmental exposure to dieldrin has no effect on mammary gland development in aged BALB/c mice.

Serum levels of insulin-like growth factor-I in relation to organochlorine pesticides exposure.

CONTEXT: Insulin-like growth factor 1 (IGF-I) and organochlorine pesticides (OCs) have been involved in the pathogenesis of several diseases like cancer, diabetes and growth disorders. OBJECTIVE AND DESIGN: The potential relationship between the serum levels of various OCs and serum IGF-I was investigated in adults (176 men and 247 women) from a representative sample of the general population of the Canary Islands (Spain). RESULTS: After adjustment for potential confounders, which include body mass index, age, and IGF-binding protein-3 (IGFBP-3), IGF-I levels were significantly lower in the 247 women who showed detectable levels of p,p'-DDD (a DDT-metabolite) than in women who presented non-detectable levels of this pesticide (p=0.030), specially in 36-50 years old women. A similar negative relationship was also found between IGF-I and aldrin (a non-DDT-derivative) in women (p=0.049). In the group of 176 men, aldrin seemed to exert a similar negative effect on IGF-I (p=0.046) and this effect was clearly significant in the oldest group (51-65 years) (p=0.009). A non-linear dose-response curve was observed between Total Cyclodienes Body Burden (Total Cyclodienes; sum of aldrin, dieldrin and endrin) and IGF-I in men (p=0.024). These findings suggest that OCs could modulate the IGF-system in a way that is highly influenced by gender, age and by chemical or combination of chemicals implicated. Such circumstances may contribute to the development of a number of diseases related to IGF-I and should be taken into account in public health decisions.

Quantification of low levels of organochlorine pesticides using small volumes (

A solid phase extraction and gas chromatography with negative chemical ionization mass spectrometry in scan mode (GC-NCI-MS) method was developed to identify and quantify for the first time low levels of organochlorine pesticides (OCs) in plasma samples of less than 100 microl from wild birds. The method detection limits ranged from 0.012 to 0.102 pg/microl and the method reporting limit from 0.036 to 0.307 pg/microl for alpha, gamma, beta and delta-hexachlorocyclohexane (HCH), heptachlor, aldrin, heptachlor epoxide, endosulfan I, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), dieldrin, endrin, endosulfan-II, endrin-aldehyde and endosulfan-sulfate. Pesticide levels in small serum samples from individual Falco sparverius, Sturnella neglecta, Mimus polyglottos and Columbina passerina were quantified. Concentrations ranged from not detected (n/d) to 204.9 pg/microl for some OC pesticides. All levels in the food web in and around cultivated areas showed the presence of pesticides notwithstanding the small areas for agriculture existing in the desert of Baja California peninsula.

Distribution of persistent organochlorine contaminants in infertile patients from Tanzania and Germany.

PURPOSE: To test whether environmental pollutants could affect fertility in humans. METHODS: 31 women and 16 men from Tanzania and 21 couples from Germany were included (n = 89). Pesticides and polychlorinated biphenyls were measured in serum, follicular fluid or seminal plasma by gaschromatography and related to sperm quality and pregnancy rates. RESULTS: Higher concentrations of DDT+DDE and dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were detected. All compounds showed higher concentrations in serum and lowest concentrations in seminal plasma. A lower pregnancy rate in German women with high serum concentrations of DDT+DDE was observed. The toxins had no impact on sperm quality. CONCLUSIONS: The distribution of toxins between agricultural and industrial countries is different. Seminal plasma seems to be inert against chemicals. In patients with high serum concentrations of DDT and DDE pregnancy rates were impaired.

Validation of a prediction model for estimating serum concentrations of chemicals which are equivalent to toxic concentrations in vitro.

The objective of the present study was to evaluate the validity of a recently developed extrapolation model for the prediction of concentrations of chemicals in serum which are equivalent to in vitro effective nominal concentrations. Necessary input data are in vitro toxic concentrations and distribution relevant system and substance specific parameters, e.g. lipid volume fractions and albumin concentrations, octanol/water partition coefficients and specific binding to albumin. It was investigated whether the influence of human and bovine serum, respectively, on nominal cytotoxic potencies (EC(50)-values) of selected chemicals in vitro can be properly predicted using this algorithm. Cytotoxicity was determined as growth inhibition of proliferating Balb/c 3T3 cells after exposure for 72 h. Concentration-effect relationships were measured in the presence of 2% foetal bovine serum (FBS) and, additionally, 18% FBS or human serum (HS), or 1% (w/v) bovine (BSA) or human (HSA) albumin, respectively. Addition of HSA and BSA increased the EC(50)-values of the different chemicals by factors of 2.1 - 22 and 1.7 - 29, respectively. From these measurements values for the specific binding of the test compounds to BSA and HSA were derived. Addition of 18% HS increased the EC(50)-values by factors between 4.2 and 52, while addition of 18% FBS resulted only in 1.5 - 10.4-fold increases. A comparison of experimentally determined and calculated EC(50)-values revealed that the differing influence of human and bovine serum was quite well predicted by the extrapolation model. Deviations did not exceed the factor 3 and were in most cases lower than 2. It is concluded that the extrapolation model is quite well suited to predict equivalent concentrations in serum from in vitro effective concentrations.

Absorption of p,p'-dichlorodiphenyldichloroethylene and dieldrin in largemouth bass from a 60-d slow-release pellet and detection using a novel enzyme-linked immunosorbent assay method for blood plasma.

This work describes the uptake of two organochlorine pesticides from slow-release pellets by largemouth bass and the utility of a blood plasma enzyme-linked immunosorbent assay (ELISA) method for exposure verification. We measured blood and tissue levels by gas chromatography/mass spectrometry and by a novel ELISA method, and present a critical comparison of the results.

Age at natural menopause and exposure to organochlorine pesticides in Hispanic women.

A cross-sectional study was conducted to evaluate the relationship between exposure to selected organochlorine pesticides (OCP) (p,p'-DDT, p',p'-DDE, dieldrin, hexachlorobenzene, beta-hexachlorocyclohexane [beta-HCH], oxychlordane, trans' nonachlor) and age at natural menopause in a sample of 219 menopausal women participating in the Hispanic Health and Nutrition Examination Survey in 1982-1984. Information on age at menopause, reproductive history, demographic variables, and potential confounding variables was collected via interview. Analysis of variance was employed to compare adjusted mean age at natural menopause among women by category of serum OCP level. Serum levels of p,p'-DDT, p,p'-DDE, beta-HCH, and trans-nonachlor were associated with a younger age at menopause. In particular, women with exposure levels in the highest exposure categories (serum p,p'-DDT > or = 6ppb, beta-HCH > or = 4ppb, or trans-nonachlor > or = 2ppb) had an adjusted mean age at menopause on average 5.7, 3.4, and 5.2 yr earlier, respectively, than women with serum levels of these pesticides below the detection limit. Women with serum p,p'-DDE levels greater than 23.6 ppb (highest quintile) had an adjusted mean age at menopause 1.7 yr earlier than women with serump,p'-DDE levels less than 5.5 ppb (lowest quintile). However, no consistent dose-response effect was apparent across low, medium, and high exposure categories. Interactions were detected for p,p'-DDT in combination with beta-HCH, trans-nonachlor, or oxychlordane, as well as beta-HCH in combination with oxychlordane.

Cancer mortality in workers exposed to dieldrin and aldrin: an update.

This study was conducted to investigate the possible long-term health effects, in particular carcinogenic effects, of occupational exposure to the organochlorine insecticides dieldrin and aldrin. We updated an earlier cohort mortality study of 570 employees involved in the production of these insecticides. All of the employees had worked in the production plants between 1 January 1954 and 1 January 1970 and were followed for cause-specific mortality until 1 January 2001. Based on dieldrin levels in blood samples taken during the exposure period, available for 343 workers, individual estimates of the total intake of dieldrin were estimated for all individual subjects in the cohort. The estimated total intake ranged from 11 to 7755 mg of dieldrin, with an average of 737 mg. One hundred and seventy-one workers had died before 1 January 2001, compared with an expected number of 226.6, giving a standardized mortality ratio (SMR) of 75.6 [95% confidence interval (CI): 64.6-87.7]. This deficit in total mortality was mainly attributable to a deficit in cardiovascular disease mortality, but cancer mortality was also lower than expected. The observed number of deaths from rectal cancer was significantly higher than expected (SMR = 300.0; 95% CI: 109.5-649.3), but was most pronounced in the low-intake subgroup and appears to be unrelated to exposure to dieldrin and aldrin. This study reinforces the earlier findings that occupational exposure of workers to significant amounts of dieldrin and aldrin has not led to a higher cancer mortality than would be found in an unexposed population.

[DDT and related pesticides in maternal milk and other tissues of healthy women at term pregnancy]. / DDT y plaguicidas relacionados presentes en la leche materna y otros tejidos de mujeres sanas con embarazos de término.

Ten healthy patients with term pregnancy resolved by abdominal via. During the surgical procedure samples of umbilical chord serum and maternal adipose tissue, were taken. In all the samples, together with the maternal milk collected the day 10 of puerperium, the concentrations of the following organochlorine pesticides, were measured up: (PCC); beta-BHC; gamma-BHC; heptachloride; aldrin; dieldrin, DDE, DDD, DDT and methoxychloride. The identification and quantification of pesticides was done by the comparison with standards certified by NIST (National Institute of Standard Technology). The general characteristics of the participants were: primigestas of 24.1 years aged, married and of a low socioeconomical level. As to the neonates, of 39 weeks of gestational age, female sex; 3,311 g of corporal weight and size of 51.1 cm. In all the analyzed samples at least one of the organochlorine pesticides was present. The results of correlation analysis between DDT concentration, present in the maternal serum with those identified in the adipose tissue and serum from the umbilical chord were highly significant: a = 0.97 and 0.87, respectively. In the maternal milk the highest concentrations of total DDT, were found, average of 2053 ng/g lipidic base, which is 2.8 times more of daily accepted intake. Likewise, DDT concentration in maternal serum kept exponential relation, growing with age (a = 0.99).