Endocrine disrupters

Introduction:

In this context:
Agents behaving like female hormones (oestrogenic)
Agents antagonizing male hormones (anti-androgenic)

Summary overview of the evidence:

• A number of reports show decreasing sperm counts with time from successive subjects in the same locality but not all these types of studies are consistent.
• Defects evident in the male at birth such as hypospadias (abnormal position of the opening of the urethra) appear to be getting commoner. Cryptorchidism (failure of normal descent of the testis) is being reported with increasing frequency, and it should be noted that there has not been a corresponding increase in equivalent malformations of the female.
• The incidence of cancers of the male reproductive organs (testis and prostate) appears to be increasing, even after standardising for age, while in contrast, the incidence of reproductive cancers in the female has not increased.
• The above three types of observations may be linked to increased oestrogenic influences. For example when pregnant women were once treated with Diethyl Stilboestrol (DES)  in utero to prevent miscarriages, this had then resulted not only in tumours in females, but also the following in male offspring:-


Male malformations
Testicular tumours
Decreased sperm quality
 

• Some animal data is also consistent with the epidemiologic evidence although the routes of exposure and doses in those experiments or observations are not necessarily comparable with the human experience.

Thus in laboratory experiments many chemicals are oestrogenic, for example:
DDT & other organochlorine pesticides
PCBs, Dioxins & Dibenzofurans
Phthalate esters
Others (including ‘natural’ weak dietary oestrogenic agents)

Changes in aquatic life have been observed observed (? because of oestrogenic pollution):
Sex ratio changes
Intersex morphology

However there are problems with a large part of the evidence (positive or negative). These include bias
chance, and confounding. It should be borne in mind that adverse effects on reproduction can arise through exposures other than endocrine disruption, for example through thermal effects, psychological stress and other effects e.g. of a directly toxic non-endocrine type.
 

Possible causal agents and mechanisms:

• Some foods, such as soya but also various cereals, man may contain weak but abundant phyto-oestrogens.
• Medical therapeutic agents e.g the contraceptive pill or its metabolites
• Many chemicals of industrial origin have been implicated – and the risks associated with exposure to these substances need to be assessed both because of the potential consequences for the workforce, and for the wider community. There are a few well substantiated reports of male infertility resulting from specific occupational exposures. Many of the suspect endocrine disrupters are ubiquitous in industry, with functions ranging from plasticisers to pesticides. Their chemical identities are also diverse, ranging from phthalates to to bisphenols to halogenated hydrocarbons (such as dibromochloropropane DBCP, or polychlorinated hydrocarbons such as PCBs). It should be noted that other exposures, such as to lead, may have effects on reproduction.

Evidence in an Occupational Context:

Infertility:

Semen parameters:

Hormone measurements:

Occupational Hygiene Implications

• Extent of human exposure and uptake

• Laboratory Studies

• Retrospective studies e.g.:

• Prospective studies e.g.:

There is also a need for more awareness in practice:
 

• Identify putative exposure

• Identify, report  and investigate possible health effects

• Communicate, inform and debate - especially re the ‘Precautionary Principle’

• Hence apply agreed level of control

Conclusion

More research is needed in order to assess the risks associated with these exposures. Epidemiologic studies in progress are using birth cohorts or case-control methods in attempts to answer important questions of causality. For example the author is a co-investigator in a study on male reproductive health in a Scottish birth cohort. However systematic industry based approaches are also needed in order to help assess the risks, and subsequently to reduce the likelihood of harm through reduction of exposure.

More debate and consensus on precautionary principles is probably needed.
 

Internet Links related to endocrine disrupters:

• An account from the BMJ on the controversy of whether sperm counts are falling.
• A research project on Male Reproductive Health

• European Endocrine Disrupters Research Inventory
• Environmental Estrogens and Other Hormones (EEOH)
• MAFF UK - Phthalates in Food (March 1996)
• MAFF UK - Phthalates in Infant Formulae (May 1996)