Mixture effects of JP-8 additives on the dermal disposition of jet fuel components

Citation
Re. Baynes et al., Mixture effects of JP-8 additives on the dermal disposition of jet fuel components, TOX APPL PH, 175(3), 2001, pp. 269-281
Citations number
42
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN journal
0041008X → ACNP
Volume
175
Issue
3
Year of publication
2001
Pages
269 - 281
Database
ISI
SICI code
0041-008X(20010915)175:3<269:MEOJAO>2.0.ZU;2-7
Abstract
Aliphatic and aromatic components in formulated jet fuels can cause occupat ional dermatitis. However, the influence of JP-8 performance additives (DIE GME, 8Q21, and Stadis450) on the dermal disposition of fuel components is n ot well understood. These additives are formulated with commercial Jet-A to form military JP-8 fuel. The purpose of this study is to assess the influe nce of these additives on the dermal disposition of marker aromatic and ali phatic components, naphthalene and dodecane, respectively. Porcine skin sec tions in an in vitro system were used to characterize chemical-biological i nteractions that modulate diffusion of jet fuel components and isolated per fused porcine skin Raps (IPPSFs) were used to evaluate diffusion in a viabl e skin model with an intact microvasculature. In these 5-h studies, Jet-A, Jet-A + DIEGME, Jet-A + 8Q21, and Jet-A + Stadis450, Jet-A + DIEGME + 8Q21, Jet-A + DIEGME + Stadis450, Jet-A + 8Q21 + Stadis450, and JP-8 mixtures we re tested. In general, naphthalene absorption (0.76-2.39% dose) was greater than dodecane absorption (0.10-0.84% dose), while the IPPSFs alone demonst rated that dodecane absorption was significantly greater in JP-8 than in Je t-A. Synergistic interactions with 8Q21 + Stadis450 appear to enhance syste mic absorption of either naphthalene or dodecane, while DIEGME + Stadis450 increased naphthalene (1.88% dose) and dodecane (2.02% dose) penetration in to the skin and fat tissues of IPPSFs. These findings were supported by the fact that 8Q21 + Stadis450 significantly increased dodecane flux and perme ability in porcine skin sections, but 8Q21 alone reduced marker diffusion i n both membrane systems. Furthermore, dodecane is more likely than naphthal ene to remain in the stratum corneum and skin surface at 5 h, and DIEGME mi xtures played a significant role in skin and surface retention of both mark ers. In summary, the data suggest that various combinations of these three performance additives in JP-8 can potentially alter the dermal disposition of aromatic and aliphatic fuel components in skin. More importantly, produc ts of two-factor interactions were not predictable from single-factor expos ures and, by extension, cannot be extrapolated to three-factor interactions . (C) 2001 Academic Press.