In this article we will discuss about:- 1. Classification of Organochlorine Insecticides 2. Mechanism of Toxic Action of Organochlorines 3. Absorption and Fate.
Classification of Organochlorine Insecticides:
The organochlorine insecticides can be divided into three groups as:
(i) Dichlorophenylethanes (DDT and related compounds)
(ii) Cyclodiene and related compounds
(iii) Hexachlorocyclohexanes and others.
Although there is no structure common to all organochlorines, they are all characterized by one or more chlorine atoms positioned around one or more hydrocarbon rings. Members of each group of organochlorines share similar or identical compositions although they may have very different three-dimensional structures and shapes. These isomers may differ significantly in their toxicities and other characteristics.
DDT (p,p: Dichloro Diphenyl Trichloro-ethane)
On exposure, DDT is dechlorinated to p, p’ DDD and p, p’ DDE which are less toxic than DDT.
DDT was first synthesized by O. Ziedler, a German chemist, in 1874 but its insecticidal property was reported by Paul Muller in 1939.
DDT is a highly effective insecticide at broad spectrum. It acts as a contact and stomach poison having longer residual action. It is insoluble in water, fairly soluble in organic solvents and highly soluble in xylene. It is stable under most conditions and possesses a very low vapour pressure. DDT, once introduced into the environment, keeps circulating for many years.
Uses:
It is used for cotton, soyabean and peanut pests. It is also used for mosquito control. Its persistence in the environment causes accumulation in food chain. DDT use has been eliminated in U.S. though it is still applied in many regions throughout the world.
A. Permissible Limit in Freshwater — 0.001 µg/L:
a. It affects the nervous system and causes violent agitation in insects followed by paralysis and death. However, it acts very slowly.
b. It represents the best example of biological magnification as represented in an aquatic ecosystem (Table 3.7) where concentration of DDT continuously increased from water to birds:
c. The oral Ld50, (96 hours) of DDT for rats is of 250 mg – 300 mg/kg. A dose of 10 mg/kg produces illness in man.
d. The half-life of DDT in humans range from 0.5 – 0.7 years. Not only does the accumulation pose a hazard of unknown consequences, but also carries with it the potential of being transferred and secreted in human milk.
e. DDT possesses carcinogenic property, as it leads to tumour formation in liver of mouse and rat. Evidence for hepatic carcinogenicity in human is inadequate.
f. DDT inhibits Calcium ATPase in CNS.
g. Large doses of DDT may produce a moderate leucocytosis and a decrease in hemoglobin without a decrease in the concentration of red cells.
Symptoms of DDT Poisoning in Man:
a. Acute Symptoms:
Paresthesia, ataxia, dizziness, headache, restlessness, nausea, vomiting, fatigue, hyperexcitability, tremor etc.
Anorexia, weight loss, anaemia, tremor, weakness, hyperexcitability, anxiety, leucocytosis, etc.
Methoxychlor:
It is also known as methoxy DDT. Its chemical name is 1,1,1: Trichloro -2, 2-bis methoxyphenyl ethane.
Pure methoxychlor is a colourless crystalline solid. Technical methoxychlor is 88 – 90% pure. Its vapour pressure is very low. Melting point is 77°C. It is not accumulated in fatty tissues or excreted in milk as DDT. Therefore, methoxychlor is preferred to DDT for use on animals, in animal feed, and in barns. Since it is more unstable, it has less residual effect.
Major products of its breakdown in a neutral solution are anisoin, anisil and also p, p- dimethoxydichloroethane (DMDE). Its half-life in river water may be 5-10 hours but in soil is approximately 120 days.
Uses:
It is a highly popular organchlorine insecticide and is a DDT substitute derivative.
B. Permissible Limit in Freshwater — 0.003μ/L
a. Actually methoxychlor is practically non-toxic via the oral route, with reported (96 hours) oral LD50 values of 5,000 – 6,000 mg/ kg in rats, 1,850 mg/kg in mice and 2,000 mg/kg in hamsters. The lowest oral dose that can cause lethal effects in humans is estimated to be 6,400 mg/kg and the lowest dose through the skin that produces toxic effect in humans is 2,400 mg/kg based on behavioural symptoms.
b. Symptoms of high acute exposure include CNS depression, progressive weakness and diarrhea. Extremely high doses may cause death within 36 – 48 hours.
c. High doses of methoxychlor (88 – 90% pure) or its metabolites may have estrogenic or reproductive effects. In rats, dietary doses of about 125 mg/kg/day reduced mating and many did not produce litters. Rats fed doses of about 50 mg/kg/day had normal fertility and fecundity but their offspring had abnormal reproductive functioning.
It is unlikely that methoxychlor may cause reproductive effects in humans at expected exposure levels.
Testicular atrophy has been observed in rats at level of about 500 mg/kg/day over an unspecified period.
a. Methoxychlor is slightly toxic to bird species with reported acute oral (96 hours) LD50 values of greater than 2,000 mg/kg in the mallard duck and sharp-tailed grouse.
b. Methoxychlor is very highly toxic to fishes and aquatic invertebrates. Reported 96 hour LC50 values are less than 20μg/l for cutthroat trout, book trout and Atlantic salmon. Reported LC50 values (96 hours) are between 20 – 65 µg/l in Rainbow trout, Goldfish, Channel catfish and Yellow perch.
c. Methoxychlor is non-toxic to bees.
(ii) Cyclodienes:
Chlordane:
It is also known as Kilex Lindane or Kypchlor or Octachlor or Toxichlor. Chlordane is no longer distributed in the US since 1988 because of concern about the risk of cancer. The only commercial use still permitted is for ant and termite control.
Properties:
Chlordane is a persistent cyclodiene insecticide. It kills insects when ingested and on contact. It is metabolized to oxychlordane. Consequently oxychlordane is stored in fat and is excerted in the milk of lactating animals. It does not appear to be a residue of concern, at least in plants. It is a neurotoxicant.
Uses:
It is very much effective against termites and ants.
C. Permissible Limit in Freshwater — 0.01 µg/L:
It is moderately to highly toxic through all routes of exposure. The oral (96 hours) LD50 for Chlordane in rats is 200 – 700 mg/kg, in mice 145 – 430 mg/kg, and in rabbits 20 – 300 mg/kg.
Symptoms usually start within 45 minutes to several hours after exposure to its toxic dose. Convulsion may be the first sign of poisoning or they may be preceded by nausea, vomiting and gut pain. Initially poisoning victims may appear agitated or excited, but later they may become depressed, uncoordinated, tired or confused. Other symptoms include headache, dizziness, vision problems, irritability, weakness and muscle twitching. In severe cases respiratory failure and even death may occur.
Liver lesions and changes in blood serum occurred in rats exposed to 1.0 mg/l chlordane. Increased kidney weights occurred in rats exposed to 10.0 mg/l. Animal studies have shown that consumption of chlordane caused damage to the liver and the CNS.
Chlordane affects reproduction in test animals. Fertility was reduced by about 50% in mice injected with Chlordane at 22 mg/kg once a week for 3 weeks. However, data reveal that reproductive effects in humans are unlikely at expected exposure levels.
b. Mutagenic Effects:
Chlordane is weakly mutagenic or non-mutagenic.
c. Carcinogenic Effects:
It is a probable human carcinogen.
CNS, liver and blood disorders have been reported in human exposed to chlordane. It may also cause blood diseases, including aplastic anemia and acute leukemia in rats.
Endosulfan:
Trade or other names for endosulfan products include Afidan, Endocel, Malix, Thiodan and Thiotox. It is an acarcide of the cyclodiene sub-group. Technical endosulfan is composed of a mixture of two molecular forms (isomers) of endosulfan, the alpha and the beta isomers.
It is a brownish crystalline solid, insoluble in water but soluble in xylene. It is a stomach and contact poison with slight fumigant action. It is not compatible with alkaline materials. The alpha isomer is considered to be more toxic than the beta isomer. Its average half-life in soil is 50 days.
Uses:
Endosulfan acts as a poison to a wide variety of insects and mites on contact. Although it may also be used as a wood preservative, it is used primarily on a wide variety of food crops, including tea, coffee, fruits and vegetables as well as on rice, cereals, maize, sorghum or other grains.
D. Permissible Limit in Freshwater —0.01 μ/L:
Endosulfan is highly toxic via the oral route, with reported oral (96 hours) LD50 values ranging from 18 -160 mg/kg in rats, 7 – 36 mg/kg in mice and 77 mg/kg in dogs. It is reported not to cause skin or eye irritation in animals. Stimulation of the central nervous system is the major characteristic of endosulfan poisoning.
Symptoms reported in actually exposed humans include incoordination, imbalance, difficulty in breathing, gazing, vomiting, diarrhea, agitation, convulsions and loss of consciousness. In an accidental exposure, sheep and pigs grazing on a sprayed field suffered a lack of muscle coordination and suffered from blindness.
In rats, oral doses of 10 mg/kg/day caused high rates of mortality within 15 days, but doses of 5 mg/kg/day caused liver enlargement over the same period. Reports reveal that administration of this dose over 2 years in rats also caused reduced growth and survival, changes in kidney structure and blood chemistry.
Oral doses for 15 days at 10 mg/kg/day in male rats caused damage to the seminiferous tubules and lowered testes weight. It is unlikely that endosulfan may cause reproductive effects in humans at expected exposure levels.
An oral dose of 5 – 10 mg/kg/day in rats in a three generation study resulted in bone deformity in the offspring. Teratogenic effects in humans are unlikely at expected exposure levels.
Endosulfan is reported to be a mutagenic to bacterial and yeast cells. Evidence suggests that exposure to Endosulfan may cause mutagenic effects in human if exposure is great enough.
Reports reveal that Endosulfan is not carcinogenic.
Data from animal studies reveal that the organ tissues most likely to be affected include kidney, liver, blood and the parathyroid gland.
Endosulfan is highly to moderately toxic to bird species, reported oral (96 hours) LD50 values in mallards range from 31 – 243 mg/kg.
Endosulfan is reported to be highly toxic to various fish species. The reported 96 hour LCS0 values in µg/l for some fishes are:
Rainbow trout- 1.5
Fathead minnow- 1.4
Channel catfish- 1.5
Blue gill sunfish- 1.2
c. Effects on Non-Target Species:
Endosulfan is moderately toxic to bees, however, it is relatively non-toxic to other beneficial insects such as parasitic wasps, lady-bird beetles, etc.
Hexachlorobenzene:
Trade names for hexachlorobenzene (HCB) products include Perchlorobenzene, Bentcure and Granero.
Note:
This compound should not be confused with hexachlorohexane (HCH), which has historically been referred to as benzene hexachloride (BHC) and is also commonly known as lindane, a name proposed after Van der Linden, a German chemist, who isolated this isomers of HCB.
It has strong musty odour, its melting point is 226°C. It is a colourless crystalline solid at room temperature. HCB is a highly persistent compound with reported field-half lives in the soil environment ranging from 2.7 – 7.5 years. Evaporation is rapid while it is on soil surfaces, but considerably less so when it is mixed into the soil. It may be degraded’ both aerobically and anaerobically. It has a low water solubility. It has been banned from use in U.S.
E. Permissible Limit in Freshwater — 0.01 µg/L
Uses:
HCB is a selective fungicide used as a seed protectant, especially on wheat, to control common and dwarf bunt. It may be used with or without other seed treatments, fungicides and/or insecticides.
HCB is slightly to practically non-toxic via the oral route of exposure. The reported acute oral (96 hours) LD50 values are 3,500 mg/kg in the rat, 4,000 mg/kg in the mouse and 2,600 mg/kg in the rabbit.
Dietary doses to rats of approximately 50 mg/kg/day killed 95% of the females and 30% of the males within 120 days. Almost all survived when the dose rate was reduced to approximately 5 mg/ kg/day. Rats receiving doses of 25 – 50 mg/kg/day showed nervous system effects such as tremor, hyper excitability and lethargy, skin eruption, as well as increases in weights of liver, kidneys, spleen and lungs.
A syndrome called “porphyria” is associated with HCB exposure as well. It is one of the most effective compounds in inducing porphyria in humans and other animals. Symptoms of the HCB- induced porphyria consist of blistering/scarring of the skin, light sensitivity, susceptibility to skin infection and possibly osteoporosis (decreased bone calcium content).
In a four generation reproduction study of rats at doses of approximately 8 mg/kg/day, decreased fertility was observed. However, it does not appear that exposure to HCB at normal levels will cause reproductive effects in human population.
Doses of 80 mg/kg/day for one or more days of pregnancy reduced fetal birth weights and caused a slight increase in 14th ribs in rats. The potential for HCB to cause birth defects in human population is likely to be small at common levels of exposure.
Available data reveal that it is unlikely that HCB is mutagenic.
HCB caused increased numbers of tumours per animal in a long-term study where the lowest dose tested was 4 mg/kg/day. Increases in tumours of the lung, thyroid and spleen were noted. However, the potential for HCB to cause carcinogenic effect in human at normal levels of exposure is not known.
Available data from animal tests indicate that the nervous system, liver, kidneys, spleen and lungs are the target organs affected by exposure to HCB.
HCB is slightly to moderately toxic to bird species.
b. Effect on Aquatic Organisms:
HCB is slightly toxic to fish species, with reported (96 hours) LC50 values:
Channel catfish 11 -16 mg/l
Bluegill 12 mg/l
Fathead minnow 22 mg/l
Coho salmon >50 mg/l
Available data reveal that HCB possesses a significant potential for bioaccumulation.
c. Effect on Non-Target Species:
HCB is non-toxic to bees.
Lindane:
Trade or other names for lindane include BHC, (benzene hexachloride), Gammexane, Hexachlorocyclohexane, (HCH), gamma – HCH, Linox, Triple six (C6H6Cl6) etc.
Lindane is a moderately toxic compound. It possesses high potential to cause cancer; hence it is no longer manufactured in US. It is a grayish or browny amorphous solid and has a strong musty odour. It is highly persistent in most soils, with a field half-life of approximately 15 months. When sprayed on the surface, the half-life was typically much shorter. Its melting point is approximately 113°C.
Uses:
Lindane has been used on a wide range of soil-dwelling and phytophagous insects. It is commonly used on a wide variety of crops, in warehouses, in public health to control insect-borne diseases and (with fungicides) for seed treatment. Lindane is also presently used in lotions, creams and shampoos for the control of lice and mites (scabies) in humans. There are 4 isomers of HCH — alpha, beta, delta and gamma. However, gamma HCH (gamma hexachlorocyclohexane) i.e., lindane, has been shown to be the insecticially effective isomer.
F. Permissible Limit in Freshwater — 0.01μg/L
Toxic Effects:
i. Acute Toxicity:
Lindane is a moderately toxic compound via oral exposure, with a reported (96 hours) oral LD50 88 – 190 mg/kg in rats; 100 -127 mg/kg in guinea pigs. Effects of high acute exposure to lindane may include mental/motor impairment, excitation, toxic convulsions, increased respiratory rate and/or failure, pulmonary edema and dermatitis. Other symptoms in human are more behavioural in nature, such as loss of balance, grinding of the teeth and hyperirritability. Most acute effects in humans have been due to accidental or intestinal ingestion.
No observable effects over periods of up to 2 years have been found in mice, rats and dogs at doses of 1.25 mg/kg day. Doses of 40 – 80 mg/kg/ day were rapidly fatal to dogs in a study over 2 years.
In rats, doses of 10 mg/kg/day for 138 days resulted in marked reductions in fecundity and litter size. In general, lindane has been found to be slightly estrogenic to female rats and mice, and also caused the testes of male rats to become atrophied. It is unlikely that lindane will cause reproductive effects at the expected low levels, of exposure in human population.
Though doses as low as 0.5 mg/kg/day over four months in rats decreased growth in offspring, it appears that lindane is unlikely to cause developmental effects at expected low levels of exposure in human population.
Most tests on microbes and mice have shown no mutagenicity due to lindane exposure and it is unlikely that lindane would pose a mutagenic risk in humans at normal exposure levels.
Studies reveal that rodents may suffer from liver tumor from high doses of the gamma-isomer i.e., lindane. The available evidence is contradictory and does not allow assessment of the potential for carcinogenic effects in humans from lindane exposure.
Data from animal tests indicate that lindane may affect the CNS, liver, kidneys, pancreas, testes and nasal mucus membranes.
Lindane is moderately to practically non-toxic to bird species, with a reported (96 hours) LD50 of more than 2,000 mg/kg in the mallard duck.
b. Effect on Aquatic Organisms:
Lindane is highly to very highly toxic to fishes and aquatic invertebrate species. Reported (96 hours) LC50 values range from 1.7-90 μ g/l in trout (rainbow, brown and lake), coho, salmon, fathead minnow, blue gill and yellow perch.
Effects on Non-Target Species:
Lindane is highly toxic to bees.
Mechanism of Toxic Action of Organochlorines:
The chlorinated hydrocarbons are stimulants of the nervous system. Their mode of action is similar in insects and humans. They affect nerve fibers, by disturbing the transmission of the nerve impulse. More specifically, the members of this group of pesticides disrupt the sodium/potassium balance that surround the nerve fibers. The result of this imbalance is a nerve that sends transmissions continuously rather than in response to stimuli.
Despite the similarity of many of the compounds within each of three subgroups, the individual toxicities vary greatly. The compounds also vary greatly in their ability to be stored in tissue. For example, the structure of methoxychlor is very similar to DDT, but its toxicity is far lower, as is its tendency to accumulate in fatty tissue. Storage in fatty tissue is a strategy that die body uses to remove toxic materials from active circulation. Fatty storage prevents the toxic agent from reaching in the circulation and consequently on various organs like liver, kidney etc.
DDT type insecticides interact with the neuronal membrane by altering the membrane permeability (transport) for potassium and sodium and the calcium mediated processes. By inhibiting these functions, the repolarization of the nerves is distributed resulting in hyper excitability.
Cyclodienes and cyclohexane compounds have a central nervous system stimulating mode of action. These compounds antagonize the neurotransmitter, gammaminobutyric acid (GABA), permitting only partial repolarization of the neuron and, thus, uncoordinated nervous excitation.
Owing to their lipophilicity, organochlorine compounds are partitioned and stored largely in adipose tissues, where they are biologically inactive. There is an equilibrium between body fat and free circulating compounds. Redistribution and mobilization of fat, for example, due to disease, ageing or fasting, may result in mobilization of stored organochlorines in quantities that may lead to manifest toxicity. Owing to the different patterns of use of organochlorine insecticides in industrialized and developing countries, the pattern of distribution of the residues in human fat (including breast milk) differs between countries.
Absorption and Fate of Organochlorines:
i. These compounds are insoluble in water but soluble in lipids — so absorption from the gut is very poor.
ii. In oily base, these are rapidly absorbed and get bound to glycoproteins.
iii. After absorption, these are stored in body fats. However, these do not accumulate in any vital organ.
iv. Excretion is via urine and milk.