Hexachlorocyclohexanes

Source:

  • Hexachlorocyclohexanes (HCH) are a group of synthetic chemicals that used to be manufactured for use as a pesticide and as a prescription medication to treat lice. HCH exists in eight different isomers that are named according to the position of the hydrogen atoms in the structure of the chemical (1) and is an insecticide available in solid and liquid states.

Structures of four hexachlorocyclohexane (HCH) isomers | Download Scientific Diagram

Figure 1: isomers of HCH. From: https://www.researchgate.net/figure/Structures-of-four-hexachlorocyclohexane-HCH-isomers_fig1_7454055

Biotransformation:

  • Biotransformation is different among species depending on which isomer is involved, and an important aspect of these biotransformations is that some species can transform most of these toxicants to even more toxic and lipophilic products (2). HCH is rapidly metabolized by humans and it is excreted in urine.

Toxicokinetics:

  • A. Administration
    • Administration can occur in humans in a variety of routes that include oral, inhalation, and transdermal.
  • B. Distribution
    • Distribution occurs when HCH enters the body and is transported to other parts of the body.
  • C. Metabolism
    • A series of enzymes are involved in metabolism.
  • D. Excretion
    • HCH is excreted through the urine.

Carcinogenicity:

  • According to The International Agency for Research on Cancer (IARC), HCH is potentially carcinogenic to humans.

Mechanism of Action:

  • This also depends on the isomer involved, but it is largely involved at the synapse and intereferes with the GABA system. More research is being done on it (3).

Target organ(s):

  • Lymphatic organs seem to be heavily affected by HCH exposure (1).

Signs and symptoms of toxicity:

  • Apprehension, excitability, dizziness, headache, disorientation, weakness, paresthesia, muscle twitching, tremor, tonic and clonic convulsion and unconsciousness are the major manifestations. Soon after ingestion, nausea and vomiting commonly occur. When chemicals are absorbed by skin, apprehension, twitching, tremors, confusion and convulsions may be the first symptoms. Respiratory depression is caused by the pesticide and by the petroleum solvents in which these pesticides are usually dissolved. Rhabdomyolysis may occur. Even though convulsive activity may be severe, the prognosis is fairly good. Although fatalities have occurred following absorption of large amounts of some organochlorine, there is a substantial likelihood of complete recovery if convulsions can be controlled, and vital functions sustained (3).

Genetic susceptibility or heritable traits

  • N/A

Historical or unique exposures

  • A. In Greece, seventy-nine persons were poisoned by a 40% dry powder of HCH or the same powder mixed with either water or a petroleum solvent which was sprinkled on ground, walls and over clothing, bedding and bodies of people. Symptoms were related to gastrointestinal tract and CNS. Eighteen were seriously affected but all survived (3).
  • B. Occupational exposure to HCH in 45 males working in manufacture of hexachlorocyclohexane, including handlers (production workers likely to have the most exposure) and non-handlers (factory operator) has been studied. Exposure occurred primarily via skin. Subjective symptoms included paresthesia, headache, giddiness, vomiting, apprehension and insomnia (3).

Treatments

  • No antidotes are available, but charcoal can be used if ingested to induce vomiting and prevent HCH from being further absorbed.

Biomarkers

  • There are no general biomarkers of effect for HCHs analogous to red blood cell or plasma cholinesterase for organophosphorous insecticides (1).

Sources:

1. Hexachlorocyclohexane(Mixed isomers)(PIM 257) [Internet]. [cited 2021 May 26]. Available from: http://www.inchem.org/documents/pims/chemical/pim257.htm#7.1%20Mode%20of%20Action.

2. Biotransformations of cyclodienes and their photoisomers and hexachlorocyclopentadiene in mammals and fish. Toxicology of Halogenated Hydrocarbons. 1981 Jan 1;271–88.

3. United States, Agency for Toxic Substances and Disease Registry. ATSDR’s toxicological profiles. [Internet]. Boca Raton, Fla.: CRC Press; 2003 [cited 2021 May 26]. Available from: http://www.crcnetbase.com/isbn/9781420061888.