Noteworthy Keyword
Endocrine Disrupters (Environmental Hormone)

Yoshinari Kobuke

Hyogo Prefectural Institute of Public Health and Environmental Sciences

Environmental endocrine disrupters are chemicals that influence the endocrine system (hormones) when they enter the body of both humans and wildlife from the environment. They are called environmental hormones because of similarity to hormones produced by organisms internally. A by-product like dioxin generated as a result of human industry, synthetic organic compounds, industrial chemicals like plasticizer, pesticide, and synthesized hormone are suspected to be endocrine disrupters.

 At an international symposium held in 1991 in Wingspread, Wisconsin, USA, chaired by T. Colborn, an American zoologist, this issue was addressed by participating researchers. After this conference there was a shift in the emphasis of research from their previous studies [1) Influence of diethylstilbestrol (DES) on humans; 2) Influence of chemical substances on organisms; 3) Quantitative and qualitative changes of human sperm; 4) Chemical substances and breast cancer; 5) Influence of chemical substances on the cranial nerve system] to the study of endocrine disrupters.

Subsequently, the 1996 publication of “Our stolen future” by Colburn focused on this problem, and dramatically raised public awareness. In Japan a sense of anxiety was widespread as well. Chemical leaching from plastic utensils became a public health concern. In 1998, at its peak, about 150 related articles were found in the papers during a one month period.

 Regarding the effects of endocrine disrupters, the hormonal binding process to target-cell receptors is well-documented. In addition to this, there are hormonal synthesis and emission processes (aromatase inhibition of sex hormonal synthesis system produced by tributyltine), signaling processes after hormonal binding to the target-cell receptors (inhibition of second messenger compounds caused by lindane) and hormone metabolism and emission processes (estrogen metabolic stimulation generated by dioxin). In the process of the hormonal binding to the target-cell receptors, there is a stimulating effect (hormone-like agonistic effect) and a competitive inhibition effect (hormone-like antagonist effect). Both Estrogen-like effects (PCB, o, p’-DDT, nonyl phenol, p-Octylphenol, Bis Phenol A and phytoestrogen) related to the female hormone estrogen, and anti-estrogen tamoxifen, as well as antiandrogen-like effects (p, p’-DDT, etc.) associated with male androgens are present.

 The previously held hypothesis that characteristically endocrine disruptors have no adverse effect in low concentrations, has recently been challenged. It has been noted that there seems to be a “window of receptivity” in which an inverse U shape dose-response relationship can be observed in fetal developmental stages. Recent evidence suggests there is a likely correlation.  For example, the previously mentioned endocrine disruptors, even in low concentration, may have an effect on 7- 12 week external sex organ formation. It has been noted that malformation of external genitalia often occurs. Also, it has been suggested that chemicals with the effects of endocrine disruptors are likely to influence the endocrine system as well as the immune system, brain and the nervous system by similar action via receptors on respective cells. On the other hand, although variations in development do occur and the reverse reaction of hormone-like endocrine disruptors cannot be ruled out when this kind of change is observed, their presence of should be thoroughly investigated when this kind of reaction occurs, and other factors may be the cause.

 Research in this field is focusing on the development of testing methodology, creation of a detection system, determination of toxicity and its related mechanism, effects on humans and animal species, as well as risk assessment and management. In particular, the OECD (Organization for Economic Co-operation and Development), for the purpose of creating a viable means of testing methodology and detection of endocrine disrupters, has been developing methods of standardization using various test organisms in  two-generation studies.

Governments of many countries have been making efforts to reduce endocrine disruptors. The E.U. comparatively has made further steps by implementing the REACH program (registration, evaluation and authorization of chemical substances). After 1998, the Japanese Ministry of the Environment announced their corresponding policy named SPEED '98 or ExTEND2005. Experimental findings on the two-generation study in fish indicated that four substances, namely nonylphenol, p-Octylphenol, Bis Phenol A and o,p’-DDT specifically among the 36 substances investigated contained endocrine disruptors. Government response has not been adequate and will require more definitive regulations on chemical substances which have been determined to cause abnormal change in various organisms and potentially humans at different stages of development (specifically fetuses and infants).

 


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