The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.
Introduction: Triphenyl phosphate is used as an antioxidant, corrosion inhibitor, antiwear additive, and stabilizer in the polymer industry. It was selected for evaluation as a sensitizing agent for allergic contact hypersensitivity in mice.
Design: Triphenyl phosphate was obtained from Aldrich Chemical Company, Inc. (Milwaukee, WI) as a white granular solid (99+%) and was prepared in acetone which also served as the vehicle. No concentration tested demonstrated significant irritation. In the hypersensitivity study mice were divided into 11 treatment groups of 8 mice/group as shown in Table 1. The mice were sensitized dermally to either 0, 1.0, 3.0, or 10% solutions of TPP daily for five consecutive days and challenged 7 days later with a 30% solution. A 0.5% solution of 1-fluoro-2,4-dinitrobenzene (DNFB, Sigma Chem. Corp.; 99.6%. and 98.6% pure as determined by HPLC), was used as challenge dose for a positive control. Site preparation included intradermal injection of Freund's complete adjuvant in some mice. Irritancy responses were determined by monitoring the extravasation of 125I bovine serum albumin into the treated area. Allergic contact hypersensitivity responses were determined by the mouse ear swelling test (MEST) and a modification of the local lymph node assay (MLLNA).
|2 (8)||Baseline Control||+||Vehicle||30% TPP|
|3 (8)||Experimental||+||1.0% TPP||30% TPP|
|4 (8)||Experimental||+||3.0% TPP||30% TPP|
|5 (8)||Experimental||+||10% TPP||30% TPP|
|6 (8)||DNFB Positive Control||-||0.25% DNFB||0.5% DNFB|
|7 (8)||DNFB Baseline Control||-||Vehicle||0.5% DNFB|
|8 (8)||Baseline Contol||-||Vehicle||30% TPP|
|9 (8)||Experimental||-||1.0% TPP||30% TPP|
|10 (8)||Experimental||-||3.0% TPP||30% TPP|
|11 (8)||Experimental||-||10% TPP||30% TPP|
|Abbreviations: TPP = Triphenyl phosphate; FCA = Freund's complete adjuvant; DNFB = 1-fluoro-2,4-dinitrobenzene|
Results: There were no treatment related effects on survival or body weights. A statistically significant, dose dependent allergic contact hypersensitivity response was demonstrated in mice pretreated with complete Freund's adjuvant, and assayed by MEST and MLLNA on the second day following challenge. Two concentrations tested (3.0 and 10%) caused a significant positive response in the MEST. Only the 10% concentration caused a significant response in the MLLNA. The positive control group (6) produced a statistically significant contact hypersensitivity response at a sensitizing concentration Of 0.25% and challenge concentration of 0.5% DNFB.
Conclusion: A significant and dose-dependent allergic contact hypersensitivity response could be demonstrated in B6C3F1 female mice to triphenyl phosphate.
Report Date: June 1992