Organochlorine pesticides, oxidative stress biomarkers, and leukemia: a case-control study.

Exposure to pesticides has been linked to an elevated risk of leukemia. The present research aimed to evaluate the relationship between organochlorine (OC) pesticides and biomarkers of oxidative stress in patients with leukemia. This work was conducted on 109 patients with leukemia and 109 healthy controls. The serum concentrations of seven derivatives of OCs including alpha-hexachlorocyclohexane (HCH), beta-HCH, gamma-HCH, 2,4-dichlorodiphenyltrichloroethane (DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (DDE), and 4,4-DDE along with acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), paraoxonase-1 (PON1), and catalase (CAT) activities as well as total antioxidant capacity (TAC), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) levels were measured in all the subjects. Levels of OCs were remarkably higher in patients with leukemia compared with the controls (p<0.05). In addition, levels of SOD, AChE, GPx, PON1, and TAC were remarkably lower in patients with leukemia compared with controls (p<0.05). In contrast, MDA, NO, and PC concentrations were higher in patients with leukemia than in the controls (p<0.05). Moreover, the serum level of 4,4-DDE was negatively associated with GPx activity (p=0.038). Our findings suggest that OCs may play a role in the development of leukemia by disrupting the oxidant/antioxidant balance.

Prostate cancer risk and exposure to pesticides in British Columbia farmers.

BACKGROUND: Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. Our aim was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides. METHOD: A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants' lifetime cumulative exposure to approximately 180 active compounds in pesticides. Conditional logistic regression was used to assess prostate cancer risk, adjusting for potential confounding variables and effect modifiers. These include age, ethnicity, alcohol consumption, smoking, education, and proxy respondent. RESULTS AND CONCLUSIONS: The significant association between prostate cancer risk and exposure to DDT (OR = 1.68; 95% CI: 1.04-2.70 for high exposure), simazine (OR = 1.89; 95% CI: 1.08-3.33 for high exposure), and lindane (OR = 2.02; 95% CI: 1.15-3.55 for high exposure) is in keeping with those previously reported in the literature. We also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in our study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.

Cancer mortality among men occupationally exposed to dichlorodiphenyltrichloroethane.

Several studies have evaluated cancer risk associated with occupational and environmental exposure to dichlorodiphenyltrichloroethane (DDT). Results are mixed. To further inquire into human carcinogenicity of DDT, we conducted a mortality follow-up study of 4,552 male workers, exposed to DDT during antimalarial operations in Sardinia, Italy, conducted in 1946 to 1950. Detailed information on DDT use during the operations provided the opportunity to develop individual estimates of average and cumulative exposure. Mortality of the cohort was first compared with that of the Sardinian population. Overall mortality in the cohort was about as expected, but there was a deficit for death from cardiovascular disease and a slight excess for nonmalignant respiratory diseases and lymphatic cancer among the unexposed subcohort. For internal comparisons, we used Poisson regression analysis to calculate relative risks of selected malignant and nonmalignant diseases with the unexposed subcohort as the reference. Cancer mortality was decreased among DDT-exposed workers, mainly due to a reduction in lung cancer deaths. Birth outside from the study area was a strong predictor of mortality from leukemia. Mortality from stomach cancer increased up to 2-fold in the highest quartile of cumulative exposure (relative risk, 2.0; 95% confidence interval, 0.9-4.4), but no exposure-response trend was observed. Risks of liver cancer, pancreatic cancer, and leukemia were not elevated among DDT-exposed workers. No effect of latency on risk estimates was observed over the 45 years of follow-up and within selected time windows. Adjusting risks by possible exposure to chlordane in the second part of the antimalarial operations did not change the results. In conclusion, we found little evidence for a link between occupational exposure to DDT and mortality from any of the cancers previously suggested to be associated.

Breast cancer risk and historical exposure to pesticides from wide-area applications assessed with GIS.

Pesticides are of interest in etiologic studies of breast cancer because many mimic estrogen, a known breast cancer risk factor, or cause mammary tumors in animals, but most previous studies have been limited by using one-time tissue measurements of residues of only a few pesticides long banned in the United States. As an alternative method to assess historical exposures to banned and current-use pesticides, we used geographic information system (GIS) technology in a population-based case-control study of 1,165 women residing in Cape Cod, Massachusetts, who were diagnosed with breast cancer in 1988-1995 and 1,006 controls. We assessed exposures dating back to 1948 (when DDT was first used there) from pesticides applied for tree pests (e.g., gypsy moths), cranberry bogs, other agriculture, and mosquito control on wetlands. We found no overall pattern of association between pesticide use and breast cancer. We found modest increases in risk associated with aerial application of persistent pesticides on cranberry bogs and less persistent pesticides applied for tree pests or agriculture. Adjusted odds ratios for these exposures were 1.8 or lower, and, with a few exceptions, confidence intervals did not exclude the null. The study is limited by uncertainty about locations of home addresses (particularly before 1980) and unrecorded tree pest and mosquito control events as well as lack of information about exposures during years when women in the study lived off Cape Cod and about women with potentially important early life exposures on Cape Cod who were not included because they moved away.

Potential exposure to PCBs, DDT, and PBDEs from sport-caught fish consumption in relation to breast cancer risk in Wisconsin.

In Wisconsin, consumption of Great Lakes fish is an important source of exposure to polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ethers (PBDEs), and other halogenated hydrocarbons, all of which may act as potential risk factors for breast cancer. We examined the association between sport-caught fish consumption and breast cancer incidence as part of an ongoing population-based case-control study. We identified breast cancer cases 20-69 years of age who were diagnosed in 1998-2000 (n = 1,481) from the Wisconsin Cancer Reporting System. Female controls of similar age were randomly selected from population lists (n = 1,301). Information about all sport-caught (Great Lakes and other lakes) fish consumption and breast cancer risk factors was obtained through telephone interviews. After adjustment for known and suspected risk factors, the relative risk of breast cancer for women who had recently consumed sport-caught fish was similar to women who had never eaten sport-caught fish [relative risk (RR) = 1.00; 95% confidence interval (CI), 0.86-1.17]. Frequency of consumption and location of sport-caught fish were not associated with an increased risk of breast cancer. Recent consumption of Great Lakes fish was not associated with postmenopausal breast cancer (RR = 0.78; 95% CI, 0.57-1.07), whereas risk associated with premenopausal breast cancer was elevated (RR = 1.70; 95% CI, 1.16-2.50). In this study we found no overall association between recent consumption of sport-caught fish and breast cancer, although there may be an increased breast cancer risk for subgroups of women who are young and/or premenopausal.

Dichlorodiphenyldichloroethane burden and breast cancer risk: a meta-analysis of the epidemiologic evidence.

The relationship of dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk has received increasing attention since the beginning of the 1990s. Contradicting published results regarding the relationship between body burden levels of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE)--the main DDT metabolite--and breast cancer, we argue that such differences stem from methodologic differences among those studies. We performed a meta-analysis of 22 articles using DerSimonian and Laird's method for random effects models. The Q-statistic was used to identify heterogeneity in the outcome variable across studies. The gradient of p,p'-DDE exposure in epidemiologic studies was homogenized to serum lipid bases (nanograms per gram). The potential for publication bias was examined by means of the Begg's test. We discuss methodologic features of the studies in an attempt to reconcile the findings. The summary odds ratio (OR) for selected studies was 0.97 (95% confidence interval, 0.87-1.09) and the gradient of exposure ranged from 84.37 to 12,948 ng/g. No overall heterogeneity in the OR was observed (chi-squared = 27.93; df = 23; p = 0.218). Neither the study design nor the lack of breast-feeding control or the type of biologic specimen used to measure p,p'-DDE levels were the causes of heterogeneity throughout the studies. Evidence for publication bias was not found (p = 0.253). Overall, these results should be regarded as a strong evidence to discard the putative relationship between p,p'-DDE and breast cancer risk. Nevertheless, the exposure to DDT during critical periods of human development--from conception to adolescence--and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood.

Avaliaçäo dos efeitos tóxicos em trabalhadores causados por inseticidas utilizados em campanhas de saúde pública / Evaluation of toxic effects of pesticides used in programs for vectors control by public health workers

Os inseticidas utilizados em saúde pública na erradicação de vetores transmissores de doenças endêmicas que acometem as populações tanto da área urbana como da área rural, têm sido apontados como componentes agressores da saúde humana. Tendo em vista a precariedade das condições de trabalho e o descaso do próprio trabalhador, avaliou-se em um grupo de trabalhadores do distrito de saúde de Conceição do Araguaia, Estado do Pará, os efeitos tóxicos causados por dois grupos de inseticidas, organofosforados e organoclorados, que causam efeitos diversos em diferentes graus de intoxicações. Conclui que os trabalhadores do distrito de Conceição do Araguaia, possivelmente estavam com intoxicações crônicas causadas mais pelo uso do DDT

Proportional mortality of dichloro-diphenyl-trichloroethane (DDT) workers: a preliminary report.

The authors conducted a proportional mortality study of 1,043 deaths that occurred between 1956 and 1992 among men who used mainly dichloro-diphenyl-trichloroethane (DDT) in an anti-malarial campaign in Sardinia, Italy, during the late 1940s. For each cause of interest, investigators compared observed deaths with expected deaths. The estimated DDT exposure ranged from 170 to 600 mg/m3 in indoor operations and from 24 to 86 mg/m3 in outdoor operations. Workers directly exposed to DDT had a significant increase in risk for liver and biliary tract cancers (PMR = 228; 95% confidence interval = 143, 345) and multiple myeloma (PMR = 341; 95% confidence interval = 110, 795). However, the PMR for liver and biliary tract cancers was also elevated among workers who did not have direct occupational contact with DDT, and the authors observed no increase in either PMR, by number of days in exposed jobs. Perhaps DDT did not increase the risk or perhaps occupational exposure, although quite high, did not further increase the risk, compared with the heavy baseline exposure of the entire Sardinian population, (i.e., mainly through diet and drinking water). Expansion of the cohort to include all exposed workers, and collection of information to improve exposure assessment are needed to clarify these findings.

Long-term health effects of the occupational exposure to DDT. A preliminary report.

We conducted a proportional mortality study of 1043 deaths among men who took part in an antimalarial campaign in Sardinia, Italy from 1946 to 1950. DDT comprised 94% of the insecticide used during the campaign, and was sprayed over the soil of the entire region at an average concentration of 10 mg/m2, as well as in all dwellings and animal shelters. Expected deaths were derived from the proportional mortality rates of the general Italian male population, specific by cause, 5-year age groups, and 5-year calendar periods in the period from 1956 to 1992. The proportional mortality ratio (PMR) for cardiovascular diseases was significantly decreased, while nonmalignant respiratory diseases showed a 22% increase in risk of borderline statistical significance. Significant increases in risk among workers exposed to DDT in application or inspection jobs were observed for liver and biliary tract cancer (PMR = 228; 95% C.I. = 143-345) and multiple myeloma (PMR = 341; 95% C.I. = 110-795). The PMR for myeloid leukemia was also increased (PMR = 189; 95% C.I. = 38-552), although it was not statistically significant. PMRs for liver and biliary tract cancer and myeloid leukemia were also elevated among workers who did not have direct occupational contact with DDT (liver and biliary cancer: PMR = 210; 95% C.I. = 117-346; myeloid leukemia: PMR = 170; 95% C.I. = 19-614). No trends occurred according to length of employment in exposed jobs. These preliminary results are somewhat in agreement with experimental studies in rodents and previous epidemiologic findings. Expansion of the cohort to include all applications, and collection of information to improve exposure assessment is needed to clarify these findings.

A probabilistic model for deriving soil quality criteria based on secondary poisoning of top predators. II. Calculations for dichlorodiphenyltrichloroethane (DDT) and cadmium.

A simplified food web with three trophic levels is designed: plants and invertebrates at the first, small birds and mammals at the second, and birds and beasts of prey at the third trophic level. Exposure of top predators via separate food chains is analyzed. However, most top predator species are exposed via more than one food chain (food web). Therefore, a species-specific approach is followed too, for which four bird of prey species and two beast of prey species with different food choices are selected: sparrow hawk, kestrel, barn owl, little owl, badger, and weasel. The most critical food chains for secondary poisoning of top predators are soil --> worm/insect --> bird --> bird of prey for dichlorodiphenyltrichloroethane (DDT), and soil --> worm --> bird/mammal --> bird of prey for cadmium (Cd). The risk for the selected top predator species is much lower than the risk based on these critical food chains because the critical food chains constitute a minor part of their food webs. Species feeding on birds (sparrow hawk) and small carnivorous mammals (barn owl) are exposed to DDT and Cd to a much higher extent than species mainly feeding on small herbivorous mammals (kestrel and weasel). It is recommended to include exposure via the pathways soil --> worm/insect --> bird/mammal --> top predator in procedures for derivation of environmental quality objectives for persistent and highly lipophilic compounds.

Pesticides--how research has succeeded and failed in informing policy: DDT and the link with breast cancer.

Investigation of chemical exposures as possible etiologic factors for breast cancer has not been a research priority in the United States, which is surprising given the evidence from animal studies that environmental chemicals cause cancer and reproductive dysfunction. Study of environmental chemicals has also been indicated by the failure of traditional epidemiologic methods to account for significant proportions of breast cancer incidence with other risk factors. The fact that breast cancer risk is strongly associated with reproductive hormones is a further clue that environmental chemicals should be investigated. In addition to cancer, specific outcomes that need to be explored are reproductive dysfunction, immunotoxicity and neurotoxicity. Policy guiding our research should encourage toxicologic investigations of exposures to environmental chemicals that use state-of-the-art methods to determine exposure and human health effects. Using the approach suggested by John McLachlan, functional toxicology should be used to assess the activity of chemicals with regard to these outcomes. Just as dioxin toxicity can be expressed as toxic equivalents, estrogenic activity, for example, can be characterized in terms of estrogenic equivalents. In addition to the need to undertake this kind of research, needs for methods development and creative research funding mechanisms are discussed. Prevention of breast cancer may require intervention at an early age. Better understanding of breast cancer etiology, and especially its environmental components, may lead us toward that goal.

A review of the significance of animal food products as potential pathways of human exposures to dioxins.

The polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are groups of compounds with similar chemical and toxicological properties. Carcinogenicity was considered the most serious toxic end point when setting previous regulatory policies, but recent concerns have focused on the possible endocrine-disrupting activities of the dioxins. Toxicity is related to the 2,3,7,8 pattern of chlorine substitution, a pattern that also leads to chemical and metabolic stability. Dioxins are practically insoluble in water and concentrate in lipids of biological systems, leading to low background concentrations in fat of the general human population. Major environmental sources of dioxins are emissions from industrial chlorination processes and combustion of materials containing chlorine. Inhalation and water have been ruled out as significant exposure pathways, which suggests that food is the primary source. Pathways of entry into food chains are atmospheric transport of emissions and their subsequent deposition on plants, soils, and water. The major food sources seem to be fat-containing animal products and some seafoods. This conclusion is based on evaluations of potential environmental pathways involving dioxins and related compounds. Generally, dioxins and other lipophilic compounds are not taken up and translocated by plants, so residues in foods and feeds derived from seeds should be negligible. Animals on high-roughage diets, or those that ingest contaminated soil, are the most likely to accumulate dioxin residues from the environment. The conclusion that animal products are a major source of human exposure requires verification by appropriate food sampling programs and animal metabolism studies. If it is desirable to reduce human exposure to dioxins via the food supply, reduction of sources would be a more effective strategy than changing agricultural practices and food consumption patterns.

Residuos de inseticidos organoclorados em sangue de indivíduos ocupacionalmente expostos ao DDT em campanhas de saúde pública no Estado da Bahia-Brasil / Residues of the organochlorine pesticides in the blood of workers exposed to DDT during compaigns of public health in the State of Bahia-Brazil

A determinaçäo de inseticidas organoclorados no soro de trabalhadores com diferentes períodos de exposiçäo ocupacional ao DDT em Campanhas de Saúde Pública demonstrou elevados níveis de absorçäo, excedendo os valores estipulados na legislaçäo de saúde ocupacional. Foi constatado ainda que esta absorçäo excessiva decorria, em parte, da necessidade de utilizaçäo de equipamentos de proteçäo individual, dos hábitos dos trabalhadores no ambiente de trabalho e, também, da falta de conscientizaçäo dos aplicadores em relaçäo `as medidas corretas de manuseio e técnicas de aplicaçäo. Verificaram-se diferenças estatisticamente significativas (p < 0,001) nos níveis séricos de p,p'-DDE e p,p'-DDT entre os grupos expostos e o grupo de controle. O p,p'-DDD e o p,p'-DDT foram encontrados em todos os grupos expostos e näo foram detectados no grupo controle. Näo se verificaram, entretanto, diferenças estatisticamente significativas (p > 0,05) nos níveis sanguíneos dos isômeros do Hexaclorociclohexano (HCH) entre tais grupos, denotando uma exposiçäo ambiental ao HCH

Determinaçäo dos níveis séricos de inseticidas organoclorados em indivíduos näo expostos da Faculdade de Farmácia da UFMG / Determination of serum levels of organochlorine insecticides in unexposed individuals from the School of Pharmacy of UFMG

Trinta amostras de sangue foram coletadas de indivíduos da Faculdade de Farmácia da UFMG e analisadas para determinaçäo dos níveis residuais séricos de inseticidas organoclorados. Todas, provenientes de indivíduos sem qualquer exposiçäo ocupacional a estes compostos. O método utilizado para igual volume de ácido fórmico, visando liberaçäo dos inseticidas de suas ligaçöes plasmáticas, permitindo a extraçäo destes com n-hexano. A identificaçäo dos inseticidas foram realizadas por cromatografia gasosa com detector de captura de elétrons. Todas as amostras analisadas evidenciaram a presença do pp'DDE, principal metabólito do DDT, diclorodifeniltricloroetano encontrado no sangue, numa concentraçäo que variou de 0,32 a 6,95 mg/dl e b HCH (isomero b do hexaclorociclohexano) em 33% das mesmas, numa concentraçäo que variou de 0,21 a 0,85 mg/dl, sendo que, em apenas 10%, evidenciou-se a presença do aHCH (isomero a do hexaclorociclohexano) numa concentraçäo de 0,07 a 0,09 mg/dl. A presente pesquisa foi realizada, visando obtençäo de dados adicionais sobre níveis residuais séricos destes compostos.

Problemas residuales por policlorados aromaticos / Residual problems caused by aromatic polychlorinated compounds

El problema de la contaminacion ambiental a traves del grupo de los bifenilos policlorados senala la necesidad de reglamentar su uso a traves de medidas estatales nacionales como internacionales. La solucion de la problematica del PCB se puede llevar a cabo a traves de la substitucion o de su limitado empleo en la produccion social. Los compuestos utilizados y sus limites de tolerancia en Colombia son ligeramente cubiertos por nuestra legislacion. Para la seguridad de los alimentos se hace imprescindible la determinacion de los valores limites para los PCB