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Home , Pesticide poisoning

Accidental with the in a few rabbit

Michel Gruaz, Esther van Praag

Lindane is a pesticide, isomer of hexachlorocyclohexane, synthesized from benzene and chlorine. In spite of its on living organisms, it has been commercialized all over the world since 1938.

Lindane possesses a broad livestock, as well as in pharmaceutical spectrum; therefore it is used both in products in order to treat mites responsible agriculture, to treat seeds, leaves of trees or for scabies and lice. Today lindane has been

Figure 1: Paralysis of the hind limbs and swelling on the back in a rabbit after it accidentally ate apples treated with the lindane pesticide. MediRabbit.com October 2015

Figure 2 : During the autopsy, lungs show multifocal hemorrhagic foci.

banned in more than 50 countries. Lindane can also cross the placenta and is found in breast milk (Saxena et al., 1981). In animals and humans, the pesticide is quickly absorbed through the skin, is inhaled Its effect on metabolism is extensive. as particles or fumes, or is ingested with Neurotoxic effects contaminated food or drinking water. Its elimination by the urine is relatively fast. Lindane is a potent neurotoxin that interferes with -aminobutyric acid, GABA, a Since 1953, negative effects of lindane neurotransmitter of the central nervous have been observed in mammals and man. system in mammals and man, which acts on The presence of different isomers of lindane the ionic channels of the GABA-A receptor in in the blood leads to their distribution in the order to regulate the conduction of the adipose tissue and, to a lesser extent, in chlorine, sodium and potassium fluxes muscles, the and brain, the (Abalis et al., 1985; Anand et al., 1998; mucous membranes of the respiratory Casida and Lawrence, 1985; Lawrence and airways and lungs, the cardiovascular Casida, 1984; Pomès et al., 1994). Exposure system, digestive organs such as the liver to high concentrations of lindane causes and spleen, kidneys, and endocrine glands neurological disorders such as convulsions, such as the pituitary and thyroid glands dizziness, and as well as changes (Ejobi et al, 1996 Schoula et al., 1996; the electrical activity of the brain (EEG Siddiqui et al, 1981; Baumann et al., 1980). abnormal rhythm).

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Lindame has additional effects on other most affected, and the state of health and organs. nutrition of the animal. The nervous system is mainly affected, with the appearance of Hemato- et immunotoxic effects neurological disorders that result in Lindane is hematotoxic. It acts on the bone hyperactivity and hypersensitivity, tonic- marrow and inhibits the hematopoietic clonic convulsions and paralysis of the system. This can lead to modifications in the hindquarters (Figure 1). These disorders composition of the blood (blood dyscrasia): precede a depression of the nervous system leukopenia, leukocytosis, granulocytopenia, sometimes accompanied by coma or death hyper-eosinophilia, lymphopenia, thrombo- of the animal. Other signs include difficult cytopenia. After an initial stimulation, breathing, diarrhea, hypothermia and nasal lindane causes a suppression of the immune bleeding (epistaxis). At necropsy, anomalies system, rendering people more susceptible were observed in the lungs, liver (localized to disease. degeneration of hepatocytes, cellular Endocrine anomalies hypertrophy, fatty degeneration) and Lindane induced endocrine abnormalities by kidneys (glomerulonephritis) (Grabarczyk et interfering with the levels of hormones in al., 1990-Szlezak Kopec et al. 1989) (Figs 2, human beings. Sperm count is reduced. It 3). seems also to mimic the action of estrogen, When a rabbit is exposed to chronic the female sex hormone. In pregnant poisoning of lindane, it becomes apathic and animals, lindane can induce resorption of loses weight. In female rabbits, the anti- fetuses and/or abortions. estrogen action of lindane causes a decrease Hepatotoxic effects in fertility and ovulation either by mimicking Exposure of liver cells to lindane causes an the action of estrogen on the hormone increase in liver enzymes. Centrilobular liver receptors, or by inferring with the hypertrophy is dose dependent. Various progesterone receptor (Lindenau and al., studies suggest that the hepatotoxic effects 1994). In pregnant females, the risk of fetal of lindane are more severe in humans than resorption or miscarriage is increased. Some in animals. fetuses exposed to lindane have a supernumerary rib, but teratogenic effects Renal toxicity of the pesticide have nonetheless been Exposure of renal cells to lindane does not excluded (Palmer et al., 1978a). cause toxic effects or impaired renal function, except in rats (Dietrich and When the chronic exposure to lindane is Swenberg, 1990, 1991). stopped, a significant but transient increase in liver enzymes (alkaline phosphatase Carcinogenic effets (ALP), alanine aminotransferase (ALT) and A further detrimental effect of lindane seems aspartate aminotransferase (AST)) is noted. to be the development of cancer, including They return to normal values between 7 and Hodgkin's lymphoma, liver and breast 14 days after the end of exposure while cancer. Specific studies are, however, pesticide residues are still measurable in the lacking and were unable to conclude that blood (Ceron et al., 1995). lindane is carcinogenic. The median lethal dose (LD50) of lindane in rabbits depend on the route by which it Toxic effets of lindane in rabbits enters the body. The LD50 ranges between Effects of an acute poisoning depend on 40 and 200 mg/kg for an oral doses, while the age of the rabbit, young rabbits being dermal exposure ranges from 50 mg/kg to www.medirabbit.com [email protected] 3

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Figure 3: The caecum of a poisoned rabbit looks dried out, as in case of enterocolitis.

4000 mg/kg depending on the type of such as benzodiazepines or second-line product applied on the skin. drugs such as barbiturates or propofol. is ineffective in the treatment of Treatment organochlorine .

Contaminated food should be removed. If the rabbit suffers from ventricular There is no treatment against lindane dysrhythmia caused by lindane, it is poisoning in rabbits. Nevertheless, the imperative to administer beta-adrenergic treatments applied in humans can be used. agents and magnesium, but not adrenaline. This helps reduce the effect of endogenous Poisoning through the digestive tract are catecholamines secreted by the adrenal the most dangerous. The rabbit must be glands on the heart muscle. constantly monitored. The depression of the central nervous and respiratory systems References prevents the immediate administration of activated charcoal or cholestyramine resin Abalis IM, Elderfrawl ME, Elderfrawl AT. (1985) - High-affinity stereospecific binding of that helps neutralize the pesticide and cyclodiene and gamma- promote its elimination from the digestive hexachlorocyclohexane to gamma- system. If no neurological disorder is aminobutyric acid receptor of rat in brain. observed after one hour, these products can Pestic Biochem Physiol, 1985;24:95-102. be given to the rabbit. Anand M, Agrawal AK, Rehmani BN, Gupta GS, A control of may be attempted Rana MD, Seth PK. Role of GABA receptor with the administration of antiepileptic drugs complex in low dose lindane (HCH) induced www.medirabbit.com [email protected] 4

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neurotoxicity: neurobehavioural, neuro- blood cells, kidney and liver tissues in rabbits. chemical and electrophysiological studies. Haematologia (Budap). 1990;23(3):171-9. Drug Chem Toxicol. 1998 Feb;21(1):35-46. Kopeć-Szlezak J, Góralczyk K, Woźniak J. Changes in serum and internal organs during Baumann K, Angerer J, Heinrich R, Lehnert G. increased accumulation of gamma- Occupational exposure to hexachlorocyclohexane in adipose tissue of hexachlorocyclohexane. I. Body burden of rabbits. Mater Med Pol. 1989 Oct- HCH-isomers. Int Arch Occup Environ Health. Dec;21(4):286-91. 1980;47(2):119-27. Lawrence LJ, Casida JE. Interactions of lindane, Casida JE, Lawrence LJ. Structure-activity and cyclodienes with brain-specific correlations for interactions of t-butylbicyclophosphorothionate receptor. Life bicyclophosphorus esters and some Sci. 1984 Jul 9;35(2):171-8. polychlorocycloalkane and insecticides with the brain-specific t- Lindenau A, Fischer B, Seiler P, Beier HM. Effects butylbicyclophosphorothionate receptor. of persistent chlorinated hydrocarbons on Environ Health Perspect. 1985 Sep;61:123- reproductive tissues in female rabbits. Hum 32. Reprod. 1994 May;9(5):772-80. Cerón JJ, Panizo CG, Montes A. Toxicological Palmer AK, Bottomley AM, Worden AN, Frohberg effects in rabbits induced by , H, Bauer A. Effect of lindane on pregnancy in lindane, and methylparathion representing the rabbit and rat. . 1978 agricultural byproducts contamination. Bull Mar;9(3):239-47. Environ Contam Toxicol. 1995 Feb;54(2):258- Pomés A, Frandsen A, Suñol C, Sanfeliu C, 65. Rodríguez-Farré E, Schousboe A. Lindane Dietrich DR, Swenberg JA. Lindane induces cytotoxicity in cultured neocortical neurons is nephropathy and renal accumulation of alpha ameliorated by GABA and flunitrazepam. J 2u-globulin in male but not in female Fischer Neurosci Res. 1994 Dec 15;39(6):663-8. 344 rats or male NBR rats. Toxicol Lett. 1990 Saxena MC, Siddiqui MK, Seth TD, Krishna Murti Sep;53(1-2):179-81 CR, Bhargava AK, Kutty D. Organochlorine Dietrich DR, Swenberg JA. NCI-Black-Reiter in specimens from women (NBR) male rats fail to develop renal disease undergoing spontaneous abortion, premature following exposure to agents that induce of full-term delivery. J Anal Toxicol. 1981 Jan- alpha-2u-globulin (alpha 2u) nephropathy. Feb;5(1):6-9. Fundam Appl Toxicol. 1991 May;16(4):749- Schoula R, Hajslová J, Bencko V, Poustka J, 62. Holadová K, Vízek V. Occurrence of persistent Ejobi F, Kanja LW, Kyule MN, Müller P, Krüger J, organochlorine contaminants in human milk Latigo AA. Organochlorine pesticide residues collected in several regions of Czech Republic. in mothers' milk in Uganda. Bull Environ Chemosphere. 1996 Oct;33(8):1485-94. Contam Toxicol. 1996 Jun;56(6):873-80. Siddiqui MK, Saxena MC, Krishna Murti CR. Grabarczyk M, Kopeć-Szlezak J, Szczepańska I, Storage of DDT and BHC in adipose tissue of Woźniak J, Podstawka U. The effect of Indian males. Int J Environ Anal Chem. gamma-hexachlorocyclohexane (lindane) on 1981;10(3-4):197-204.

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