In this large, nationally representative sample, we investigated the relationship between EDCs and atopy. We hypothesized that environmental exposure to EDCs would be associated with allergic disease. We were further interested in determining if the relationship between EDCs and allergic outcomes was dependent on the antimicrobial properties of EDCs. Of the EDCs examined, only urinary levels of triclosan and propyl and butyl paraben were significantly associated with aeroallergen and/or food sensitization. Interestingly, these compounds all have antimicrobial properties and are commonly used in personal care products and/or foods specifically for their ability to inhibit microbial growth. This raises the possibility that the mechanism by which triclosan and propyl and butyl paraben are associated with allergic sensitization may be via their antimicrobial effects rather than their EDC activity.
Several epidemiologic studies have demonstrated associations between bacterial flora and allergic disease in cross sectional and prospective studies. The presence of specific organisms24–26, 34
as well as diversity of microflora27, 35
are thought to be relevant in the relationship between allergic disease and the human microbiome. Our data adds to previous studies in that it links use of antimicrobial products to allergic outcomes.
In our study, the increased risk of sensitization was most pronounced for males for all associations identified and for triclosan, there was a statistically significant interaction between triclosan exposure and gender on the risk of food sensitization. It is well known that allergic disease is more prevalent in males31
although the mechanistic basis for this is largely unexplained. Because males are at higher risk for allergic disease in general, one potential explanation is that they may be more susceptible to the effects of a second risk factor such as antimicrobial exposure, and this may lend to the observed interaction.
We did not identify a significant association between the EDCs studied and a history of atopic asthma, wheeze, or total IgE level. For triclosan, increasing urinary concentrations were associated with an increased risk of atopic asthma and atopic wheeze, but this did not meet criteria for statistical significance. Our definition of asthma and wheeze was based on self-report rather than objective evidence, and may have resulted in misclassification of the outcome. Interestingly, we did identify a significant protective effect of methyl paraben on the risk of non-atopic asthma and wheeze. Given that methyl paraben has antimicrobial properties this is consistent with an infectious trigger for these non-atopic respiratory conditions. However the effects of methyl paraben on common viral asthma triggers has not been studied, and therefore this mechanism of protection is speculative. Total IgE and allergen sensitization may have different relationships with clinical outcomes and different determinants. For example, total IgE levels are only associated with asthma among atopic subjects36
. Here, although we found a relationship between triclosan and propyl and butyl paraben and specific sensitization, we did not find it with total IgE, indicating that the mechanism of the association between the antimicrobial EDCs and sensitization is not related to regulation of IgE itself
Our study has several limitations. The primary limitation is that our data is drawn from a cross-sectional study. In order to provide evidence that antimicrobials such as triclosan and parabens have a causal role in allergic sensitization, prospective studies documenting that exposure to these antimicrobials precedes allergic sensitization are necessary. However, our data is from a nationally representative population based study, which lends strength to our findings. Our cross sectional design is also limited by the possibility of reverse causation, in that subjects with allergy may use more products containing triclosan and parabens. Further, our use of allergen sensitization as an outcome was limited by lack of clinical correlation of allergic disease. We attempted to overcome this by use of validated specific IgE cutpoints for clinically significant food allergy, and showed that the likelihood of clinical food allergy increased with increasing exposure to triclosan. Finally, we used urinary EDC levels as biomarkers of exposure, which has been validated for milk and serum levels of triclosan37
, but validation studies for urinary triclosan as well as the other EDCs have not been reported. While urinary levels are generally assumed to correlate with exposure38
, urinary biomarkers of EDCs may not necessarily reflect actual exposure. Nevertheless, misclassification bias arising from use of urinary EDC as a biomarker for exposure would be expected to be non-differential and would not result in marked positive or negative bias.
In summary, we identified a significant concentration- dependent association between exposure to the commonly used antimicrobials triclosan and parabens and aeroallergen and food sensitization in a representative US population. Because these compounds are found in personal care products such as toothpaste and mouthwash and/or are commonly used as preservatives in foods, drugs, and cosmetics, they are frequently encountered in daily life in Western society. While triclosan has previously been associated with a history of allergic rhinitis16
, this is the first report of an association of food sensitization and likely food allergy with triclosan, and of an association with triclosan and parabens and aeroallergen sensitization. Our data suggest that the effects of these compounds on allergic sensitization may be due to their antimicrobial properties, rather than their endocrine disrupting effects. Future studies will need to examine directly the effects of these antimicrobial EDCs on skin, oral, and gut flora and to determine the temporal relationship between exposure to these compounds and the development of allergic sensitization and manifestations of allergic disease including asthma. The potential role of these compounds in the allergy epidemic warrants further study.