Parabens: endocrine disruptors in cosmetics and food?June 17, 2013 at 8:40 am | Posted in H&E Features | 4 Comments
Tags: chemicals, cosmetics, environment, health, parabens, science
Parabens are esters of p-hydroxybenzoic acid and are widely used as preservatives in cosmetics. They have appeared in the news because of concern about their endocrine-disrupting potential, in particular their ability to mimic oestrogen, with a study in 2012 finding parabens in almost 100% of breast samples from breast cancer patients (Barr et al. 2012, which attracted coverage in the UK Daily Mail).
However, people may be less aware of the use of parabens in foodstuffs, identifiable on labelling as additives E214-219. The most commonly-used parabens in food are methylparaben (food additive E218) and ethylparaben (E214) with the European Food Safety Authority setting in 2004 an Acceptable Daily Intake (ADI) of a sum total of 0-10mg/kg bodyweight per day for methyl- (E218) and ethylparaben (E214).
Methyl-, ethyl-, propyl- and butylparaben are all used in cosmetics, though methyl- and ethyl-paraben are the most commonly detected in cosmetic samples. Methyl- and propylparaben are the most commonly-detected parabens in biological samples, according to Dr Philippa Darbre, a researcher at the University of Reading.
For propylparaben (E216) there was uncertainty about what would constitute a safe dose, the problem being that propylparaben had effects on juvenile rat sperm production even at relatively low concentrations (EFSA 2004). The same was true for butylparaben. As such, EFSA was unable to set an ADI for either butyl- or propylparaben, though the Scientific Panel stated that it believed the additives were used in such small quantities (butylparaben not even being an approved food additive) that it was unlikely the general public would be at risk from exposure.
In spite of wide use, information on the occurrence of parabens in foodstuffs and dietary exposure of humans to these chemicals is not generally available, possibly due to the historical assumption (prior to concerns emerging about endocrine disruption) that these compounds exhibit low toxicity and are therefore of low priority for research as potential environmental toxicants.
As a result, the first study reporting the occurrence of parabens in foodstuffs was only published this year, based on samples of foodstuffs bought in the US (Liao et al. 2013). In this study, 267 US food samples comprising of drinks, dairy products, fats and oils, fish and shellfish, grains, meat, fruits, and vegetables were analysed for five parabens: methyl-, ethyl-, propyl-, butyl- and benzylparaben.
Over 90% of the food samples contained measurable concentrations of parabens. Methyl-, ethyl-, and propylparaben were the predominant compounds, accounting for ∼90% of the total concentrations (possibly because these are the standard food additives, with methyl- and ethylparaben being the most commonly-used according to EFSA; butyl- and benzylparaben are not permitted food additives in the EU). Butyl- and benzyl-parabens were less frequently detected. There were no significant differences in paraben concentrations among the eight food categories, including the canned foods.
On the basis of the concentrations measured and how much of each type of food an individual would be excepted to consume in a day, the researchers estimated the daily intake of parabens through diet, determining that infants were likely to consume 940 ng of parabens per kilo of body weight per day, toddlers 879, children 470, teenagers 273 and adults 307.
As one would expect from dietary exposure, the highest doses go to the youngest members of society, who are also likely to be at greatest risk from the effects of exposure to potential endocrine-disrupting chemicals.
What we do not learn, however, from exposure measurements is how much of this quantity of paraben gets into the body intact, making it very difficult to predict actual exposure to these chemicals. Parabens entering by the mouth pass through the liver where enzyme activity (specifically, esterase) breaks the alkyl group off the paraben molecule, converting it to the parent molecule p-hydroxybenzoic acid which is readily excreted.
The extent to which esterase activity converts parabens to p-hydroxybenzoic acid is therefore crucial for anticipating the likely toxic effect of paraben exposure, the thinking being that low oral doses will be fully metabolised by the body and pose little toxic threat.
It is possible to overload the oral route, as shown in a study finding that paraben consumption gives rise to reproductive issues in neonatally-exposed male rodents (e.g. Oishi 2002). This gives cause for concern about dietary exposure to parabens. Of greater concern, however, are cosmetics, as the evidence indicates esterase activity is much more readily overloaded in the skin than it is in the liver.
Several in vitro studies have shown that parabens readily cross animal skin (e.g. Pedersen et al. 2007). Human studies indicate that parabens can accumulate in the stratum corneum (the protective, outermost layer of the skin) over the period of a month and that paraben levels in the body increase after the topical application of creams containing parabens, and that different cosmetic formulations influence dermal uptake of parabens as well (see Darbre & Harvey 2008 for a comprehensive review).
The presence in urine of intact paraben esters (e.g. Calafat et al. 2010) is proof that that parabens make it past metabolism by one route or another. Given the efficiency of liver esterase activity, it is more likely that paraben exposure is dermal; however, dietary feeding studies which trace parabens into blood and urine are needed to confirm this. That way, we will have a much better sense of how much exposure there is to parabens esters via diet as opposed to cosmetics.
This is important because we need to know if diet and cosmetic exposures are combining to produce unsafe exposure to parabens: while cosmetic or food exposures taken individually may give no cause for concern (leaving to one side for now any discussion of whether there is such a thing as a safe exposure level for endocrine disruptors), total combined exposure is something which needs to be accounted for in assessing the safety of these compounds for use in consumer goods.
How to get rid of parabens from cosmetics
Preservatives such as parabens are used in cosmetics to prevent the growth of microorganisms. Microbial contamination of personal care products can spoil the smell and appearance of a product and spread infections to the user. Since bacteria and fungi are always present on the skin, a major source of cosmetic contamination is the user themselves.
Parabens can be eliminated from cosmetic formulations using two strategies:
- Changes in formulation, processes and packaging, so that no preservatives are needed
- Chemical solutions, using other preservatives than parabens
Sterisol is a Swedish company specialising in preservative-free personal care products, made possible in part by their packaging processes and technology which prevents the contents of care product dispensers becoming contaminated in the course of use. Sodium benzoate, dehydroacetic acid, benzoic acid and potassium sorbate are in use as alternative preservatives to parabens.
4-hydroxybenzoic acid is a popular antioxidant food additive partly because of its low acute toxicity. It is supposedly found naturally in a number of foodstuffs and drinks, including wine and some fruits.
Some websites say “a type of paraben” is found “naturally” in some fruits such as blueberries. If this means an actual paraben ester this is difficult to verify as the samples may have been contaminated by packaging or use of parabens on the fruit as a preservative spray; it is straightforwardly misleading if the reference is to the parent molecule 4-hydroxybenzoic acid.
To make a paraben, the hydrogen atom (R in the diagram below) on the carboxyl (-COOH) group of the 4-hydroxybenzoic acid molecule is replaced with an alkyl group. In general, the larger the alkyl group, the more estrogenic the paraben – at least from methyl- through to butylparaben.
Length is in this order: methyl (1 carbon atoms in the tail), ethyl (2 carbons in the tail), propyl (3 carbons), butyl (4 carbons), heptyl (7-C). Benzylparaben has a 6-carbon benzene ring at R instead of an alkyl group.
The most commonly-used parabens are methylparaben (food additive E218) and ethylparaben (E214). Propylparaben can no longer be used in food in the EU due to withdrawal of its ADI. Methyl-, ethyl-, propyl- and butylparaben are all used in cosmetics. Methyl- and propylparaben are the most commonly detected in tissue and urine samples.
All four of these parabens are characterised as Category 1 endocrine disruptors by the European Commission in its database of potential endocrine disruptors (meaning there is evidence of ED activity in at least one species using intact animals).
With thanks to Philippa Darbre for input. Mistakes are the author’s.