Biochemical Effects Induced by the Hexachlorocyclohexanes

Abstract

The hexachlorocyclohexanes (HCHs) are synthetic compounds that have been widely used for the control of pests. The most common HCH isomers are the α-, β-, δ-, and γ-HCH. Although the have the same chlorine substitution pattern, the spatial orientation of chlorine atoms is different on each one of them, resulting in unique structures that have distinct molecular properties. Humans are exposed to individual HCH isomers through various routes, including ingestion of contaminated water or food, absorbed through the skin or by inhalation, and because of their liposolubility, these chemicals are mostly stored in fat-containing tissues. The isomer-specific spectrum of biochemical actions for these compounds has been wee characterized for different endpoints such as enzyme activation, calcium homeostasis, gap junctional intercellular communication, endocrine disruption, and cancer, among others. The interaction with the GABA reception has been one of the most extensively studied properties of the HCHs. For instance, γ-HCH acts as a GABAA channel blocker, whereas α- and δ-HCH potentiate currents , all working as allosteric modulators of the receptor. The changes in calcium homeostasis elicited by HCHs are both isomer and cell type specific. For example, in neurons, both the δ- and γ-isomers of HCH stimulate Ca²+ influx through different voltage-gated Ca²+ channels. In human neutrophils, α-,δ-, and γ-HCH, but not β-HCH, increase intracellular Ca²+ concentrations. This isomer-dependent behavior is also similar to that observed for phospholipase A2 activation and also correlates with oxidative stress generation. On the other hand, there are several lines of evidence suggesting that HCHs alter genomic integrity, and, therefore, these compounds have been classified as possibly carcinogenic to humans . Finally, HCHs have been reported to be endocrine disrupters. In fact, γ- and β-HCH have been shown to have weak estrogenic activity, and together with the α- and the δ-isomer, also interfere with steroidogenesis. In short, the HCH isomers are good examples of structurally related chemicals, for which the geometrical patterns present in each one of the different conformers create structures that possess specific mechanisms of action and toxicological properties.

A biomonitoring study on blood levels of beta-hexachlorocyclohexane among people living close to an industrial area

“…However, knowledge of its effects on human health is limited and controversial and in many cases the evidence is based only on studies of workers employed in the production and use of lindane [5]. The most frequently reported effects are related to neurological disorders [6,7], endocrine disruption [8,9], reproductive disorders [10,11], cardiovascular effects [12] and cancer [13,14]. …”

An Update on the Safety of Foods of Animal Origin and Feeds

“…The migration of contaminants trough the food chain may have a negative impact on the health of the indigenous wildlife, farm animals and, finally, humans (Olivero-Verbel et al, 2011;Mrema et al, 2013).…”

“…Among the EDCs, the organochlorinated pesticides (OCPs) are a group of man-made chemicals characterised by the presence of organic rings substituted with chlorine atoms. These pesticides are very stable in the environment, because they are not easily metabolised, and are lipophilic, thus tending to accumulate at high amounts in fat tissues, human and animal milk, meat and eggs (Olivero-Verbel et al, 2011). The OCPs, such as the hexacholorocyclohexane isomers (HCHs; mainly the -, -, and -HCH), have been widely sold and used in developing countries for crop protection (Iwata et al, 1993), being released in the environment at rates often incompatible with the natural degradation processes.…”

In VitroEffects of the Organochlorine Pesticide β-Hexachlorocyclohexane on Bovine Peripheral Blood Mononuclear Cells

“…However, some toxic substances can be spread into the environment and contaminate soil, water, foodstuff of plant origin, fodder and feed. As a final result, the migration of contaminants along the food chain may have adverse impacts on the health of both the wildlife and farm animals and, finally, on humans (Olivero-Verbel et al, 2011;Mrema et al, 2013). Among the wide range of chemical compounds, the organochlorine pesticides (OCPs) are able to alter the proper functioning of the endocrine system in animals and humans (Toppari et al, 1996;Safe, 2005;Mrema et al, 2013).…”

“…Among the wide range of chemical compounds, the organochlorine pesticides (OCPs) are able to alter the proper functioning of the endocrine system in animals and humans (Toppari et al, 1996;Safe, 2005;Mrema et al, 2013). Organochlorine pesticides are very stable in the environment because they are not readily metabolised, and their lipophilic character makes them highly accumulable in fat tissues as well as in breast milk, farm animal milk, meat and eggs (Olivero-Verbel et al, 2011). Among other OCPs, the hexachlorocycloexane isomers (mainly the -, -, -HCH), have been widely sold and used for crop protection and sanitation (Iwata et al, 1993) and were, but in some developing countries are still, released in the environment at rates incompatible with natural degradation processes.…”