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Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin

Center for Cutaneous Toxicology and Residue Pharmacology, North Carolina State University, Raleigh, North Carolina 27606, nancy_monteiro{at}ncsu.edu

John P. Van Miller

Union Carbide Corporation, 39 Old Ridgebury Road, Danbury, Connecticut 06817

Glenn Simon

Rhodia Inc., 5171 Glenwood Avenue, Raleigh, North Carolina 27612

Ronald L. Joiner

General Electric Corporation, One Plastics Avenue, Pittsfield, Massachusetts 01201

James D. Brooks

Center for Cutaneous Toxicology and Residue Pharmacology, North Carolina State University, Raleigh, North Carolina 27606

Jim E. Riviere

Center for Cutaneous Toxicology and Residue Pharmacology, North Carolina State University, Raleigh, North Carolina 27606

The purpose of this study was to assess the percutaneous absorption of nonylphenol (NP) and the nonylphenol ethoxylates, NPE-4 and NPE-9, in human, porcine and rat skin. In vitro studies with the NPEs were conducted for 8 h in flowthrough diffusion cells using topical solutions of 0.1, 1.0 and 10% in PEG-400 or 1% in water (NPE-9 only). NP absorption was assessed as a 1% solution in PEG-400. All compounds were ¹⁴C ring-labeled and radioactivity in perfusate was monitored over time. Skin deposition was measured at the termination of the experiment. Absorption into perfusate and total penetration (compound absorbed plus compound sequestered in skin) were calculated. Absorption of NPE-4, NPE-9 and NP was similar across all species at less than 1% of the applied dose over 8 h. Penetration was generally below 5% of applied dose, the majority located in the stratum corneum. In all species and for both NPEs, the fraction of dose absorbed was highest for the lowest applied dose. Absorptions expressed as actual mass absorbed over 8 h were similar (approximately 0.3 µg/cm²) across all concentrations. Penetration, but not absorption, was greater from a water vehicle compared to a PEG-400 vehicle, particularly in rat skin. These studies suggest that NP, NPE-4 and NPE-9 were minimally absorbed across skin from all three species. Fractional absorption was concentration-dependent, making the actual absorbed flux constant across all doses.

Key Words: ethoxylated nonylphenol • nonylphenol ethoxylates • skin absorption

Toxicology and Industrial Health, Vol. 16, No. 2, 49-57 (2000)
DOI: 10.1177/074823370001600201


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