SUSPECTED CARBARYL TOXICITY IN A CAPTIVE COLONY OF STRAW-COLORED FRUIT BATS ( EIDOLON HELVUM).

Carbaryl was the first carbamate insecticide produced and remains the most widely used due to its perceived low level of toxicity in nontarget species. This report describes the management and evaluation of a group of straw-colored fruit bats, Eidolon helvum, that were exposed to carbaryl. Cholinesterase activity of blood, retina, and brain was evaluated to further investigate whether carbaryl was the causative agent. Decreased whole blood and retinal cholinesterase activity coupled with the response to atropine suggests that the cause of the clinical signs in this bat colony was due to carbaryl exposure. Whole blood and retinal tissue may be the best samples for confirming carbamate exposure in this species.

Forensic toxicological and analytical aspects of carbamate poisoning - A review.

Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans and animals due to their toxicity. Pesticides, particularly carbamates, are extensively used all over the world in crop protection and domestic pest control, however, also causing morbidity and mortality on a larger scale, which is of great significance in both clinical and criminal justice management.Carbamates are derived from a carbamic acid (NH2COOH) that are commonly used as insecticides. Ethienocarb, Sevin, Carbaryl, Fenoxycarb, Furadan, Carbofuran, Aldicarb, and 2-(1-Methylpropyl) phenyl N-methylcarbamate are examples of insecticides that include the carbamate functional group. By reversibly inactivating the enzyme acetylcholinesterase, these insecticides can induce cholinesterase inhibition poisoning.Chromatographic methods, notably gas and liquid chromatography have traditionally been employed to analyse carbamate pesticides and their metabolites in various matrices. These approaches are employed due to their ability to separate the chemicals contained in a sample; as well as identify and quantify these compounds utilizing advanced detection systems. Aside from these GC and LC conventional methods, other detection and/or hyphenated techniques such as single-quadrupole, ion-trap, triple-quadrupole, or tandem mass spectrometry, have been used in carbamate analysis to provide quick results with excellent sensitivity, precision, and accuracy.The objective of this review is to describe various analytical techniques used to detect and determine carbamate pesticides in various matrices which include urine, blood, and tissues that are commonly encountered in emergency hospital laboratories and forensic science laboratories.

Pralidoxime in carbaryl poisoning: an animal model.

INTRODUCTION: Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning. METHODS: Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test. RESULTS: Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%. CONCLUSION: When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose.

Pontine myelinolysis in a child with carbamate poisoning.

Carbamate and organophosphate pesticides are widely used all over the world. Poisoning with these substances may produce both immediate and delayed neurotoxic effects. We report the case of a 4-year-old boy who was admitted to the Pediatric Department of the Second University of Naples for evaluation of stupor, lethargy, severe hypotonia, generalized weakness of his arms and legs, ataxia, dysmetria, miosis, excessive salivation and tearing. The pesticide carbaryl (1-naphthyl-N-methylcarbamate) was identified in blood and urine samples. On admission, magnetic resonance imaging (MRI) was unremarkable; on day 11, MRI showed central pontine myelinolysis. The demyelination improved after 4 months and disappeared after 2 years. Various underlying and concomitant diseases have been described in children with central pontine myelinolysis but, to our knowledge, the finding of pontine myelinolysis after carbamate poisoning has not yet been described.

Delayed neurotoxicity after ingestion of carbamate pesticide.

We studied a patient who ingested 27 gm (500 mg/kg) of carbaryl (1-naphthyl N-methylcarbamate), a popular carbamate pesticide. After he recovered from acute cholinergic toxicity, acute weakness of arms and legs was accompanied by electrophysiologic findings consistent with axonal peripheral neuropathy. Recovery began at 1 week and continued for 9 months. A similar delayed neuropathy has been described with organophosphates but not with carbamate insecticides.

The relationship of urinary metabolites of carbaryl/naphthalene and chlorpyrifos with human semen quality.

Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects (n=272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19microg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend =0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.

Microprocedure for determination of carbaryl in blood and tissues.

A microprocedure was adapted for the extraction and cleanup of carbaryl from blood and tissues of animals poisoned with this insecticide. Ball-mill extraction using acetone and methylene chloride, removal of lipid material by a freeze-out procedure, and florisil microcolumn cleanup were employed. Derivatization of carbaryl with heptafluorobutyric anhydride in the presence of trimethylamine allowed rapid processing for gas-liquid chromatographic separation on 3% OV-17 and electron-capture detection. Limits of carbaryl detection were 0.02 ppm for blood and 0.1 ppm for tissue. This procedure allowed simultaneous processing and sensitive detection of carbaryl in numerous small samples.

Pesticide poisoning initially suspected as a natural death.

A pesticide poisoning victim suspected initially as having died a natural death was autopsied. The victim was a 47-year-old male. Macroscopically, signs of acute death and, in particular, general erosion in the mucosa of the airways and esophagus were observed. In the gastric contents, which had a pungent smell and a greenish-brown color, 5.00 g/L of propanil, 1.27 g/L of carbaryl, 0.38 g/L of ethylbenzene, and 0.32 g/L of xylene were detected. In the blood (serum), 21.6 mg/L of propanil, 8.1 mg/L of carbaryl, 1.7 mg/L of ethylbenzene, and 4.0 mg/L of xylene were identified. Postmortem methemoglobinemia (45%) was recognized. The cause of death was considered to have been pesticide poisoning; propanil was probably most responsible for his death. The police considered the case to be "death with illness as the suspected cause." By performing an autopsy, however, we were able to clarify that the cause of death was pesticide poisoning.

Lack of relay toxicity in ferret hybrids fed carbaryl-treated prairie dogs.

Carbaryl (1-napthol methylcarbamate) is being considered for control of fleas on prairie dogs (Cynomys spp.) used in black-footed ferret (Mustela nigripes) recovery in the western United States. The potential for relay toxicity in ferrets was determined by feeding carbaryl treated prairie dogs to black-footed ferret x Siberian polecat (M. eversmanni) hybrids. Adult prairie dogs were treated topically with 2.5 g of commercial 5% carbaryl dust sold as flea powder. After 14 days prairie dogs were killed and fed to ferrets. Potential for relay toxicity was evaluated by analyzing ferret blood cholinesterase (CHe), prairie dog brain Che, and hepatic carbamate concentration. There was no difference between pre- and post-exposure blood CHe activity, nor did treated prairie dog brain CHe differ significantly from controls. Post-exposure blood CHe did not exhibit reactivation after dilution in aqueous buffer. Hepatic carbaryl concentrations were less than detection limits (50 ppb). Based on these results, we conclude that short-term use of carbaryl for flea control on prairie dogs does not pose a hazard of relay toxicity in black-footed ferrets.

[Simultaneous determination of propanil, carbaryl and 3,4-dichloroaniline in human serum by HPLC with UV detector following solid phase extraction].

In case of poisoning by herbicide compounded with Propanil (DCPA) and Carbaryl (NAC), we attempted simultaneous solid-phase extractions of DCPA, NAC, and 3,4-dichloroaniline (DCA), a metabolite of DCPA, from the patient's serum, and quantitative analytical method using HPLC-UV detection. With this HPLC method, the quantitative detection limits in the serum are 0.005 microgram/ml for DCPA and DCA and 0.001 microgram/ml for NAC, and the UV spectra of all three compounds could easily be obtained using a diode-array detection limit of 0.05 microgram/ml. When the three compounds were added to serum at concentrations ranging from 0.1-10.0 micrograms/ml, the recovery rates were satisfactory at between 91.1% and 101.9%. On analysis of the serum of patient who had ingested Kusanon A Emulsion, the ingested substance apparently caused an increase in the DCA concentration, which led to the appearance of methemoglobinemia. The possibility that the DCA concentration might be used for prognostic purposes was suggested.

Skin diseases and enzymatic antioxidant activity among workers exposed to pesticides.

In this study, 150 workers exposed to pesticides and 50 healthy control subjects were given clinical and dermatological examinations, patch tests, tests of liver and renal function, complete blood count, blood sugar and urinalysis. Activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and glutathione reductase was also evaluated. Dermatological findings were positive in 78%, 76% and 54% of workers exposed to organophosphates, pyrethroids and carbamate pesticides respectively. The patch test was positive in 70% of workers exposed to pyrethroids and 64% exposed to carbamate pesticides. Liver enzyme levels were generally increased in workers while antioxidant enzyme activity was significantly decreased in all workers compared with the controls.

[Segmentary veno-occlusive disease of the liver secondary to insecticide inhalation]. / Malattia veno-occlusiva segmentaria del fegato secondaria ad inalazione di insetticidi.

We report a case of venocclusive (VOD) disease secondary to inhalation of an insecticide. Pathological features of liver injury are illustrated with regard to patchy lesions shown by a new computer assisted colorimetric method. A possible role of immuno-complexes in the development of endothelium damage to centro-lobular veins is discussed.

[Effect of acute poisoning of rats with carbaryl on transamination reactions with involving pyruvate. III. Supplementary studies of plasma aminotransferases]. / Wplyw ostrego zatrucia szczurów karbarylem na reakcje transaminacji z udzialem pirogronianu. Cz. III. Badania uzupelniajace aminotransferaz osoczowych.

Male Wistar rats were poisoned orally with one carbaryl dose 474 mg/kg (1/2 DL50). After 2, 4, 24 and 72 hours from the administration of the insecticide the activity of plasma aminotransferases catalysing the reactions between pyruvate and the following amino acids: asparagine, aspartic acid, glutamic acid, isoleucine, lysine and valine was determined. Under physiological conditions these amino acids are not participating in the transamination reactions. The activity of aminotransferases was expressed as the amount of alanine developing during incubation of 1 ml of plasma for 1 hour. Alanine was determined spectrophotometrically after chromatographic separation on paper. The results of the investigations demonstrated that acute poisoning with carbaryl caused the appearance of activity of all studied plasma aminotransferases, except for the enzyme catalysing the reaction between pyruvate and lysine. The activity of the studied aminotransferases appeared as follows: glutamic acid--pyruvate--4 hr; isoleucine--pyruvate--24 and 72 hr; asparagine--pyruvate, aspartic acid--pyruvate and valine--pyruvate--72 hr after intoxication.

[The effect of acute poisoning of rats with carbaryl on the transamination reactions involving alpha-ketoglutarate. Part I. Activity of plasma aminotransferases]. / Wplyw ostrego zatrucia szczurów karbarylem na rekcje transaminacji z udzialem alfa-ketoglutaranu. CZ. I. Aktywnosc aminotransferaz osoczowych.

White male Wistar rats were poisoned orally with a single carbaryl dose 474 mg/kg (1/2 LD50). In the plasma of control animals and 2, 4, 24 and 72 hours after administration of the insecticide the activity of aminotransferase catalysing the reactions between alpha-ketoglutarate and six amino acids (cysteine, lysine, phenylalanine, leucine, asparagine and valine) was determined. Aminotransferases activity was expressed as the amount of glutamic acid developing during incubation of 1 cm3 of plasma for 1 hour. Glutamic acid was determined spectrophotometrically after chromatographic separation on paper. The results of the investigations demonstrated that acute intoxication with carbaryl caused a statistically significant increase in the activity of two aminotransferases in the plasma of experimental animals. A rise in the activity of the enzyme catalysing the reaction between alpha-ketoglutarate and asparagine ketoglutarate and lysine was observed.

[The effect of carbaryl poisoning on noradrenaline (NA) levels in rat brain]. / Wplyw zatrucia karbarylem na poziom noradrenaliny (NA) w mózgu szczura.

The influence of acute (50% and 20% LD50), subacute (10% LB50) and 12-week (5% LD50) intoxication with carbaryl on NA level in rat brain was investigated. The level of NA was decreased by about 40% of the control level (p > 0.001) after acute and subacute intoxication. In the subchronic study (5% LD50 for 12 weeks) carbaryl significantly decreased the NA level (p < 0.001), but after 2-week intoxication only. During the next weeks NA content remained on control level (p > 0.05). These results indicate that carbaryl causes noradrenergic alterations in rat brain, which may lead to neurotoxic action.

[The effect of acute poisoning of rats with carbaryl on transamination reactions with participation of alpha-ketoglutarate. II. Activity of hepatic aminotransferases]. / Wplyw ostrego zatrucia szczurów karbarylem na reakcje transaminacji z udzialem alfa-ketoglutaranu. Cz. II. Aktywnosc aminotransferaz watrobowych.

White male Wistar rats were poisoned orally with a single carbaryl dose 474 mg/kg (1/2 LD50). The activity of aminotransferases in the cytoplasma of liver homogenates catalysing the reactions between alpha-ketoglutarate and six amino acids (cysteine, lysine, phenylalanine, leucine, asparagine and valine) after 2, 4, 24 and 72 hours from the administration of the insecticide was determined. The activity of aminotransferases was expressed as the amount of glutamic acid developing during 1 hour of incubation of liver homogenate calculated for 1 g of tissue. Glutamic acid was determined spectrophotometrically after chromatographic separation on paper. The results of the investigations demonstrated that acute poisoning with carbaryl caused a statistically significant changes in the activity of two hepatic aminotransferases. A rise was observed in the activity of the enzyme causing transamination in the reaction between alpha-ketoglutarate and phenylalanine 24 hours after insecticide administration (64.1%), and a fall of the activity of the aminotransferase catalyzing the reaction between alpha-ketoglutarate and asparagine in the 4th, 24th and 72nd hours after intoxication (16.4%, 17.3% and 19.2% respectively).

[Effect of acute carbaryl poisoning on various indicators of amino acid metabolism in rats]. / Badania wplywu ostrej intoksykacji karbarylem na niektóre wskazniki przemiany aminokwasowej u szczura.

Male Wistar rats were orally poisoned with carbaryl in a single dose 474 mg/kg (1/2 LD50). After 2, 4, 24, 72 and sometimes 120 hours from the administration of the insecticide the studied biochemical parameters have been determined. Trials showed an essential effect of carbaryl on the amino acid balance and metabolism. Significant decreases of the most amino acids concentrations in the brain tissue (a maximum decrease in the second hour) and in the liver (at 4-th h of intoxication). Normalization of the amino acid levels occurred more early in the brain than in the liver. Furthermore a decrease of total keto-acids concentration in erythrocytes (at 4-th h) and activity changes of some plasma and liver plasmatic aminotransferases in the reaction with alpha-ketoglutarate and pyruvate was observed.

Severe acute illness in a toddler exposed to multiple agricultural pesticides and an insect repellent.

Acute severe pesticide-related illness among farm worker children is rarely reported. The authors report a toddler with acute onset of apnea, cyanosis, somnolence, hypotonia, tachycardia, and miosis who required hospitalization. Health care providers suspected pesticide poisoning, but were unable to determine the causal agent. Investigation by a public health program documented four pesticide exposures that occurred within one-half hour of acute illness. This case illustrates the importance of a thorough environmental/occupational exposure history and obtaining biological samples. It also documents the need to strengthen the Worker Protection Standard for agricultural workers and the importance of reporting and investigating pesticide-related illness.

Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates.

Carbamates are widely used for pest control and act primarily by inhibition of insect and mammalian acetylcholinesterase (AChE). Accidental or intentional uptake of carbamates may result in typical signs and symptoms of cholinergic overstimulation which cannot be discriminated from those of organophosphorus pesticide poisoning. There is an ongoing debate whether standard treatment with atropine and oximes should be recommended for human carbamate poisoning as well, since in vitro and in vivo animal data indicate a deleterious effect of oximes when used in combination with the N-methyl carbamate carbaryl. Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. It became evident that pralidoxime and obidoxime in therapeutic concentrations aggravate the inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially more potent compared to 2-PAM. However, obidoxime had no impact on the decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of obidoxime to severely propoxur and carbaryl poisoned humans cannot be recommended.