Histopathological analysis of carbaryl-induced toxicity in the spleen of Levantine frog, Pelophylax bedriagae (Anura: Ranidae).

This study describes the histopathological effects of carbaryl in the spleen of Levantine frog, Pelophylax bedriage. Due to its primary role in immune system, it is important to research the toxic effects of pesticides, which play an important role in environmental pollution, on spleen. To that end, adult frogs were exposed to carbaryl for 96 h. Experimental groups contained low dose, (0.05 mg/g), medium dose (0.1 mg/g) and high dose (0.2 mg/g). After following exposure to carbaryl, the frogs were euthanised and dissected. In low-dose group, there were no important changes in spleen tissue. In medium-dose group, prominence in haemorrhage just below the capsule and an increase in the melanomacrophage number were determined. In high-dose group, in addition to increases in the melanomacrophages, separations in capsule, haemorrhage below capsule and within splenic tissue, sinusoidal enlargement, congestion in dilated sinusoid, hypertrophic plasma cells and fibrosis were determined as important histological lesions in exposed frogs. This study clearly showed that carbaryl caused important histopathological damages in splenic tissue of Pelophylax bedriagae. In view of these findings, it can be said that this insecticide has the capacity to disrupt spleen' functions.

Aged garlic extract ameliorates immunotoxicity, hematotoxicity and impaired burn-healing in malathion- and carbaryl-treated male albino rats.

Malathion and carbaryl are the most widely used organophosphate and carbamate insecticides, respectively, especially in developing countries; they pose a potential health hazard for both humans and animals. Here, we evaluated the protective effects of an odorless (free from allicin) Kyolic aged garlic extract (AGE, containing 0.1% S-allylcysteine; 200 mg/kg body weight) on the toxicity induced by 0.1 LD50 of malathion (89.5 mg/kg body weight) and/or carbaryl (33.9 mg/kg body weight) in male Wistar rats. Doses were orally administered to animals for four consecutive weeks. The present study showed that AGE completely modulated most adverse effects induced by malathion and/or carbaryl in rats including the normocytic normochromic anemia, immunosuppression, and the delay in the skin-burning healing process through normalizing the count of blood cells (erythrocytes, leucocytes and platelets), hemoglobin content, hematocrit value, blood glucose-6-phosphodehydrogenase activity, weights and cellularity of lymphoid organs, serum γ-globulin concentration, and the delayed type of hypersensitivity response to the control values, and accelerating the inflammatory and proliferative phases of burn-healing. In addition, AGE completely modulated the decrease in serum reduced glutathione (GSH) concentration and the increase in clotting time in malathion alone and carbaryl alone treated rats. Moreover, AGE induced a significant increase (P < 0.001) in serum GSH concentration (above the normal value) and accelerating burn-healing process in healthy rats. In conclusion, AGE was effective in modulating most adverse effects induced in rats by malathion and carbaryl, and hence may be useful as a dietary adjunct for alleviating the toxicity in highly vulnerable people to insecticides intoxication. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 789-798, 2017.

Histopathological study of toxic effects of carbaryl on digestive tract of Bufotes variabilis (Anura: Bufonidae).

Due to the negative effects of pesticide usage in environment, i.e., decline in amphibian populations, this study was designed to examine histopathologic changes following carbaryl exposure for 96 h in the digestive tract of variable toad, Bufotes variabilis. After exposure to single doses of carbaryl (low dose 50 µg/g, medium dose 100 µg/g, and high dose: 200 µg/g), the toads were euthanized and dissected and digestive tract samples were quickly removed. Histopathology revealed esophageal vacuolization and necrosis in esophageal cells. Hemorrhage was also observed in the esophagus. In the stomach, necrosis in the glandular epithelium, congested blood vessels, edema among gastric glands, dilated tips of the mucosal epithelial layer, gastric glandular atrophy, and hemorrhage were found. In the intestine, edema within villi, hemorrhage, inflammation, vacuolization, and necrosis in epithelial cells of villi were detected. This study clearly showed that carbaryl caused adverse effects on the digestive tract of B. variabilis in all dose groups.

Identification of polymorphisms in Cyrtorhinus lividipennis RDL subunit contributing to fipronil sensitivity.

As one of the most important predatory enemies, the miridbug, Cyrtorhinus lividipennis, plays an important role in rice planthoppers control, such as Nilaparvata lugens (brown planthopper). In order to compare insecticide selectivity between C. lividipennis and N. lugens, the contact acute toxicities of six insecticides (diazoxon, paraoxon, carbaryl, fenobucarb, fipronil and ethofenprox) were monitored. The results showed that all tested insecticides were more toxic to C. lividipennis than to N. lugens and fipronil had the biggest difference. The RDL subunit (Cl-RDL) was cloned from C. lividipennis and a RDL isoform (Cl-RDL-In) was also found with 31 amino acids insertion in RDL intracellular region. In order to understand the role of the insertion on insecticide sensitivities, three subunits (Nl-RDL, Cl-RDL and Cl-RDL-In) were constructed to obtain the functional receptors in Xenopus oocytes and the fipronil sensitivities were detected by the voltage-clamp technique. Nl-RDL (IC50=32.36 ± 4.07 µM) was more insensitive to fipronil than Cl-RDL (IC50=6.47 ± 1.12 µM). The insertion in Cl-RDL significantly reduced fipronil sensitivity with IC50 value in Cl-RDL-In of 16.83 ± 2.30 µM. Interestingly, after the elution of fipronil, the current response of Cl-RDL-In appeared obvious recovery, which were not observed in Cl-RDL and Nl-RDL. It might imply that the insertion played a special role in fipronil sensitivity.

Histopathologic changes in liver and kidney tissues induced by carbaryl in Bufotes variabilis (Anura: Bufonidae).

The purpose of this work was to investigate for the first time histopathologic effects of carbaryl in liver and kidney tissues of Bufotes variabilis. After 96h following exposure to carbaryl (low dose: 0.05, medium dose: 0.1 and high dose: 0.2mg/g), the toads were euthanized and dissected. In liver tissue, vacuolization in hepatocytes, necrosis, mononuclear cell infiltration, an increase in melanomacrophage number, enlargement of sinusoids, hemorrhage and congestion were determined in exposed toads. In kidney tissue, mononuclear cell infiltration, hypertrophied Bowman's capsule cells, deformation, vacuolization, karyolysis and necrosis of renal tubule epithelium, brush border destruction, glomerular shrinkage, hemorrhage and fibrosis were observed in carbaryl-treated groups. According to this investigation, carbaryl caused histopathologic damages in liver and kidney tissues of B. variabilis.

Subchronic neurotoxicity of chlorpyrifos, carbaryl, and their combination in rats.

Anticholinesterase pesticides have been widely used in agricultural and domestic settings and can be detected in the environment after long-term use. Although the acute toxic effects of chlorpyrifos and carbaryl have been well described, little is known about the chronic toxicity of the pesticides mixture. To investigate their chronic neurotoxicity, Wistar rats were exposed to chlorpyrifos, carbaryl, and their mixture (MIX) for 90 consecutive days. The activities of serum cholinesterase (ChE) as well as acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in nerve tissues were determined. Furthermore, the histopathological examination was carried out. The results showed that ChE activity significantly decreased in all treated rats except the rats treated with low dose carbaryl. Treatment with middle- and high-dose chlorpyrifos and MIX in rats significantly inhibited AChE activity in the central nervous tissues, whereas treatment with carbaryl alone did not. In sciatic nerve, AChE activity was significantly inhibited by high-dose carbaryl and MIX, but not by chlorpyrifos alone. No significant NTE inhibition was observed in all treatment groups. Histopathological examination revealed that both chlorpyrifos and MIX treatment induced hippocampal damage. However, no obvious hippocampal damage was found in carbaryl-treated rats. Carbaryl and MIX, but not chlorpyrifos alone, induced pathological damage of sciatic nerve. Taken together, all of the results indicated that chlorpyrifos and carbaryl have different toxicological target tissues in nervous system and showed corresponding effects in the nervous tissues, which may reflect the different sensitivity of central and peripheral nervous tissues to different pesticides individually and in combination.

Carbaryl-induced histopathologic alterations in the digestive tract of the Levantine frog, Pelophylax bedriagae (Anura: Ranidae).

In this study, histopathologic changes following carbaryl exposure for 96 hr were investigated in the digestive tract of Levantine frog, Pelophylax bedriagae. Adult frogs were exposed to carbaryl once by oral gavage in concentrations of 0.05, 0.1, and 0.2 mg/g. Histopathological changes were more prominent in medium- (0.1 mg/g) and high-dose (0.2 mg/g) groups than in the low-dose (0.05 mg/g) group. Esophageal cells showed vacuolization, cellular swelling, nuclear pyknosis, karyolysis, and necrosis. Additionally, esophageal glandular atrophy and infiltration of inflammatory cells around esophageal glands were observed at medium and high doses. In the stomach, there were prominent histopathologic defects such as cellular swelling and necrosis in gastric glands, necrotic cells within the interstitial spaces, separation of epithelial cell layer, congested vessels, and hemorrhage at medium and high doses. In the intestine, detachment of epithelial layer, epithelial cell disorganization, inflammation, and necrosis were detected at medium and high doses. The results of this study showed that carbaryl caused adverse effects on the digestive tract of the Levantine frog, P. bedriagae.

Carbaryl-induced histopathologic alterations on testes of levantine frog, Pelophylax bedriagae (Anura: Ranidae).

The aim of the study was to investigate for the first time histopathologic effects of carbaryl on the testes of adult frog, Pelophylax bedriagae. Frogs were exposed to carbaryl once by oral gavage in concentrations of 0.05, 0.1 and 0.2 mg/g. After 96 h, frogs were euthanized and dissected. Histopathological changes were more prominent in medium- (0.1 mg/g) and high-dose (0.2 mg/g) groups than in the low-dose (0.05 mg/g) group. In the low-dose group, shrinkage of some seminiferous tubules was observed. In the medium-dose group, an enlargement of interstitial spaces and germ cell necrosis were detected. In the high-dose group, prominent tubule deformation was determined. Germ cell necrosis in seminiferous tubules was frequently seen. In addition, congestion, hemorrhage, cellular infiltration and fibrosis were detected. According to these findings, it is clear that carbaryl affects male fertility in P. bedriagae.

Specific time of exposure during tadpole development influences biological effects of the insecticide carbaryl in green frogs (Lithobates clamitans).

The orchestration of anuran metamorphosis is initiated and integrated by thyroid hormones, which change dynamically during larval development and which may represent a target of disruption by environmental contaminants. Studies have found that some anurans experience increased rates of development when exposed to the insecticide carbaryl later in larval development, suggesting that this insecticide could affect thyroid hormone-associated biological pathways. However, the time in development when tadpoles are sensitive to insecticide exposure has not been clearly defined nor has the mechanism been tested. In two separate studies, we exposed recently hatched green frog (Lithobates clamitans) tadpoles to a single, three day carbaryl exposure in the laboratory at either 2, 4, 8, or 16 weeks post-hatching. We examined the impact of carbaryl exposure on mRNA abundance patterns in the brains of frogs following metamorphosis months after a single three day exposure (experiment 1) and in tadpole tails three days after exposure (experiment 2) using cDNA microarrays and quantitative real time polymerase chain reaction (QPCR) analyses. For tadpoles reared through metamorphosis, we measured tadpole growth and development, as well as time to, mass at, and survival to metamorphosis. Although carbaryl did not significantly impact tadpole development, metamorphosis, or survival, clear exposure-related alterations in both tail and brain transcript levels were evident when tadpoles were exposed to carbaryl, particularly in tadpoles exposed at weeks 8 and 16 post-hatching, indicating both short-term and long-term alterations in mRNA expression. These results indicate that carbaryl can have long-lasting effects on brain development when exposure occurs at sensitive developmental stages, which may have implications for animal fitness and function later in the life cycle.

Histopathological effects of carbaryl on digestive system of snake-eyed lizard, Ophisops elegans.

We examined the effects of carbaryl in the digestive system of Ophisops elegans. Lizards were exposed once to different concentrations of carbaryl (2.5, 25 and 250 µg/g). After 96 h, findings related to the esophagus in all treatment groups were not conspicuous. The most important histological defects were observed in the stomach. In the small intestine, collapse of villi was prominent at high-dose. In the large intestine, disintegration in epithelial cells and scattered secretory granules of goblet cells were observed at high dose.

Histopathological effects of carbaryl on testes of snake-eyed lizard, Ophisops elegans.

BACKGROUND, AIM AND SCOPE: Due to their ecological niche and insectivore nature, lizards are of increased risk of exposure to pesticides in agricultural areas. In addition to their potential direct effects on non-target species, insecticides can also result in indirect impacts on lizard population by reducing their food source. Carbaryl is a common insecticide that is widely used in areas of Turkey that are home to a variety of reptiles. However, to date, little is known about the potential effects of the exposure of reptiles such as lizards or snakes to this pesticide. The aim of the study was to investigate toxic effects of carbaryl on the testes of snake-eyed lizard, Ophisops elegans that is common to regions in Turkey where Carbaryl is applied and that it can be easily cultured in the laboratory. MATERIAL AND METHODS: Adult male lizards were exposed to carbaryl once by oral gavage in concentrations of 2.5, 25 and 250 µg/g. After 96 h, lizards were euthanized and dissected. Histopathological changes were detected by randomly counting 100 tubules in each lizard. Seminiferous tubules were categorized as normal, sloughing and disorganized tubules. Diameters of tubules were also measured. The differences in histopathological changes and tubule diameters were compared for statistical significance by one-way ANOVA, using SPSS 16.0. RESULTS AND DISCUSSION: Histopathological changes were more prominent in medium- (25 µg/g) and high-dose (250 µg/g) groups than in the low-dose (2.5 µg/g) group. In the medium-dose group, the hexagonal appearance of most tubules disappeared, and they took on an oval shape. Sloughing was the characteristic tubule appearance of the medium group. In the high-dose group, significant increases in the number of disorganized tubules and prominence of haemorrhages was observed. CONCLUSION: Carbaryl caused histopathological defects on the testes of O. elegans, so it is clear that carbaryl affects male fertility in O. elegans.

Metabolic profiles of serum from rats after subchronic exposure to chlorpyrifos and carbaryl.

Chlorpyrifos (CPF) and carbaryl (CAR) have been widely used in agricultural and domestic settings. Previous studies have demonstrated that CPF and CAR are generally neurotoxic to mammals, whereas the toxicities of these pesticides to other organs and their potential interactive effects remain unclear. The purpose of this study assessed the alterations of histopathology, biochemical parameters, and metabolic profiles of serum in rats following the treatment with CPF and CAR alone or in combination. No histopathological changes were observed in the liver and kidney tissues. Biochemical analysis of blood showed that alanine aminotransferase and total bilirubin in serum increased slightly in CPF-treated rats as compared to controls. Metabonomic analysis revealed alternations in a number of metabolites involving the metabolism of glucose, free fatty acids, and amino acids in liver mitochondria. The treatment of rats with CPF alone resulted in a decrease in lactate, low- and very low-density lipoprotein (LDL/VLDL), dimethylglycine (DMG), and aspartate. This was accompanied by an increase in isoleucine and leucine, 3-hydroxybutyrate (3-HB), N-acetylglycoprotein (NAC), acetone, succinate, glutamine, choline, creatine, glucose, and amino acids in a dose-dependent manner. Similarly, treatment with a high dose of CAR alone led to a decrease in DMG, aspartate, LDL/VLDL, and dimethylamine and an increase in taurine, glucose, and amino acids. The levels of lactate and LDL/VLDL decreased, while those of 3-HB, NAC, acetone, succinate, and glutamine elevated in the group of rats treated with a mixture of CPF and CAR as compared to the groups of CPF or CAR alone. Our results suggest that subchronic exposure to CPF and CAR alone, or in combination, could cause a disturbance in energy and fatty acid metabolism in the liver mitochondria of rats. Overall, we have shown that analysis of metabolic profiles can make exceptional contributions to the understanding of the individual or mutual effects following exposure to a low dose of pesticides.

A multianalyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat.

The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte profile (MAP) of 58 serum biomarkers to rats exposed acutely to two anticholinesterase insecticides, chlorpyrifos (CHP) and carbaryl (CAR). Male, Long-Evans rats were dosed orally with 30 mg/kg CHP, 75 mg/kg CAR or the corn oil vehicle. Doses were selected based on their equivalent physiological effects (hypothermia and reduced motor activity). The animals were terminated 24h or 7 days after dosing. Serum was collected and analyzed for 58 biomarkers consisting primarily of cytokines, chemokines, and a few hormones. There were changes in six analytes (four up, two down) following CHP and eight analytes (five up, three down) following CAR at 24h. There were significant changes in only two biomarkers when measured 7 days after dosing with CHP. Overall, the MAP detected a broad spectrum of unique effects for CHP and CAR. It is concluded that the MAP is a useful tool to screen for in vivo effects of environmental toxicants and its use could lead to the discovery of novel mechanisms of action.

Effect of carbaryl on some biochemical changes in rats: the ameliorative effect of bee pollen.

In this study, 42 female Wistar albino rats, weighing between 200 and 250 g, were used and they were divided into six equal groups. Group 1 was allocated as the control group. Rats included in groups 2 and 3 were administered a water-solubilized extract of bee pollen at a dose of 50 mg/kg bw/day and 100 mg/kg bw/day, respectively. Group 4 received 225 mg/kg bw/day carbaryl. Groups 5 and 6 were given a water-solubilized extract of bee pollen at a dose of 50 mg/kg bw/day and 100mg/kg bw/day, respectively, plus 225 mg/kg bw/day carbaryl. The indicated administrations were continued for 21 days for groups 1-6 by gavage. MDA levels and the activities of CAT, SOD and GSH-Px were analysed in blood and tissues (liver, kidney, brain and heart). At the same time, levels/activities of total protein, albumin, glucose, triglyceride, T-cholesterol, T-bilirubin, BUN, creatinine, uric acid, GGT, LDH, AST, ALT and ALP, magnesium, sodium, potassium and chloride were evaluated in serum samples. In conclusion, carbaryl was determined to cause negative changes in most of the oxidative stress markers and serum biochemical parameters investigated. These effects were observed to alleviate with the administration of bee pollen.

Molecular characterization of two acetylcholinesterase cDNAs in Pediculus human lice.

Two cDNA sequences encoding Drosophila Ace-orthologous and -paralogous acetylcholinesterase precursors (AO- and AP-AChE precursors, respectively), were identified from the body louse, Pediculus humanus humanus L. In vitro inhibition studies with an insecticide-susceptible body louse strain exhibited a simplex inhibitory response of AChE. The I50 values of fenitroxon and carbaryl were estimated to be 2.2 and 1.9 microM for the susceptible lice, respectively. The mRNA level of AP-AChE gene was 3.1- and 9.3-fold higher than that of AO-AChE gene in the abdomen and the combined parts of the head and thorax, respectively, suggesting, due to its abundance, the potential significance of the AP-AChE isoform in Pediculus human lice in association with the efficacy of AChE-targeting pediculicides.

Inhibition of mitochondrial bioenergetics by carbaryl is only evident for higher concentrations -- Relevance for carbaryl toxicity mechanisms.

Although pesticides have been useful in agriculture pest control, there is a considerable risk for human health and damage to ecosystems. Carbaryl is a carbamate often taken as a safe insecticide, although data on metabolic activities is still scarce, viz. mitochondrial toxicity. Therefore, it is the goal of this work to assay the compound on isolated mitochondria, a biochemical model already used with other pesticides. Mitochondria isolated from the livers of Wistar rats were assayed for bioenergetic parameters, namely mitochondrial respiration, membrane potential, membrane integrity and enzyme activities. For higher concentrations, it was observed that carbaryl has a depressive effect on mitochondrial respiration and on the generation of mitochondrial membrane potential, but with preservation of membrane integrity. A locus between Complex II and III appears particularly affected and the mitochondrial phosphorylation system relatively insensitive. Therefore, carbaryl inhibits mitochondrial respiration without affecting the phosphorylation complex. Carbaryl is toxic for mitochondria, although at concentrations higher as compared with other insecticide compounds. Mitochondrial toxicity should be excluded as one of the primary causes for carbaryl immediate toxicity, as concluded from the range of concentrations where carbaryl shows effective mitochondrial toxicity.

[Effects of carbaryl on serum steroid hormone and the function of antioxidant system in female rats].

OBJECTIVE: To investigate the effects of carbaryl on serum steroid hormone and function of antioxidant system in female Sprague Dawley rats. METHODS: Carbaryl was administrated to the adult female rats at doses of 0, 1.028, 5.140 and 25.704 mg x kg(-1) x d(-1) for 30 d. Vaginal smears of rats were taken to determine estrous cycle. Serum 17beta-estradiol (E(2)) and progesterone (P(4)) concentrations were measured by radioimmunoassay. The activities of superoxide dismutase (SOD) and glutathione-s-transferase (GST), and the levels of malondialdehyde (MDA) and glutathione (GSH) were measured by spectrophotometry. RESULTS: The number of estrous cycle in exposed groups were obviously lower than in control group (P < 0.05, P < 0.01). Body weight gain in high dose group (25.704 mg x kg(-1) x d(-1)) was significantly lower than that in control. Meanwhile, the organ coefficient of ovary and uterus declined in a dose-dependent manner. Serum E(2) level [(19.93 +/- 2.21) nmol/L] in 25.704 mg group was lower than in control group [(28.76 +/- 6.12) nmol/L, P < 0.05], and P(4) level (1.21 +/- 0.40) nmol/L in 1.028 mg group was higher than that in control group [(0.63 +/- 0.39) nmol/L, P < 0.05]. The activity of SOD first reduced then rose in ovary, and first rose then reduced in serum. The contents of MDA increased in ovary, while decreased in the serum. GSH contents and GST activity increased in ovary, while in serum GSH contents decreased and GST activity first increased then decreased. CONCLUSION: Carbaryl could disrupt estrous cycle and affect serum steroid hormone, and the function of antioxidant system in female SD rats.

Alachlor and carbaryl suppress lipopolysaccharide-induced iNOS expression by differentially inhibiting NF-kappaB activation.

Nitric oxide (NO) produced by macrophages plays an important role in host defense and inflammation. We found that two agrochemicals, alachlor and carbaryl, inhibit lipopolysaccharide (LPS)-induced NO production by macrophages. In the present study, we investigated this inhibitory mechanism in RAW 264 cells. Both chemicals inhibited LPS-induced iNOS protein and mRNA expression as well as murine iNOS promoter activity. When treating these chemicals with reducing agents, the inhibition by carbaryl was reversed, but not the inhibition by alachlor. These chemicals also inhibited LPS-induced interferon-beta (IFN-beta) expression, an indispensable factor for LPS-induced iNOS expression. The inhibited iNOS expression, however, was not restored by exogenous IFN-beta supplementation. LPS-induced nuclear translocation of NF-kappaB, which is necessary for the expression of IFN-beta and iNOS, was inhibited by these chemicals: however, the LPS-induced degradation of IkappaB-alpha and IkappaB-beta was inhibited only by alachlor. These results indicate that alachlor and carbaryl differentially impair the LPS-induced NF-kappaB activation, leading to the inhibition of NO production.

Tumorigenic potential of carbaryl in the heterozygous p53 knockout mouse model.

The heterozygous p53 knockout mouse model was used to assess whether vascular tumors noted in a 2-year carcinogenicity study in CD-1 mice with carbaryl were induced through a genotoxic mechanism. This knockout mouse model was selected for carbaryl because of the high sensitivity of this model to genotoxic events and its low spontaneous incidence of tumors until 9-12 months of age. Carbaryl was administered continuously via the diet to groups of 20 male heterozygous p53 knockout mice at concentrations of 0, 10, 30, 100, 300, 1000 and 4000 ppm for 180 days. Histopathological examinations revealed no evidence of carbaryl-induced neoplasms of any type. In particular, no neoplastic or preneoplastic changes were noted in the vascular tissue of any of the organs examined. Only neoplasms, recognized as those that occur spontaneously in untreated mice of this strain, were sporadically observed in a few animals from the intermediate dose groups with no evidence of a dose- or treatment-related effect. Therefore, under the conditions of this study, the no-observed-effect level (NOEL) of carbaryl for neoplastic changes in male mice was 4000 ppm (around 716 mg/kg body weight/day). We conclude: (1) carbaryl does not appear to be a genotoxic carcinogen at least in male mice; (2) if the vascular tumors observed in the CD-1 mice are treatment-related, they could have been induced by a non-genotoxic mechanism; (3) the response in transgenic animals may provide useful complementary results to better assess carbaryl's potential genotoxic hazard to humans.

Effects of combinations of endosulfan, dimethoate and carbaryl on immune and hematological parameters of rats.

IgG and IgM levels and hematological parameters (red and white blood cell counts, thrombocyte, monocyte, lymphocyte and granulocyte counts and hemoglobin concentrations) were determined in albino rats exposed to combinations of endosulfan, dimethoate and carbaryl. Two and 3 combinations of 100- and 1000-fold acceptable daily intake (ADI) of endosulfan (ADI = 0.00612 mg/kg), dimethoate (ADI = 0.0204 mg/kg) and carbaryl (ADI = 0.0101 mg/kg) were administered po to male albino rats for 3.5 mo. Animals were immunized s.c. with tetanus toxoid in Freund's complete adjuvant 20 d before terminating exposures. At 100-fold ADI dosing, administration of each of the pesticides alone did not cause any difference in the parameters, but numbers of white blood cells and monocytes increased in rats given endosulfan + dimethoate while numbers of red blood cells increased with dimethoate + carbaryl. Rats given 1000-fold ADI endosulfan + dimethoate + carbaryl had significant differences in almost every parameter, while IgG, IgM white blood cells and lymphocytes decreased, and monocytes and % granulocytes increased from single endosulfan dosing. Lymphocyte counts were reduced by single dimethoate or carbaryl dosing. Endosulfan + dimethoate + carbaryl produced the most effective changes in comparison to single dosing or other pesticide combinations.