An assessment of the ability of phthalates to influence immune and allergic responses.
It has been suggested that one possible contributor to the increasing prevalence of atopic (IgE-mediated) allergic diseases and asthma in Europe and the US is exposure to chemicals that may act as adjuvants. Certain commonly used phthalate plasticisers, such as di-(2-ethylhexyl) phthalate, have been implicated in this regard. The evidence for the ability of phthalates to impact on immune and allergic responses has been examined, encompassing epidemiological investigations and results deriving from studies using experimental animals and from analyses in vitro. The epidemiological data provide some evidence that exposure to phthalates may be associated with increased risk of development of allergies and asthma, however, the lack of objective exposure information limits the interpretation. A variety of studies have been performed in mice to examine the influence of phthalate (delivered via various routes of exposure) to impact on immune responses. Measurement of antibody responses is the commonest read out, although other parameters of inflammation such as eosinophil infiltration and cytokine production have been used also. Although certain phthalates, when delivered at appropriate doses, and via an appropriate route, have been reported to impact on immune and inflammatory function in rodents, as yet no consistent pattern has emerged. Results ranged from potentiation of immune or inflammatory responses, to the absence of any effect, to inhibitory or immunosuppressive activity. In addition, comparatively low doses of phthalates have been associated with immune effects only when routes of administration (subcutaneous or intraperitoneal) are used that do not reflect, and are much less relevant for, opportunities for human contact with phthalates. There is clearly a case to be made for the design of more definitive animal studies that will allow development of a more detailed understanding of whether and to what extent, and under what conditions, phthalates are able to effect meaningful changes in immune function that may in turn impact on human health.
Kimber
Ian
I
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK. ian.kimber@manchester.ac.uk <ian.kimber@manchester.ac.uk>
Dearman
Rebecca J
RJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007274:Injections, Intraperitoneal; D051379:Mice; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D010795:Phthalic Acids; D010968:Plasticizers; C032279:phthalic acid