ß-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B.

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on ß-hexachlorocyclohexane (ß-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of ß-HCH, already established in our previous studies, the aim of this work is to assess whether ß-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM ß-HCH. The obtained results strongly support the carcinogenic potential of ß-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize ß-HCH, which appears to be a full-fledged carcinogenic agent.

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.

Veterinary utility of dried blood spots for analysis of toxic chlorinated hydrocarbons.

Dried blood spots (DBS) on filter paper provide a simple and convenient means of collecting, storing and shipping samples for veterinary diagnostics related to toxin exposures. This paper presents validation data on analysis of DBS for chlorinated persistent organic pollutants, specifically 4,4'-dichloro-diphenyl-trichloroethane (4,4'-DDT) and its breakdown product 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE), lindane and a representative polychlorinated biphenyl (PCB) congener PCB-153. Analysis was by gas chromatography with electron capture detection (GC-ECD). The method required one 12.5 mm diameter spot representing application of 50 µL of blood, and working limits of detection (LOD) for each of the compounds was 5 ppb. Data are presented on development and description of the method, assay precision, LOD and quantitation, linearity, accuracy, specificity, effects of long-term storage and ruggedness. The method was also applied to 27 avian DBS, and 4,4'-DDE was detected in the majority of samples.

Efficacy and safety of a lindane 1% treatment regimen for scabies, confirmed by dermoscopy-guided skin scraping with microscopic examination.

BACKGROUND: This is the first study investigating scabies treatment since 1992 to involve examination of patients with microscopically confirmed scabies. AIM: To assess the efficacy of 1% lindane cream in treating microscopically confirmed scabies, and to determine the utility of dermoscopy-guided skin scraping with microscopic examination (DSGSS-ME) in evaluating the efficacy of scabies treatment. METHODS: This retrospective study analysed patients treated for scabies between January 2012 and December 2013. From the hospital database, 287 cases of scabies were identified and 50 were enrolled in the study. Patients were treated with 1% lindane cream twice weekly (days 0 and 1) and were evaluated with DSGSS-ME on day 7. Treatment and evaluations were repeated once weekly until a negative DSGSS-ME result was obtained. RESULTS: The cumulative efficacy of lindane 1% cream was 40% (20/50) after 1 week, 88% (44/50) after 2 weeks and 98% (49/50) after 3 weeks of treatment. There was a statistically significant difference between the 1- and 2-week (P = 0.03), and 1- and 3-week (P = 0.02) treatments. A total of 90 post-treatment DSGSS-MEs were performed, with a sensitivity of 97.3% (95% CI 85.8-99.9) and a negative predictive value of 98.2% (95% CI 90.1-100). Specificity and positive predictive value were 100%, as this procedure cannot yield false-positive results, because it relies on finding mites, eggs or faeces. CONCLUSIONS: We suggest that a twice-weekly schedule (on consecutive days) of 1% lindane treatment lasting at least 2 weeks is required to clear scabies. DSGSS-ME appears to be a good method to evaluate the efficacy of scabies treatment. This study introduces a safe and effective method to treat scabies, and to accurately monitor infestation status in patients.

Treatment of Scabies: Comparison of Lindane 1% vs Permethrin 5.

Scabies, whose etiologic agent is Sarcoptes scabiei, is a neglected parasitic disease that is a major public health problem in many resourcepoor regions. Its current therapies include benzyl benzoate, lindane, permethrin, sulfur, crotamiton, monosulfiram, and oral ivermectin. The aim of this study was to compare the efficacy and safety of lindane 1% lotion vs permethrin 5% in the treatment of scabies. A total of 120 patients with scabies attending a dermatology outpatient department were included. Patients were randomly divided into two groups. Sixty patients and their family contacts received 5% permethrin cream and the other 60 received 1% lindane lotion. Treatment was evaluated at intervals of 2 and 4 weeks. Permethrin provided improvement in 48 patients (80%) after 2 weeks, whereas lindane was effective in only 28 patients (46.6%). Permethrin (5%) cream was found to be significantly more effective in the treatment of scabies compared with lindane in this study. Adverse effects were rare in both the permethrin and lindane groups.

Lice.

Pediculosis (capitis, corporis, and pubis) share well-known features: worldwide prevalence (involving millions of people annually); parasites inducing skin lesions directly, and indirectly as a result of itching and hypersensitivity to parasites; and treatment based on good entomological knowledge of the parasite and practical considerations (ie, most available treatments do not act on eggs and should be repeated, depending on the life cycle of the parasites). Infestations are spread most commonly by close contacts. Social stigma and persistent misconceptions complicate the implementation of appropriate management strategies. Head and pubic lice infestations are diagnosed by the visualization of insects or viable nits (eggs). Primary treatments are topical pediculicides (permethrin or malathion), used twice, but emergence of resistance against pediculicides has created the need of alternative treatments including topical or oral ivermectin. Pubic lice are treated the same as head lice, but this finding should prompt evaluation for other sexually transmitted diseases. Body lice infestation should be suspected when symptoms of generalized itching occur in persons who do not change or wash their clothing or bedding regularly; lice may be found in the seams of their clothing.Topically administered permethrin may help to eradicate body lice, but personal hygiene measures are essential for successful treatment. Environmental treatment is also necessary for the eradication of the infestation. Health care personnel who come into contact with this population need to be well informed of the facts in order to disseminate accurate information for diagnosis and management.

Comparison of the effects of ivermectin, permethrin, and gamma benzene hexachloride alone and with that of combination therapy for the management of scabies.

RESULTS: The present study compared three scabicidal agents alone or with combination, the currently considered medicine of choice permethrin, oral ivermectin, and gamma benzene hexachloride in the local population of India. A total of 120 patients were studied. They were randomly divided into four groups -Group A, Group B, Group C, and Group D. Group A received topical 5% permethrin and oral placebo. Group B was given topical placebo cream and oral ivermectin in two dose regimen. Group C received topical 1% gamma benzene hexachloride with oral placebo, and Group D was given topical 5% permethrin and oral ivermectin. The improvement of lesions and pruritus were assessed in the next three follow-ups, i.e., on the 7th day, 14th day, and 28th day along with any adverse drug reactions (ADRs). It was found that Group A had 83%, 90%, 97%, and Group B had 70%, 81%, and 91% improvement of lesions in the three follow-ups respectively. Group C showed 57%, 70%, 86%, and Group D had 82%, 90%, 97% efficiency to decrease lesion count (p>0.05) respectively. Again, Group A observed 77%, 88%, and 94% improvement in pruritus in subsequent follow-ups, while for Group B it was 63%, 76%, and 86%. Group C had 55%, 71%, 85% efficiency, and Group D had recorded 77%, 88%, and 94% improvement to decrease pruritus (p>0.05). The incidence of adverse effects was found to be less in Group B, Group C, and Group D when compared to Group A. CONCLUSION: Group D or a combination therapy was a better choice for scabies in comparison to other monotherapy due to its better efficacy and safety profile.

Histological effects of sublethal concentrations of insecticide Lindane on intestinal tissue of grass carp (Ctenopharyngodon idella).

This study investigates acute toxicity and histological effects of Lindane insecticide on intestinal tissues of immature grass carp (Ctenopharyngodon idella). For these purposes, 105 fish were exposed to different concentrations of Lindane for 96 h in 5 groups with 3 replications. Samples of intestinal tissues were prepared in both control and exposure groups during and after the toxicity test. Vaculation, necrosis, bleeding and epithelial degeneration were apparent in the intestine tissue of treated individuals. The LC50 96 h of Lindane was 0.788 ppm in the present study, also the results showed besides pesticide-induced lesions, symptoms of abnormal swimming, anxiety, tendency to swim near the surface, and death due to terminal toxicity with mouth widely open. The exposed fish were pale in color, showed oxygen deficit and severe respiratory problems. Overall, our results confirm the toxicity of different concentrations of Lindane insecticide affecting behavior, intestinal function and inducing tissue lesions of immature grass carp.

DDE in mothers' blood during pregnancy and lower respiratory tract infections in their infants.

BACKGROUND: Dichlorodiphenyldichloroethylene (DDE) and other organochlorines suppress immunity biomarkers in animals and humans. Our aim was to study the association between prenatal levels of DDE and lower respiratory tract infection in infants independently from polychlorinated biphenyls (PCBs) and other organochlorines. METHODS: Maternal levels of p'p'-DDE, dichlorodiphenyltrichloroethane (p'p-DDT), PCB congeners 28, 118, 138, 153, and 180, hexachlorobenzene, and beta-hexachlorocyclohexane were measured in first trimester serum of 584 pregnant women from a general population-based cohort in Sabadell (Catalonia, Spain). Mothers reported lower respiratory tract infection in interviewer-led questionnaires administered at infant age 6 and 14 months. RESULTS: Thirteen percent of babies had recurrent lower respiratory tract infection during the first 14 months of life. Among the organochlorines, DDE showed the highest levels (median = 112 ng/g lipid); dichlorodiphenyltrichloroethane was not detectable. The median total PCB level was 85 ng/g. DDE was the only organochlorine that showed an association with recurrent lower respiratory tract infection (at levels >83 ng/g, the first tertile, relative risk = 2.40 [95% confidence interval = 1.19-4.83]), lower respiratory tract infection at 6 months (1.68 [1.06-2.66]), and lower respiratory tract infection at 14 months (1.52 [1.05-2.21]). Adjusting for PCBs, hexachlorobenzene or beta-hexachlorocyclohexane did not confound the association. CONCLUSIONS: Immunologic suppression by DDE as observed in experimental studies could explain the relation between DDE and lower respiratory tract infection, independently of PCBs. Exposure to DDE during prenatal life could be critical for the development of the immune and respiratory systems.

[Laboratory monitoring of pesticide residues in the environment].

The paper presents the results of laboratory monitoring pesticide residues in the environment in the Republic of Mordovia in 2000 to 2007. It gives examples how to determine organic chlorine pesticides in the foodstuffs and environment, by stating the concentrations of ingredients. The entry route of pesticides and their action on human beings are shown. The main preventive measures are indicated for persons handling pesticides.

[Morphogenesis of acetate-induced gastric ulcer upon chronic exposure to the pesticide hexachlorocyclohexane].

Morphological, histochemical, and histoenzymatic studies were employed to study the morphogenetic features of acetate-induced gastric ulcer in 40 rats during chronic enteral administration of the organic chlorine pesticide hexachlorocyclohexane. The authors first established the structural and metabolic bases of mucosal regeneration defects in the region of an ulcer upon chronic enteral exposure to the toxic agent and the dose dependence of the chronic nature of acute gastric ulcer.

Is Chronic Exposure to Low-Dose Organochlorine Pesticides a New Risk Factor of T-cell Immunosenescence?

Background: T-cell immunosenescence, a hallmark of an aging immune system, is potentially linked to the risk of developing cancer and other aging-related diseases. Chronic infection by cytomegalovirus (CMV) has been widely studied as a risk factor for T-cell immunosenescence, but the role of persistent chemicals has never been examined. As a typical example of persistent chemicals, we evaluated whether organochlorine pesticides (OCPs) are related to T-cell immunosenescence in the general population.Methods: Serum concentrations of ß-hexachlorocyclohexane, p,p'-DDT, p,p'-DDE, and trans-nonachlor were measured in 95 Korean adults ages 30 to 64 years. T-cell immunosenescence was assessed by the frequencies of CD8+CD57+, CD8+CD28-, CD4+CD57+, and CD4+CD28- T lymphocytes in 20 mL of fresh peripheral blood.Results: The senescence of CD8+ T lymphocytes was the most consistently associated with OCPs. For quartiles of measurements of OCPs, adjusted mean percentages of CD8+CD57+ and CD8+CD28- T lymphocytes in the CD8+ T lymphocyte population were 23.9, 27.6, 31.0, and 38.7 (P trend < 0.01) and 25.6, 27.3, 28.0, and 35.5 (P trend = 0.02), respectively. When we compared the strength of the associations among OCPs, CMV IgG titer, and age, OCPs showed the strongest association with markers of immunosenescence. Importantly, the association between OCPs and immunosenescence markers was more prominent among participants without known risk factors, such as a young age or low CMV immunoglobulin G titer.Conclusions: Chronic exposure to low-dose OCPs may be a new risk factor for T-cell immunosenescence.Impact: T-cell immunosenescence may be one possible mechanism linking low-dose OCPs and many chronic diseases. Cancer Epidemiol Biomarkers Prev; 27(10); 1159-67. ©2018 AACR.

Health effects of common home, lawn, and garden pesticides.

Children encounter pesticide products and their residues where they live and play and in the food supply. Pesticide exposure affects pediatric health both acutely and chronically; effects range from mild and subtle to severe. Pediatricians play an important role in identifying and reducing significant pesticide exposure in their patients by taking an exposure history to clarify the extent and types of exposures that may have occurred during acute care and preventive care visits. Developing knowledge about the toxicity of various chemicals, identifying reliable resources for pesticide information, and providing a common-sense approach toward recommending the safest practical alternatives is necessary.

Lindane: serious neurological effects.

(1) Cutaneous application of lindane carries a risk of systemic adverse effects, including serious neurological disorders. Lindane is readily absorbed through the skin, especially damaged skin and in children. (2) In practice, lindane has no place in the treatment of either lice or scabies.

Interaction between ß-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults.

Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of ß-HCH (P < 0.001). Furthermore, the synergistic interaction between ß-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of ß-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and ß-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

Lindane (Kwell)-induced aplastic anemia.

Numerous toxic exposures have been implicated in causing aplastic anemia. Thirteen cases of aplastic anemia and 5 cases of other blood dyscrasias, eg, red blood cell aplasia and thrombocytopenia, associated with lindane, have been reported in the literature. However, aplastic anemia secondary to the scabicidal product (lindane [Kwell]) has not been documented, to our knowledge. We present the case of a 21-year-old man with a diagnosis of aplastic anemia, known prolonged exposure to lindane, and documented elevated serum lindane levels. His clinical course is described as well as various defects are explored for the aplasia.

Topical application of lindane cream (Kwell) and antipyrine metabolism.

The transcutaneous absorption of a 1% lindane cream (Kwell) was determined after application according to the official label. By 3 days after application the plasma lindane level increased from nondetectable to 10.3 +/- 2.2 ng/ml. Sufficient lindane was absorbed to increase the plasma clearance of antipyrine from 0.027 +/- 0.009 to 0.037 +/- 0.011 1/kg/hr (p less than 0.05). these findings indicate significant transcutaneous absorption of lindane occurs following a single application and are compatible with the neurological toxicity reported following the topical application of lindane cream.

Environmentally relevant xenoestrogen tissue concentrations correlated to biological responses in mice.

The effects of xenoestrogens have been extensively studied in rodents, generally under single, high-dose conditions. Using a continuous-release, low-dose system in ovariectomized mice, we correlated the estrogenic end points of uterine epithelial height (UEH) and vaginal epithelial thickness (VET) with concentrations of two organochlorine pesticide isomers in fat and blood. Silastic capsules containing a range of doses of either ss-hexachlorocyclohexane (ss-HCH) or o, p'-dichlorodiphenyltrichloroethane (o,p'-DDT) were implanted subcutaneously, and animals were killed after 1 week. Average blood levels achieved by the various doses were 4.2-620 ng/mL for o,p'-DDT and 5.0-300 ng/mL for ss-HCH. Fat concentrations of o,p'-DDT and ss-HCH correlated linearly to blood levels (o,p'-DDT, r(2) = 0.94; ss-HCH, r(2) = 0.83). Fat concentrations (nanograms per gram of tissue) were higher than blood concentrations (nanograms per milliliter) by 90 +/- 5- and 120 +/- 9-fold (mean +/- SE) for o, p'-DDT and ss-HCH, respectively. The VET ranged from 12 +/- 0.9 microm in controls to 114 +/- 8 microm in treated animals, and was correlated to blood levels of either treatment compound. The UEH ranged from an average of 7.7 +/- 0.3 microm in controls to 26 +/- 2 microm in high-dose o,p'-DDT-treated animals. The UEH was also correlated with ss-HCH concentration, but it plateaued at approximately 11 microm at the highest doses. The lowest blood concentrations that produced statistically significant increases in VET or UEH were 18 +/- 2 ng/mL o,p'-DDT and 42 +/- 4 ng/mL ss-HCH. These values are within the same order of magnitude of blood concentrations found in some human subjects from the general population, suggesting that human blood concentrations of these organochlorines may reach estrogenic levels.

Reduced birthweight and length in the offspring of females exposed to PCDFs, PCP, and lindane.

The objective of this study was to investigate a broad range of adverse health outcomes and their potential association to wood preservative used in daycare centers. This article focuses on reproductive effects. A sample of 221 exposed teachers was provided by the employer's liability insurers. A comparison group (n = 189) insured by the same two organizations was recruited from nonexposed daycare centers. In a face-to-face interview, job history and reproductive history of 398 female teachers were ascertained. Data on exposure were provided, including measurements on concentration of pentachlorophenol (PCP) and lindane in wood panels, and of PCP, lindane, polychlorinated dibenzo-p-dioxins and dibenzofurans in indoor air. An exposure matrix based on individual job history, independent exposure information from each center, and reproductive history was set up with regard to the vulnerable time windows for each pregnancy. Using this approach, 49 exposed and 507 nonexposed pregnancies were identified, including 32 exposed and 386 nonexposed live births. For subgroup analyses the observations were restricted to independent pregnancies, excluding multiple and consecutive births. The data were analyzed with linear regression techniques, taking confounders into account. The crude median difference between exposed and nonexposed was 175 g in birthweight and 2 cm in length. Controlling for confounders, the results show a significantly reduced but weight (p = 0.04) and length (p = 0.02) in exposed pregnancies, even after restricting the data to independent pregnancies and pregnancies for which data could be validated from the mother's health cards. These differences were not explained by differences in gestational age indicating that a toxic effect, which could cause small-for date newborns, might have affected the fetus.