INDUSTRY AND POLLUTION CAMPAIGN
BRIEFING SHEET


THE EFFECT OF ENVIRONMENTAL OESTROGENS ON HUMANS
SUMMARYFriends of the Earth argues that based on the weight of current evidence, a precautionary
ban should be placed on further manufacture, use and disposal of those substances implicated in damage to the hormone systems of both humans and animals.

BACKGROUND

Disturbing evidence of the trends of adverse effects on the ability of humans to reproduce
has emerged over the last few decades. There is particular concern over symptoms such as falling sperm count and cancer of the testicles in men, and breast cancer in women. The plausible explanation for these trends is the effect of pollutants in the environment that interfere with the action of the hormone oestrogen.

THE HUMAN REPRODUCTIVE SYSTEM

Sexuality in humans is determined by the balance of sex hormones. There are those, such as testosterone, which have a masculinizing effect (hair growth etc.) and oestrogens, which are feminising (breast development etc.). Both ovaries and testes produce testosterone and oestrogen. Sexual differentiation into male and female occurs early in fetal development.

An important feature of the male testes is the lining of Sertoli and Leydig cells. They play a crucial role in the development of sperm. Prior to puberty the Sertoli cells are able to convert testosterone into the oestrogen. Exposure to oestrogens in the environment
has the potential to damage Sertoli and Leydig cells and their important function of masculinization and sperm development.

In adult women, exposure to abnormally high levels of oestrogen can affect the fertility of the ovaries and the efficiency of the oviduct. It can stimulate excessive growth of tissue in the uterus and in the breast leading to cancer.

MALE HEALTH EFFECTSSperm counts and sperm quality: A number of studies have now shown the extent of the fall in male fertility this century. A study by Carlsen [1] showed that there had been a fall of 40% between 1940 and 1990. A study in Paris [2] has shown a decline at the rate of 2.6% per year over from 1973 to 1992.

Cryptorchidism (Undescended testicles): The most comprehensive study of this symptom was carried out in the Oxford area over the period 1984-88 [3]. The study showed an increase of 93% in incidence over the period for children at three months of age.

Hypospadias (Urethral opening under the penis): Between 1965 and 1983 the number of cases of hypospadias has increased by 157 per cent in the UK and Wales [4]. An increasing incidence has also been reported in many other countries such as Sweden, Norway, Denmark, Finland and Spain.

Testicular Cancer: There has been an increase in the frequency of this problem in England and Wales of 35 per cent from 1979 to 1987 [5]. Increases have also been identified in the Nordic countries for the period 1943-1980 [6]. It is thought that this cancer is initiated by factors acting early on

in life, possibly before birth.

FEMALE HEALTH EFFECTSBreast Cancer: This has been increasing in a number of countries over the past few decades. A 1 per cent annual increase has occurred in the USA since the 1940s [7]. Although there has been debate on the influence of the use oral contraceptives on breast cancer, recent research has been directed towards environmental pollution, especially organochlorine compounds such as DDT and polychlorinated biphenyls (PCBs).

Cardiovascular System: Oestrogen treatment has a clear benefit for many post-menopausal women for whom the rates of cardiovascular mortality drop significantly after treatment [8].

XENOESTROGENSXenoestrogens are chemicals which interfere with or mimic oestrogens. A number of organochlorine compounds have been shown to interfere with hormonal systems in experiments in laboratories and animals. Certain foodstuffs have been shown to have these properties.

SOURCES AND MECHANISMS OF ACTION

The biological effects of xenoestrogens depends on their availability and concentration within body tissue and fluids, their functioning alongside certain proteins and their binding to oestrogen receptors. They may come from a variety of sources: as pharmaceuticals or oral contraceptives, as naturally occurring substances in foodstuffs, particularly vegetables, and as man-made chemicals present as environmental pollution.

Their effects may well be complex. Some chemicals have been shown to have anti-oestrogenic properties such as the dioxin TCDD and the bioflavanoids found widely in food..

NATURAL AND SYNTHETIC HORMONES

Apart from the pill, the best known example is that of DES which was administered to women to prevent miscarriages from the early 1950s until its use was stopped in the early 1970s. A significant number of female offspring developed problems with their reproductive organs, pregnancies and menstrual cycles. Male offspring developed symptoms which included cryptorchidism microphallus and decreased sperm count. DES has been used as a growth promoter in cattle exposing humans via meat products.

Evidence of environmental pollution by the large amounts of oestrogen excreted by pregnant women and female animals has been elusive.

PHYTOESTROGENS (plant derived)

These are compounds with oestrogenic activity found naturally in edible plants such as peas, beans, cabbage, sprouts, spinach, grains and hops. If consumed in large quantities there is evidence of significant biological effects. Some phytoestrogens also act as anti-oestrogens. Whilst there may be adverse effects from such substances in the diet it is probable that this is balanced by the benefits of a high plant food diet.

ORGANOCHLORINE PESTICIDES

Whilst the use of organochlorine compounds such as DDT, dieldrin, lindane, chlordecone
and others as pesticides has declined in the industrialised world over recent decades, their ability to accumulate and concentrate in biological systems remains a source of concern. Their residues can remain in human tissue for long periods. A recent study [9] has shown that one of the breakdown

products of DDT, known as p,p'-DDE, is an especially effective anti-androgen. Some studies have linked DDE with lactation failure in mothers and breast cancer.

POLYCHLORINATED BIPHENYLS

Despite decreasing use and bans on the production of PCBs, large quantities have been dispersed into the environment. Studies have indicated a number of ways in which PCBs can interfere with the human hormone system and may be linked to breast cancer. However, conclusive evidence has been difficult to achieve because of the large number of varieties (congeners) of PCBs and the probability that effects vary between each. Two major accidents involving PCBs in the Far East produced abortions and low birth weight in surviving children.

DIOXINS

This family of substances known as PCDDs (dioxins) and PCDFs (furans) are not commercial products but arise from incineration and as waste products from industry. Though the volume produced is very low the toxicity is extremely high. Human exposure is usually via food, especially meat, milk and fish. Dioxins have been shown to operate as anti-oestrogen and to have an adverse effect even at very low levels on the sexual behaviour and sperm production of rats. Another study has linked dioxins with endometriosis (abnormal growth of uterine tissue) in monkeys.

ALKYLPHENOL POLYETHOXYLATES (APES)

These are chemicals introduced into the UK in the 1940s and used extensively in cleaning
products, paints, herbicides and other industries. Whilst there has been special concern about the pollution of rivers from the discharges of these chemicals by industry because of their toxicity to aquatic life, human exposure also exists via other routes such as cosmetics.

Data on the potential health effects on humans is sparse; the main areas of concern arise from the possible intake via drinking water or by eating contaminated fish. APEs are known to have weak oestrogenic properties but may cause symptoms by working with other pollutants in the environment.

OTHER XENOESTROGENS

Herbicides atrazine and simazine: though neither of these chemicals has shown especially strong oestrogenic activity in studies, atrazine has been linked to breast cancer. Government studies have detected concentrations in sea water samples around the UK, the highest being around the Humber and Mersey estuaries.

Fungicide vinclozolin: Kelce [10] demonstrated that this chemical had effective anti-androgen properties on rats causing hypospadias, cleft phallus and other symptoms. It was concluded that similar effects could occur in the human fetus.

Phthalates: The phthalate DEHP is known to be toxic and to cause cancer in animals and may well be a hazard to humans because of its use as a plasticiser in medical and food packages and subsequent leaching out into the product [11]. Occupational exposure to high levels of phthalates has been shown to cause miscarriages in Russian workers [12].

RELATIVE LEVELS OF OESTROGEN INTAKE

The problem of assessing exposure to oestrogenic substances is compounded by the several factors such as the potential for accumulation and persistence versus the speed of degradation; the uptake of man-made chemicals in the environment has to be balanced against levels found naturally in foods or administered as drugs.

CONCLUSIONSIt is generally accepted that there is strong evidence for adverse trends in the incidence of breast cancer in women and testicular cancer and falling sperm count in men. This decline corresponds with the increased exposure of humans, especially in the developed world to hormonal substances in medicine, oral contraceptives and the environment at large. Whilst the picture is very difficult to interpret at the moment because of the number of chemicals and their various properties and routes into the human body, the probability is that more substances will be identified as having these oestrogenic properties.

There is an urgent need to take action to reduce the levels of exposure in order to protect public health. This can most effectively be done by introducing a ban on the production and disposal of those chemicals that are implicated in damage to the hormone systems of humans and animals. We believe that action by the Government is required to introduce such a ban and we can point to countries such as Switzerland where preventative action has already been taken.

REFERENCES

[1] J. Augur et al. (1995) Decline in semen quality among fertile men in Paris during the past 20 years. New Engl. J. Med., 332, 281-285

[2] E. Carlsen et al. (1992) Evidence for decreasing quality of semen during past 50 years. Brit. Med. J., 305, 609-613

[3] John Radcliffe Hospital Cryptorchidism Study Group (1992) Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. Arch. Dis. Childhood, 67, 892-899

[4] WHO (1991) Congenital Malformations Worldwide: A Report from the International
Clearinghouse for Birth Defects Monitoring Systems, Oxford, Elsevier, pp.113-118

[5] On the State of The Public Health (1992) The Annual Report of the Chief Medical Officer of the Department of Health for the year 1993, London, HMSO

[6] T. Hakulinen et al., (1986) Trends in cancer incidence in the Nordic countries. A
collaborative study of the five Nordic Cancer Registries. Acta Pathologica Microbiologica
Immunologica Scandinavia 94 (Section A), Suppl. 288, 1-151

[7] E.Feuer & L-P Wun (1992) How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilisation? Am. J.Epidemiol., 136, 142301436

[8] WHO (1995) Research in the menopause in the 1990s (Technical Report Series), Geneva, World Health Organisation

[9] W.R.Kelce et al. (1995) Persistent DDT metabolite p,p' DDE is a potent androgen receptor antagonist. Nature, 375, 581-585

[10] W.R.Kelce et al. (1994) Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by anti-androgenic metabolites. Toxicol. Appl. Pharmacol., 126, 276-285

[11] B.J.Davis et al. (1994) Di-(2-ethylhexyl) phthalate supresses estradiol and ovulation in cycling rats. Toxicol. Appl. Pharmacol., 128, 216-223

[12] M.V. Aldyreva et al. (1975) The influence of phthalate plasticizers on the generative function. Gi. Trud. prof. Zool., 12, 25-29

OTHER READING

Warhurst, A.M. (1995) An environmental assessment of alkylphenol ethoxylates and alkylphenol., Edinburgh, Friends of the Earth

Medical Research Council, Institute for Environment and Health (1995) IEH assessment on Environmental Oestrogens: Consequences to Human Health and Wildlife, IEH

July 1995

Published by Friends of the Earth Ltd
26-28 Underwood Street
London N1 7JQ
020 7490 1555

Printed on 100% recycled paper