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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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.
Oleic acid diethanolamine, widely used in the chemical and pharmaceutical industries, is an intermediate in the production of emulsifiers, soaps, detergents, solubilizers, cosmetics, drugs, and textile-finishing agents. This compound was selected for evaluation as a sensitizing agent for contact hypersensitivity in mice because of the potential for wide-spread dermal exposure in humans.
Oleic acid diethanolamine was obtained from Onx Chemical Co (Lot #DA021) and was determined to be 90% pure by HPLC analysis, with 7.94% amine, presumed to be residual diethanolamine. The test compound was prepared in an acetone-olive oil (4:1) solution. In the primary irritancy studies concentrations up to 30% oleic acid diethanolamine did not produce evidence of irritation. Female B6C3F1 mice were sensitized dermally to either 0, 1.0%, 3.0%, or 10.0% solutions of the test compound daily for 5 consecutive days and challenged 7 days later with a 30% solution. Mice were divided into 10 treatment groups of 8 mice per group as shown in Table 1. 1-fluoro-2,4-dinitrobenzene (DNFB, Sigma Chemical Co.; Lot 88F-3833; > 99% pure as determined by HPLC) was used as a positive control at a concentration of 0.5%. Site preparation included dermabrasion as well as intradermal injection of Freund's complete adjuvant (FCA) into some mice. The irritancy response was determined by monitoring the extravasation of 125I-bovine serum albumin into the treated area. The contact hypersensitivity response was determined by monitoring the infiltration of 125I- iododeoxyuridine labeled cells into the challenge site.
There were no treatment-related effects on either survival or body weights. Contact hypersensitivity responses to oleic acid diethanolamine in the test mice are shown in Figure 1. No statistically significant hypersensitivity response was elicited in mice with any concentration of oleic acid diethanolamine, with or without Freund's complete adjuvant. The positive response using 0.5% 1-fluoro-2,4-dinitrobenzene (Group 6) is shown for comparison.
Under these experimental conditions, no dose-dependent or statistically significant irritancy or contact hypersensitivity responses to oleic acid diethanolamine were observed in mice by dermal exposure.
Table 1. Study Design: Contact Hypersensitivity Study with Oleic Acid Diethanolamine
|2 (8)||Baseline Control||+||Vehicle||30% OAD|
|3 (8)||Experimental||+||1% OAD||30% OAD|
|4 (8)||Experimental||+||3% OAD||30% OAD|
|5 (8)||Experimental||10% OAD||30% OAD|
|6 (8)||DNFB Positive Control||-||0.5% DNFB||0.5% DNFB|
|7 (8)||DNFB Negative Control||-||Vehicle||0.5% DNFB|
|8 (8)||Baseline Control||-||Vehicle||30% OAD|
|9 (8)||Experimental||-||3% OAD||30% OAD|
|10 (8)||Experimental||-||10% OAD||30% OAD|
Note: OAD = oleic acid diethanolamine; FCA = Freund's complete adjuvant; DNFB = 1-fluoro-2,4-dinitrobenzene