Chemical study on estrogens

Abstract

General Natural estrogens are mainly formed in the ovary, during pregnancy in the placenta and in smaller quantities in the adrenal glands and testicles. Natural estrogens control the development of secondary female sex characteristics and together with the gestagens control almost all of the reproductive processes in women. Synthetic estrogens are used as a pharmaceutical product as an oral contraceptive and hormonal replacement therapy. In the USA synthetic estrogens are also used in veterinary the induce growth of animals. The most commonly used synthetic estrogen is 17a-ethinyloestradiol. A synthetic estrogen is in principle a more stable compound in order to fullfill a wanted effect, before the substance is degraded and metabolised. Sources and emissions Primary production of natural estrogens occurs in female mammalian animals and in female humans. Synthetic estrogens as 17ß-oestradiol and 17a-ethinyloestradiol are produced in the Netherlands, Germany and the USA but production volumes are largely unknown. The total emissions of endogenous estrogens by human beings and animals in the Netherlands can be estimated at approximately 50 kilograms per day. This figure is possibly an underestimate, since neither, other livestock - such as rabbits, ducks, sheep, goats, horses, etc - nor companion animals, were included. Emissions of ethinyl oestradiol ('the pill') are estimated at 43 grams per day. This may be an underestimate, in view of the fact that the progestagens that are also in the anticonception pill, may also be metabolised to steroid metabolites. In any case, this contribution is insignificant compared with the estimated total emissions of natural estrogens (50 kg/day). It should be noted that emissions from countries surrounding the Netherlands have not been taken into consideration. Assuming a leaching of 3% from applied manure to surface water and an average rainfall of 60 mm/month, the concentration in surface water, will be 1.3 ?g/l after application of the maximum allowed amount of manure of sows in 1 month and 0.43 ?g/l in 3 months in local waters. After application of manure of cows in the maximum allowed amount in 1 month, the concentration in surface water is 0.9 ?/l and in 3 months 0.3 ?g/l in local waters. Estimated concentrations in regional waters range from 19-76 ng/l for the river Rhine and from 35-140 ng/l for the river Meuse. Environmental characteristics and toxicity in aquatic systems All oestradiols, oestrone and ethinyloestradiol have a low vapour pressure and a low water solubility. The log Kow varies from 3.13 for oestrone to 4.01 for both oestradiols. This indicates a moderate potential to bioaccumulate. There are no data on bioaccumulation. Occurrence and behaviour in aquatic systems There is no information on hydrolysis or photolysis. There are some differing results for biodegradation in STP in Germany and Brazil. The differences are probably due to the difference in temperature. Based on the limited data it can be concluded that oestradiols and oestrone are fairly rapidly degraded. Ethinyloestradiol seems to be more persistent. Under anaerobic conditions degradation is considerably lower. Concentrations in the Netherlands have only been measured in one study in 1997. Highest concentrations were measured in Lobith and Eijsden (upto 5.5 ng/l). In large surface waters and marine waters, dilution occurs and concentrations are hardly detectable. Concentrations in sewerage in The Netherlands are lower than in the surrounding countries (UK, Germany) There are very limited data on concentrations in food: milk of carying cows contains about 1 ?g estrogen/l. Toxicity Estrogens are (de)oxidated, hydrolysed and methylised in liver and conjugated with glucuronic acid or sulfate. 17ß-oestradiol is easily oxidised to oestrone, which is further metabolised to oestriol or 2-methoxy-oestrone. Ethinyloestradiol is metabolised to hydroxy-ethinyloestradiol and further metabolised to methoxyethinyloestradiol or deethinylated to oestrone. Estrogens are excreted in faeces and urine. All estrogens are suspected carcinogens. Data on acute toxicity indicate that estrogens are very toxic to mammalians. Toxicity data are scarce. Based on endocrine disrupting effects all estrogens are very toxic. Based on acute effects on survival and reproduction 17aethinyloestradiol is also very toxic to freshwater algae and crustaceans. Based on chronic effects on survival and reproduction 17ß-oestradiol, oestrone and 17a-ethinyloestradiol are only slightly toxic to marine crustaceans. There are no limit values derived for the estrogens. There is a iMPC derived for 17a-ethinylopestradiol of 1 ?g/l. Concentrations in surface water in the Netherlands do not exceed this iMPC. Policy There is hardly any policy on estrogens in relation to the environment. 17ß-Oestradiol, oestrone and 17-ethinyloestradiol are on the OSPAR list VI. However there are no actions to this group of substances, yet. There is, however, a ban on the use of estrogens as growth inducers in farm animals in Europe (88/146/EEC). In Canada and the USA estrogens are still used for this purpose. This ban on meat from farm animals treated with estrogens, has led to an discussion with Canada and the USA. Furthermore there is a regulation that estrogen may not be part of cosmetic products (76/768/EEC). There are also plans for a directive on assessing the risk of environmental exposure of veterinary products and a similar directive on medicines is launched as a draft. Conclusions and recommendations In general data on estrogens are very scarce. Data should be produced on behaviour, distribution, production and emission. Also, more data on acute and chronic toxicity should be produced. Furthermore there should be a guideline on how to treat effects on the endocrine system. Especially interesting is, how these endocrine effects influence the populations. Recommended is to conduct a study into the production volumes of estrogens and the concentrations of estrogens in groundwater, drinking water and food.