Evaluation of percutaneous penetration of natural rubber latex proteins.

Latex allergy is recognized worldwide as a serious health risk. To date, exposure assessment and intervention strategies have focused primarily on respiratory protection; this work evaluates the potential role of dermal protein penetration in the development of latex allergy. In vitro penetration models using flow-through diffusion cells and both human surgical specimens and hairless guinea pig skin (CrL: IAF/HA) demonstrated iodinated latex proteins (ammoniated and non-ammoniated) penetrating into and through both intact and abraded skin. Although less than 1% penetration was observed with intact skin, up to 23% of latex proteins applied to abraded skin were recovered from receptor fluid within 24 h of exposure. Phosphoimaging of the concentrated effluent revealed proteins ranging in size from 3 to 26 kDa. Using a (3)H(2)O penetration assay to evaluate barrier integrity, the amount of latex protein penetration was found to positively correlate with the degree of dermabrasion. Immunohistochemistry of the skin localized latex proteins in the Langerhans cell-rich epidermis and in the dermis. Both in vitro penetration studies and immunohistochemistry supported the use of hairless guinea pig skin as a surrogate for human skin in evaluating latex protein penetration. In studies performed in vivo, 35% of hairless guinea pigs topically exposed to latex proteins (100 microg) 5 days per week for 3 months demonstrated elevations in latex-specific IgG1. The implication for these data is that the skin is not only a plausible route for latex sensitization but can be a major exposure route when the integument has been compromised.

Contact sensitivity to selected acrylate compounds in B6C3F1 mice: relative potency, cross reactivity, and comparison of test methods.

Given the increasing prevalence of occupational sensitization to acrylate compounds, n-butyl acrylate (BAC), ethyl acrylate (EAC), and trimethylol propane triacrylate (TMT) were recommended by the National Toxicology Program for hypersensitivity testing in female B6C3F1 mice. The objectives of these studies were to determine the irritating and sensitizing potential of these three compounds using an irritation assay, the murine Local Lymph Node Assay (LLNA), and the Mouse Ear Swelling Test (MEST). The minimal irritating concentration for TMT was determined to be 1.0%, whereas BAC and EAC demonstrated no irritation up to 30%, the highest concentration tested. TMT tested positive in the LLNA at concentrations as low as 0.1% whereas an induction concentration of 0.3% was required to elicit a positive response in the MEST. Furthermore, BAC tested negative in the MEST at induction concentrations as high as 30%, but yielded positive results in the LLNA at concentrations as low as 20%. EAC, at all concentrations tested, was negative in both the MEST and the LLNA. Cross reactivity was only seen when mice were sensitized with TMT and challenged with BAC. In these studies, the LLNA was a more sensitive indicator of the allergic potential of these three acrylates when compared to the MEST.

Contact hypersensitivity to dicyclohexylcarbodiimide and diisopropylcarbodiimide in female B6C3F1 mice.

Dicyclohexylcarbodiimide (DCC) and diisopropylcarbodiimide (DIC) are two commonly used coupling reagents in protein synthesis resulting in exposure of individuals in chemical and pharmaceutical industries as well as research laboratories involved in protein synthesis and recombinant DNA techniques. The objectives of these studies were to determine the irritation and sensitizing potential of these two compounds when applied topically to B6C3F1 mice. Sensitization potential was assessed by the Mouse Ear Swelling Test (MEST) and the murine Local Lymph Node Assay (LLNA). Concentrations used in the contact hypersensitivity assays were determined by primary irritancy studies. DCC and DIC were identified as both irritants and contact sensitizers with the MEST being a more sensitive indicator of sensitization potential. The MEST identified DCC as a sensitizer at concentrations as low as 0.006% (w/v) 24 hr and 48 hr post challenge and DIC at 0.3% (w/v) and 1.5% (w/v) 24 and 48 hr post challenge, respectively. In the LLNA, the lowest concentrations yielding a significant response were 0.06% (w/v) for DCC and 10% (w/v) for DIC.