Evaluation of the sensitization potential of two lubricant additives, phenyl-alpha-naphthylamine and alkylated phenyl-alpha-naphthylamine: a comparison of data from the local lymph node assay, the buehler guinea pig assay, and human repeat insult patch test.
Azadi S; Meade J; Kashon ML; Bailey PT; Mann CL
Toxicologist 2003 Mar; 72(S-1):229
Phenyl-alpha-naphthylamine (PAN) and alkylated phenyl-alpha-naphthylamine (APAN), two high temperature anti-oxidants commonly used in aviation turbine lubricants have been widely used for many years with relatively few associated cases of contact allergy reported. In these studies PAN and APAN were evaluated for sensitization potential and potency using the local lymph node assay (LLNA), and these results were compared with data previously generated using a modified Buehler guinea pig test and the human repeated insult patch test (HRIPT). Chemicals were tested using female CBA mice at concentrations raging from 1-100%. Both chemicals tested positive in the LLNA inducing dose responsive and statistically significant increases in lymph node cell proliferation reaching a stimulation index (SI) greater than or equal to 3. A series of non-linear regression models were applied to the data and the model which fit the data best based on likelihood ratio tests was subsequently utilized in a bootstrap analysis to obtain an uncertainty distribution around the calculated EC3 (the chemical concentration required to induce a SI of 3). Based on this analysis, the mean EC3 values and 90 % confidence bounds were 2.29% (0.01%, 6.4%) and 11.76% (4.4%, 24.6%) respectively for PAN and APAN. This data correlated positively with the guinea pig data where induction and challenge with equal concentrations of chemicals resulted in a greater percentage of animals responding and higher severity indices for PAN versus APAN. The LLNA data also correlated positively with the human data where HRIPT showed that use levels of both PAN and APAN failed to induce sensitization when applied in lubricants at concentrations of 1.5% and 2.5%, respectively, levels lower than their calculated EC3 values.
Sensitization; Lubricants; Phenyl-compounds; Lymph-nodes; Antioxidants; Animal-studies; Animals; Laboratory-animals
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah