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.

Chloropicrin-induced toxicity in the respiratory system.

Chloropicrin is a volatile and reactive chemical that has been utilized as a warfare agent and a pesticide to fumigate soil against insects, fungi and nematodes. It poses a health risk to humans and animals if inhaled. The main source of chloropicrin exposure is occupational and occurs during its manufacture, transport and fumigation. Chloropicrin is toxic via all routes of exposure but the main route of systemic exposure is inhalation of the ambient air. Thus, the toxicity mainly affects the respiratory system. After a low level exposure, the first sign is irritation of the upper respiratory tract and eyes. Irritation is mediated by the sensory nerve fibers, which coordinate further activation of various protective reflexes. Chloropicrin-induced irritation is generally reversible but can alter airway responsiveness to other inhalation toxicants. Severe exposures cause injuries in the respiratory tract, inflammation, and even life-threatening edema. Much of the chloropicrin-caused symptoms and toxicity in the respiratory system displays similarities with those evoked by chlorine, which is also a breakdown product of chloropicrin. This review summarizes the latest information on chloropicrin with emphasis on the toxicity in the respiratory system. The data indicates that oxidative stress, modification of macromolecules, mutations, dysfunctions of cell organelles and cell death are involved in acute chloropicrin-induced toxicity in the respiratory system.

Incidences of mortality of Indian peafowl Pavo cristatus due to pesticide poisoning in India and accumulation pattern of chlorinated pesticides in tissues of the same species collected from Ahmedabad and Coimbatore.

Incidences of mortality of Indian peafowl Pavo cristatus, the national bird (Schedule I Indian Wild Life Protection Act 1972), are rampant in India. Between January 2011 and March 2017, around 550 peafowl in 35 incidences were reported dead across the country. Due to the non-availability of fresh carcases, poisoning could not be confirmed. Birds which died due to kite string injuries in Ahmedabad (15) and accidents in Coimbatore (5) were tested for residues of chlorinated pesticides, namely hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane (DDT), endosulfan, heptachlor, dicofol, dieldrin and cholipyrifos. The liver, kidney and muscle were the tissues considered to document pesticide load. Total load ranged from BDL to 388.2 ng/g. DDT (95%) and HCH (80%) were detected more frequently. DDT (40%) and endosulfan (26%) contributed maximum to the total pesticide load followed by HCH (21%). Pesticide accumulation pattern among the organs was in the order of liver (123.9 ng/g) > kidney (91.9 ng/g) > muscle (19.5 ng/g) with significant difference (p < 0.05). Peafowl from Ahmedabad had significantly (p < 0.05) higher level of total pesticide (149.0 ng/g) than birds from Coimbatore (47.8 ng/g). Although varying levels of chlorinated pesticide were detected, they were below reported toxic limits. Nevertheless, persistence of chlorinated pesticides and poisoning due to modern pesticides across the entire distribution range of Peafowl in India is a cause for concern.

Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population-based case-control study in four Nordic countries.

The aim of this study was to assess the effect of occupational solvent exposure on the risk of adult chronic lymphocytic leukemia (CLL). The current case-control study was nested in the Nordic Occupational Cancer Study (NOCCA) cohort. 20,615 CLL cases diagnosed in 1961-2005 in Finland, Iceland, Norway, and Sweden, and 103,075 population-based controls matched by year of birth, sex, and country were included. Occupational histories for cases and controls were obtained from census records in 1960, 1970, 1980/1981, and 1990. Exposure to selected solvents was estimated by using the NOCCA job-exposure matrix (NOCCA-JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Overall, nonsignificant CLL risk elevations were observed for methylene chloride, perchloroethylene, and 1,1,1-trichloroethane. Compared to unexposed, significantly increased risks were observed for cumulative perchloroethylene exposure ≤13.3 ppm-years (OR = 1.85, 95% CI 1.16-2.96) and average life-time perchloroethylene exposure ≤2.5 ppm (1.61, 95% CI 1.01-2.56) among women, and cumulative methylene chloride exposure ≤12.5 ppm-years (OR = 1.19, 95% CI 1.01-1.41) and 12.5-74.8 ppm-years (OR = 1.23, 95% CI 1.01-1.51) among men in an analysis with 5 years lag-time, though without dose-response pattern. Decreased CLL risk was observed for aliphatic and alicyclic hydrocarbon solvents and toluene. This study did not support associations for solvent exposure and CLL. Observed weak associations for methylene chloride, perchloroethylene, 1,1,1-trichloroethane exposures, aliphatic and alicyclic hydrocarbons and toluene were not consistent across sexes, and showed no gradient with amount of exposure.

[Effects of organochloride pesticides on dyslipidemias].

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.

Bayesian modeling of time-dependent vulnerability to environmental hazards: an example using autism and pesticide data.

BACKGROUND: Flexible modeling of time-dependent effects is required when vulnerability to hazards can be expected to vary over time, but the nature of this temporal dependency cannot be specified in advance. We present an analytic approach requiring minimal a priori assumptions about temporal parameters and producing measures of uncertainty for these parameters. METHODS: As a demonstration, we employ data describing autism spectrum disorders and applications of organochlorine pesticides in proximity to maternal residence before, during, and after pregnancy. We formulate a Bayesian model specifying temporal vulnerability as a flexible step function and constrain the dose-response relationship to be linear. We separately pooled information regarding hazard frequency and magnitude among cases and controls and used it as inputs for a Metropolis-within-Gibbs algorithm. To assess statistical significance, we conduct Monte Carlo simulations based on parameters calculated in the Gibbs portion of the algorithm. RESULTS: This method delineated two discrete periods of association between hazard and outcome. The first corresponded to a previously noted period of vulnerability with the added information of wide credible intervals, suggesting a high degree of uncertainty with respect to timing. Parameters for the second, previously unobserved period displayed slightly higher precision. Assessment of model fit favored the simultaneous inclusion of both these periods, and both periods appeared statistically significant on the basis of posterior distributions of specific parameters using Monte Carlo simulations. CONCLUSIONS: This method enabled a fuller accounting of time-dependent associations between hazards and outcomes without specifying temporal structure in advance.

Protective effects of fenugreek (Trigonella foenum graecum L.) upon dieldrin-induced toxicity in male rat.

The purpose of this study was to evaluate the protective effects of fenugreek (Trigonella foenum graecum L.) upon dieldrin-induced perturbations of haematological parameters and damages to liver and kidney of male Wistar rats. Under our experimental conditions, dieldrin poisoning resulted in 1) an alteration of several haematological parameters, 2) an oxidative stress evidenced by an increase of lipids peroxidation level associated with an increase of superoxide dismutase activity and a decrease of glutathione peroxidase and catalase activities in hepatic and renal tissues, 3) increased levels of glucose, total cholesterol, triglycerides, creatinine, urea, uric acid and proteins in blood, 4) increased activities of lactate dehydrogenase, alkaline phosphatase and transaminases in blood. Previous administration of fenugreek was found to hinder these dieldrin-induced damages: all hematological, renal and hepatic biomarkers, level of lipids peroxidation and activities of catalase and glutathione-peroxidase in liver and kidney were kept close to control values. This protective effect is mainly attributed to antioxidant properties of fenugreek.

Changes of serum biochemical parameters and liver pathology in 18 patients with 1,1,2,2-tetrachloroethane-induced hepatotoxicity.

OBJECTIVE: To evaluate the changes of serum biochemical parameters and liver pathology in patients with 1,1,2,2-tetrachloroethane (TTCE)-induced hepatotoxicity. METHODS: A total of 18 patients were diagnosed as TTCE-induced hepatotoxicity with an incubation period of 11-56 days. Blood samples were obtained from all patients and liver biopsy was performed in 16. RESULTS: All patients had fatigue, poor appetite and dark urine, 15 of whom suffered nausea, vomiting, abdominal distension and other gastrointestinal disorders. All patients had various degrees of liver function damage, and one died from liver failure. The prothrombin time was significantly prolonged in 6 patients. Histological findings showed varying degrees of necrosis, fatty degeneration and fibrosis in portal areas without cirrhosis. Patients with more severe jaundice had more severe pathologic changes, including piecemeal and bridge necrosis, and cholestasis. CONCLUSIONS: TTCE-induced hepatotoxicity may cause the changes in serum biochemical parameters and liver pathology. Most patients might recover with regular treatment. Prevention and early diagnosis of TTCE-induced hepatotoxicity are necessary.

Metalworking fluid exposure and cancer risk in a retrospective cohort of female autoworkers.

OBJECTIVES: Metalworking fluids (MWFs) have been associated with cancer of several sites, but the risks have been primarily examined in men or in studies that adjusted for gender in analyses. To evaluate whether risks were similar in women, we report cancer mortality risk among 4,825 female autoworkers within the united autoworkers-general motors autoworkers cohort. METHODS: Standardized mortality rates (SMRs) were calculated based on Michigan death rates (1980-2004). Internal comparisons (1941-2004) were examined using Cox regression for straight, soluble, and synthetic MWFs, and their corresponding oil- and water-based fractions. RESULTS: MWF exposure levels in the female cohort were generally less than two-third the MWF levels in the male cohort. Female autoworkers had an excess of cancer from all sites (SMR, 1.10; 95 % confidence interval (CI), 0.98-1.22) and lung cancer (SMR, 2.08; 95 % CI, 1.71-2.52). Colon cancer risk increased with straight (mineral oil) MWF exposure (exposure > median; hazard ratio = 3.1; 95 % CI, 1.2-8.0). A protective effect was observed for ovarian cancer with the soluble MWFs and water-based MWF metrics. Although bladder, rectal, and laryngeal cancers and malignant melanoma have been associated with straight MWF exposure and pancreatic cancer with synthetic MWF in men, there were too few deaths in this female subcohort to examine exposure-response relations for these sites. Results were null for lung and breast cancer. CONCLUSIONS: Our findings support an association between colon cancer and straight MWFs, but we found limited evidence of risk for other tumor sites at the lower exposure levels experienced by the female autoworkers.

Health effects of persistent organic pollutants: the challenge for the Pacific Basin and for the world.

Persistent organic pollutants include some organo-metals, such as methylmercury; lipophilic halogenated organics, such as dioxins, polychlorinated biphenyls, chlorinated pesticides, and polybrominated flame retardants; and perfluorinated compounds used as repellants. These compounds are resistant to degradation both in the environment and in the human body and tend to bioaccumulate within the food chain. Persistent organic pollutants cause a variety of adverse health effects, including cancer, immune system suppression, decrements in cognitive and neurobehavioral function, disruption of sex steroid and thyroid function, and at least some of them increase the risk of chronic diseases, such as hypertension, cardiovascular disease, and diabetes. Some compounds are byproducts of industry and combustion. Although the manufacture and use of most man-made chemicals has been reduced in recent years, the levels currently present in the population are still associated with an elevated risk of human disease. Others are still manufactured and used. These are dangerous chemicals that have contaminated even areas remote from the industrialized world, such as the polar regions.

Alpha-fetoprotein, carcinoembryonic antigen and beta2-microglobulin in adult population highly exposed to organochlorinated pollutants (PCB, DDE and HCB).

OBJECTIVE: It is aimed to obtain some general information about the prevalence of certain biomarkers in highly exposed population and on the interrelations between their serum level as related to that of some major organochlorines (OCs). METHODS: The level of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta2-microglobulin (beta2-MG) as well as that of polychlorinated biphenyls (Σ15PCBs), dichlorodiphenyl-dichloroethylene (DDE) and hexachlorobenzene (HCB) was estimated in 2046 adults (834 males and 1212 females) from highly polluted Eastern Slovakia. RESULTS: Great majority of blood levels was lower than two specific units used for individual markers, while the prevalence of values higher than two specific units of appropriate markers. At the same time, the prevalence of all markers level higher than 2 specific units was highly significantly increasing with of stratified PCBs level quintiles which were also positively related to these of DDE and HCB. Some significant correlations between biomarkers level and age were also observed. CONCLUSIONS: Although from the data obtained within this multipurpose field survey any notable interrelations between AFP, CEA and beta2-MG and some specific diseases and/or malignant processes could not be retrospectively specified, from the data obtained it appears that some of such interrelations cannot be definitely excluded.

Acute intentional toxicity: endosulfan and other organochlorines.

INTRODUCTION: Organochlorine pesticides continue to be used in several developing countries despite concerns regarding their toxicity profile. Endosulfan is an organochlorine recognized as an important agent of acute toxicity. METHODS: In this retrospective study, the clinical features, course, and outcomes among patients with acute endosulfan poisoning requiring admission to the hospital during an 8-year period (1999-2007) were reviewed. RESULTS: Among 34 patients hospitalized during this study period for alleged organochlorine poisoning, 16 patients with endosulfan poisoning were identified. The majority (75%) received initial treatment at a primary or secondary center. Neurological toxicity predominated, particularly low sensorium (81%) and generalized seizures (75%), including status epilepticus (33%). Other features observed included hepatic transaminase elevation, azotemia, metabolic acidosis, and leukocytosis. Mechanical ventilation was required in 69% and vasoactive agents in 19%. In-hospital mortality was 19%. There were no gross neurological sequelae at discharge. In three other patients who presented with organochlorine poisoning, the compounds ingested were lindane, endrin, and dicofol (n = 1 each). The course and outcomes in these patients were unremarkable and all three patients survived. CONCLUSIONS: Endosulfan is capable of high lethality and significant morbidity. The commonest manifestations are neurological although other organ dysfunction also occurs. In the absence of effective antidotes, restriction of its availability, along with prompt treatment of toxicity, including preemptive anticonvulsant therapy are suggested.

[Posictal neurogenic pulmonary edema secondary to acute poisoning by organochlorine pesticide in an adolescent suicide attempt]. / Edema pulmonar neurogénico posconvulsión secundario a intoxicación aguda intencional por pesticida organoclorado en una suicida adolescente.

We reported the case of an adolescent, without neurological background, who attempted suicide by organochlorine pesticide ingestion. The acute intoxication was expressed as a convulsive status epilepticus followed by an acute neurogenic pulmonary edema with rapid recovery within 48 hours. The diagnosis of neurogenic pulmonary edema in pediatrics, and particulary after a seizure, is unusual and often an exclusion one. Its evolution tends to be favorable, but can be fatal if it is not recognized and treated early. An acute nervous system injury associated with signs and symptoms of respiratory failure suggests the diagnosis. Other causes of pulmonary edema must be ruled out in order to avoid evaluation and treatment mistakes.

Environmental oestrogens and breast cancer: evidence for combined involvement of dietary, household and cosmetic xenoestrogens.

UNLABELLED: Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. CONCLUSION: If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.