The Health Controversies of Parabens

Mark G. Kirchhof, MD, PhD; Gillian C. de Gannes, MD, MSc, FRCPC


Skin Therapy Letter. 2013;18(2) 

In This Article

Toxicity and Adverse Effects of Parabens

Human and animal studies have failed to show that parabens have any acute toxicity by various routes of administration. As such, many of the studies examining paraben toxicity have focused on the long-term effects of chronic exposure.

The estrogenic activity of parabens was first identified in 1998 and has since been validated in vitro and in vivo.[1,29,30] Parabens bind human estrogen receptors, although with affinities 10,000 to 1,000,000 times less than estradiol.[29,31] Butylparaben and propylparaben have higher estrogenic activity than methylparaben or ethylparaben, but butylparaben and propylparaben are detected at concentrations 10 to 1000 times less than methylparaben in humans.[32] The estrogenic effects in vivo have been demonstrated by uterotrophic (uterine growth) assays in mice and rats.[1,33] However, this effect did not prevent implantation of a fertilized egg, which is considered the most sensitive measure of estrogen toxicity.[33,34] As mentioned, it has been hypothesized that the estrogenic activity of parabens may promote breast cancer development. The concentration of estradiol in normal human breast tissue is 55.3 pg/g, suggesting there is a safety margin of 10 to 1000 times for parabens to approximate normal estradiol activity.[1,25,32] The paraben breast cancer data shows no or low parabens in a subset of patients and there are no comparisons with normal controls.[2,25] Hence, having not established a clear correlation, it is difficult to put forth a causal relationship between parabens and breast cancer development.

Another major area of study has been the effect of parabens on the male reproductive system, but findings are conflicting.[35] One in vitro study found that human sperm were not viable when exposed to parabens at concentrations of 1 mg/mL.[36] In vivo studies in mice did not replicate this result, with no spermatotoxic effects at paraben concentrations of 1%.[37] Conflicting results have also been reported in rats, with one study showing decreased sperm number and activity while another study found no adverse reproductive effects.[35,38] In humans, men with fertility problems including low sperm count and decreased motility were assayed for paraben exposure by measuring urine paraben levels.[23] No correlation between sperm count or motility and parabens levels was found.

Parabens, as is the case for many preservatives, can be allergenic in a small subset of the population. This sensitization commonly manifests as an eczematous rash. The rates of reported sensitization to parabens range from 0.5% to 3.5%.[17] These rates of sensitization are amongst the lowest of all preservatives.[17,18] In addition, there are reports of immediate immunoglobulin Emediated allergic reactions to parabens resulting in urticaria and, in one case, bronchospasm.[39,40] However, these immediate allergic reactions are extremely rare.