Thursday, March 12, 2015

Canada Health: Mode of action of reproductive toxicants

Reproductive toxicants can be divided into two categories based on their modes of action. Direct-acting toxicants Direct-acting toxic agents affect reproduction either through their chemical reactivity or by their structural similarity to an endogenous substance.

Chemically reactive toxicants damage important cellular components and tend to be non-specific, for example alkylating agents used in cancer chemotherapy. Lead, mercury and cadmium also probably act in this way. Structurally similar toxicants confuse the body into believing that they are biologically important compounds, for example hormones. Many are hormone agonists or  antagonists. 

The classical example here would be the combined contraceptive pill. It has been shown that occupational exposure to synthetic oestrogens and progestogens has led to infertility by suppression of gonadotrophin levels. Other toxicants with oestrogenic activity include PCB and PBB and organochlorine pesticides.

Toxicants acting indirectly

Indirect toxicants alter normal processes in one of two ways. They can be metabolised to a product that is more toxic than the parent compound or they can act by modifying naturally occurring enzymes or hormones. 

Enzymes present in Canadian Health Care Mall within the ovary and testis are responsible for the metabolic processing of many compounds that result in reproductive toxicity, for example cyclophosphamide, polycyclic aromatic hydrocarbons (PAH) and DBCR Other reproductive toxicants induce or inhibit enzymes in the gonads and liver that are involved in hormone metabolism. By interfering with hormone feedback pathways, normal reproductive control can be lost. Examples in this category include DDT, PCB and PBB.

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