REASONABLY ANTICIPATED TO BE CARCINOGEN:
LINDANE AND OTHER HEXACHLOROCYCLOHEXANE ISOMERS

INTERNATIONAL PESTICIDE TRADE: IS THERE ANY HOPE FOR THE EFFECTIVE REGULATION OF CONTROLLED SUBSTANCES

Lindane Case Study

Lindane (>99 percent gamma isomer of hexachlorocyclohexane [HCH]) is a persistent organochlorine compound that has been in commercial use since 1938. It is used primarily as an insecticide and fumigant, and has a wide variety of applications, ranging from seed treatment for crops to control of scabies and lice in domestic and agricultural animals and in humans. In Canada, its most common use is as a treatment for canola seeds. It is a relatively low-cost pesticide, and until very recently there was no registered equivalent alternative. The use of lindane has come under scrutiny in the late 1990s for several reasons:

• Two six-year studies have found significant levels of persistent organic pollutants (POPs) in northern peoples, including high levels of the various isomers of hexachlorocyclohexane.
• Canada has signed an international protocol under the Convention on Long-range Transboundary Air Pollution (LRTAP) committing us to reassessing all uses of lindane by 2002.
• The U.S. Environmental Protection Agency (EPA) has made it clear that it would be illegal to import lindane-treated canola seed into the United States, since lindane is not registered for use as a canola seed treatment in that country.
• The Canola Council of Canada and the Canadian Canola Growers Association have worked with registrants¹ to voluntarily withdraw the use of lindane for seed treatment.
• Canada is currently participating in global negotiations, initiated under the United Nations Environment Programme (UNEP), to reduce and/or eliminate the use of specific persistent organic pollutants. Although lindane is not included in the proposed treaty at this time, it is being considered as a potential addition.

These factors have been critical in leading the Pest Management Regulatory Agency (PMRA) to conduct a special review of pest control products containing lindane. The following paper outlines the process and events that led up to this special review, the proposed voluntary withdrawal of lindane as a seed treatment for canola, and Canada’s position on lindane in international negotiations.

National Round Table on the Environment and the Economy
http://www.nrtee-trnee.ca/eng/programs/health/LINDANE_e.htm

INTERNATIONAL PESTICIDE TRADE: IS THERE ANY HOPE FOR THE EFFECTIVE REGULATION OF CONTROLLED SUBSTANCES?

[61] See Greenpeace Presses Global POPs Ban, Pan Hits U.S. Exports, supra note 32. The Pesticide Action Network (PAN) reported the U.S. exported aldicarb, camphechlor, chlordane, heptachlor, chlordimeform, DBCP, DDT, aldrin, dieldrin, endrin, EDB, HCH/BHC, lindane, paraquat, parathion, methyl parathion, pentachlorophenol and 2,4,5-T. Aldicarb was registered with the EPA in 1995 for use on potatoes. See id. PAN reports that aldicarb is so toxic that "[o]ne drop . . . absorbed through the skin is enough to kill the average adult." Id. In ad dition, several shampoos sold in the United States for the treatment of hair lice have been found to contain lindane, a substance linked to blood disease, lymphoma, seizures and brain damage. See id  

Back to Top

A study of maternal milk carried out in 1990 in the Metropolitan Region, (Santiago), detected the presence of metabolites of DDT and lindane in all the samples; 44% of the samples belonging to high socio-economic strata surpassed the 50 ug/kg. Lindane, on the other hand, had a bigger presence in the samples belonging to low socio-economic strata, probably due to a bigger use of the chemical by the Ministry of Health in the control of the scabies and pediculosis. (9)

Recent data published by Codex Alimentarius, the international authority which determines Acceptable Daily Intakes (ADIs) for potentially harmful substances in food, shows that a person consuming an average local diet in any region of the world will exceed the ADI for lindane (0.001mg per kg of body weight) by between 3.8 and 12 times. The highest consumption of lindane occurs in Europe where a theoretical maximum daily intake of lindane in a typical European diet would reach 0.742mg, or 1237% of the ADI.¹²

Title: Influence of hexachlorocyclohexane isomers on dechlorination rate of lindane in rat liver

Authors: Biočić-Steiner, Ivka (78315) Glavaš-Obrovac, Ljubica Grgić, Zdravko

Journal: Acta Pharmaceutica
ISSN: 1330-0075
Volume: 44
Year: 1994
Pages: from 273 to 277
Language: engleski
Summary: Influence of hexachlorocyclohexane isomers on rate dechlorinationof lindane in rats' tissues was investigated. Experimentalanimals, male Wistar rats, were fed for 20 days with threedifferent diets:a) standard food for laboratory animals withundetectable amounts of HCH isomers;b) standard food containing250 ppm lindane; c) standard food containing alpha, beta andgamma isomers in ratio 100:250:100 ppm. Investigation was done onliver and adipose tissues. Extraction of HCH isomers and itsmetabolites was made by the Stein et al. method. Qualitative andquantitative determination of organochlorine insecticides wasdone by gas chromatography. Results of this examination showed that in first 9 hrs after foodintake which contained HCH isomers, lindane was dechlorinatedinto chlorbenzene and benzene. The rate of dechlorination oflindane in microsomal fraction of rat liver was much slower inthe presence of other hexachlorocyclohexane isomers compared tothe rate of dechlorination of lindane itself. Due to the slowerrate of dechlorination, the concentration of HCH isomersincreases in adipose tissue. For that the products ofdechlorination mechanisms were not present.
Keywords: hexachlorocyclohexane, lindane, HCH, isomers, dechlorination, liver, adipose tissue, rat

Title: The levels of hexachlorocyclohexane isomers in tissues of the prenates

Authors: Biočić-Steiner, Ivka (78315) Glavaš-Obrovac, Ljubica

Journal: L' Igiene Moderna
Volume: 101
Year: 1994
Pages: from 663 to 666
Language: engleski
Summary: The levels of hexachlorocyclohexane isomers in organs ofpremature delivered and premature death children wasinvestigated. Investigation was done on liver, brain kidney andadipose tissue. Extraction of HCH isomers was made by the ShellDev. Co. method. Qualitative and quantitative determination wasdone ba gas chromatography. Results of this examination showed that hexachlorocyclohexane(lindane) was present in significantly concentration in allinvestigated organs. Alpha and beta HCH isomer are also presentin all investigated organs. Average concentration of lindane was1.8-7.5 ppm and present in each samples. Because lindane is acarcinogenic molecule, found amount can lead metabolicmalfunction in fetus. Mayor concentration of lindane was found inadipose tissue. No significant correlation was observed betweenHCH isomers and tissues.
Keywords: hexachlorocyclohexane, lindane, isomers, prenates

Title: INFLUENCE OF HEXACHLOROCYCLOHEXANE ISOMERS ON RATE DECHLORINATION LINDANE IN RAT TISSUES

Authors: Biočić-Steiner, Ivka (78315) Glavaš-Obrovac, Ljubica

Proceedings title: Godišnji sastanak hrvatskih biokemičara
Language: engleski
Place: Zagreb
Year: 1993
Pages: from 133 to 133
Meeting: Godišnji sastanak hrvatskih biokemičara sa međunarodnim sudjelovanjem
Held: from 06/17/93 to 06/18/93
Summary: Influence of hexachlorocyclohexane (HCH) isomers on ratedechlorination of lindane in rat's tissues has beeninvestiagated. Experimental animals, male Wistar rats, were fedfor 20 days with three different diets: a) control diets -standard food for laboratory animals with undetectable amounts ofHCH isomers; b) diets 1. - standard food containing 250 ppmlindane; c) diet 2. - standard food containing alpha, beta andgama-HCH isomers in ratio 100:250:100 ppm. Investigation was donein blood, liver and adipose tissue. Extraction of HCH isomers wasmade by Stein et al. (1984) method. Qualitative and quantitativedetermination of organochlorine insecticides was done by gaschromatography. Primary pathways of lindane biotransformation inmammals is achieved by dechlorination. Results of our examinations show that the rate of dechlorination of lindane is much slower in the presence of other hexachlorocyclohexan isomers when compared with dechlorination in the diet that contains only lindane.
Keywords: hexachlorocyclohexane, HCH,lindane, blood, liver, adipose tissue, rat

Epoxidation of the lindane metabolite, beta-PCCH, by human- and rat-liver microsomes.

Fitzloff JF, Pan JC

Human- and rat-liver microsomes convert the lindane metabolite, beta-PCCH (beta-1,3,4,5,6-pentachlorocyclohex-1-ene (3,4,6/5-PCCH] to the metabolites: 1,2,4-TCB (1,2,4-trichlorobenzene), 1,2,3,4-TTCB (1,2,3,4-tetrachlorobenzene), 2,4,5-TCP (2,4,5-trichlorophenol), 3,4,5/6-PCCOL (1,2,4,5,6-pentachlorocyclohex-1-en-3-ol) and beta-PCCH oxide (1,2,3,4,5-pentachloro-7-oxabicyclo[4.1.0]heptane) or (3,4,6/5-PCCH oxide). The identity of the beta-PCCH oxide is confirmed by column chromatography and g.l.c.-mass spectrometry, in comparison to characterized synthetic material. The stability of the beta-PCCH oxide is indicated by its resistance to hydrolysis by microsomal epoxide hydrolase (EC. 3.3.2.3), or various aqueous acid conditions. It shows no mutagenicity using S. typhimurium strain TM677. However, in levels above 0.05 mg/ml it was lethal to the test cells. It is not a substrate for and is only a weak inhibitor of epoxide hydrolase. A stable halogenated hydrocarbon epoxide metabolite is described. Its toxicological role, if any, remains unaccounted for.

PMID: 6209866, UI: 85067891

Pesticides & brain-function changes in a controlled environment

Abstract: The purpose of the present study was to determine (1) the extent to which chlorinated hydrocarbon pesticides in environmentally sensitive patients would be reduced by Environmental Control Unit (ECU) treatment programs and (2) the correlation of brain-function/psychological test results with treatment effect. Before and after therapy studies were performed on 40 ECU patients with proven levels of blood pesticides. There was a significant decrease in magnitude of blood pesticides and a significant increase in performance on brain-function/psychological tests after ECU treatment. There was also a corresponding decrease in symptoms overall. It was concluded that rigid environmental controls in treatment strongly contributed to the decrease in blood pesticide levels. Further, a more serious psychological profile was associated with these patients who showed improvement consistent with treatment.

http://www.aehf.com/articles/A30.htm

Abstract:
Thyroid function and effects on reproduction in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol (PCP) from conception.

Beard AP, Rawlings NC J Toxicol Environ Health 1999 Dec 24;58(8):509-30  

Critical Windows of Exposure for Children's Health: Cancer in Human Epidemiological Studies and Neoplasms in Experimental Animal Models

In humans, lindane is a central nervous system stimulant which suggests that it acts as an acetylcholinesterase inhibitor.  

Effects Of Lindane (Gamma-BHC) And Related Convulsants On GABA(A) Receptor-Operated Chloride Channels In Frog Dorsal Root Ganglion Neurons

Brain Research
April 1994 v 643 n1/2 p. 66

In layman's terms, it's damn near impossible for a frog to keep its eyes on a fly after being jammed with even a tiny dose of BHC-Lindane.

TCDD, Endrin And Lindane Induced Oxidative Stress In Fetal Ad Placental Tissues On C57BL/6J And DBA/2J Mice

Comparative Biochemistry And Physiology
1996 v115 n1, page 11

Let's understand something - many of these pesticides are designed to cross biological barriers put in place by insect reproductive systems - so what's the surprise that these compounds cross the human placental barriers with apparent ease? The only surprise would seem to be that the connection between pesticides and tobacco products hasn't been made yet by those studying EITHER the effects of smoking or the effects of pesticides.

Pesticides News Subject Index

The following index refers to articles in Pesticides News from issue No 1 (June 1988) to No 35 (March 1997): for more information contact the Pesticides Trust - Email: pesttrust@gn.apc.org