Malathion

Description

Malathion, a clear amber liquid, is sparingly soluble in water but soluble in a majority of organic solvents. The U.S. Environmental Protection Agency (U.S. EPA) grouped malathion under GUP, meaning general use pesticide. It is used as an insecticide as well as an acaricide for the control of pests. Malathion is used for the control of sucking insects and chewing insects on fruits and vegetables. Malathion is an effective insecticide for the control of several household pests such as houseflies, cockroaches, mosquitoes, aphids, animal ectoparasites, and human head and body lice. Malathion is also found in formulations with many other pesticides.

Chemical Properties

Malathion is a deep-brown to yellow liquid with a garlic-like odor. Clear and colorless when pure; freezing/melting point5 3C;

Chemical Properties

Malathion is a clear amber liquid. It is sparingly soluble in water, but soluble in a majority of organic solvents. The US EPA grouped malathion under GUP. It is used as an insecticide as well as an acaricide for the control of pests. Malathion is used for the control of sucking insects and chewing insects on fruits and vegetables, and is an effective insecticide for the control of several household pests, such as housefl ies, cockroaches, mosquitos, aphids, animal ectoparasites, and human head and body lice. It is also found in formulations with many other pesticides

Physical properties

Clear, yellow to yellow-orange to brown liquid with an unpleasant garlic, skunk, or mercaptanslike odor

Originator

Prioderm,Purdue Frederick,US,1982

Uses

Insecticide for control of sucking and chewing insects and spider mites on vegetables, fruits, ornamentals, field crops, greenhouses, gardens and forestry.

Uses

Used as an insecticide

Uses

Malation is a pestanal and used primarily as an insecticide.

Uses

Malathion is used to control a wide spectrum of insect pests in many types of crops and disease vectors in public health programmes. It is also used to control ectoparasites of both humans and animals.

Uses

Organophosphorus insecticide.

Uses

anticholinergic

Indications

Malathion (Ovide) is highly effective in the prevention and treatment of pediculosis. It displays 95% ovicidal activity and has no scabicidal activity. It works through cholinesterase inhibition.

Definition

ChEBI: A diester that is butanedioate substituted by a (dimethoxyphosphorothioyl)sulfanediyl group at position 2.

Manufacturing Process

The feed materials for malathion manufacture are O,O-dimethyl phosphorodithioic acid and diethyl maleate or fumarate which react according to the equation:
An antipolymerization agent such as hydroquinone may be added to the reaction mixture to inhibit the polymerization of the maleate or fumarate compound under the reaction conditions. This reaction is preferably carried out at a temperature within the range of 20°C to 150°C. This reaction is preferably carried out at atmospheric pressure. Reaction time of 16 to 24 hours have been specified for this reaction by J.T. Cassaday. The reaction is preferably carried out in a solvent such as the low molecular weight aliphatic monohydric alcohols, ketones, aliphatic esters, aromatic hydrocarbons or trialkyl phosphates.
The reaction may be accelerated by using an aliphatic tertiary amine catalyst, usually within the range of 0.2 to 2.0% based on the total weight of the reactants. A stirred, jacketed reactor of conventional design may be used. After cooling, the reaction mixture may be taken up in benzene. It is then washed with 10% Na2CO3 and with water. The organic layer is dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the final product as residue.

Therapeutic Function

Pediculicide

General Description

Malathion, 2-[(dimethoxyphosphinothioyl)thio]butanedioic acid diethyl ester, is a water-insolublephosphodithioate ester that has been used as an agriculturalinsecticide. Malathion is a poor inhibitor of cholinesterases.Its effectiveness as a safe insecticide is a result of the differentrates at which humans and insects metabolize the chemical.Microsomal oxidation, which causes desulfuration,occurs slowly to form the phosphothioate (malaoxon),which is 10,000 times more active than the phosphodithioate(malathion) as a cholinesterase inhibitor. Insects detoxifythe phosphothioate by a phosphatase, forming dimethylphosphorothioate, which is inactive as an inhibitor.Humans, however, can rapidly hydrolyze malathion by acarboxyesterase enzyme, yielding malathion acid, a stillpoorer inhibitor of AChE. Phosphatases and carboxyesterasesfurther metabolize malathion acid to dimethylphosphothioate.

General Description

Yellow to dark-brown liquid with a skunk-like odor. Sinks in water. Freezing point is 37°F.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Malathion is a yellow to brown liquid that solidifies at 2.9° C, moderately toxic. Organic phosphate insecticide, acts as an inhibitor of cholinesterase. When heated to decomposition Malathion emits toxic fumes of oxides of sulfur and phosphorus [Lewis, 3rd ed., 1993, p. 789].

Hazard

Absorbed by skin, cholinesterase inhibitor. Questionable carcinogen.

Health Hazard

Cholinesterase inhibitor; toxic propertiessimilar to those of parathion; however,less toxic than parathion; moderately toxicby ingestion and possibly other routes ofexposure; toxic symptoms include excessivesalivation, lacrimation, blurred vision, con-striction of the pupils, nausea, vomiting,abdominal pain, and difficulty in breathing;also coma and death can result form largeintake; ingestion of 10–25 g could be fatalto adult humans; skin contact can produceallergic sensitization reaction; also absorbedthrough skin, causing systemic poisoning;experimental teratogen; LD50 data reportedin the literature show wide variation.
LD50 oral (rate): 300–2800 mg/kg
LD50 skin (mouse): 2000–3000 mg/kg
Benslama et al. (2004) have reported twounusual cases of malathion poisoning with arare-type of complication from “intermediatesyndrome” arising 2 to 4 days after the onsetof cholinergic effects. The symptoms wererespiratory paresis with difficulties of wean-ing from assisted respiratory, deficit of proximal limbs, neck flexors and cranial nerves.The authors attributed this syndrome to pro-longed inhibition of acetyl-cholinesterasesand not to any muscular fiber’s necrosis.

Health Hazard

Exposure to fumes from a fire or to liquid causes headache, blurred vision, constricted pupils of the eyes, weakness, nausea, cramps, diarrhea, and tightness in the chest. Muscles twitch and convulsions may follow. The symptoms may develop over a period of 8 hours.

Health Hazard

Acute and prolonged period of exposures to high concentrations of malathion cause poisoning in animals and humans. The symptoms of poisoning include, but are not limited to, numbness, tingling sensations, incoordination, headache, dizziness, tremor, nausea, abdominal cramps, sweating, blurred vision, diffi culty breathing or respiratory depression, and slow heart beat. Very high doses may result in unconsciousness, incontinence, and convulsions, or fatality. Malathion did not indicate any kind of delayed neurotoxicity in experimental studies with hens. Reports have indicated that because of and accidental exposures through severe skin absorption, malathion caused poisoning and fatalities among workers associated with the malaria control operations in Pakistan. In certain cases, development of pulmonary fi brosis following the poisoning has also been observed. Reports have indicated that malathion is neither mutagenic nor teratogenic to animals and humans. In animals, malathion induced liver carcinogenicity at doses that were considered excessive. However, available information is not adequate to confi rm the carcinogenicity of malathion to animals and humans. The IARC has determined that malathion is unclassifi able as to its carcinogenicity to humans. The IARC observed that the available data do not provide evidence that malathion or its metabolite malaoxon is carcinogenic to experimental animals and there is no data on humans and classifi ed as Group 3 meaning, not classifi able as to carcinogenicity for humans.

Agricultural Uses

nsecticide: Not approved for use in EU countries. Malathion is a non-systemic, wide-spectrum organophosphate insecticide. It was one of the earliest organophosphate insecticides developed (introduced in 1950). Malathion is suited for the control of sucking and chewing insects on fruits, vegetables, citrus, cotton, corn, sorghum, ornamentals and stored products, and is also used to control mosquitoes, flies, household insects, farm and livestock parasites (ectoparasites), and head and body lice. Malathion may also be found in formulations with many other pesticides; the U.S. EPA lists 2,283 current and canceled labels of products containing malathion. Malathion is marketed as 99.6% technical grade liquid. Available formulations include wettable powders (25% and 50%), emulsifiable concentrates, dusts and aerosols.

Trade name

AI3-17034®; AGRICHEM GREENFLY SPRAY®; ALCO® Malathion; ALL PURPOSE GARDEN INSECTICIDE®; AMERICAN CYANAMID 4,049®; ATRAPA 5E®; BAN-MITE®; CALMATHION®; CARBETOVUR®; CARBETOX®; CELTHION®; CHEMATHION®; CIMEXAN®; COMPOUND 4049®; CROMOCIDE®; CYTHION®; SPRAY CONCENTRATE®; CYTHION®; DETMOL MA®; DETMOL® 96%; DETMOL MALATHION®; DURAMITEX®; EMMATOS EXTRA®; EL 4049®; EMMATON®; EMMATOS®; ETIOL®; EVESHIELD CAPTAN/MALATHION®; EXATHIOS®; EXTERMATHION®; FYAFANON®; FISONS GREENFLY AND BLACKFLY KILLER®; FOG® 3; FORMAL®; FORTHION®; FOSFOTHION®; FOSFOTION®; FYFANON®; ETHIOLACAR®; GREEN DEVIL®; GREENFLY AEROSOL SPRAY®; HILTHION®; KARBOFOS®; KOPTHION ®; KYPFOS®; MALACIDE®; MALAFOR®; MALAGRAN®; MALAKILL®; MALAMAR®; MALASOL®; MALASPRAY®; MALATAF®; MALATHION 60®; MALATHION E50®; MALATOL®; MALTOX®; MOSCARDA®; ORTHO MALATHION®; PBI CROP SAVER®; PRENTOX®; PRIODERM®; PROKIL® Malathion; SADOFOS®; SADOPHOS®; SF® 60; SIPTOX I®; SUMITOX®; TAK®; TM-4049®; VETIOL®; ZITHIOL®

Contact allergens

This organophosphorus pesticide is used as an insecticide and an acaricide, particularly against head lice. Sensitization was reported in farmers.

Safety Profile

A human poison by ingestion and skin contact. Can penetrate intact skin. An experimental poison by ingesuon, inhalation, intraperitoneal, intravenous, intraarterial, and subcutaneous routes. Human systemic effects by ingestion: coma, blood pressure depression, and dfficulty in breathmg. Questionable carcinogen. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. Has caused allerglc sensitization of the skin. An organic phosphate cholinesterase inhibitor. When heated to decomposition it emits toxic fumes of POx and SOx. See also PHOSPHATES and PARATHION.

Potential Exposure

Malathion is marketed as 99.6% technical grade liquid. Available formulations include wetable powders (25% and 50%), emulsifiable concentrates, dusts, and aerosols. Malathion is used as a broad spectrum insecticide and acaricide in the control of certain insect pests on fruits, vegetables, and ornamental plants. It has been used in the control of houseflies, mosquitoes, lice; and on farm and livestock animals.

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Speed in removing material from skinis of extreme importance. Shampoo hair promptly if contaminated. Seek medical attention immediately. If thischemical has been inhaled, remove from exposure, beginrescue breathing (using universal precautions, includingresuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.Note to physician or trained medical personnel: Administeratropine, 2 mg (0.030 g) intramuscularly or intravenously assoon as any local or systemic signs or symptoms of anintoxication are noted; repeat the administration of atropineevery 3°8 min until signs of atropinization (mydriasis, drymouth, rapid pulse, hot and dry skin) occur; initiate treatment in children with 1 mg of atropine. Watch respirationand remove bronchial secretions if they appear to beobstructing the airway; intubate if necessary. Give 2-PAM(Pralidoxime; Protopam), 2.5 g in 100 mL of sterile wateror in 5% dextrose and water, intravenously, slowly, in15°30 min; if sufficient fluid is not available, give 1 g of2-PAM in 3 mL of distilled water by deep intramuscularinjection; repeat this every half hour if respiration weakensor if muscle fasciculation or convulsions recur.

Carcinogenicity

There was no evidence of carcinogenicity in rats given diets that contained 4700 or 8150 ppm (about 270 mg/kg and 466 mg/kg) for 80 weeks and observed for an additional 33 weeks, in rats given diets that contained 2000 or 4000 ppm malathion (about 115 mg/ kg/day and 230 mg/kg/day) for 103 weeks, or in rats given diets that contained 500 or 1000 ppm malaoxon for 103 weeks .

Environmental Fate

Biological. Walker (1976) reported that 97% of malathion added to both sterile and nonsterile estuarine water was degraded after incubation in the dark for 18 days. Complete degradation was obtained after 25 days. Malathion degraded fastest in nonsterile soils and decomposed faster in soils that were sterilized by gamma radiation than in soils that were sterilized by autoclaving. After 1 day of incubation, the amounts of malathion degradation that occurred in autoclaved, irradiated and nonsterile soils were 7, 90 and 97%, respectively (Getzin and Rosefield, 1968). Degradation of malathion in organic-rich soils was 3 to 6 times higher than in soils not containing organic matter. The half-life in an organic-rich soil was about 1 day (Gibson and Burns, 1977). Malathion was degraded by soil microcosms isolated from an agricultural area on Kauai, HI. Degradation half-lives in the laboratory and field experiments were 8.2 and 2 hours, respectively. Dimethyl phosphorodithioic acid and diethyl fumarate were identified as degradation products (Miles and Takashima, 1991). Mostafa et al. (1972) found the soil fungi Penicillium notatum, Aspergillus niger, Rhizoctonia solani, Rhizobium trifolii and Rhizobium leguminosarum converted malathion to the following metabolites: malathion diacid, dimethyl phosphorothioate, dimethyl phosphorodithioate, dimethyl phosphate, monomethyl phosphate and thiophosphates. Malathion also degraded in groundwater and seawater but at a slower rate (halflife 4.7 days). Microorganisms isolated from paper-mill effluents were responsible for the formation of malathion monocarboxylic acid (Singh and Seth, 1989).
Paris et al. (1975) isolated a heterogenous bacterial population that was capable of degrading low concentrations of malathion to b-malathion monoacid. About 1% of the original malathion concentration degraded to malathion dicarboxylic acid, O,O-dimethyl
Matsumura and Bousch (1966) isolated carboxylesterase(s) enzymes from the soil fungus Trichoderma viride and a bacterium Pseudomonas sp. obtained from Ohio soil samples that were capable of degrading malathion. Compounds identified included diethyl maleat
Soil. In soil, malathion was degraded by Arthrobacter sp. to malathion monoacid, malathion dicarboxylic acid, potassium dimethyl phosphorothioate and potassium dimethyl phosphorodithioate. After 10 days, degradation yields in sterile and nonsterile soils were 8, 5, 19% and 92, 94, 81%, respectively (Walker and Stojanovic, 1974). Chen et al. (1969) reported that the microbial conversion of malathion to malathion monoacid was a result of demethylation of the O-methyl group. Malathion was converted by unidentified microorganisms in soil to thiomalic acid, dimethyl thiophosphoric acid and diethylthiomaleate (Konrad et al., 1969).
The half-lives for malathion in soil incubated in the laboratory under aerobic conditions ranged from 0.2 to 2.1 days with an average of 0.8 days (Konrad et al., 1969; Walker and Stojanovic, 1973; Gibson and Burns, 1977).

Metabolic pathway

Malathon is a very widely used insecticide of low mammalian toxicity. Many studies have identified the products of degradation in a very wide range of organisms and the following is necessarily a selection of only some of them which have been used to illustrate the principles of its metabolism.
The much more toxic isomalathion, which can be produced by heating malathion, is sometimes present in commercial samples and is a very active acetylcholinesterase dubitor. The principal route of malathion metabolism in animals and plants is via de-esterification to the α- and β-malathion monocarboxylic acids followed by further metabolism to the dicarboxylic acid. This is a facile esterase-catalysed detoxification route which is considered to be responsible for the low vertebrate toxicity of malathion. The analytical methods which have been used to determine the structure of the metabolites have frequently not distinguished between which monocarboxylic acid isomer is formed, and what evidence there is is often equivocal as to which is actually produced. Malathion can decompose in aqueous solution via an elimination mechanism yielding diethyl fumarate and O,O-dimethyl phosphorodithioate; however, derivatives of fumaric acid are usually only encountered in small amounts in vivo indicating that this is probably not an important route of detoxification. There is evidence that the dicarboxylic acid derivative is not subject to this elimination reaction. Most studies indicate that the selective toxicity of malathion can be accounted for by the balance between bioactivation (oxidative desulfuration) yielding the active acetylcholinesterase inhibitor malaoxon and detoxification via deesterification. Insecticide resistance is frequently found to involve the malathion-resistant insects being able to de-esterify malathion rapidly.

storage

Color Code—Blue: Health Hazard/Poison: Storein a secure poison location. Prior to working with thischemical you should be trained on its proper handling andstorage. Store in tightly closed containers in a cool, wellventilated, uninhabited area below 25℃. Store to avoidcontact with oxidizers and alkaline pesticides. Store wherepossible leakage from containers cannot endanger theworker. Maintain regular inspection of containers for anyleakage. Sources of ignition, such as smoking and openflames, are prohibited where this chemical is handled, used,or stored.

Shipping

UN2783 Organophosphorus pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials

Degradation

When heated, malathion waS isomerised via a thiono-thiolo rearrangement to yield isomalathion (2). This reaction proceeded rapidly above 100 °C (O'Brien, 1956). [¹⁴C-succinyl]Malathion was hydrolysed rapidly in neutral and basic solution. The half-lives at pH values 5, 7 and 9 were 107, 6.2 and 0.5 days, respectively, at 25 °C. The identified products of hydrolysis were, in order of decreasing abundance, α- and β-malathion monoacids (3 and 4), monoethyl fumarate (5), diethyl thiomalate (6) and malathion dicarboxylic acid (7). Products were identified by TLC, GLC and MS (PSD, 1995). It was probable that the mechanism for the production of monoethyl fumarate (5) involved a base-catalysed elimination (El) reaction of malathion monoacid with O,O-dimethyl phosphorodithloate (8) acting as the leaving group. In a second study which monitored the products of hydrolysis at pH 8 and 25 °C by GLC, diethyl fumarate (9) and O,O-dimethyl phosphorodithioate (8) were identified in addition to the compounds found in the previous work. Higher temperatures favoured the formation of elimination (fumarate) products. Malathion dicarboxylic acid did not give any elimination products but instead produced O,O-dimethyl phosphorothioate (10) and thiomalic acid (12). The end products of base-catalysed degradation of malathion were fumaric acid (11), O,O-dimethyl phosphorodithioate (8), O,O-dimethyl phosphorothioate (10) and thiomalic acid (12) (PSD, 1995).
The aqueous photolysis of malathion irradiated with a xenon arc lamp was studied in sterile water buffered at pH 4 in order to minimise hydrolytic and microbial breakdown. The half-life of the irradiated sample was 98 days, approximately one-third of the value for a sample kept in the dark. The major metabolites which were identified in both the irradiated and dark samples were the same although larger amounts were found in the irradiated samples. These were desmethylmalathion (13), and the α-and β-malathion monoacids (3 and 4). Minor metabolites were diethyl maleate (14), monoethyl maleate (15) and diethyl thiomalate (6). Analysis was by TLC and HPLC (PSD, 1995).

Toxicity evaluation

Acute oral LD₅₀ for rats: 1,375-2,800 mg/kg

Incompatibilities

Reacts violently with strong oxidizers, magnesium, alkaline pesticides. Attacks metals including iron, steel, tin plate; lead, copper; and some plastics, coatings, and rubbers

Waste Disposal

Malathion is reported to be “hydrolyzed almost instantly” at pH 12; 50%; hydrolysis at pH 0 requires 12 hours. Alkaline hydrolysis under controlled conditions (0.5 n NaOH in ethanol) gives quantitative yields of (CH3O)2P(S)SNa, whereas hydrolysis in acidic media yields (CH3O)2P(S)OH. On prolonged contact with iron or iron-containing material, it is reported to break down and completely lose insecticidal activity. Incineration together with a flammable solvent in a furnace equipped with afterburner and scrubber is recommended. In accordance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office