Doses Of Endosulfan Research Articles

In ovum exposure to pesticides increases the egg weight loss and decreases hatchlings weight of Caiman latirostris (Crocodylia: Alligatoridae)

The increasing use of pesticides affects ecosystem health. Caiman latirostris is a South American species with ecological and physiological features that render it vulnerable to exposure to pesticides with endocrine disruptor's action. Our main objective was to test the effect of in ovum exposure to atrazine and endosulfan on the sex ratio of caiman hatchlings; however, we are also presenting unexpected findings regarding pesticide effects on egg weight loss during incubation and hatchlings relative weight. Caiman eggs were incubated under controlled temperature (30 and 33 °C) and humidity (>90%). They were treated with vehicle, 17 β-estradiol (1.4 ppm), atrazine (0.2 ppm) and endosulfan (0.02; 2; 20 ppm). Pesticides did not cause estrogen-like effects on sex determination. Greater egg weight loss was observed in eggs treated with atrazine and higher doses of endosulfan (2 and 20 ppm) ( p=0.0005). These pesticides also caused a reduction in hatchling fractional weight ( p=0.0497). These effects might have a significant impact on caiman population dynamics.

DNA damage and mutagenicity induced by endosulfan and its metabolites

Endosulfan is a widely used broad-spectrum organochlorine pesticide, which acts as a contact and stomach poison. Nontarget species, such as cattle, fish, birds, and even humans, are also affected. Studies on the genotoxicity and mutagenicity of endosulfan have been inconsistent and nothing is known about the genotoxicity of its metabolites. In the present study, endosulfan (as a commercial isomeric mixture and as the alpha- and beta-isomers), and metabolites of endosulfan (the sulfate, lactone, ether, hydroxyether, and diol derivatives) were assayed for their ability to induce DNA damage in Chinese hamster ovary (CHO) cells and human lymphocytes using the Comet assay and were assayed for their mutagenicity using the Salmonella reversion assay (Ames test with TA98, TA97a, TA102, TA104, and TA100, with and without S9 activation). The compounds produced statistically significant (P < 0.01), concentration-dependent (0.25-10 microM) increases in DNA damage in both CHO cells and human lymphocytes. Endosulfan lactone caused the most DNA damage in CHO cells, while the isomeric mixture of endosulfan produced the greatest response in lymphocytes. The test compounds also were mutagenic in Salmonella strains at concentrations of 1-20 mug/plate (P < 0.05), with TA98 being the most sensitive strain and the diol and hydroxyether metabolites producing the highest responses. The results indicate that exposure to sublethal doses of endosulfan and its metabolites induces DNA damage and mutation. The contribution of the metabolites to the genotoxicity of the parent compound in Salmonella and mammalian cells, however, is unclear, and the pathways leading to bacterial mutation and mammalian cell DNA damage appear to differ.

Genotoxicity evaluation of acute doses of endosulfan to freshwater teleost Channa punctatus (Bloch) by alkaline single-cell gel electrophoresis

The Indian freshwater air-breathing teleost fish Channa punctatus (Bloch) was exposed to acute concentrations of the organochlorine pesticide endosulfan. In flow-through bioassays the 24, 48, 72, and 96 h LC 50 values were estimated as 19.67, 12.95, 10.15, and 7.75 ppb, respectively. DNA damage (single-strand breaks) was also studied in gill and kidney tissues at single-cell levels in the specimens, exposed to different acute doses of endosulfan, by applying single-cell gel electrophoresis or comet assay. Dose-dependent responses were observed in DNA damage in both tissues. A comparison of DNA damage in both tissues at different doses indicated that the gill cells were more sensitive to the pesticide exposure than the kidney cells. This study explored the utility of the comet assay for in vivo laboratory studies using fish for screening the genotoxic potential of various agents.

Growth, photosynthesis, active oxygen species and antioxidants responses of paddy field cyanobacterium Plectonema boryanum to endosulfan stress

The present paper deals with the insecticide endosulfan (5, 10 and 20 microg/ml)-induced changes in physiological and biochemical parameters related to photosynthesis and defense systems in paddy field cyanobacterium Plectonema boryanum grown under laboratory conditions. Growth and photosynthetic pigments, i.e., chlorophyll a, carotenoids and phycocyanin, were adversely affected by endosulfan treatment and the inhibition was found to be dose dependent. The toxic effect of endosulfan was more pronounced on phycocyanin; however, a considerable reduction in chlorophyll a and carotenoids was also noticed. 14C-fixation appeared to be more sensitive to insecticide than whole cell oxygen evolution. Spheroplasts treated with endosulfan exhibited a severe effect on PSII activity which was mainly due to blocking of the electron flow at the water oxidation side. In contrast to this, similar doses of endosulfan caused the least effect on PSI activity (DCPIP/ASC-->MV). Furthermore, endosulfan with increasing doses accelerated the formation of active oxygen species, i.e., O2- and H2O2, in cells progressively, whereby an enhanced peroxidation of lipid and leakage of cell membrane were noticed. As a consequence of active oxygen species (AOS) generation in endosulfan-treated cells, the activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was enhanced considerably. Besides the accelerated action of enzymatic defense systems, chemical antioxidant ascorbate showed a decreasing trend with the rising concentration of endosulfan (5, 10 and 20 microg/ml).

Pre and postnatal exposure to endosulfan in Wistar rats.

The possible reproductive adverse effects of the pesticide endosulfan on male offspring rats exposed in utero and during lactation were investigated. Dams were treated orally with 0, 0.5 or 1.5 mg of endosulfan/kg 21 days prior to mating, during the mating, pregnancy and lactation. Maternal and reproductive outcome data and male sexual development landmarks (testis descent and preputial separation) were assessed. Reproductive endpoints of the male offspring were examined at adulthood: sex organ weights, daily sperm production, spermatid number, sperm transit, sperm morphology and testosterone level. No signs of maternal toxicity were detected at the dose levels tested. Sexual development landmarks were also unaffected. Moreover, with the exception of a significant increase in the relative epididymis weight seen in the group treated with the lowest dose, we have not found any statistically significant adverse effect in the reproductive endpoints investigated at adulthood. The results of the present study indicate that pre and postnatal exposure to low doses of endosulfan (0.5 and 1.5 mg/kg) do not induce significant adverse effects in the reproductive system of male offspring Wistar rats at adulthood.

Exposure to Low Doses of Endosulfan and Chlorpyrifos Modifies Endogenous Antioxidants in Tissues of Rats

Two experiments were conducted in male SD rats (225–250 g) to determine changes in the activities of endogenous antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and concentrations of glutathione (GSH) in tissues after exposure to low doses of endosulfan and chlorpyrifos using a whole body exposure technique. In both experiments, 6 rats/group were exposed 3 hr/day, 5 days/week for 30 days to: 0 (control), 5, 10, 20, 40 and 60% of LD50 of either pesticide in 50% ethanol; actual concentrations were: endosulfan = 0, 0.5, 1.0, 2.0, 4.0, 6.0 mg/250 g body weight; chlorpyrifos = 0, 1.9, 3.8, 7.6, 15.2, and 22.8 mg/250 g body weight. Endosulfan decreased erythrocyte SOD by 21% in all groups and chlorpyrifos increased SOD by 18% in groups 40 and 60. Liver SOD was 12%–20% lower after endosulfan exposure; lung SOD was altered: endosulfan decreased activity by 21% and 51% and chlorpyrifos by 58 and 75% in the 40 and 60 groups, respectively (P ≤ 0.05). Both pesticides increased plasma GPX activity at lower levels and reduced it by 26% and 19% in groups 40 and 60, respectively (P ≤ 0.05). Liver GPX increased in the 60 group and lung GPX declined between 20% and 38% after endosulfan exposure. GSH in the liver and lung: endosulfan reduced GSH by about 30% at lower levels and increased by 41% or 70% at higher levels; chlorpyrifos decreased GSH by 28–40% in 20 and 60 groups, respectively (P ≤ 0.05). Exposure to low, increasing levels of endosulfan and chlorpyrifos can differentially modify endogenous antioxidants SOD, GPX and GSH, which may lead to the development of oxidative stress in some tissues.

Oxidative stress and loss of cortisol secretion in adrenocortical cells of rainbow trout ( Oncorhynchus mykiss) exposed in vitro to endosulfan, an organochlorine pesticide

The effects of endosulfan, a widely used organochlorine pesticide, on cortisol secretion, cell viability, antioxidants and lipid peroxidation were investigated in enzymatically dispersed head kidney cells of rainbow trout ( Oncorhynchus mykiss). ACTH- and dbcAMP-stimulated cortisol secretion, and cell viability were impaired in a dose-related manner following acute in vitro exposure to endosulfan (EC 50 19 μM, LC 50 366 μM) and the loss of cortisol secretion was detected even at concentrations of endosulfan that did not decrease cell viability. Stimulation with dbcAMP did not restore cortisol secretion in endosulfan exposed cells while stimulation with pregnenolone maintained cortisol secretion until viability of cells was affected. Thus endosulfan may disrupt processes between the step generating cAMP and the step where pregnenolone is used. Activity of catalase increased at concentrations of endosulfan that did not impair cortisol secretion, and decreased at higher doses. Glutathione peroxidase (GPx) activity was significantly reduced at doses of endosulfan that also reduced levels of glutathione, an essential cofactor of GPx. Exposure up to 1×10 −7 M endosulfan increased the activity of glutathione transferase. The present in vitro study identified endosulfan as a chemical inducing a loss of secretory responses in teleost adrenocortical steroidogenic cells and alterations in the activity of enzymes known to be involved in oxidative stress pathways. Moreover, the significant increase in lipid hydroperoxides levels provided further evidence for endosulfan-induced oxidative stress.

Regional Modification of [3H]Ethynylbicycloorthobenzoate Binding in Mouse Brain GABAA Receptor by Endosulfan, Fipronil, and Avermectin B1a

[3H]Ethynylbicycloorthobenzoate ([3H]EBOB), a high affinity radioligand for the noncompetitive blocker site of the GABAA receptor, is used here for quantitative autoradiography to determine regional binding in mouse brain and the effects on this binding of administering toxic doses of endosulfan, fipronil, and avermectin B1a (AVM). Animals were euthanized 4–8 min after 1 LD50 or 2 LD50 doses of the two channel blockers and 32 min after 1 LD50 or 4 LD50 doses of the channel activator AVM. Specific binding of [3H]EBOB was determined for 20-μm brain sections as the difference in labeling on incubation with 2 nM [3H]EBOB either alone (total binding) or with 5 μM α-endosulfan (nonspecific binding). The highest specific labeling was observed for layers I and IV of the cerebral cortex, the globus pallidus, and the medial septal nucleus/nucleus of the vertical limb of the diagonal band. Dose-dependent inhibition by endosulfan was highest in the nucleus accumbens and least in the cerebellum and periaqueductal gray matter. Fipronil had much less effect on binding even at severely toxic doses. AVM increased [3H]EBOB binding in most regions and was the only one of the three agents inhibiting in vitro [3H]strychnine binding to the glycine receptor. In summary, the noncompetitive blocker site was strongly inhibited with dose dependence and regional selectively by α-endosulfan but was generally poorly inhibited or activated by fipronil and was activated by avermectin.

Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation.

1. The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2. The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3. The daily sperm production (x10(6)) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4. Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5. The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.

Ultrastructural alterations in the liver and intestine of carp Cyprinus carpio induced orally by ultra-low doses of endosulfan.

In order to elucidate the importance of food-borne chemical contamination in fish, cytological and ultrastructural alterations in hepatocytes and enterocytes of common carp Cyprinus carpio L. exposed for 5 wk to 0.5 microgram endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9a-hexahydro-6,9-methano-2,4,3-benzo- dioxyanthiepin-3-oxide) kg-1 food dry weight, equivalent to an ultra-low dosis of 15 ng kg-1 fish d-1, were investigated by means of light and electron microscopy. Observations on liver alterations were quantified by morphometric analysis. Livers show enlargement of the nucleolus, increase in number and size of both Golgi fields and rough endoplasmic reticulum (ER) lamellae, as well as proliferation of peroxisomes and lysosomes. Taken together, these alterations represent the morphological equivalent of a general stimulation of hepatic metabolism. Proliferation of the smooth ER is indicative of the onset of biotransformation processes under the influence of food-borne endosulfan. Further pathological processes in the liver were evident by glycogen and lipid depletion, invasion of phagocytic macrophages, and accumulation of myelinated bodies in endothelial cells of hepatic sinusoids. In the intestinal tract, exposure to endosulfan is associated with a complete lack of chylomicrons in the epithelial lining, which indicates disturbance of intestinal absorption. The reaction of the gut epithelium also included considerable distension of the intercellular space and an elevated number of lysosomal inclusions in enterocytes. An increased rate of mucous cell precursors was detectable, and macrophages were numerous. Results are consistent with endosulfan resorption by the intestinal epithelium and the coexistence of gut and liver ultrastructural changes at extremely low doses. Thus, the substantiation of pathological alterations in organs sequentially in contact with toxicants appears useful as a biomarker of pollutant exposure and effect. With regard to a chemical spill into the Rhine river at Basel, Switzerland, in November 1986, endosulfan, as a component of the mixture of toxic substances, may well have contributed to the overall toxicity of the chemicals released during the accident and the subsequent fish kill, less as a toxicant in itself than as a stimulant for the toxicity of other xenobiotics.

Effects of single and repeated administration of endosulfan on behaviour and its interaction with centrally acting drugs in experimental animals: a mini review

The organochlorine cyclodiene insecticide, endosulfan readily penetrates into the brain. The neurotoxic action of endosulfan has been attributed to its α-isomer. Endosulfan sulphate which is a chief metabolite of endosulfan seems to contribute to its acute neurotoxic action which is manifested by clonic convulsions in experimental animals. Convulsant and proconvulsant effects of endosulfan are apparent after its chronic exposure at low dose levels. These effects have been attributed to its γ-aminobutyric acid antagonistic action. Repeated exposure to low doses has resulted in behavioral changes too. Endosulfan-induced hyper-excitability has been associated with its muscarinic receptor stimulating action. The insecticide has been shown to produce aggressive behaviour and learning impairment by activating serotonergic mechanism. A dopaminergic involvement has been suggested for endosulfan-induced hypermotoractivity and circling movement. Animals exposed chronically to low doses of the insecticide have responded more markedly than control animals to the pharmacological actions of diazepam, chlorpromazine, pentobarbital and ethanol. The findings reviewed here emphasize awareness that chronic occupational exposure to low doses of endosulfan may result not only in behavioral abberations but in hazardous interaction with centrally acting drugs too.

Effect of endosulfan on the testis of growing rats.

Endosulfan, a chlorinated cyclodiene compound is used worldwide as insecticide & acaricide for the control of various pests in agriculture. The effect of endosulfan on laboratory animals reported so far is restricted to immunological, neurological and genotoxic studies (Toxicological Profile 1993). Few reports on the effect of endosulfan on reproductive functions are also available but are restricted to adult animals only (Dikshith et.al. 1984; Singh and Pandey, 1990; Sinha et.al., 1995). No report is available on the effect of endosulfan on the testicular maturation. This is significant in view of the fact that young growing animals are more susceptible to the toxicity of xenobiotics (Sjoberg et. al., 1985;Saxena et.al .,1990). The risk of exposure to any xenobiotic during the prepubertal stage of sexual maturity may lead to permanent damage to the gonads. Therefore, in the present study we have studied the effect of various doses of endosulfan on growing rats from weaning to 90 days of age to see the effect of this pesticide on the testis attaining sexual maturity. MATERIALS AND METHODS Twenty weaned male Druckrey rats (3 weeks old; 4850g b.wt) were procured from the Industrial Toxicology Research Centre colony .The rats were divided into four groups of five rats each. Group II, III and IV were given endosulfan (95.32% purity) at a dose of 2.5, 5.0 or 10 mg/kg body weight in 0.2 ml peanut oil through oral incubation (Pandey et.al., 1990; Sinha et. al., 1995). Group I served as control and was given peanut oil only .The treatment was carried out till 90 days of age , the dose schedule being five days a week. Body weight was monitored twice a week. The animals were housed in stainless steel cages in an air conditioned room where regular alternate cycles of 12 h light and darkness were maintained and supplied with pelleted diet (Lipton India Ltd., animal feed, India) and tap

A sex-related difference in the neurobehavioral and hepatic effects following chronic endosulfan treatment in rats

The neurobehavioral and hepatic effects following chronic endosulfan administration were studied in adult male and female rats. The neurobehavioral effect was determined by testing spontaneous motor activity, motor coordination and learning and memory processes in rats of either sex, 30 days after treating the animal orally with endosulfan (3.0 and 6.0 mg/kg per day). Mortality occurring during the treatment and body weight gain at the termination of treatment were also recorded. Liver weight and liver and serum concentrations of glutamic oxaloacetic transamine, glutamic pyruvic transaminase and acetylinesterase were measured in order to determine the hepatotoxic effect of endosulfan. Body weight gain, motor coordination and acetylcholinesterase activity were unaltered in either sex. Learning and memory processes were impaired in both groups indistinguishably. Liver weight and liver and serum transaminases concentrations were increased more markedly in female than in male animals. A 30% mortality occurred in female group that received 6 mg/kg of endosulfan. Endosulfan stimulated spontaneous motor activity more markedly in male than in female animals. These findings suggest that a sex-related difference seems to occur in the stimulation of spontaneous motor activity, liver injury and mortality that result from repeated exposure to sublethal doses of endosulfan in rats.

Seizure thresholds in kindled animals are reduced by the pesticides lindane and endosulfan.

Lindane and endosulfan are chlorinated hydrocarbon pesticides that bind to the gamma-aminobutyric-acidA (GABAA) receptor ionophore complex. We have previously demonstrated development of a persistent predisposition to the seizure-inducing properties of these pesticides following repeated administration of initially subconvulsive doses. A subsequent facilitation of electrical kindling development indicated that a chemical kindling mechanism may contribute to this enhanced sensitivity. We tested the bidirectionality of kindling transfer induced by chemical and electrical means by comparing the convulsive thresholds of lindane and endosulfan in electrically kindled and nonkindled animals. Amygdala kindled, implanted/nonstimulated, and nonimplanted controls were administered 0, 5, 10, or 20 mg/kg of lindane or endosulfan in corn oil by gavage, and each animal's behavior was scored for the presence of myoclonic jerks (MCJ) and clonic seizures. Dose-related increases in the number of animals displaying convulsions in response to both of these pesticides were observed. The dose of lindane (4.5 mg/kg) and endosulfan (4.3 mg/kg) producing MCJs in 50% of the animals (ED50) was reduced by more than 60% in kindled animals relative to controls. A second experiment evaluated the generalized seizure threshold in previously kindled animals treated with low doses of endosulfan (0, 2.5, and 5 mg/kg, po by gavage). Endosulfan reduced the intensity of electrical stimulation required to evoke seizures in amygdala kindled animals. These data indicate that these chlorinated hydrocarbon insecticides reduce seizure thresholds in amygdala-kindled animals with acute administration, and together with previous findings (see ref. 20) demonstrate bidirectional transfer between chemical and electrical kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of endosulfan on lipid synthesis by the hepatopancreas of the field crabParatelphusa hydrodromus

Abstract The effect of repetitive sublethal doses of endosulfan on the synthesis of lipids by the hepatopancreas of the field crab, Paratelphusa hydrodromus, was tested. The lipid content of the tissues tested decreased during the course of poisoning. The decrease in total lipids correlates with increased lipase activity in the hepatopancreas. The incorporation of 14C acetate into lipids by the hepatopancreas exposed to sublethal concentrations of endosulfan declined. The decline in the in vitro as well as in vivo incorporation suggest endosulfan's involvement in inhibiting the lipid synthesizing ability of the hepatopancreas.

A characterization of chemical kindling with the pesticide endosulfan

In a companion article (see this issue), the proconvulsant properties of the pesticide endosulfan in electrical kindling of the amygdala are described. In the present report, an evaluation of the chemical kindling properties of endosulfan is presented. Repeated administration (3 times per week for a total of 21 doses) of endosulfan (5 and 10 mg/kg in corn oil, PO) was found to induce behavioral seizures in rats. Behavioral seizure development was most apparent in the high dose group (10 mg/kg). Heightened seizure responsiveness to a challenge dose was maintained following a two-week, drug-free period, arguing against cumulative toxicity as a mechanism for seizure induction. Electrical kindling induced by once daily stimulation of the amygdala began approximately 4 weeks after the final dose of endosulfan. In the absence of further dosing, a significant facilitation in the rate of kindling development was evident as a function of prior treatment with endosulfan. An enhancement in the rate of kindling was also evident in the low dose group (5 mg/kg) in the absence of clonic seizure development during dosing. A history of endosulfan treatment failed to affect threshold for inducing an afterdischarge (AD) and had equivocal effects on the development of AD with repeated stimulation. Pretreatment with a single high dose of endosulfan 2 weeks prior to electrical kindling was without effect on the development of the kindled response. Endosulfan has been reported to decrease binding of gamma-amino-butyric acid (GABA). Chemical kindling with endosulfan may result from the interaction of this pesticide with GABA-mediated neurotransmission in the central nervous system (CNS). Positive transfer to electrical kindling following a regimen of endosulfan dosing that produced only minor increases in the incidence of clonic seizures indicates that behavioral observations alone cannot predict the long term consequences of repeated exposure to pesticides.

Residues in fish exposed to sublethal doses of endosulfan and fish collected from cotton growing area.

A one step extraction and cleanup procedure for determining endosulfan in fish was investigated. Minced Fish was mixed with trisodium citrate, disodium hydrogen orthophosphate and sodium sulphate into a dry powdery mixture, which was eluted through silicic acid and alumina with a mixture of dichloromethane and hexane. The eluate was concentrated and chromatographed on GLC using an EC detector without further cleanup. Three species of fresh water fish exposed to 0.7-16 micrograms/litre-1 technical grade endosulfan in tanks for various periods of time were found to concentrate both alpha and beta endosulfan and metabolise them to sulfate, diol, ether and lactone. Fish collected from Gwydir River in the cotton growing area in summer (Dec. 1986-Feb. 1987) were found to contain endosulfan residues suggesting endosulfan is quite stable in the environment and can cause residues.

Effects of sub-chronic DDT exposure on humoral and cell-mediated immune responses in albino rats.

The present study was designed to evaluate the effect of sub-chronic doses of endosulfan on humoral and cell-mediated immune (CMI) responses in albino rats. Male albino rats were given a diet containing 5, 10 or 20 ppm endosulfan for 8–22 weeks and immunized with tetanus toxoid in Freund's complete adjuvant subcutaneously 20 days before terminating the exposure. The humoral immune response was studied by serum globulin level, immunoglobulin (IgM and IgG) concentration and antibody titre against tetanus toxoid. The CMI response was studied by leucocyte migration inhibition (LMI) and macrophage migration inhibition (MMI) factors. The antigen-induced increases in serum globulin fraction and immunoglobulin level were reduced at high doses of the endosulfan after 12 weeks of exposure. Antibody titre was significantly decreased in endosulfan-exposed rats at 10 and 20 ppm levels and a consistent trend was observed. Rats in the 10 and 20 ppm dose groups had significantly depressed LMI and MMI responses. Results obtained in this study revealed marked suppression of the humoral and CMI responses in rats administered with sub-chronic doses of endosulfan. Both cellular and humoral immune responses were decreased in a dose-time dependent pattern. Suppression of immune responses by endosulfan is clearly an important aspect of its toxicology.

Effects of endosulfan on humoral and cell-mediated immune responses in rats

Endosulfan (6,7,8,9,10,10a-hexa-chloro-1,5,5a,6,9,9a-hexahydro, 6,9-methano-2,4,3-benzodioxathiepin-3-oxide), a polycyclic chlorinated hydrocarbon of cyclodien group, is a well known insecticide. Food is the main source of exposure of the general population to endosulfan. The physical, chemical as well as toxicological effects of endosulfan in experimental animals have been reported by various workers. However, the reports regarding the effect of endosulfan on immune system are not available. In view of its widespread use there is an urgent need to investigate the immunotoxicological effect of endosulfan in mammals for the safety evaluation of this insecticide. This has, therefore, prompted the authors to investigate the effect of endosulfan on immune system employing albino rats as the experimental animals. Included in this report are their preliminary findings on humoral and cell-mediated immune responses in rats exposed to sub-chronic doses of endosulfan.

Effect of sub-chronic endosulfan exposure on humoral and cell-mediated immune responses in albino rats.

The present study was designed to evaluate the effect of sub-chronic doses of endosulfan on humoral and cell-mediated immune (CMI) responses in albino rats. Male albino rats were given a diet containing 5, 10 or 20 ppm endosulfan for 8-22 weeks and immunized with tetanus toxoid in Freund's complete adjuvant subcutaneously 20 days before terminating the exposure. The humoral immune response was studied by serum globulin level, immunoglobulin (IgM and IgG) concentration and antibody titre against tetanus toxoid. The CMI response was studied by leucocyte migration inhibition (LMI) and macrophage migration inhibition (MMI) factors. The antigen-induced increases in serum globulin fraction and immunoglobulin level were reduced at high doses of the endosulfan after 12 weeks of exposure. Antibody titre was significantly decreased in endosulfan-exposed rats at 10 and 20 ppm levels and a consistent trend was observed. Rats in the 10 and 20 ppm dose groups had significantly depressed LMI and MMI responses. Results obtained in this study revealed marked suppression of the humoral and CMI responses in rats administered with sub-chronic doses of endosulfan. Both cellular and humoral immune responses were decreased in a dose-time dependent pattern. Suppression of immune responses by endosulfan is clearly an important aspect of its toxicology.