Search

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., Competing Interests: None

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 LC 50 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., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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 (P trend = 1.7 × 10 -4 ), chlordane (P trend = 1.0 × 10 -3 ) and DDT (P trend = 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; P trend = 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., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

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.

Objectives: The cytochrome P-450c17α enzyme encoded by the cytochrome P-450c17α (CYP17A1) gene plays a role in oestrogen synthesis. Genetic variation in the maternal CYP17A1 gene leads to differences in oestrogen level that affect fetal growth and cause small for gestational age (SGA). Organochlorine pesticides (OCPs) are endocrine disruptors that alter the normal oestrogen-progesterone balance, and are associated with adverse reproductive outcomes. This study was designed to investigate the effect of the gene-environment interaction between maternal CYP17A1 gene polymorphisms and maternal and cord OCP levels on the risk of SGA., Study Design: Maternal and cord blood samples of 50 term SGA cases (birth weight <10th percentile for gestational age as per Lubchenco's growth chart) and 50 normal pregnancies (controls) were collected. Women with occupational exposure to OCPs, anaemia, hypertension, antiphospholipid antibody syndrome, medical disease, parity of more than four, or a history of smoking, alcohol consumption or chronic drug intake were excluded from both groups. Maternal and cord blood samples were collected at the time of delivery or after delivery, respectively. The OCP levels of the samples were analyzed using a gas chromatography system equipped with an electron capture detector, and polymerase chain reaction-restriction fragment length polymorphism was used for polymorphic analysis of the CYP17A1 gene., Results: Significantly (p<0.05) higher levels of α-hexachlorocyclohexane (HCH), β-HCH and γ-HCH were found in maternal and cord blood samples of the SGA cases compared with the controls. The frequency of the A1A2/A2A2 genotype was significantly lower [p=0.041, odds ratio (OR) 0.421, 95% confidence interval (CI) 0.184-0.966] in the SGA cases compared with the controls. When gene-environment interactions between CYP17A1 gene polymorphisms and OCP levels were considered, a significant (p=0.004) association was found between a high level of endosulfan in cord blood and the A1A1 (wild-type) genotype of CYP17A1, leading to an estimated reduction in birth weight of 315g., Conclusions: Higher OCP levels and the A1A1 genotype of CYP17A1 in pregnant women may be considered as important aetiological factors in idiopathic SGA. This study provides evidence that genetic variation and its interaction with environmental exposure may increase the risk of SGA. Further studies are needed with a larger sample size, incorporating other gene polymorphisms and environmental exposures, to strengthen these observations., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Insecticide treatment resistance is considered to be a major factor in the increasing number of infestations by head lice. The large insecticide selection pressure induced by conventional topical pediculicides has led to the emergence and spread of resistance in many parts of the world. Possible mechanisms of resistance include accelerated detoxification of insecticides by enzyme-mediated reduction, esterification, oxidation that may be overcome by synergistic agents such as piperonyl butoxide, alteration of the binding site, e.g. altered acetylcholinesterase or altered nerve voltage-gated sodium channel, and knockdown resistance (kdr). Clinical, parasitological and molecular data on resistance to conventional topical pediculicides show that treatments with neurotoxic insecticides have suffered considerable loss of activity worldwide. In particular, resistance to synthetic pyrethroids has become prominent, probably because of their extensive use. As other treatment options, including non-insecticidal pediculicides such as dimeticone, are now available, the use of older insecticides, such as lindane and carbaryl, should be minimized, owing to their loss of efficacy and safety concerns. The organophosphorus insecticide malathion remains effective, except in the UK, mostly in formulations that include terpineol., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: Organochlorine pesticides (OCPs) and oxidative stress are reported to be associated with adverse reproductive outcomes. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous toxins including OCPs. OCPs are endocrine disrupter and prenatal exposure to them may be associated with fetal growth restriction (FGR). The objectives of the present study were (i) to determine the frequencies of polymorphic alleles of GSTM1 and GSTT1 genes in women with idiopathic FGR, (ii) to analyze the maternal and cord blood levels of the OCPs, and (iii) to identify the gene environment interaction that increases the risk of FGR., Study Design: Maternal and cord blood samples of 50 FGR cases (birth weight <10 percentile for gestational age as per Lubchenco's growth chart) and equal number of normal pregnancies who were occupationally non exposed to OCPs and excluding all the known high risk factors such as anemia, hypertension, antiphospholipid antibody syndrome, medical disease, dietary habit, living style, parity, and BMI. The collected samples at the time of delivery/after delivery were analyzed for OCPs levels by gas chromatography and polymorphic analysis for GSTM1/GSTT1 gene using multiplex PCR., Results: Significantly higher levels of α,β,γ-HCH and p,p'-DDT were found in maternal blood and significantly higher levels of β and γ-HCH and p,p'-DDT were found in cord blood of FGR cases as compared to controls. The genotypic distribution of GSTM1/GSTT1 was almost similar in both the groups, but the frequency of GSTM1-/GSTT1- (null) genotype was significantly higher in FGR cases as compared to controls (p<0.05, OR=6.42). When interaction between GSTM1/GSTT1 genes polymorphism-OCPs levels and birth weight (gene-environment interaction) was ascertained, a significant association was seen between β-HCH and GSTM1- genotype with reduction in birth weight of 213g., Conclusion: Higher levels of OCPs in pregnant women may be considered as an important aetiological factor in 'idiopathic' FGR. GST polymorphism can influence the relationship between prenatal exposure to pesticides and FGR. The present study provides evidence that polymorphism in xenobiotic metabolising genes may modify the effect of environmental health hazards and increase the risk of FGR., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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.

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.

Lindane (gamma-benzene-hexachloride) has been widely used as an antiscabetic and a pediculicidal agent for the past 50 years with reasonably good efficacy. After its initial use as a first-line therapy, there have been several reports of its neurotoxicity, especially among infants and young children. Literature review reveals that the risk of its neurotoxicity is minimal if used properly and strictly according to the prescribed recommendations. However, following availability of other safer and equally efficacious alternatives, it is now being regarded as a second-line therapy for scabies and pediculosis.

Lindane (gamma benzene hexachloride) is a widely prescribed topical scabicide because of its efficacy and cost-effectiveness. Although toxicity from a single proper application of lindane is generally not observed, the hazards of repeated applications, industrial exposure, and accidental ingestion have been well documented. We herein describe an infant with reversible neurotoxicity following repeated applications of 1% lindane for the treatment of scabies. The role of factors predisposing to increased absorption and the recommendations to minimize potential neurotoxicity are emphasized.

Head lice infestation is a common and growing problem that primarily affects school-aged children. Most cases of head lice are diagnosed and treated by nonphysicians. Misdiagnosis may lead to treatment when no lice are present. Treatment failure may lead to repeated use of and improperly applied pediculicides, potentially resulting in overexposure to pesticides. These treatment failures are primarily due to the emergence of treatment-resistant lice. In regions where resistant lice are common, patients may self-treat numerous times with over-the-counter pediculicides before seeking treatment from a physician. Resistance has decreased the efficacy of lindane, a prescription pediculicide that has been used for decades. In addition, the Food and Drug Administration recently warned of potentially serious adverse effects associated with lindane and recommended strict controls for its use. Malathion, recently reintroduced in the United States as a prescription pediculicide, has not been associated with treatment resistance or notable adverse effects, although it is flammable due to its alcohol base. Because of concerns about decreasing efficacy due to resistance and safety concerns about over-the-counter products and some prescription pediculicides, a reassessment of pediculicide safety is warranted. The safety and efficacy of commonly used over-the-counter and prescription pediculicide products are discussed, along with the safety and efficacy of other treatments, such as ivermectin, that are not indicated for the treatment of head lice but are being used increasingly.

Background: Lindane (gamma-benzene hexachloride), commonly used as a treatment for pediculosis, has been associated with adverse reactions and has recently undergone increased regulation., Objective: We sought to describe the patterns of a large number of lindane exposures reported to poison centers in Texas during 1998-2002., Methods: Data on all lindane exposures for pediculosis reported to the Texas Poison Center Network were analyzed., Results: There were 528 reported human exposures to lindane for pediculosis. The incidence of lindane exposures has decreased by 52% from 1998 to 2002. Misuse or abuse of lindane was reported in at least 87% of the cases. Of those cases with a known patient age, 45% were less than age 6 yrs, 23% age 6-19 yrs, and 32% over age 19 yrs. Female patients accounted for 55% of reported cases. Of those cases with a known medical outcome, 61% reported no effects. The most frequently reported symptoms were vomiting, nausea, and ocular irritation or ocular pain., Conclusion: The number of reported lindane exposures in Texas is decreasing. The majority of reported exposures involve misuse or abuse of the product. The pattern of symptoms reported in Texas was consistent with the literature.

Daily intake of lead, cadmium, aluminium, radiocaesium, DDT and metabolites, and lindane in the whole-day food rations collected in hospital canteens in Kraków, Łódź, Olsztyn and Poznań in winters of 1993-1994, 1995 and 1996 were determined. The diets contained almost 40 microg of cadmium, corresponding to 70% of PTWI, and compared to the levels recognised as safe (ADI or PTWI) small amounts of the other contaminants. The highest content of Pb, Cd, Al and lindane was determined in the diets collected in Kraków, that of radiocaesium in Łódź, and DDT level was the highest in Poznań. The whole-day food rations from Olsztyn, situated in a region called "green lungs of Poland", were not statistically less contaminated than the diets from the other towns. The Pb and radiocaesium levels decreased significantly with time.

Contamination of persistent organochlorines (OCs) such as PCBs (polychlorinated biphenyls), DDT and its metabolites (DDTs), HCH (hexachlorocyclohexane) isomers (HCHs), chlordane compounds (CHLs), and HCB (hexachlorobenzene) were examined in mussels collected from coastal waters of Asian countries such as Cambodia, China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Far East Russia, Singapore, and Vietnam in 1994, 1997, 1998, 1999, and 2001 to elucidate the contamination status, distribution and possible pollution sources and to assess the risks on aquatic organisms and human. OCs were detected in all mussels collected from all the sampling sites investigated. Considerable residue levels of p,p(')-DDT and alpha-HCH were found in mussels and the concentrations of DDTs and HCHs found in mussels from Asian developing countries were higher than those in developed nations suggesting present usage of DDTs and HCHs along the coastal waters of Asian developing countries. On the other hand, lower concentrations of PCBs detected in mussels from Asian developing countries than those in developed countries indicate that PCBs contamination in mussels is strongly related to industrial and activities. To our knowledge, this is a first comprehensive report on monitoring OCs pollution in the Asia-Pacific region.

Objective: To examine the association between DDT (dichlorodiphenyl trichloroethane) and HCH (hexachlorocyclohexane) exposure and intra-uterine growth retardation (IUGR, <10th percentile of birth weight for gestational age)., Method: We detected p,p'-DDT, o,p'-DDT, p,p'-DDD, p,p'-DDE and alpha-HCH, beta-HCH, gamma-HCH, delta-HCH in maternal blood, placenta and cord blood, collected at parturition, from mothers with IUGR babies ( n=30) and from those with babies of normal weight ( n=24), using gas-liquid chromatography equipped with electron capture detector ((63)Ni). The adjusted odds ratios (ORs) for these pesticides in mothers and infants were determined by multiple logistic regression., Results: There were statistically significant associations ( P<0.05) between maternal blood levels of alpha-HCH (OR=1.22; 95% CI: 1.02-1.46), gamma-HCH (OR=1.38; 95%CI: 1.05-1.80), delta-HCH (OR=1.61; 95% CI: 1.01-2.54), total HCH (OR=1.07; 95% CI: 1.01-1.13) and p,p'-DDE (OR=1.21; 95%CI:1.03-1.42) and IUGR after adjustment for potential confounders. Also, significant association (P<0.05) between cord blood levels of gamma-HCH (OR=1.14; 95% CI: 1.00-1.31), delta-HCH (OR=1.31; 95% CI: 1.00-1.75), total HCH (OR=1.07; 95% CI: 1.00-1.14) and IUGR were found after adjustment for potential confounders. A significant negative correlation between body weight of newborn babies and p,p'-DDE in maternal blood (r= -0.25; P<0.05) and delta-HCH and p,p'-DDE in the cord blood (r= -0.27 and -0.26; P<0.05) was noticed after gestational age had been accounted for., Conclusion: Exposure of pregnant women to organochlorine pesticides may increase the risk of IUGR, which is a contributing factor for infant mortality in India.

In this laboratory study, we address the effect of Chironomus bioturbation (0, 2,000, 6,000, and 18,000 ind/m2) and sediment organic matter content (10, 20, and 40%) on the fate, distribution, and bioavailability of 14C-lindane under standardized conditions in toxicity tests with artificial sediment. The results show that both Chironomus burrowing activity and sediment organic matter strongly modify test conditions. Larval mortality and development were inversely related with Chironomus densities and lindane concentration. Sediment organic matter content affected larval development rates but not mortality. Partitioning of lindane between the sediment, overlying water, and interstitial water was affected negatively by Chironomus larval densities: however, sediment partitioning was positively affected by sediment organic matter content. Bioturbation by Chironomus resulted in a remobilization of particle-associated lindane to the interstitial and overlying water, implying an increase in the bioavailability of the test compound. Strong positive relationships were found between Chironomus densities and lindane concentrations in interstitial water. The presence of Chironomus also resulted in lower label recovery. Label recovery on sediment particles ranged from 49 to 61% of initially added label in microcosms without Chironomus, from 41 to 56% at low larval densities, and from 15 to 50% at high larval densities. These results show that large discrepancies may exist between nominal test concentrations (from test compound additions) and true exposure concentrations even under standardized test conditions, which can introduce a relatively large error term in risk assessments. Calculations show that volatilization may be a quantitatively important sink for test compounds.

The authors studied the in vitro effects of lindane on macrophage-activating factor (MAF) production by peripheral blood leukocytes (PBLs) in rainbow trout. MAF production by PBLs induced normally by mitogens concanavalin A (ConA) and phorbol myristate acetate (PMA) was not modified by a pretreatment with lindane (from 2.5 to 50 microM). Only a concentration of 100 microM lindane decreased MAF production, associated with cellular death. Moreover, MAF activities were detected in supernatants of PBL cultures treated with lindane from 2.5 to 10 microM in absence of ConA/PMA stimulation. Factors present in these supernatants remain to be identified. Lindane, at concentrations which did not induce MAF production (50 and 100 microM) led to an increase in PBL calcium levels by acting on the endoplasmic reticulum calcium stores. Although the intracytosolic calcium concentration ([Ca(2+)](i)) increase seems to be associated with cell death, lindane-induced MAF production may be linked with other intracellular mechanisms.

Acute and chronic ecotoxicity tests with lindane were carried out using the soil invertebrates Eisenia fetida, Enchytraeus albidus, and Folsomia candida. To assess the influence of soil type on the bioavailability, these tests were carried out in a standard artificial OECD soil and in sandy and loamy field soil. For each species, differences in lindane toxicity were observed for the three soil types. These differences were, however, not related to the organic matter content. The relative differences in lindane toxicity between the soils was species-specific. These results therefore indicate that the pore-water hypothesis, i.e., the pore-water contaminant fraction being the toxicological bioavailable fraction, is not always applicable for organic substances. NOEC, NEC, as well as EC10 data were subsequently used to calculate hazardous concentrations for 5% of the species; this methodology, aimed at setting environmental quality criteria, is discussed.

The effect of hexachlorocyclohexane (HCH) singly and in combination with iron was studied on chlorophyll, malondialdehyde, cysteine, total -SH contents and potassium ion leakage in the plants of Hydrilla verticillata. The effect of HCH was also studied on glutathione (reduced and oxidised) content and superoxide dismutase activity. The results showed an increase in malondialdehyde content and potassium ion leakage with increase in HCH concentrations, however, the presence of Fe played a protective role. The chlorophyll content was decreased with increase in HCH concentrations and exposure period. However, the chlorophyll content at 2 and 5 microg ml(-1) was significantly higher in HCH-treated plants as compared to HCH + Fe after 168 h, showing protective role of Fe. The results showed significant increase up to 1 microg ml(-1) in cysteine content with increase in concentrations in both the treatments. The total -SH content was increased with increase in concentrations in both the treatments. In HCH-treated plants, non-significant change was noticed in reduced glutathione (GSH) content however, oxidised glutathione (GSSG) content was increased significantly after 168 h, indicative of oxidative stress. In addition, superoxide dismutase activity was increased non-significantly with increase in HCH concentrations. The accumulation of HCH singly and in presence of Fe was concentration- and duration-dependent. The accumulation of HCH was decreased in presence of Fe at higher concentrations. In contrast, the accumulation of Fe was increased in presence of HCH at higher concentrations. The results showed that malondialdehyde content and potassium ions leakage are the primary responses of toxicity.

Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei var. Hominis. It is a very contagious parasitosis with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, wrists, axillary folds, abdomen, buttocks, inframammary folds and, in men, the genitalia. It is characterized by intense nocturnal pruritus. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Definitive diagnosis is made when the scabies mites or their eggs or fecal pellets can be identified on a light microscope. New techniques for diagnosis include the use of the epiluminiscence microscopy. The most common topical treatments for scabies include lindane and permethrin. Permethrin provides a greater margin of tolerability because of its low inherent toxicity and low percutaneous absorption. Oral ivermectin is the most recently developed treatment for scabies. A single oral dose of ivermectin 200 microg/kg of bodyweight is a well-tolerated and very effective treatment. It is especially indicated in crusted scabies, scabies in immunocompromised hosts and infestations in crowded communities. It is also useful as a simple treatment in the prophylaxis of close contacts.

The present paper bears on the main effects of lindane (gamma isomer of hexachlorocyclohexane) on endocrine and reproductive functions in mammals. This pesticide, once widely used to kill lice and a variety of pests that attack agricultural products, livestock and trees, has been progressively eliminated from many applications since the mid-1970s in Europe or USA, but is still used in the rest of the world. Lindane is absorbed through respiratory, digestive or cutaneous routes and accumulates in fat tissues. It damages human liver, kidney, neural and immune systems and induces birth defects, cancer and death. Chronic administration results in endocrine disruption in birds as well as in mammals. Treatment with 1-40 mg of lindane/kg b.w. disrupts testicular morphology, decreases spermatogenesis, inhibits testicular steroidogenesis, reduces plasma androgen concentrations and may adversely affect reproductive performances in males. In females, lindane disrupts the estrous cycle, reduces serum estrogen and progesterone levels, decreases sexual receptivity whereas in pregnant dams it decreases whelping rate and litter size. These effects were also observed in some rats exposed to residual environmental doses. In addition, there is concern that irreversible effects may be induced when animals are exposed to endocrine disrupting chemicals during critically susceptible phases of sexual differentiation or development. These effects would results from (i) alterations of gonade or gamete cell membranes (ii) cell metabolism changes including alterations of ionic exchanges (mainly calcium or potassium), direct or free radical-mediated inhibition of steroidogenesis (iii) or neuroendocrine changes leading to a decrease in sexual performance of either parents or their offsprings exposed in utero or through lactation.

The goal of the present review is to collect information concerning membrane effects induced by lindane intoxication, a y isomer of hexachiorocyclohexane (gamma-HCH) that has been largely used as an insecticide and disinfectant in agriculture and entered also in the composition of some lotions, creams and shampoos used against parasites (lice and scabies). Absorbed through respiratory, digestive or transcutaneous pathways, lindane accumulates within lipid rich tissues. Lindane accumulation depends on the duration of the exposure and affects tissues in the following order: adipose tissues > brain > kidney > muscle > lungs > heart > liver > blood. Whatever the mode of lindane absorption, it accumulates in blood and is distributed throughout the body. It may affect human health by exerting systemic, immunologic, teratogenic, and/or cancerogenic effects. The symptoms of lindane intoxication are different according to the mode of intoxication, acute or chronic. The absorption of high doses of gamma-HCH is particularly toxic for the central nervous system and for the female and male reproduction apparatus in mammals where lindane is considered as an endocrine disruptor. Lindane is highly lipophilic and incorporates into biological membranes according to the following sequence: mitochondria > sarcoplasmic reticulum > myelin > brain microsomes > erythrocytes. Lindane exerts a stimulating action on synaptic transmission and inhibits the chloride current activated by gamma-amino butyric acid (GABA) of many muscular and nervous preparations by interacting with the receptors GABA-chloride channel complex. It seems to affect calcium homeostasis of many tissues. The similarity between lindane and inositol (1, 4, 5) phosphate (IP3) suggested that lindane releases Ca2+ from IP3-sensitive intracellular stores in macrophages and myometrial cells. Ca2+ release from reticulum endoplasmic, mitochondria and other Ca2+ stores has been reported in cat kidney cells. Lindane altered energetic metabolism of hepatic mitochondria and the inositol-phosphate synthesis in neuronal cells. However, lindane does not compete with the IP3 receptor. Lindane produces a Ca2+ influx in mice peritoneal macrophage cells responsible for the Ca2+ induced Ca2+ release produced by phospholipase C via IP3 pathway and resulting in a maintained increase of the free cytosolic Ca2+ concentration. Lindane decreased the membrane erythrocyte and cerebral cell concentration of phosphatidyl inositol PI, PIP and PIP2 in rats repetitively exposed to lindane for 3 or 6 months. Lindane induces oxidative stress; it modifies the activity of the scavenger enzymes. This effect is involved in the inhibition of intercellular gap junctions. Modifications of the electrocardiogram (ECG), sinusal rhythm alteration and negative and dysphasic variations of T wave, similar to those produced by hyperkaliemia, have been reported after lindane absorption. During acute lindane poisoning, the activities of serum transaminases (SGOT, SGTP), and lactate deshydrogenase (LDH) increase. Lindane produces histological alterations of cardiac tissues and a cardio-vascular dystrophy (contracture, degenerescence and necrosis) mainly in the left ventricular wall and a hypertrophy of the left ventricle. Chronic application of residual doses of lindane shortened the action potential duration in rat papillary muscle. These effects were similar to those induced by hyperthyroidism. Lindane increases the triiodothyronine (T3) serum level in hyperthyroid rats. T3 plays an important role in the postnatal development of the rat ventricle by increasing the density of potassium channels which contribute to action potential shortening during the development. Thyroid hormones influence the regulation and the expression of messengers ARN which encode different potassium channels involved in action potential repolarization (Kvl.2; Kvl.4; Kvl.5; Kv2.1; Kv4; HCN2). The thyrotropine-releasing hormone (TRH) modulates the HERG-type rapid delayed potassium channel (IKr) encoded by the human gene ether-a-go-go in rat anterior pituitary cells GH3/B6. This channel is involved in the cardiac long QT syndrome. TRH modifies the current kinetics of human HERG potassium channel co-expressed in Xenopus oocytes with the TRH receptor, whose activity is modulated via the protein kinase C pathway linked to a G protein-coupled receptor and is regulated by changes in the PIP2 concentration in the membrane. IKr channels regulation is also dependent on sexual hormones. In conclusion, lindane affects the excitable membranes and the cardio circulatory system. These alterations (may) represent a potential risk for human health.

The effect of 0, 1, 5, 25 and 50 mg/kg body weight (b.w.) lindane, administered in corn oil by gavage, on cytochrome P450 (CYP) phenotype was investigated in the liver of ovariectomized (ovx), sham operated (sham-ope) and nonovariectomized (n/ovx) adult Wistar rats. Total hepatic microsomal CYP content and the O-dealkylation of 7-ethoxy- (EROD), 7-methoxy- (MROD), 7-pentoxy- (PROD) and 7-benzyloxy-resorufin (BROD) were assayed. In addition, CYP1A1, 2B1/2B2, 2C11 and 3A2 proteins were determined by western blot using specific anti-rat antibodies. Protein bands were visualised by chemiluminescence and their intensities were compared among groups. A statistically significant, dose-dependent increase of all parameters studied was observed in all three animal groups after lindane administration. Ovx rats, however, responded differently to lindane administration than n/ovx or sham-ope animals. At the highest doses in ovx rats, the relative liver weight was more increased and the total CYP content was less increased than in n/ovx or sham-ope animals. Moreover, the degree of induction of PROD and BROD activities was higher and that of EROD activity was lower in ovx than in either n/ovx or sham-ope animals. Accordingly, CYP2B1/2B2 protein showed the largest increase in ovx rats, whereas CYP1A protein increased more in n/ovx or sham-ope animals. CYP2C11, a cytochrome predominantly expressed in males, was also more strongly induced in ovx than in n/ovx or sham-ope animals. CYP3A2 was slightly expressed in ovx but not in n/ovx non-treated rats, although the effect of induction was clearly greater in the latter. These results, overall, indicate that ovariectomy significantly affects, both qualitatively and quantitatively, CYP expression following induction by lindane and support the anti-estrogenic effect of lindane in rats. The pathophysiological and toxicological relevance of liver CYP induction by lindane and possibly other organochlorine xenobiotics in females with a lack or deficiency of estrogen supply remains to be investigated.

Chironomus riparius Meigen were exposed to 0, 0.01, 0.1, 0.5, 0.75 and 1.0 ppm lindane for 48 h as fourth instar larvae. Exposure had no effect on glutathione-S-transferase (GST) activity in larvae snap-frozen immediately following exposure. In contrast, exposure had longer-term consequences affecting developmental parameters. Concentrations above 0.5 ppm lindane affected larval behaviour, reduced adult body size and fecundity and delayed emergence times. The lack of significant change in GST activity when life history characters were affected by high concentrations of lindane, suggests that in C. riparius, GST is not a sensitive biomarker of pesticide exposure or effect.

We have studied the influence of metabolites of chlorinated pesticides (lindane, pentachlorophenol, hexachlorobenzene) on proliferation and differentiation in two stroma-free murine bone marrow culture models, a multipotent progenitor cell line (FDCP-mix) and primary lineage-depleted bone marrow cells. Tetrachlorohydroquinone (Cl(4)pHQ), tetrachloro-p-benzoquinone (Cl(4p)BQ), but not their positional isomers, tetrachlorocatechol (Cl(4)oHQ) and tetrachloro-o-benzoquinone (Cl(4)oBQ), nor 2,4,6-trichlorophenol (2,4,6-Cl(3)P), were much more toxic to FDCP-mix cells cultured under conditions which lead to self-renewal than under conditions which lead to granulocyte-macrophage differentiation. Under the latter conditions, Cl(4)pHQ and Cl(4p)BQ even stimulated growth at intermediate concentration levels. In the primary cell cultures, pronounced differences were observed in the sensitivity between individual developmental pathways and between the different compounds. The percent of cells differentiating into the granulocytic lineage was increased at high concentration levels of each test compound. However, stimulatory effects on the macrophage lineage were observed at intermediate concentration levels of Cl(4)pHQ, Cl(4p)BQ and 2,4,6-Cl(3)P, and differentiation into erythrocytes was stimulated at low concentrations of 2,4,6-Cl(3)P. It is concluded that chlorinated monocyclic pesticides, after biotransformation to quinoid metabolites, may interact directly with haemopoietic progenitor cells with differential effects on self-renewal and differentiation. These mechanisms could lead to myeloplastic disorders.

Endocrine disrupting properties of organochlorine(chlorinated hydrocarbon) insecticides are reviewed. Physicochemical properties such as water solubility and partition coefficient of the organochlorine insecticides greatly influence their environmental fates. Insolubility in water and high partition coefficient usually enhance the environmental persistence of the compounds. On the endocrine disrupting properties, an important metabolite of p,p'-DDT, p,p'-DDE, is known to exhibit weak anti-androgenic properties. An isomer o,p'-DDT is estrogenic. Metabolites of methoxychlor, mono-demethylated and di-demethylated methoxychlor derivatives, are weakly estrogenic. Their dehydochlorinated product also exhibits estrogenicity. HCH isomers are environmentally persistent compounds, but there is few reports on their endocrine disrupting properties. Some other organochlorine pesticides such as cyclodienes and chlordecone is reported to be estrogenic.

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.

Under the action of hexachlorcyclogexan in concentration not exceeding the pesticides residues in food staffs the prominent adaptive mechanisms stress of gematoalveolar barier is seen. However, the adaptation has the extensive character and is caused by increase of alveolar monocytes in broncho-alveolar lavage. The phagocytosis functional reservers exceed the control values, but phagocytes activity and phagocytory index remain decreased and reach norms just after the xenobiotic abolition.

Background: The adverse neurobehavioral effects of long-term low exposure to wood-preserving chemicals (WPC) containing solvents, pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (gamma-HCH; lindane), and other neurotoxicants were investigated in a neuropsychological group study., Methods: Out of a population of 2,000 women visiting the outpatient practice of a gynecological department, a sample of 15 women aged 31-56 (mean 43) with long-term exposure to WPC verified by self-report, biological monitoring, and environmental samples was investigated. Fifteen controls aged 42 (31-56) years were drawn from the same population and pair-wise matched with respect to sex, age, education, and estimated intelligence., Results: For the exposed group, mean PCP serum level was 43.6 micrograms/l and mean gamma-HCH blood level was 0.085 microgram/l. Mean duration of exposure was 10 (5-17) years. Intellectual functioning, attention, memory, and visuo-motor performance were examined, suggesting significant group differences in visual short-term memory (Benton Test; d = 1.5, P = .005), verbal memory (paired associate learning and Peterson paradigm; d = 4.3 and 1.6, P < .001), and an incidental learning task (d = 2.3; P = .001). Frequent subjective complaints as assessed by questionnaire were attenuated motivation (d = 1.7; P = .001), increased fatigue (d = 1.6; P = .001), distractibility (d = 1.0; P = .003), and depressed mood (d = 1.9; P = .004). PCP blood level was significantly associated with paired-associate learning, Benton Test, and reading/naming speed., Conclusions: Long-term low-dose exposure to WPC in the domestic environment could be related to subjective complaints (attention, mood, and motivation) and to subtle alterations of neurobehavioral performance (e.g., working memory) in women.

Background: Epidemiologic studies have recently related benzene hexachloride (BHC) to breast carcinoma risk. Experimental studies have also shown that beta-BHC is weakly estrogenic, hence supporting the alleged association. By directly comparing beta-BHC levels in breast adipose tissue from incident breast carcinoma cases and controls, this study examined the hypothesis that exposure to beta-BHC increases the risk of breast carcinoma in females., Methods: A total of 490 Connecticut women (304 cases and 186 controls) were enrolled in the study during the period 1994-1997. Cases were patients ages 40-79 years with histologically confirmed incident primary breast carcinoma. Controls were patients with histologically confirmed incident benign breast disease. Breast adipose tissue was collected and analyzed for BHC isomers. A linear logistic regression model was used to adjust for potential confounders in estimating the association of exposure with disease., Results: No significant differences in breast adipose tissue levels of beta-BHC were observed between the cases and their controls overall, nor by menopausal status or estrogen and progesterone receptor status of the breast carcinoma cases. A nonsignificant reduced risk was observed among all subjects and among pre- and postmenopausal women when the highest quartile was compared with the lowest. Parous women with higher beta-BHC levels, regardless of lactation status, had a nonsignificantly reduced breast carcinoma risk, whereas a nonsignificantly increased risk was observed among nulliparous women with higher beta-BHC levels, based on very few study subjects., Conclusions: The results of this study do not support the hypothesis that increasing adipose tissue levels of beta-BHC are associated with an increased risk of breast carcinoma in females.

Terrestrial epiphytic algae were used to absorb atmospheric pollutants and this material was then fed to larvae of a bagmoth to assess the toxicological effects of the pollutants. Samples of algae were amended with pesticides to simulate agricultural spray drift and with vehicle exhaust gases to simulate road traffic emissions. Larval mortality, immobilization, and feeding were used as the toxicological endpoints. Feeding was the most sensitive of these, but clear dose-response relationships were observed with all three endpoints. The effects of atmospheric pollution on an impacted environment were then investigated using these organisms. Algal samples were collected along a transect that included an area of arable farming, a motorway, and a woodland. Feeding was reduced when the larvae were fed algae from the areas proximal to the arable land and to the motorway. It is suggested that pesticide spray drift and vehicle exhaust emissions may have been the causal agents for these effects., (Copyright 1999 Academic Press.)

Objectives: This study sought to identify possible illnesses of people exposed to lindane and methyl mercury following a pollution incidence in Somerton, Somerset, UK., Methods: A self-administered questionnaire survey was posted to 1500 residents in three selected areas of Somerton to identify symptoms of possible illness over a 3 month period., Results: There was a 74% response rate. People living near the stream had higher levels of reported mental symptoms and itching skin than in controls. Poisoning as the cause of the mental symptoms was excluded as the individuals had normal blood levels of lindane or mercury. Other symptoms were no higher in one area than another or from one time period to another., Conclusions: The survey, using controls in time and space, was able to explore, the pollution incident's contribution to the toxicity of residents and how this related to mental symptoms experienced by the residents.

Adult male Swiss albino mice when exposed to a chlorinated insecticide hexachlorocyclohexane (HCH or BHC) at 100 mg/mouse/ once oral and i.p. both for acute exposures and 500 ppm and 10 ppm in food for 100 and 400 days respectively for intermediate and chronic exposures. Haematological observations revealed HCH-induced anaemia.

The study was carried out in Allahabad district, (Uttar Pradesh) with 260 spraymen as test subjects and 50 persons as controls from a sprayed and unsprayed village respectively. Majority of the spraymen (44%) had worked for 3-4 years (seasons) and 31% had worked in the programme for 5-10 years. The spraymen were relatively healthy with no complaints in 77% whereas the figures were 76% for the Community living in the sprayed village, and 50% for the Community in the unsprayed village. A comparison of the biochemical parameters revealed lowered Cholesterol more than 150 mg % in 38% of the spraymen and 58% had altered A:G ratio. Other biochemical estimations were not significantly different from the control population. The mean residue of Alpha, Beta and Gamma Isomers and the total Alpha, Beta and Gamma isomers were 0.0317, 0.2254, 0.0288 and 0.2859 mg/1 respectively; the corresponding mean values in the control population were 0.0211, 0.1112, 0.0197 and 0.1520 mg/1 respectively. The values in spraymen were twice those of the general population. A significant association (p < .05) was observed between their length of exposure and the levels of Cholesterol and HCH isomers in blood of spraymen. No significant morbidity was evident in spraymen due to HCH exposure.

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.

Exposure to polychlorinated biphenyls and organochlorine pesticides through traditional food resources was examined for Arctic Indigenous women living in two cultural and environmental areas of the Canadian Arctic--one community representing Baffin Island Inuit in eastern Arctic and two communities representing Sahtú Dene/Métis in western Arctic. Polychlorinated biphenyls, toxaphene, chlorobenzenes, hexachlorocyclohexanes, dichlorodiphenyltrichloroethane, chlordane-related compounds and dieldrin were determined in local food resources as normally prepared and eaten. Quantified dietary recalls taken seasonally reflected normal consumption patterns of these food resources by women in three age groups: 20-40 y, 41-60 y and > or = 61 y. There was wide variation of intake of all organochlorine contaminants in both areas and among age groups for the Sahtú. Fifty percent of the intake recalls collected from the Baffin Inuit exceeded the acceptable daily intake for chlordane-related compounds and toxaphene, and a substantial percentage of the intake records for dieldrin and polychlorinated biphenyls exceeded the acceptable or tolerable daily intake levels. Primary contributing foods to organochlorine contaminants intake for the Baffin Inuit were meat and blubber of ringed seal, blubber of walrus and mattak and blubber of narwal. Important foods contributing organochlorine contaminant to the Sahtú Dene/Métis were caribou, whitefish, inconnu, trout and duck. The superior nutritional benefits and potential health risks of traditional food items are reviewed, as are implications for monitoring organochlorine contaminant contents of food, clinical symptoms and food use.

Twenty-six farm workers handling about 4 kg of commercial grade hexachlorocyclohexane (HCH)/y for 2-5 y and 21 control subjects were studied for chronic effects in clinical, hematological and cardiac variables. No clinically apparent morbidity was detected, but changes in hemoglobin and electrocardiograms were early effects of HCH exposure.

Background: An observational, epidemiological study was undertaken to evaluate the safety of permethrin 1% creme rinse (Nix) for treatment of head lice infestations., Methods: Thirty-seven local public health departments enrolled a total of 38,160 patients for 47,578 treatments with permethrin or other pediculicides from September 1, 1986, through January 31, 1988. Follow-up safety information was collected between 7 and 14 days following treatment via return visit or telephone contact., Results: One hundred three adverse events were reported among 41,955 evaluable treatments. The rates of reported adverse events were 2.2 per 1000 treatments among permethrin treatments, 3.4 per 1000 treatments among lindane treatments, and 1.5 per 1000 treatments among other over-the-counter treatments. No serious, unexpected adverse events were detected in the 18,950 patients treated with permethrin., Conclusions: This study confirmed the safety profile of permethrin in conditions of general use, as seen in clinical trials. Postmarketing safety monitoring in public health departments of drugs used to treat public health conditions was shown to be feasible.