Transcriptional regulation of xenobiotic detoxification in Drosophila.

Living organisms, from bacteria to humans, display a coordinated transcriptional response to xenobiotic exposure, inducing enzymes and transporters that facilitate detoxification. Several transcription factors have been identified in vertebrates that contribute to this regulatory response. In contrast, little is known about this pathway in insects. Here we show that the Drosophila Nrf2 (NF-E2-related factor 2) ortholog CncC (cap 'n' collar isoform-C) is a central regulator of xenobiotic detoxification responses. A binding site for CncC and its heterodimer partner Maf (muscle aponeurosis fibromatosis) is sufficient and necessary for robust transcriptional responses to three xenobiotic compounds: phenobarbital (PB), chlorpromazine, and caffeine. Genetic manipulations that alter the levels of CncC or its negative regulator, Keap1 (Kelch-like ECH-associated protein 1), lead to predictable changes in xenobiotic-inducible gene expression. Transcriptional profiling studies reveal that more than half of the genes regulated by PB are also controlled by CncC. Consistent with these effects on detoxification gene expression, activation of the CncC/Keap1 pathway in Drosophila is sufficient to confer resistance to the lethal effects of the pesticide malathion. These studies establish a molecular mechanism for the regulation of xenobiotic detoxification in Drosophila and have implications for controlling insect populations and the spread of insect-borne human diseases.

Malathion dermal permeability in relation to dermal load: Assessment by physiologically based pharmacokinetic modeling of in vivo human data.

Estimates of dermal permeability (Kp), obtained by fitting an updated human PBPK model for malathion to previously reported data on excreted urinary metabolites after 29 volunteers were dermally exposed to measured values of [14C]malathion dermal load (L), were used to examine the empirical relationship between Kp and L. The PBPK model was adapted from previously reported human biokinetic and PBPK models for malathion, fit to previously reported urinary excretion data after oral [14C]malathion intake by volunteers, and then augmented to incorporate a standard Kp approach to modeling dermal-uptake kinetics. Good to excellent PBPK-model fits were obtained to all of 29 sets of cumulative urinary metabolite-excretion data (ave. [±1 SD] R2 = 0.953 [±0.064]). Contrary to the assumption that Kp and L are independent typically applied for dermally administered liquids or solutions, the 29 PBPK-based estimates of Kp obtained for malathion exhibit a strong positive association with the 2/3rds power of L (log-log Pearson correlation = 0.925, p = ∼0). Possible explanations of this observation involving physico-chemical characteristics and/or in vivo cutaneous effects of malathion are discussed. The PBPK model presented, and our observation that Kp estimates obtained by fitting this model to human experimental urinary-excretion data correlate well with L2/3, allow more realistic assessments of absorbed and metabolized dose during or after a variety of scenarios involving actual or potential dermal or multi-route malathion exposures, including for pesticide workers or farmers who apply malathion to crops.

Exposure to environmentally relevant concentrations of malathion induces significant cellular, biochemical and histological alterations in Labeo rohita.

The extensive use of malathion, an organophosphate pesticide, raises the possibility of its undesirable toxicity to non-target organisms. Agricultural run-off and vector control sprays are the major sources of exposure to this pesticide for aquatic organisms. Some earlier studies have reported the presence of malathion at concentrations ranging from 18.12µg/L to 105.2µg/L in various water samples. In this study, we have tested the hypothesis that these sub-lethal yet environmentally significant concentrations of malathion has serious toxicological implications on the fingerlings of Labeo rohita. Exposure to increasing concentration of malathion (10, 50 and 100µg/L) was reflected in the serum concentration of the pesticide and also in the inhibition of acetylcholinesterase activity in fish brains. Increased abnormalities in liver function test coupled with a rise in the oxidative stress response were observed in gills, liver and kidney. However, the increase in antioxidant enzyme activities like superoxide dismutase and glutathione-S-transferase by malathion exposure suggested a hormetic response. Tissue injury due to malathion was evident from the morphological and nuclear anomalies in the H-E stained sections of gill, liver and kidney. Cell cycle analysis of these organs further fortified the histopathological findings. This study elucidates the sub-lethal toxicity of environmentally relevant malathion concentrations on Labeo rohita which indicates the potential health hazard posed to human beings consuming this fish. This calls for careful application of malathion in areas adjoining to inland fisheries.

Nutritional aspects of detoxification in clinical practice.

Detoxification is a vital cellular task that, if lacking, can lead to early morbidity and mortality. The process of detoxification involves the mobilization, biotransformation, and elimination of toxicants of exogenous and endogenous origin. This article discusses the phase I and phase II detoxification and biotransformation pathways and promotes using food to support these highly complex processes. The author identifies the comprehensive elimination diet as a useful therapeutic tool for clinicians and patients to use to achieve detoxification. Using this diet, the patient removes the most common allergenic foods and beverages from the diet and replaces them with nonallergenic choices for a period of 4 wk, gradually adding back the eliminated foods and observing their effects. Another effective clinical tool that the author discusses is the detox-focused core food plan, which identifies the variety of foods required to supply key nutrients that can maximize the effectiveness of detoxification. Finally, the author provides a case study in which these tools were used to help a patient suffering from major, debilitating illnesses that resulted from exposure to malathion, including severe vomiting and diarrhea, headaches, night sweats, severe arthralgias and myalgias, episcleritis, and shortness of breath. The article details the interventions used and the clinical results (ie, successful resolution of most issues after 3 mo).

Absorption and excretion of organophosphorous insecticide biomarkers of malathion in the rat: implications for overestimation bias and exposure misclassification from environmental biomonitoring.

Malathion is an organophosphorous (OP) insecticide widely used for crop protection. Its degradates, malathiondiacid (MDA), malathion monoacid (MMA), dimethylphosphate (DMP), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) are formed in strawberries and other produce. These same chemical biomarkers are measured in urine in human studies as quantitative measures of exposure. The excretion of malathion and its common biomarkers including MDA, MMA, DMP, DMTP and DMDTP at equal molar doses (73 µmol/kg b.w.) was studied following oral dosing of female Holtzmann rats (240-300 g). Following MDA administration, 36.3±5.4% was recovered as MDA, 0.05±0.02% as DMP, 5.5±0.3% as DMTP, 3.8±2.9% as DMDTP (mole percent), and totally 45.6±7.0% of administered dose in urine after 120 h (over 94% in the first 24h). Following DMTP administration, 8.3±7.7% was recovered as DMP, 46.6±16.5% as DMTP, and totally 55.0±10.3% of administered dose in urine after 120 h (over 92% in the first 24h). Similar results were obtained with other malathion biomarkers. Preformed biomarkers of malathion and other OP insecticides when ingested in produce are readily absorbed and excreted. Low level human dietary and non-occupational urine biomonitoring studies will be confounded by preformed pesticide biomarkers used to infer potential human pesticide exposure. This has profound implications for epidemiology studies where subject's biomarker excretion is used as a surrogate for OP exposures that cannot be related to a particular insecticide residue.

Effects of human serum albumin on post-mortem changes of malathion.

Malathion, diethyl 2-[(dimethoxyphosphinothioyl)thio]butanedioate, is one of most widely used organophosphoryl pesticide, and it has been detected in several clinical cases of accidental exposure and suicide. It is reported that the observed malathion concentration in blood of persons who suffer from malathion poisoning is smaller than the expected concentration. Because malathion is bound to human serum albumin (HSA), recovery of malathion in the free form is insufficient. We detected malathion adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that malathion was preferably bound to the lysine (K) and cysteinylproline (CP) residues of HSA. The K- and CP-adducts of malathion were increased in vitro with a dose-dependent fashion when its concentration was smaller than the lethal dose. Further, the K-adduct was also detected in post-mortem blood of an autopsied subject suffering from intentional malathion ingestion. These results suggest that the K-adduct seems to be available to use a biomarker of malathion poisoning, and the determination of the K-adduct could make possible to estimate the amount of malathion ingestion.

Acute toxicity and tissue distributions of malathion in Ambystoma tigrinum.

The kinetics of the bioaccumulation of malathion (O,O-dimethyl phosphorodithioate of diethyl mercaptosuccinate) and the biological impact of exposure for tiger salamanders, Ambystoma tigrinum, were assessed through exposure to soil surface contaminated with 50 microg/cm(2) or 100 microg/cm(2 )malathion and ingestion of an earthworm exposed to soil contaminated with 200 microg/cm(2) malathion. Malathion and malaoxon burdens in salamanders sampled at different times after exposure(s) were measured by gas chromatography in four tissue/organ subgroups: liver, epaxial muscle, pooled viscera (except the liver and brain), and pooled avisceral carcass (muscle, skin, and bone). The total tiger salamander xenobiotic burdens were calculated from these data. The malathion/malaoxon burden 1 day after exposure was greatest in the avisceral carcass and 2 days after exposure was greatest in the viscera. Bioconcentration and bioaccumulation factors remained less than unity throughout the experiment and did not support the hypothesis of bioaccumulation of malathion in the tiger salamander. Biological impact was assessed with a colorimetric brain cholinesterase microassay. Brain cholinesterase activities in salamanders exposed to malathion-contaminated soil (50 microg/cm(2) or 100 microg/cm(2 )malathion) were suppressed approximately 50-65% and 90%, respectively, compared to unexposed controls. The exposed animals did not exhibit overt clinical signs of malathion toxicosis.

[Changes in the toxicity and immunotoxity of tetrachloromethane and carbophos under the action of 2,4,6-triphenyl-4H-selenopyran and their connection with cytochrome P-450 dependent monooxygenase system].

It is established in experiments on noninbred rats that 2,4,6-triphenyl-4H-selenopyrane (peroral administration in a dose of 0.8 mg/kg during 3 days) induces cytochrome P450, thus increasing the toxicity and immunotoxicity of carbon tetrachloride (metabolized via "lethal synthesis"), and reduces the analogous effects of carbophos, the biotransformation of which proceeds via the formation of low-toxicity and nontoxic metabolites.

In vitro dermal absorption of methyl salicylate, ethyl parathion, and malathion: first responder safety.

In vitro tests with fresh dermatomed (0.3 to 0.4 mm thick) female breast skin and one leg skin specimen were conducted in Bronaugh flow-through Teflon diffusion cells with three chemicals used to simulate chemical warfare agents: 14C-radiolabeled methyl salicylate (MES), ethyl parathion (PT), and malathion (MT), at three dose levels (2, 20, and 200 mM). Tests were conducted at a skin temperature of 29 degrees C using a brief 30-min exposure to the chemical and a 6.5-h receivor collection period. Rapid absorption of all three chemicals was observed, with MES absorbed about 10-fold faster than PT and MT. For MES, PT, and MT, respectively, there was 32%, 7%, and 12% absorption into the receivor solution (Hank's HEPES buffered saline with 4% bovine serum albumin [BSA], pH 7.4) at the low dose (2 mM), 17%, 2%, and 3% at the medium dose (20 mM), and 11%, 1%, and 1% at the high dose (200 mM) levels. Including the skin depot for MES, PT, and MT, respectively, there was 40%, 41%, and 21% (low dose), 26%, 16%, and 8% (medium dose), and 13%, 19%, and 10% (high does) absorption. Efficacy of skin soap washing conducted at the 30 min exposure time ranged from 31% to 86%, varying by chemical and dose level. Skin depot levels were highest for the relatively lipophilic PT. "Pseudo" skin permeability coefficient (K(p)) data declined with dose level, suggesting skin saturation had occurred. An in-depth comparison with literature data was conducted and risk assessment of first responder exposure was briefly considered.

Potential uses of biomonitoring data: a case study using the organophosphorus pesticides chlorpyrifos and malathion.

BACKGROUND: Organophosphorus pesticides such as chlorpyrifos and malathion are widely used insecticides. They do not bioaccumulate appreciably in humans and are rapidly metabolized and excreted in the urine. In nonoccupational settings, exposures to these pesticides are typically sporadic and short-lived because the pesticides tend to degrade in the environment over time; however, dietary exposures may be more chronic. Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion; thus, the information base on these compounds is data rich. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. For assessing early effects and susceptibility, cholinesterase and microsomal esterase activities, respectively, have been measured. OBJECTIVES: Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. We present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications.

Decreasing malathion application time for lice treatment reduces transdermal absorption.

OBJECTIVE: Head lice are the most common parasitic infestation in the United States requiring topical treatment with pediculicides. Ovide, the 0.5% malathion formulation used in treatment of head lice requires placement on dry hair for 8-12 h. Malathion, however, is effective at killing lice and nits in 10 min. Our concern of over exposing children to malathion has led us to examine whether significantly more malathion will penetrate transdermally when applied for the recommended 8 h than for a shorter but apparently equally effective period. METHODS: In vitro absorption studies were performed across haired rat skin and human abdominal skin to determine whether reducing malathion application time decreased skin absorption. RESULTS: A 0.5 h exposure caused 0.36+/-0.14% of the donor malathion to penetrate through human skin after 24 h and 2.1+/-0.6% remained in the skin after washing with shampoo. After 8 h of topical applications penetration was approximately three-fold greater (1.02+/-0.41) and 3.4+/-0.5% remained in the skin (p<0.05 versus 0.5 h). The relationship between absorption and exposure time also occurred for haired rat skin (p<0.05). This differential continued for 72 h even after removal of the source. CONCLUSIONS: Significantly less malathion penetrated from Ovide after 0.5 h versus the suggested 8 h application, without decreasing the product's efficacy. Further clinical studies in children are warranted to confirm the efficacy of this shortened application time.

A toxicokinetic model of malathion and its metabolites as a tool to assess human exposure and risk through measurements of urinary biomarkers.

A toxicokinetic model is proposed to predict the time evolution of malathion and its metabolites, mono- and dicarboxylic acids (MCA, DCA) and phosphoric derivatives (dimethyl dithiophosphate [DMDTP], dimethyl thiophosphate [DMTP], and dimethyl phosphate [DMP]) in the human body and excreta, under a variety of exposure routes and scenarios. The biological determinants of the kinetics were established from published data on the in vivo time profiles of malathion and its metabolites in the blood and urine of human volunteers exposed by intravenous, oral, or dermal routes. In the model, body and excreta compartments were used to represent the time varying amounts of each of the following: malathion, MCA, DCA, DMDTP, DMTP, and DMP. The dynamic of intercompartment exchanges was described mathematically by a differential equation system that ensured conservation of mass at all times. The model parameters were determined by statistically adjusting the explicit solution of the differential equations to the experimental human data. Simulations provide a close approximation to kinetic data available in the published literature. When simulating a dermal exposure to malathion, the main route of entry for workers, the model predicts that it takes an average of 11.8 h to recover half of the absorbed dose of malathion eventually excreted in urine as metabolites, compared to 3.2 h following an intravenous injection and 4.0 h after oral administration. This shows that following a dermal exposure, the absorption rate governs the urinary excretion rate of malathion metabolites because the dermal absorption rate is much slower than biotransformation and renal clearance processes. The model served to establish biological reference values for malathion metabolites in urine since it allows links to be made between the absorbed dose of malathion and the time course of cumulative amounts of metabolites excreted in urine. From the no-observed-effect level (NOEL) of 0.61 micromol/kg/day derived from the data of Moeller and Rider (1962), the model predicts corresponding biological reference values for MCA, DCA, and phosphoric derivatives of 44, 13, and 62 nmol/kg, respectively, in 24-h urine samples. The latter were used to assess the health risk of workers exposed to malathion in botanical greenhouses, starting from urinary measurements of MCA and DCA metabolites.

Percutaneous absorption, dermatopharmacokinetics and related bio-transformation studies of carbaryl, lindane, malathion, and parathion in isolated perfused porcine skin.

The percutaneous absorption of topically applied pesticides is a primary route for systemic exposure and potential toxicity. The isolated perfused porcine skin flap (IPPSF) is an in vitro model for studying percutaneous absorption of xenobiotics as well as cutaneous metabolism and toxicity in an anatomically intact viable skin preparation. In the present studies, percutaneous absorption of four different pesticides, carbaryl (C), lindane (L), malathion (M), and parathion (P), was assessed topically in an ethanol vehicle. A 4-compartment pharmacokinetic model was utilized to model their absorption profile. The order of absorption was C > P > L > M for the 8-h experimental period, but C > L > P > M for a model-extrapolated 6-day prediction. Metabolism of C and P was also assessed by high performance liquid chromatography (HPLC). The HPLC results indicate a significant first-pass effect for both pesticides after topical application, with parathion being metabolized to paraoxon and para-nitrophenol and carbaryl to naphthol. In addition, comparison of the metabolic data of P with previous results underscores the difference between non-recirculating and recirculating IPPSF systems in xenobiotic metabolism studies.

Dimethylphosphorus metabolites in serum and urine of persons poisoned by malathion or thiometon.

The urinary excretion rates of dimethyl-phosphate, -phosphorothioate and -phosphorodithioate were studied in six persons of whom four had ingested a concentrated solution of malathion and two of thiometon. The concentration decrease of single and total dimethylphosphorus metabolites was biphased, with a fast initial rate and a slow later rate. The excretion rate of total metabolites in the faster phase depended on the initial concentration in urine. At concentrations higher than 100 nmol/mg creatinine, the excretion half-times ranged from 7.5 to 15.4 h and at concentrations between 52 and 95 nmol/mg creatinine from 34.7 to 55.4 h. Non-metabolized malathion was detected only in one urine sample collected from one person immediately after hospitalization. Two persons poisoned with malathion were taken blood serum samples for the analysis of the parent pesticide and its metabolites on a daily basis after hospitalization. The parent pesticide was detectable in the serum only one day after the poisoning. The concentration of total malathion dimethylphosphorus metabolites in serum decreased very quickly within 1.5 days after hospitalization. The total metabolite elimination half-times were 4.1 and 4.7 h in the initial phase, and 53.3 and 69.3 days in the later slower elimination phase. There was no correlation between maximum concentrations of total metabolites measured in serum and/or urine on the day of admission to hospital and the initial depression of serum cholinesterase (BChE, EC 3.1.1.8) and erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7).

Monitoring of pesticide applicators for potential dermal exposure to malathion and biomarkers in urine.

Malathion was applied to roses in three Finnish greenhouses by hand held lance sprayers. The potential dermal exposure of applicators to this insecticide was measured. Total urine production of each applicator was also collected up to 24 h post application. In the urine samples the specific metabolite of malathion, malathion monocarboxylic acid (MMA), and the creatinine content were determined. The potential dermal exposure results show that during the application of malathion, the applicators' lower limbs accounted, on average, for 48%, while the upper limbs accounted for 19% of the potential dermal exposure. Moreover, hands and chest and back and head regions accounted for 30 and 3%, respectively. Based on the urine measurements, it was observed that the excretion of MMA was very rapid reaching a maximum at about 6-7 h after the completion of the application. In the urine samples collected, MMA was found to be present in relatively small amounts.

Percutaneous penetration and skin retention of topically applied compounds: an in vitro-in vivo study.

Radiolabeled compounds with varying partition coefficients (paraoxon, benzoic acid, parathion, and DDT) were chosen to study the percutaneous penetration and extent of dermal retention in pig skin both in vitro and in vivo. Radiolabel distributions within the skin were determined from 1 min to 24 h after application in ethanol. The distribution of radioactivity in the skin during the first 4 h was comparable between in vitro and in vivo experiments. At 24 h, radioactive residues in the dermis were significantly higher in vitro than in vivo for DDT, the most lipophilic compound. Increasing air flow over the skin surface significantly increased evaporative loss for volatile compounds (benzoic acid, N,N-diethyl-m-toluamide, malathion, parathion, and DDT), significantly decreased the residues in the upper skin layer for N,N-diethyl-m-toluamide, malathion, parathion, and DDT, significantly decreased the dermal residue for malathion, and significantly decreased the penetration of N,N-diethyl-m-toluamide, malathion, and parathion. On a percentage basis, increasing the dose of parathion and paraoxon from 4 to 1000 micrograms/cm2 resulted in significantly lower residues in the dermis. When applied to the dermis, the more hydrophilic benzoic acid and paraoxon better penetrated the dermis than the more hydrophobic parathion and DDT. An ethanol vehicle facilitated the penetration of parathion into the dermis and receptor fluid. These results indicate that the dermis interacted with the penetrant during both in vitro and in vivo percutaneous absorption. Factors such as partition coefficient and dose of the penetrant, air flow over the skin, and vehicle changed the distribution of penetrants in the skin and percutaneous penetration.(ABSTRACT TRUNCATED AT 250 WORDS)

Residues of methamidofos, malathion, and methiocarb in greenhouse crops.

The diminution of methamidofos, malathion, and methiocarb in different crops grown in greenhouses has been studied, including the presence of metabolites such as malaoxon, methiocarb sulfoxide, and methiocarb sulfone. The analytical method is based on dichloromethane extraction and GC-PFPD analysis. It has been validated establishing performance parameters such as recovery rates, precision, linear ranges, and limits of detection and quantification, which are low enough for ensuring that their corresponding MLRs can be adequately quantified. Samples of treated cucumbers and peppers grown in greenhouses were collected and analyzed during a 15-day period for obtaining the diminution rates of methamidofos and malathion. The behavior of methiocarb in treated green beans and tomatoes has been studied using analysis of variance (ANOVA) as the statistical tool, for establishing the influence of crop, season, application dose, and greenhouse design.

In vitro percutaneous absorption of model compounds glyphosate and malathion from cotton fabric into and through human skin.

Chemicals are introduced to fabric at many steps during manufacture and use. Fabrics containing chemicals can cause medical problems such as dermatitis and death. Insecticides impregnated into uniforms worn by "Desert Storm" personnel are implicated in "Gulf War Syndrome'. These chemicals must get from fabric into and through skin to cause toxic effects. The objective of the present study was to determine in vitro percutaneous absorption of model chemicals glyphosate (water soluble) and malathion (relative water insoluble) from cotton fabric into and through human skin. The percutaneous absorption of glyphosate from water solution was 1.42 +/- 0.25% dose. This decreased to 0.74 +/- 0.26% for glyphosate added to cotton sheets and immediately put onto skin. If the cotton sheets were dried for 1 or 2 days, then applied to skin, absorption was 0.08 +/- 0.02% and 0.08 +/- 0.01% respectively. However, wetting the 2-day dried cotton sheet with water to simulate sweating or wet conditions increased absorption to 0.36 +/- 0.07%. Similar results were found for malathion. Absorption of malathion from aqueous ethanol solution was 8.77 +/- 1.43%. This decreased to 3.92 +/- 0.49%, 0.62 +/- 0.11% and 0.60 +/- 0.14% for 0, 1- and 2-day-treated cotton sheets. However, malathion absorption from 2-day treated/dried cotton sheets increased to 7.34 +/- 0.61% when wetted with aqueous ethanol. These results show that chemicals in fabric (clothing, rug, upholstery, etc.) can transfer from fabric into and through human skin to cause toxic effects.

Malathion immunotoxicity in the American lobster (Homarus americanus) upon experimental exposure.

A lobster die-off reduced the 1999 fall landings in western Long Island Sound by up to more then 99%. The die-off corresponded in time with the application of pesticides for the control of mosquitoes that carried West Nile virus, a new emerging disease in North America at the time. In order to determine the possible implication of pesticide application as a direct cause or contributing factor in the die-off, we studied the effects of experimental exposure to malathion on the health of lobsters. Lobsters were exposed in 20 gallon tanks, and the direct toxicity as well as sub-lethal effects on the immune system were determined. The 96 h LC50 for malathion upon single exposure was 38 microg/l. Malathion degraded rapidly in sea water, with 65-77% lost after 1 day and 83-96% lost after 3 days. Phagocytosis was significantly decreased 3 days after a single exposure to initial water concentrations as low as 5 ppb, when measured water concentrations were as low as 0.55 ppb. Similarly, effects on phagocytosis were observed at 1, 2 and 3 weeks after the initiation of weekly exposures. Cell counts did not differ significantly upon exposure to malathion. Malathion was not detected in muscle and hepatopancreas of exposed lobsters. Evaluation of phagocytosis is a sensitive indicator of subtle sub-lethal effects of malathion, and relatively small concentrations of malathion (6-7 times lower than the LC50) can affect lobster defense mechanisms.

Distribution of malathion in body tissues and fluids.

Six cases of suspected poisoning were studied. The various body tissues and fluids of all the cases were analysed and malathion was found positive. The quantitative analysis was performed using high performance liquid chromatography. The distribution of malathion was studied in lungs, liver, kidneys, spleen, brain, heart, blood, muscles, urine and gastric contents.