Organochlorine Insecticides

Organochlorine Insecticides W-T Tsai, National Pingtung University of Science and Technology, Pingtung, Taiwan Ó 2014 Elsevier Inc. All rights reserved. This article is a revision of the previous edition article by Benny L. Blaylock, volume 3, pp 301–302, Ó 2005, Elsevier Inc.

Background Organochlorine pesticides (OCPs) or insecticides are synthetic chlorinated hydrocarbons, which are used to kill insects (e.g., mosquitoes, termites, head lice, fire ant) and to even control insect-borne diseases in a diversity of fields, including agriculture, industry, medicine, and the household. Organochlorine insecticides may be divided into three basic groups: dichlorodiphenylethanes (e.g., dichloro-diphenyl-trichloroethane (DDT)), cyclodienes (e.g., chlordane), and hexachlorocyclohexanes (e.g., lindane). Table 1 lists the chemical identities and the information on environmental persistence, endocrine disrupting, carcinogenicity, and partition property of common organochlorine insecticides, including aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, lindane, and toxaphene. Obviously, these insecticides have molecular weights greater than 291 by virtue of their cyclic structure. DDT or 1,1,1-trichloro-2,2-bis-(4-chlorophenyl)ethane (Chemical Abstracts Service Registry Number 50-29-3), the first of the chlorinated organic insecticides, was originally synthesized in 1874. It was enormously used as an insecticide against a very wide range of insect pests during World War II and thereafter because of its insecticidal properties and useful properties (i.e., low-cost, broad-spectrum activity, lengthy persistence, and relative safety to humans and domestic animals). The success of DDT as an organochlorine insecticide triggered the synthesis and commercial use of chemically similar organochlorines, such as aldrin, chlordane, dieldrin, endrin, heptachlor, lindane, and toxaphene, during the decade after World War II. It has been estimated that the cumulative world production of organochlorine insecticides was about 10 million tons during the period 1945–65.

These insecticides are believed to be one of the major factors behind the increase in agricultural productivity in the twentieth century. Initially, the environmental properties (i.e., low volatility, lipid solubility, and its resistance to destruction by light and oxidation) of these organochlorine insecticides made them useful and effective in agricultural applications. Starting in the 1960s, there were concerns about the environmental problems as a result of the long-term persistence and fat solubility for nearly all organochlorine insecticides; that is, they have the potential to significantly alter ecosystems and be toxic to human health because of their environmental persistence, long-term (chronic) toxicity, and bioaccumulation (bioconcentration) in the food chain. Furthermore, many species of insects developed resistance to DDT and other organochlorine insecticides; thereafter these insecticides were discovered to be highly toxic to humans and animals (especially fish). Since the early 1970s, the use of DDT and common organochlorine insecticides has been banned in the United States and Europe, but they are still manufactured and used in developing countries to control malaria-causing mosquitoes. Although the environmental levels of organochlorine insecticides are now slowly declining, most of them are classified as endocrine disrupting chemicals (EDCs) because of their hormone-like effects on the endocrine systems of wildlife and humans, and persistent organic pollutants (POPs) under the Stockholm Convention. Some organochlorine pesticides, including mirex (CAS 2385-85-5), chlordecone (CAS 143-50-0), a-hexachlorocyclohexane (CAS 319-84-6), b-hexachlorocyclohexane (CAS 319-85-7), endosulfan (CAS 115-29-7), hexachlorobenzene (CAS 118-74-1), and pentachlorobenzene (CAS 608-93-5) are not discussed here, but are listed in the Convention.

Table 1 Information on environmental persistence, endocrine disrupting, carcinogenicity, and partition properties of common organochlorine insecticides Organochlorine insecticides

CAS no.

Mol. formula

Aldrin Chlordaneg DDT Dieldrin Endrin Heptachlor Lindane Toxaphene

309-00-2 12789-03-6 50-29-3 60-57-1 72-20-8 76-44-8 58-89-9 8001-35-2

C12H8Cl6 C10H6Cl8 C14H9Cl5 C12H8Cl6O C12H8Cl6O C10H5Cl7 C6H6Cl6 C10H16Cl8

Mol. wt. (g mol 1)

POPs a

EDCs b

IARC c carcinogenicity

USNTP d carcinogenicity

Kowf

364.9 409.8 354.5 380.9 380.9 373.4 290.8 413.8

Listed Listed Listed Listed Listed Listed – Listed

Listed Listed Listed Listed Listed Listed Listed Listed

Group 3 Group 2B Group 2B Group 3 Group 3 Group 2B Group 2B Group 2B

–e – Reasonable suspected – – – Reasonable suspected Reasonable suspected

6.50 5.54 6.36 4.32 5.20 5.27 3.55 4.83

a

Listed in the Stockholm Convention on Persistent Organic Pollutants (POPs) by the United Nations Environment Programme (UNEP). Listed in the endocrine disrupting chemicals (EDCs) by the Ministry of the Environment (Japan). Overall evaluations of carcinogenicity to humans by the International Agency for Research on Cancer (IARC); Group 1: Carcinogenic to humans; Group 2A: Probably carcinogenic to humans; Group 2B: Possibly carcinogenic to humans; Group 3: Not classifiable as to carcinogenicity to humans. d United States National Toxicology Program (USNTP) by the Department of Health and Human Services; Reasonable suspected: Reasonably anticipated to be a human carcinogen. e Not listed. f Octanol/water partition coefficient (as logarithmic scale). g Technical grade. b c

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Organochlorine Insecticides

Table 2

Health hazards and exposure limits of common organochlorine insecticides

Organochlorine insecticides Target organs a

OSHA-PELb (mg m 3)

ACGIH-TLV c (mg m 3)

Aldrin

Central nervous system, liver, kidneys, skin

0.25 (skin)

0.05

Chlordane DDT

0.5 (skin) 1 (skin)

0.5 1

Dieldrin

Central nervous system, eyes, lungs, liver, kidneys Eyes, skin, central nervous system, kidneys, liver, peripheral nervous system Central nervous system, liver, kidneys, skin

0.25 (skin)

0.25

Endrin

Central nervous system, liver

0.1 (skin)

0.1

Heptachlor Lindane

Central nervous system, liver Eyes, skin, respiratory system, central nervous system, blood, liver, kidneys Central nervous system; skin

0.5 (skin) 0.5 (skin)

0.05 0.5

0.5 (skin)

–d

Toxaphene

TLV-basis Central nervous system impairment; liver and kidney damage Liver damage; (skin)e Liver damage Liver damage; central nervous system convulsion; (skin) Liver damage; central nervous system impairment; headache; (skin) Liver damage; (skin) Liver damage; central nervous system impairment; (skin) –

a

National Institute for Occupational Safety and Health (NIOSH), NIOSH Pocket Guide to Chemical Hazards. OSHA-PEL: Occupational Safety and Health Administration – Permissible Exposure Limit based on 8-h time-weighted average. c ACGIH-TLV: American Conference of Governmental Industrial Hygienists – Threshold Limit Value based on 8-h time-weighted average. d Not available. e The designation ‘skin’ refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes. b

Mode of Action

Acute (Short-Term) Health Effects

DDT and other organochlorine insecticides act on the nervous system at the axon, and thus disrupt the movement of ions such as sodium into and out of nerve cells of insects. On the other hand, the high lipophilic nature of these chlorinated compounds facilitates absorption through the insect cuticle and further penetration to the nerve tissues. The axonal voltage-gated sodium channel is the target of organochlorine insecticides acting as modulators. The death of insects results from metabolic exhaustion and the production of an endogenous neurotoxin.

Although the health effects of organochlorine insecticides depend on the specific insecticide, level of exposure, and time of exposure, as well as the individual, their acute toxicities, in general, tend to be similar, as listed in the column of target organs (Table 2). The acute health effects from the exposure of organochlorine insecticides include irritation of the nose, throat, and skin, causing burning, stinging, and itching as well as rashes and blisters. Nausea, vomiting, dizziness, and diarrhea also have been observed.

Major Uses

Chronic (Long-Term) Health Effects

Organochlorine insecticides are commonly used in agricultural fields, including crops, grains, fruit, seeds, and vegetables, in the control of insects (e.g., ticks, mosquitoes, and fire ants) and insect-borne diseases (e.g., malaria, dengue fever, and yellow fever). They are also used as a soil insecticide for controlling termites and soil-borne insects whose larvae feed on the roots of plants.

Concerns about organochlorine insecticides have focused on their chronic health effects, including cancer (especially in breast cancer from exposure DDT) and other tumors, brain and nervous system damage, birth defects, infertility and other reproductive problems, and damage to the liver, kidney, lung, and other body organs. It should be noted that these compounds are xenobiotic chemicals that may induce the hormone-like effects on the endocrine systems of wildlife and humans. The endocrine and reproductive effects of these insecticides are believed to mimic or disrupt the effect of endogenous estrogens. In the Strategic Programs on Environmental Endocrine Disruptors ’98 by the Ministry of the Environmental Government of Japan, common organochlorine insecticides have been incorporated into endocrine disrupting chemicals (EDCs), as shown in Table 1. Regarding the chronic toxicities of organochlorine insecticides, carcinogenicity is the most important concern as compared with mutagenicity, teratogenicity, neurotoxicity, and reproductive toxicity. As also summarized in Table 1, the United States National Toxicology Program (USNTP) listed DDT, lindane, and toxaphene as ‘reasonably anticipated to be

Exposure Routes and Pathways Inhalation (pulmonary route) is the main source of toxic exposure to organochlorine insecticides. Skin absorption and/or contact (dermal exposure), as well as eye contact may also occur. Ingestion would be intentional. Because they are no longer used in the developed countries as agricultural and domestic insecticides, the exposure to organochlorine insecticides can occur via contaminated air, water, and foods (e.g., fish, meat, poultry and dairy products, and leafy vegetables), or through the respiratory and/ or skin pathways in developing countries where they are still used.

Organochlorine Insecticides

a human carcinogen’ based on sufficient evidence of carcinogenicity in experimental animals. To be consistent with USNTP, the International Agency for Research on Cancer (IARC) has classified these insecticide-POPs and other POPs (i.e., chlordane and heptachlor) as possibly carcinogenic to humans (group 2B). By contrast, aldrin, dieldrin, and endrin have been considered as Group 3 (not classifiable as to carcinogenicity to humans).

Exposure Standards/Limits Regarding the exposure standards/limits of organochlorine insecticides (seen in Table 2), some insecticide-POPs, including chlordane, heptachlor, and toxaphene, have been set the occupational exposure limit (OEL) to be 0.5 mg m 3 (8-h time-weighted average) with the ‘skin’ notation (dermal absorption) in the permissible exposure limit (PEL) by the Occupational Safety and Health Administration (OSHA) and the Threshold Limit Value by the American Conference of Governmental Industrial Hygienists (ACGIH).

See also: Aldrin; Dieldrin; Hexachlorocyclohexanes Including Lindane; Federal Insecticide, Fungicide, and Rodenticide Act, US.

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Further Reading American Conference of Governmental Industrial Hygienists, 2009. Documentation of the Threshold Limit Values and Biological Exposure Indices. ACGIH, Cincinnati, Ohio, USA. Krieger, R., 2010. Hayes’ Handbook of Pesticide Toxicology, third ed. Elsevier, Amsterdam. Ma, S.W.Y., Yang, R.R., 2007. Persistent organic pollutants in Hong Kong. In: Li, A., Tanabe, S., Jiang, G., Gisey, J.P., Lam, P.K.S. (Eds.), Persistent Organic Pollutants in Asia: Sources, Distributions, Transport and Fate. Elsevier, Amsterdam, pp. 313–373. Mackay, D., Shiu, W.Y., Ma, K.C., Lee, S.C., 2006. Handbook of Physical–Chemical Properties and Environmental Fate for Organic Chemicals, second ed. CRC Press, Boca Raton, FL, USA. National Institute for Occupational Safety and Health, 2004. NIOSH Pocket Guide to Chemical Hazards. NIOSH, Atlanta, USA. Safe, S., 2003. Toxicology and risk assessment of POPs. Part O. In: Fiedler, H. (Ed.), The Handbook of Environmental Chemistry-Persistent Organic Pollutants, vol. 3. Springer-Verlag, Berlin, Germany, pp. 223–235. Tsai, W.T., 2010. Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan. International Journal of Environmental Research & Public Health 7, 3615–3627.

Relevant Websites http://toxnet.nlm.nih.gov/ – National Library of Medicine's Toxicology Data Network (TOXNET). http://npic.orst.edu/ – National Pesticide Information Center. http://www.pesticideinfo.org/ – Pesticide Action Network. http://www.chem.unep.ch/pops/ – The Stockholm Convention on Persistent Organic Pollutants (POPs).