Effects Of Lindane Research Articles

Association between Scabies Treatment and Parkinson's Disease: A Nationwide, Population-Based Study.

Scabies is typically treated with scabicides like lindane, which poses a risk for acute neural toxicity. Lindane's prolonged use, particularly in agriculture, is linked to neurodegenerative diseases, including Parkinson's disease (PD), the second most common neurodegenerative disorder. This study aimed to evaluate whether scabies patients, particularly those treated with topical lindane, are at increased risk of developing PD. A nationwide population-based cohort study was conducted using data from Taiwan's National Health Research Institutes claims database from 2000 to 2018. The study included 27,173 patients with scabies, matched to a control group, with both groups followed for up to 18 years. The primary outcome was the incidence of newly diagnosed PD, and the hazard ratio (HR) for PD was calculated, focusing on those treated with topical lindane. Among the 54,346 patients, 1639 (3.0%) were newly diagnosed with PD, with 993 (60.6%) from the scabies group and 646 (39.4%) from the control group. Scabies patients had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.32-1.63) for developing PD compared to controls. However, patients treated with topical lindane had a significantly lower aHR for PD at 0.15 (95% CI 0.12-0.19; p < 0.001), with a lower cumulative incidence of PD also observed in this group (p < 0.001). Scabies patients are at a 1.46-fold increased risk of developing PD, but those treated with lindane exhibit a significantly lower risk, suggesting potential protective effects of lindane against PD.

Linking pesticide exposure to neurodegenerative diseases: An in vitro investigation with human neuroblastoma cells

Although many organochlorine pesticides (OCPs) have been banned or restricted because of their persistence and linkage to neurodegenerative diseases, there is evidence of continued human exposure. In contrast, registered herbicides are reported to have a moderate to low level of toxicity; however, there is little information regarding their toxicity to humans or their combined effects with OCPs. This study aimed to characterize the mechanism of toxicity of banned OCP insecticides (aldrin, dieldrin, heptachlor, and lindane) and registered herbicides (trifluralin, triallate, and clopyralid) detected at a legacy contaminated pesticide manufacturing and packing site using SH-SY5Y cells. Cell viability, LDH release, production of reactive oxygen species (ROS), and caspase 3/7 activity were evaluated following 24 h of exposure to the biocides. In addition, RNASeq was conducted at sublethal concentrations to investigate potential mechanisms involved in cellular toxicity. Our findings suggested that aldrin and heptachlor were the most toxic, while dieldrin, lindane, trifluralin, and triallate exhibited moderate toxicity, and clopyralid was not toxic to SH-SY5Y cells. While aldrin and heptachlor induced their toxicity through damage to the cell membrane, the toxicity of dieldrin was partially attributed to necrosis and apoptosis. Moreover, toxic effects of lindane, trifluralin, and triallate, at least partially, were associated with ROS generation. Gene expression profiles suggested that decreased cell viability induced by most of the tested biocides was related to inhibited cell proliferation. The dysregulation of genes encoding for proteins with anti-apoptotic properties also supported the absence of caspase activation. Identified enriched terms showed that OCP toxicity in SH-SY5Y cells was mediated through pathways associated with the pathogenesis of neurodegenerative diseases. In conclusion, this study provides a basis for elucidating the molecular mechanisms of pesticide-induced neurotoxicity. Moreover, it introduced SH-SY5Y cells as a relevant in vitro model for investigating the neurotoxicity of pesticides in humans.

Human effects of lindane in a one health perspective. A review

Lindane or gamma-hexachlorocyclohexane is a chloro-organic insecticide marketed since 1938. The demonstration of significant toxic effects for humans, including neurological, hepatic, hematological, and carcinogenic effects, led to its ban. Since 2000, the use of lindane has declined, but attention to the possible effects on public health must remain high, given the bio persistence of the toxicant. The purpose and aim of this study were to recapitulate the effects that lindane may have on humans, based on a review of the literature. The results indicate that, despite the many years that have passed since the demonstration of the toxic effects of lindane, the high persistence and accumulation of the substance in ecosystems, make it even possible that it plays a role in the genesis of chronic degenerative diseases. The connection between human, animal, and ecosystem health which is contained according to the World Health Organization in the “One Health” model, urges us not to slow down our vigilance on these substances.

A novel automated method for the simultaneous detection of breathing frequency and amplitude in zebrafish (Danio rerio) embryos and larvae

Stress responses of fish to disruption of oxygen homeostasis include adjusted oxygen consumption rate (MO2) as well as the hyperventilation consisting of changes in breathing frequency (fv) and amplitude (fampl). However, studying the HVR in very small organisms such as zebrafish (Danio rerio) embryos and larvae is challenging, and breathing movements (i.e., fv) are usually manually counted, which is time- and human resource-intense, error-prone and does not provide information on the amplitude of breathing movements of the response, the breathing amplitude (fampl). Hence, in the present study, a new automated method was developed to simultaneously measure fv and fampl in small zebrafish embryos and larvae with the computer software DanioScope™. To compare HVR strategies at different life-stages of zebrafish and the physiologically linked MO2, hatched 4 d old embryos and early gill-breathing 12 d old larvae were treated with the HVR-inducing neurotoxic compound lindane (γ-hexachlorocyclohexane; γ-HCH) as a model substance. Comparison of manually counted fv with fv data measured by DanioScope™ at both life-stages showed high to moderate agreement between the two methods with respect to fv in control fish and in fish treated with lower lindane concentrations (3 - 18% deviation at 25 µg/L γ-HCH). With increasing lindane concentrations (100 and 400 µg/L γ-HCH), however, manual counts showed an average underestimation of fv by up to 30%, mainly due to very fast, rapidly successive, and indistinct movements of the fish, which cannot be properly detected by manual counts. Automated measurement thus proved significantly more sensitive, although several pre- and post-processing steps are needed. The improved automated detection of fv and the first reliable estimation of fampl in small fish embryos and larvae, as well as the inclusion of MO2, may provide new insights into different respiratory strategies and may, thus, represent a tool to lower the detection limit for reactions of different life-stages of fish to environmental stressors. In the present study, this became evident, as early gill-breathing 12 d old zebrafish larvae showed symptoms of respiratory failure (i.e., increase in fv, fampl and MO2, followed by subsequent lethargy) after exposure to lindane, whereas skin-breathing in 4 d old embryos proved mainly insensitive to the paralytic effects of lindane.

STUDY OF THE INFLUENCE OF LINDANE AND SODIUM BICHROMATE ON THE MYOCARDIUM.

Aim: The aim of the research is to study the immunohistochemical markers of the endothelium of blood vessels and myocardial ventricles under chronic exposure to sodium bichromate and lindane, as well as in conjunction with damaging biochemical agents contained in the blood. Materials and Methods: The object of the experiment was outbred white mice (males). The study was carried out in 3 groups: 1st group - control, 2nd group - exposure to sodium bichromate 5 mg/kg, 3rd group - exposure to organochlorine pesticide lindane 100 mg/kg. In this experiment authors used the next methods: immunohistochemical method., biochemical research, statistical analysis. Results: The data obtained from an experimental study show that the level of cardiomarkers in blood plasma is characterized by different changes when exposed to these two compounds. Basically, the predominance of the effect of sodium bichromate on the LDH level is noted as compared to the effect of lindane; on the CK-MB level, their effects were the same, i.e., there is an increase in their level in blood plasma. Conclusions: Thus, long-term exposure to sodium bichromate leads to the activation of angiogenesis, destruction of the integrity of the endothelium, and this, in turn, leads to reparative changes located around in the myocardial cells.

Effect of Lindane (δ- isomer) on Serum cholesterol and Liver enzyme markers in mice (Mus musculus)

In the present study, we investigate the serum cholesterol level and the liver enzymes (alkaline phosphatase, alanine transaminase, and aspartate aminotransferase) in mice. Lindane (δ- isomer), 100mg/kg body weight, injected subcutaneously for 30 days. Our present study found that after 30 days of lindane administration, after sacrificing the mice, a significant increase in serum cholesterol levels observed. Alkaline phosphatase levels significantly decreased, whereas the alanine transaminase and aspartate aminotransferase levels significantly increased.

The Toxic Effects of Lindane via the Impact of pH and Dissolved Organic Matter on Microcystis aeruginosa

The toxic effects of Lindane (γ-BHC) on Microcystis aeruginosa were studied under lab culture conditions. Total protein levels, as well as malondialdehyde (MDA) levels and superoxide dismutase (SOD) enzyme activity, in algal cells, were determined after exposure to different concentrations of Lindane. The bioaccumulation of Lindane, as well as the influence of pH and dissolved organic matter (DOM) on the toxic effects, was also evaluated in algal cells. The growth of M. aeruginosa was inhibited by the Lindane treatment (96 h), resulting in a 50% maximal effect (EC50) concentration of 442 μg/L. In addition, the lowest observed effect concentration (LOEC) was found to be 120 μg/L; the no observed effect concentration (NOEC) was found to be 60 μg/L, and the maximum acceptable toxicant concentration (MATC) was 85 μg/L. With increasing concentrations of Lindane and exposure time, M. aeruginosa growth was significantly inhibited; in addition, the total protein levels and SOD activity significantly decreased. MDA concentration, however, showed an insignificant increase after 96 h. Lindane has the potential for bioaccumulation in algal cells with a bioconcentration factor (BCF) of 340. Furthermore, the toxic effects of Lindane on M. aeruginosa were influenced by environmental factors, such as pH and DOM. The toxic effects decreased with increasing pH and humic acid concentrations. Ultrastructure cell images were used to depict Lindane-induced apoptosis.

INFLAMMATORY AND REDOX CHANGES IN MICE CHRONICALLY EXPOSED TO LINDANE IN DRINKING WATER

"Background. Lindane is an organochlorine pesticide considered as Persistent Organic Pollutant with immunosuppressive effects in acute exposure, but data on chronic exposure to low doses are still inconclusive. Aim. The aim of the study was to investigate immune and redox changes in mice chronically exposed to low doses of lindane. Experimental setting. Mice were chronically exposed for 6 months to lindane (5 mg/L) in drinking water, and subsequently a subgroup was challenged orally with S. typhimurium. The inflammatory factors MMP-9, IL-6 and KC, along with the antioxidant GSH were assessed in lungs, livers and kidneys. Splenocytes were stimulated ex vivo with TLR2 or TLR4 agonists, and the levels of released IL-6, IFNγ, TNFα and KC were measured in cell supernatants. Results. A decrease of IL-6 and MMP-9 lung levels and decreased IL-6 production by LPS-activated splenocytes from lindane-exposed mice were evidenced as compared to control groups. A slight increase of MMP-9, IL-6 and KC levels, and a decrease of GSH were observed in the liver of lindane exposed mice, while increased GSH levels were registered in infected lindane-exposed mice. Infection generally delivered stronger signals then lindane, but an immunomodulatory effect of lindane was shown in particular cases in splenocytes from infected lindane-exposed mice. Conclusion. Chronic exposure of mice to a low dose of lindane delivered in drinking water can induce both systemic immune suppression related to particular inflammatory factors, and inflammation, depending on the organ. Moreover, some immunomodulatory effects of lindane were highlighted in particular experimental settings."

Морфофункциональная характеристика эндокринного отдела поджелудочной железы под воздействием γ-ГХЦГ

In the last decades of the twentieth century, in the national economy of many countries, organochlorine pesticides were most widely used, characterized by stability in the external environment, the ability to cumulate in various tissues of organisms. Lindane (the gamma isomer of hexachlorocyclohexane) is listed as a restricted persistent organic pollutant and is an ecotoxic substance with severe and chronic effects on the human body. The study of the effect of lindane on carbohydrate metabolism at the present stage is still insufficient. This fact led to the study of the effect of γ-HCH on the insulinogenic function of the pancreas in in vivo and in vitro experiments. In experiments in vivo, the animals of the experimental groups were once orally administered γ-HCH at a dose equal to 1/5 DL50. Isolated pancreatic islets, precipitated in vitro and fixed on mica plates, were exposed to γ-HCH in amounts equivalent to 1/5 to 1/4 DL50. Paraffin sections of pancreatic tissue from experimental and control animals were stained with aldehyde fuchsin according to Gomori, and tissue preparations were also examined by a highly specific method for detecting insulin in β-cells using diethylpseudoisocyanin staining, followed by examination of the preparations in the ultraviolet light of a luminescent microscope. The samemethods were used to study preparations of isolated pancreatic islet tissue on the 4th day of cultivation. The influence of orally administered γ-HCH on the level of immunoreactive insulin in the blood of experimental animals was also studied. The insulin level was determined by the enzymatic-immunological method. The concentration of IRI was established before the start of the experiment and 4-4.5 hours after acute inoculation. Results and their significance. In the study of stained preparations of the pancreas of experimental animals, numerous islets of ordinary sizes were revealed, the cytoplasm of which was filled with aldehyde-fuccin granularity in quantities indistinguishable from those observed by microscopy of preparations of control animals. The value of the fluorescence coefficient in the histofluorimetric study of the control and experimental preparations did not differ significantly. However, the content of IRI in the blood serum showed a distinct decrease in the first hours after priming. In experiments in vitro, when studying the effect of γ-HCH on cultured tissue, introduced into the nutrient medium on the second day, in the field of view of the microscope, single, small pancreatic islets were revealed. Their number on a constant area of the plates was significantly lower than the value of the same indicator in the study of control preparations. Thus it has been shown that γ-HCH does not affect the histostructure of the endocrine pancreas, but causes a significant decrease in IRI in the blood serum, as well as a change in the histochemical characteristics of cultured β-cells.

Toxicity of lindane induced by oxidative stress and intestinal damage in Caenorhabditis elegans

Lindane, a lipophilic pollutant, may be toxic to organisms. To explore the toxic effects of lindane and the underlying mechanisms of this toxicity, the animal model Caenorhabditis elegans (C. elegans) was exposed to lindane for 3 d at environmentally relevant concentrations (0.01–100 ng/L) and the physiological, biochemical, and molecular indices were evaluated. Subacute exposure to 10–100 ng/L of lindane caused adverse physiological effects on the development, reproduction, and locomotion behaviors in C. elegans. Exposure to 1–100 ng/L of lindane increased the accumulation of Nile red and blue food dye, which suggested high permeability of the intestine in nematodes. Lindane exposure also significantly influenced the expression of genes related to intestinal development (e.g., mtm-6 and opt-2). Moreover, reactive oxygen species production, lipofuscin accumulation, and expression of oxidation resistance genes (e.g., sod-5 and isp-1) were significantly increased in C. elegans exposed to 10–100 ng/L of lindane, which indicated that lindane exposure induced oxidative stress. According to Pearson correlation analyses, oxidative stress and intestinal damage were significantly correlated with the adverse physiological effects of lindane. Therefore, the adverse effects of lindane may have been induced by intestinal damage and oxidative stress, and mtm-6, opt-2, sod-5, isp-1, and mev-1 might play important roles in the toxicity of lindane.

The effects of hydrogen sulfide synthesis inhibition in lindane-induced seizures in rats: A behavioral and EEG study

Lindane-induced seizure in rats is a model of refractory generalized epilepsy. Hydrogen sulfide (H2S) is a gasotransmitter with different physiological and pathological roles. Cystathionine-?-synthase (CBS) is a major enzyme responsible for H2S production in the brain. The aim of this study was to investigate the effects of H2S production inhibition using aminooxyacetate (a CBS inhibitor) on behavioral and EEG manifestations of lindane-induced seizures. Male Wistar rats with previously implanted EEG electrodes were intraperitoneally (i.p.) treated with 4 mg/kg lindane and observed for convulsive behavior and EEG manifestations during the next 30 min. Aminooxyacetate (5, 15 and 25 mg/kg, i.p.) or saline, was injected 30 min prior to lindane. Convulsive behavior was assessed by seizure incidence, latency time and severity (grades 0-4). The number and duration of ictal periods in the EEG were also analyzed. Seizure incidence was higher in rats treated with aminooxyacetate (AOA) before lindane, but not significantly when compared with those treated only with lindane. However, AOA significantly decreased the latency time and augmented the severity of lindane-induced seizures in a dose-dependent manner. EEG analysis revealed an increased number and duration of ictal periods in rats receiving AOA prior to lindane. H2S production inhibition aggravated lindane-induced seizures, which showed a functional relationship between H2S and the effects of lindane.

Development of microbial communities in organochlorine pesticide contaminated soil: A post-reclamation perspective

In order to meet constantly increasing demands for land without damaging pristine environments like forests or grasslands, reclamation and re-purposing of historically contaminated areas should become a priority. Successful reclamation goes hand in hand with the soil functional recovery potential and with resilient microbial communities capable of performing the necessary ecosystem services. In this context, we designed a greenhouse pot experiment as a mock reclamation situation, where traces of lindane at hazard threshold and twice the concentration accepted for waste deposits are left in the soil after conventional clean-up by excavation and land filling. We assessed the effects of lindane at 50 and 100 mg kg−1 regarding crop growth and nutrient turnover (with focus on the nitrogen cycle) as two key parameters for soil functions. The bulk and rhizosphere soil bacterial community composition were chosen as parameters for soil resilience in lindane contamination conditions. Lindane severely affected plant growth and development. The potential nitrogen fixation, quantified as nifH gene copy number, suffered direct negative effects of lindane contamination in bulk soil, which could represent an additional obstacle for phytoremediation. Changes in rhizosphere bacterial community composition were related to lindane toxic effects towards the plants, which might have supported the growth of opportunists and saprophytes. In bulk soil, the bacterial community shifted towards lindane tolerant taxa like Sphingomonas and Porphyrobacter that are interesting with regard to their applications in bioremediation. We concluded that lindane at hazard threshold concentration left in soil after clean-up has negative effects both soil functionality, and the recovery of the bacterial communities to their original composition when lindane resistant plant crops are not involved.

Risk assessment from exposure to chemical contaminants in food

There was investigated the impact of chemical substances contained in the public health foodstuffs in eight regions of the Republic of Tatarstan on 11 product groups: meat and meat products, fish and fish products, milk and dairy products, bread and bakery products, sugar and confectionery products, vegetables and melons (excluding potatoes), potatoes, fruits and berries, vegetable oil, eggs and egg products, salt. In total there were analyzed more than 240 thousand samples offood raw materials andfood products over the period offrom 2006 to 2014. The study took place on 27 priority chemicals, including thirteen carcinogens (benzo (a) pyrene, DDT, hexachlorobenzene, hexachloran, heptachlor, alpha-lindane, beta-lindane, lindane, cadmium, arsenic, lead, derivatives of 2,4-D acid, cypermethrin). Exposition load is calculated by the 50 (median), and 90 percentiles of the content ofpollutants in food products. There were calculated carcinogenic risks, HQ coefficients and HI indices for chronic non-cancer exposure. High values of the total cancer risk (3.31*10 at the median level of 1.49*10+ at the 90 percentile) are associated with the exposure to tohexachlorane and alpha-lindane seem to be alarming (from 1.73*10 to 9.68*10) with the effect of lindane, cadmium and lead with dominant contribution to the total risk in the use of meat and meat products, milk and dairy products. The warning value of Hazard ratios (HQ 1.1-3) at 90-percentile were shown on nitrate, lead, beta-lindane, high (HQ >3), for DDT and its metabolites, lindane and arsenic, with the dominant contribution to the exposure of vegetables and melons (excluding potatoes), potato, milk and milk products.

Assembly of root-associated microbiomes of typical rice cultivars in response to lindane pollution

Organochlorine pesticides have been extensively used for many years to prevent insect diseases of rice (Oryza sativa L.), but little is known about their residual impacts on the underground micro-ecology in anaerobic environment. In this glasshouse study, we characterized the lindane effects on the assembly of root-associated microbiomes of commonly used indica, japonica and hybrid rice cultivars, and their feedback in turn, in modifying lindane anaerobic dissipation during 60 days' rice production. The results showed that rice growth inhibited the anaerobic dissipation of lindane, but was not affected apparently by lindane at initial spiked concentration of 4.62 and 18.54 mg kg−1 soil. Suppressed removal of lindane in rice planted treatments as compared with that in unplanted control was likely due to inhibited reductive dechlorination induced by a comprehensive effect of radial O2 secretion of rice root and co-occurring Fe(III) reduction that consumed electron competitively in rice rhizosphere. However, the hybrid cultivar exhibited a less suppression than the conventional cultivars in high polluted soils. Bacteria was more sensitively responded to lindane pollution than fungal taxa, and Actinobacteria, Chloroflexi, Verrucomicrobia and Proteobacteria were the main different phyla between hybrid and conventional cultivars, with a more stable community structure exhibited in the hybrid rice under lindane stress. Our study highlights the assembly and variation of root-associated microbiomes in responses of lindane pollution, and suggests that hybrid rice cultivar might be most competent for cultivation in paddy fields polluted by lindane and other organochlorine pesticides, especially in the area with high residual levels.

Multi-generational effects of lindane on nematode lipid metabolism with disturbances on insulin-like signal pathway

Influences on lipid metabolism and multi-generational obesogenic effects raised new concerns on lipophilic pollutants (e.g., lindane). Yet, the mechanisms remained unanswered. The present study exposed Caenorhabditis elegans to lindane for 4 consecutive generations (F0 to F3) at 1.0 ng/L, and measured effects in the directly exposed generations (F0 to F3), indirectly exposed ones (T1 and T1′) and un-exposed ones (T3 and T3′). Lindane stimulated fat storages in all generations. At the biochemical level, lindane stimulated both acetyl-CoA carboxylase (ACC) and carnitine palmitoyl-transferases (CPT) in F0, T1 and T2, while inhibited them in F3, T1′ and T3′, demonstrating the balance between fatty acid synthesis and its depletion toward fat accumulation over generations. Moreover, lindane caused different effects on insulin among generations. It inhibited insulin in F0 and F3 and exhibited consistent effects on the expression changes of daf-2, sgk-1 and daf-16 genes in insulin-like signal pathway. Lindane also inhibited insulin in T1 and T3 but exhibited consistent effects on the expression changes of daf-2, akt-1 and daf-16. Different roles of sgk-1 and akt-1 indicated the response strategies from tolerance (F0 and F3) to avoidance (T1 and T3). Lindane stimulated insulin in T1′ and T3′ and exhibited consistent effects on expression changes of daf-2, sgk-1 and daf-16 genes that were similar in F0 and F3.

Effect of lindane on some selected electrolytes and metabolites of Clarias gariepinus (juveniles)

Effect of lindane on some selected electrolytes and metabolites of Clarias gariepinus (juveniles)

A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP’s inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10−6M and 0.9×10−3M) and human myometrial contractions (EC50 16.3×10−6M and 1.1×10−3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

Comparative study of toxicological effects of lindane and isoproturon pesticides in the Saccharomyces cerevisiae

Comparative study of toxicological effects of lindane and isoproturon pesticides in the Saccharomyces cerevisiae

Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: A case study of lindane-induced neurotoxicity

Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans. Time- and concentration-dependent lindane dosimetry was determined in primary cultures of rat cortical neurons in vitro using “faux” (without electrodes) microelectrode arrays (MEAs). In vivo data were derived from literature values, and physiologically based pharmacokinetic (PBPK) modeling was used to extrapolate from rat to human. The previously determined EC50 for increased firing rates in primary cultures of cortical neurons was 0.6μg/ml. Media and cell lindane concentrations at the EC50 were 0.4μg/ml and 7.1μg/ml, respectively, and cellular lindane accumulation was time- and concentration-dependent. Rat blood and brain lindane levels during seizures were 1.7–1.9μg/ml and 5–11μg/ml, respectively. Brain lindane levels associated with seizures in rats and those predicted for humans (average=7μg/ml) by PBPK modeling were very similar to in vitro concentrations detected in cortical cells at the EC50 dose. PBPK model predictions matched literature data and timing. These findings indicate that in vitro MEA results are predictive of in vivo responses to lindane and demonstrate a successful modeling approach for IVIVE of rat and human neurotoxicity.

Effects of Lindane on Lindane-Degrading Azotobacter chroococcum; Evaluation of Toxicity of Possible Degradation Product(s) on Plant and Insect

The effects of lindane on growth and plant growth-promoting traits of two lindane-degrading Azotobacter chroococcum strains (JL 15 and JL 104) were determined. The potential of both A. chroococcum strains to degrade lindane was also determined. Lower concentrations of lindane had a stimulatory effect, and higher concentrations generally had an inhibitory effect on growth and plant growth-promoting activities. A high percentage (>90%) of lindane was degraded by both strains at a lindane concentration of 10ppm. Lindane at 1,000ppm decreased seed germination and reduced seedling fresh weight. However, the possible degradation products for a starting lindane concentration of 10ppm was found to be non-phytotoxic. Toxicity studies with larvae of Spilarctia obliqua resulted in an LC50 estimate of 3.41ppm for lindane solutions into which leaf discs were dipped. No toxicity was observed for possible degradation products.