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.

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.

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.

CYP17A1 gene polymorphisms and environmental exposure to organochlorine pesticides contribute to the risk of small for gestational age.

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), ß-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.

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.

A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides.

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,ß,γ-HCH and p,p'-DDT were found in maternal blood and significantly higher levels of ß 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 ß-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.

[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.

Maternal and cord blood levels of organochlorine pesticides: association with preterm labor.

OBJECTIVES: Organochlorine pesticides (OCPs) have been reported to cause adverse reproductive outcomes. Hence, the present study was conducted to estimate and compare the levels of OCPs in maternal and cord blood of preterm labor and full term labor cases as well as assess their role in preterm delivery. DESIGN AND METHODS: 23 cases each of preterm labor and full term labor were included in the study. Maternal and cord blood OCP levels were determined by using a GC-MS equipped with an electron capture detector. RESULTS: Maternal and cord blood levels of alpha-HCH, beta-HCH, gamma-HCH, total-HCH, p,p'DDE and p,p'DDT were found higher in preterm labor than full term labor cases. However, a statistically significant relation was observed between preterm birth and beta-HCH levels only. CONCLUSIONS: Higher blood levels of beta-HCH may be associated with risk of preterm labor.

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.

Lindano: efectividad y riesgos: síntesis de evidencia / Lindane: effectiveness and risks: summary of evidence

La presente nota técnica responde a una solicitud del la División de Rectoría y Regulación Sanitaria del Ministerio de Salud, en el marco del proceso de actualización del Formulario Nacional de Medicamentos y la formulación del Reglamento de pesticidas. La solicitud deriva de incertidumbres sobre el balance de efectividad y riesgos del lindano como pediculicida y escabicida, y del eventual impacto medioambiental del producto. Ambos aspectos han sido objeto de debate recientemente en distintas partes del mundo. Este debate abarca no sólo la seguridad del producto, sino también la calidad de las revisiones sistemáticas disponibles, y la importancia del surgimiento de resistencia en la evaluación de la efectividad de los preparados existentes.

[Relationship between organochlorine pollution in soil and rice and the incidence of colorectal cancer in Jiashan county, Zhejiang province].

OBJECTIVE: To study the relationship between organochlorine and colorectal cancer. METHODS: With multistage cluster random sampling, 11 towns were drawn based on the standardized incidence of colorectal cancer. Administrative and natural villages were drawn subsequently. Rice and soil samples in the paddy fields were collected in the villages. The contents of organochlorine were detected. Rank correlation analysis was performed together with the data of colorectal cancer incidence. RESULTS: The contents of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) in both rice and soil samples were below the amounts of the country. Statistics showed that the standardized incidence rates were significantly different among the 11 towns. The contents of delta-HCH, gamma-HCH, sodium pentachlorophenate in rice and those of delta-HCH in soil were statistically different among the towns through the rank sum test. The standardized incidence of colorectal cancer was significantly connected with the content of total DDT in rice while rectal cancer with total DDT and PP'-DDE and colon cancer with 1245 of polychlorinated biphenyl (PCBs). The correlation coefficients were 0.636, 0.691, 0.716 and 0.658 respectively (P < 0.05). CONCLUSIONS: Rectal cancer was statistically correlated with organochlorine, mainly for total DDT and dichlorodiphenyldichloroethylene (PP'-DDE). Colon cancer was significantly associated with 1245 of PCBs. Further study should be performed since this research was only an ecological study.

Persistent chlorinated pesticides and intra-uterine foetal growth retardation: a possible association.

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.

Oxidative stress induced by HCH in Hydrilla verticillata (l.f.) Royle: modulation in uptake and toxicity due to Fe.

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.

[Reproductive toxicity of lindane]. / Toxicité du lindane sur la reproduction.

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.

[Cardiotoxicity of lindane, a gamma isomer of hexachlorocyclohexane]. / Cardiotoxicité du lindane, un isomère gamma de l'hexachlorocyclohexane.

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.

Proliferation and differentiation of murine haemopoietic progenitor cells in stroma-free culture in the presence of metabolites of chlorinated pesticides.

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.

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.