PARABENS ARE OESTROGENIC IN FISH?
This is the third in a series of articles in each of which I will focus on one specific study that has contributed to the current concerns over the use of parabens in cosmetics. If you have not already done so, it may be useful for you to read – Parabens in Perspective: Introductory, Part I and Part II that posted earlier, before reading this one.
The paper I will critique in this article is:
The preservatives ethyl-, propyl- and butylparaben are oestrogenic in an in vivo fish assay
Pedersen K .L., Pedersen S. N., Christiansen L.B., Korsgaard B., Bjerregaard P., – Pharm & Tox 86, 110-113 (2000)
This study consisted of the dosing of fish with the aforementioned parabens and, additionally, the breakdown product common to all parabens – p-hydroxybenzoic acid. The oestrogenic activity was then measured using detection of a specific yolk protein (vitellogenin). Two doses were applied by intraperitoneal injection – on day 0, and day 6 of the study.
The conclusions of this study were that the parabens tested “were shown to be oestrogenic in vivo while the metabolite [p-hydroxybenzoic acid] known to result from hydrolysis did not show any activity in the present test system. Oestrogenicity and toxicity both occurred in a dose interval between 100 and 300mg/kg”.
The authors’ stated aim was “to demonstrate the intrinsic oestrogenicity of the parabens as an inherent molecular property of these compounds . . . . . not to investigate the oestrogenicity in fish per se”. However, despite the real aim of the study, anyone reading the title will make the assumption that parabens are oestrogenic in fish. They will then extrapolate this to humans. What is needed is to look at the study and the results a little more closely.
Butylparaben had a weak oestrogenic effect at a dose of 50mg/kg; this effect was more marked at 100mg/kg
Propylparaben was not tested at 50mg/kg, but a dose of 100mg/kg produced a weak response; a dose of 300mg/kg provoked “a pronounced oestrogenic response”.
Ethylparaben produced only a weak oestrogenic response at 300mg/kg
p-hydroxybenzoic acid demonstrated no oestrogenic activity in this study.
Methylparaben was not tested, as the authors deemed it unlikely to elicit any oestrogenic response.
The problem with figures like 50mg/kg, 100mg/kg, etc is that they are fairly meaningless in isolation. It is far better to place them in some sort of context. The figures here refer to the dose applied to the fish – by injecting them with the dose. As far as I know, fish are not noted for their ability to handle a hypodermic syringe, so they would not normally be exposed to parabens in this manner, and nor would they be exposed to these concentrations. For comparison, a study that determined the environmental concentrations of parabens [Lee et al, J Chromatogr. A 1094 (2005) 122-129] found levels of around 2 parts per trillion (that’s 0.0000000002%!) in the inflow to a sewage treatment plant. The outflow showed less than 0.04 parts per trillion (0.000000000004%!). 50mg/kg = 0.005% – a factor of around 1 trillion times higher than would be expected in the environment after passing through a sewage works! How could fish be exposed to concentrations of similar magnitude to those tested in this study? Clearly, leaving to one side the possibility of a spillage during production or transportation of the parabens, only an accidental spillage of a cosmetic product could do this. But to achieve these levels of parabens in an environmental situation would require the accidental spillage of 250 tonnes of a product containing 0.3% parabens in the volume of an Olympic-sized swimming pool. What this suggests is that parabens are NOT responsible when there are claims that environmental xenoestrogens are changing the sex of fish, despite the title of this study.
Whilst the authors may have intended only to test the sensitivity of their method as an academic exercise, they failed to consider the possible consequences of publication of the results. This is a common issue with academic research – the researchers are often only interested in the results for the results’ sake. They do not feel the need to put the results in any real context.
This study is taken out of context on two levels:
1) The concentrations of parabens tested are around 1 trillion times higher than typical environmental concentrations
2) There is rarely good correlation in the toxicological response between test species and humans
The bottom line for this study is that it is relatively meaningless outside of the narrow intentions of the authors. It does not prove that parabens are unsafe for use in cosmetics, but it DOES prove that environmental concentrations of parabens do not contribute any significant threat to the environment in terms of adding to the xenoestrogen burden, with a safety factor of around one trillion!
For completeness, I will report that this research group (based at the University of Southern Denmark, Odense) have also carried out other studies on parabens, using oral administration, which is far more relevant than intraperitoneal injection. It is less simple to interpret the results because the dose was given in both the food and the water, and at different concentrations. However, the results were:
In the water, 225 micrograms/litre (= 0.000225%, or 225 parts per trillion) showed some oestrogenic activity, but 50 micrograms/litre showed none. Bear in mind that only these two concentrations were tested, and there is a large gap between 50 and 225, so the “no effect” concentration may be almost anywhere between these two points but, taking 50 micrograms/litre as the worst case, this is still 1250 times higher than the environmental concentrations found by Lee et al.
This was a separate study, and the concentrations differed slightly from those used for propylparaben, but a dose of 201 micrograms/litre gave a weak oestrogenic response. Therefore, a similar conclusion may be drawn as for propylparaben – environmental concentrations are unlikely to pose an oestrogenic threat to fish. Additionally, and importantly, there was no evidence of bioaccumulation in the fish in either of these oral studies.