Exposure to organochlorine pesticides as a predictor to breast cancer: A case-control study among Ethiopian women.

Breast cancer (BC) is becoming one of the most prevalent non-infectious disease in low and middle income countries. The steady rise of BC incidence may be related to the different risk factors. Among many, rampant presence of environmental pollutants might be one of the risk factors. Therefore, the aim of this study is to investigate exposure to organochlorine pesticides as a risk factor to breast cancer. A case-control study design was employed among breast cancer patients and non-breast cancer individuals (controls). Blood samples were collected from 100 study participants (50 cases and 50 controls) followed by serum separation, extraction and cleanup using standard analytical procdures. The findings revealed that ten organochlorine pesticides were detected in the serum of the study participants. From the detected organochlorine pesticides, heptachlor was observed at higher concentration for breast cancer patients (6.90±4.37 µg/L) and controls (9.15±3.84 µg/L). Mean serum level of p,p'-DDE, p,p'-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in the serum of breast cancer patients than the controls. From the studied pesticides, p,p'-DDT and gamma-chlordane are significant predictors for BC, while, others are equivocal. A unit increment of the concentration of p,p'-DDT (AOR; 2.03, 95% CI: 1.041-3.969) increased the odds of developing breast cancer by two, while for gamma-chlordane (AOR;3.12, 95% CI; 1.186-8.203) by three. Our study results suggesting that, organochlorines are a risk factors for breast cancer in Ethiopia. Decreasing exposure to such organochlorines might have a significant public health relevance in reducing non-communicable chronic illnesses. Besides, continues monitoring of persistent organic pollutants using body biomarkers is important for disease prevention and device mitigation measures.

Insecticide use and risk of non-Hodgkin lymphoma subtypes: A subset meta-analysis of the North American Pooled Project.

Insecticide use has been linked to increased risk of non-Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self-reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype-specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20-2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17-2.16: FL, SLL) and DDT (OR = 1.36, 1.06-1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (Ptrend = 1.7 × 10-4 ), chlordane (Ptrend = 1.0 × 10-3 ) and DDT (Ptrend = 4.2 × 10-3 ), however, the exposure-response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45-9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75-16.53; Ptrend = 3.6 × 10-3 ). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure.

Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.

Organochlorine pesticides and prostate cancer, Is there an association? A meta-analysis of epidemiological evidence.

PURPOSE: The results of epidemiological studies about exposure to organochlorine pesticides (OCPs) and risk of prostate cancer (PC) are inconclusive. We conducted a meta-analysis to evaluate the association between exposure to specific OCPs and PC. METHODS: We searched PubMed, Scopus, and Web of science databases for case-control and cohort studies published till March 2015 that provided data about exposure to OCPs and PC. We also contacted authors and hand-searched references of the included articles. We calculated pooled estimates using random effects model and explored heterogeneity between studies. RESULTS: We systematically reviewed 15 articles and based our meta-analysis on 10 articles covering nine case-control studies and a large prospective cohort study. Pooled estimates of PC for highest versus lowest exposed category to p,p'-DDE was 1.02 (0.69-1.35), I (2) = 12.7 %, p = 0.333, trans-nonachlor, 0.88 (0.45-1.31), I (2) = 0.00 %, p = 0.892, oxychlordane, 0.91 (0.46-1.35), hexachlorobenzene, 0.88 (0.18-1.57), I (2) = 36.0 %, p = 0.210 from combining results of studies that applied serum OCPs measurements among the general population. For DDT, stratifying studies by exposed population revealed homogeneity, pooled estimate for serum level measurement for the highest exposed versus the lowest exposed of the general population was 0.81 (0.95-1.26), I (2) = 0.00 %, p = 0.400, and for occupational exposure 1.30 (0.94-1.67), I (2) = 13.4 %, p = 0.315. A positive but also insignificant association was obtained for pooling results for high exposure to lindane among farmers and pesticide applicators, 1.56 (0.82-2.29), I (2) = 41.7 %, p = 0.180. CONCLUSIONS: The existing epidemiological data do not support the hypothesis that exposure to specific OCPs is associated with an increased incidence of PC in the general population.

Pesticides and cancer.

Epidemiologic evidence on the relationship between chemical pesticides and cancer is reviewed. In animal studies, many pesticides are carcinogenic, (e.g., organochlorines, creosote, and sulfallate) while others (notably, the organochlorines DDT, chlordane, and lindane) are tumor promoters. Some contaminants in commercial pesticide formulations also may pose a carcinogenic risk. In humans, arsenic compounds and insecticides used occupationally have been classified as carcinogens by the International Agency for Research on Cancer. Human data, however, are limited by the small number of studies that evaluate individual pesticides. Epidemiologic studies, although sometimes contradictory, have linked phenoxy acid herbicides or contaminants in them with soft tissue sarcoma (STS) and malignant lymphoma; organochlorine insecticides are linked with STS, non-Hodgkin's lymphoma (NHL), leukemia, and, less consistently, with cancers of the lung and breast; organophosphorous compounds are linked with NHL and leukemia; and triazine herbicides with ovarian cancer. Few, if any, of these associations can be considered established and causal. Hence, further epidemiologic studies are needed with detailed exposure assessment for individual pesticides, taking into consideration work practices, use of protective equipment, and other measures to reduce risk.

A method evaluating population risks from chemical exposure: a case study concerning prohibition of chlordane use in Japan.

The proposed method evaluating population risks from chemical exposure is based on estimation of the individual variabilities in the internal concentration of the chemical of concern and estimation of the magnitude of toxic effect caused at a given internal concentration. We assume a log-normal distribution for individual variability and propose loss of life expectancy (LLE) as a measure of the magnitude of toxic effects. We applied it to the evaluation of the governmental action of prohibiting the use of chlordane as a termiticide in Japan. Because the method is applicable to both carcinogenic and noncarcinogenic chemicals, the cancer risk due to chlordane and the noncancer risk due to chlorpyrifos, a major substitute, were evaluated and compared. The estimated values of risk represented in terms of LLE are 0.10 days for residents of untreated houses, 1.9 days for residents of treated houses, and 4.4 days for termite control workers when chlordane is used, and 0, 2.8, and 31 days when chlorpyrifos is used, respectively. From the result of the case study, we can see that the prohibition of chlordane is not necessarily effective in reducing risk.

Immune alterations in humans exposed to the termiticide technical chlordane.

Lymphocyte phenotype frequencies and in vitro functional assays were studied in 27 individuals who had been exposed to technical chlordane in their homes or at their places of work. A control group consisted of 118 individuals who were similar to the exposed group with respect to age and sex distribution, and who had not knowingly experienced exposure to technical chlordane, was chosen for study. A significantly increased frequency of cortical thymocytes in the circulation (CD1) (p less than .001) and a decreased frequency of the suppressor-inducer phenotype CD45RA/T4 (p less than .01) were noted in the exposed group. Both kappa and lambda light-chain frequencies were elevated (p less than .01). Proliferative responses to the three mitogens tested, PHA, CONA, PWM, and to allogeneic lymphocytes in the mixed-lymphocyte culture assay were significantly lower than in controls (p less than .01). Responses in assays of the natural killer function were not significantly different from those of controls, but Fc receptor-associated K cell function was significantly greater than responses in controls. Of 12 individuals tested for evidence of autoimmunity, 11 demonstrated some increased titer of a form of autoantibody. This cluster of significant findings demonstrates the emergence of aberrant peripheral T and B cell regulation and a potential for autoimmune activation, detectable up to 10 y after exposure to technical chlordane.

Chlordane: 24-month tumorigenicity and chronic toxicity test in mice.

Four groups of 80 ICR SPF mice of each sex were fed 0-12.5 ppm technical chlordane for 104 weeks. Male and female mice were examined for hematological, biochemical, urinary, and pathological changes at 52 and 104 weeks of exposure. Serum AST (= SGOT) and ALT (= SGPT) were elevated in treated males and females, liver weights were increased in the 12.5-ppm groups, and masses were seen in the livers of 12.5-ppm males. Increased liver cell volume was seen in 5- and 12.5-ppm males and females, while hepatocyte degeneration and necrosis were seen only in treated males. Hepatic hemangiomas and hepatocellular adenomas typically occurred together and were significantly increased in 12.5-ppm males. No other significant changes were detected. However, the incidence of tumors in the 12.5-ppm males was within the range of historical controls. Accordingly, there was no evidence that chlordane induced tumors in the ICR mice. A long-term no-observed-effect level (NOEL) of 1 ppm chlordane in the diet was found.

Leukemias and blood dyscrasias following exposure to chlordane and heptachlor.

We present 25 new cases of blood dyscrasia, including leukemias, production defects, and thrombocytopenic purpura, generally following home termite treatment with the chlorinated hydrocarbon pesticides chlordane and heptachlor (C/H). These newly reported cases are consistent with 34 previously published case reports associating blood dyscrasias with C/H exposure. Additionally, the newly reported leukemias are consistent with epidemiologic evidence of excess risk of leukemia and other cancers in C/H-exposed populations and with the carcinogenic action of C/H in animals. The importance of case reports in warning of the association of blood dyscrasias to C/H exposure is emphasized. Until the voluntary halt in production in July 1987, millions of homes in the United States were treated with chlordane and heptachlor for termites even though their agricultural uses were phased out in 1978, largely on the grounds of "imminent hazard" because of carcinogenicity. In view of the recognized myelotoxicity, carcinogenicity, and other chronic toxic effects of these pesticides, a national program for monitoring all homes treated is urgently needed to detect persistent contamination.

Mortality of workers employed in the manufacture of chlordane and heptachlor.

A retrospective mortality study has been carried out on workers employed in the manufacture of chlordane and heptachlor between 1946 and 1976. The study group was comprised of 1403 white males who worked for more than three months at either of the two plants in the United States now producing these compounds. Information on deaths among terminated employees was obtained from the Social Security Administration and supplemented by information collected by another investigator by individual follow-up. There were 113 deaths observed in the group, compared to 157 expected, giving a standardized mortality ratio (SMR) of 72. There was no overall excess of deaths from cancer, even among workers followed twenty or more years after entry into the occupation. There was one death from liver cancer. An excess of deaths from lung cancer (12 observed, 9.0 expected) was not statistically significant and was not distributed by duration of exposure or of latency in any pattern suggesting an etiologic role for chlordane-heptachlor exposure. Although diseases of the circulatory system as a whole showed fewer deaths than expected (SMR 83), there was a statistically significant excess of deaths from cerebrovascular disease (17 observed, 9.3 expected). This excess was not related to duration of exposure or latency and occurred exclusively after termination of employment.