National Toxicology Program

National Toxicology Program
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Abstract from Report IMM20302 on 5-Amino-O-Cresol

ABSTRACT

Report on the Assessment of Contact Hypersensitivity to 5-Amino-O-Cresol in BALB/c Female Mice (Dermal Studies) (CAS No. 2835-95-2)

Report Date: September 2006

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.


Abstract

5-Amino-o-cresol is an oxidative intermediate used in hydrogen peroxide-induced coupling reactions in permanent hair dye formulations. In 1986, 5-amino-o-cresol was used in 149 out of 960 hair dye formulations, according to the Food and Drug Administration product formulation data, compiled through voluntary filing in accordance with Title 21 of the Code of Federal Regulations. Six products contained greater than 1-5% 5-amino-o-cresol, 70 products contained greater than 0.1-1%, and 73 products contained 0.1% or less. Consumer exposure to 5-amino-o-cresol occurs through the use of hair coloring cosmetic products. It is estimated that one in three women above the age of 18 and one in ten men above the age of 40 uses some type of hair coloring. Permanent coloring accounts for approximately 70% of the dollar volume of the retail market and 85% of the professional market.2 According to the study by Beck and co-workers, both pig skin (in vitro) and rat skin (in vivo) are permeable to 5-amino-o-cresol. Furthermore, there is evidence that 5-amino-o-cresol produced weak sensitization in skin sensitization tests in guinea pigs.

The objective of this study was to determine the potential for AOC to elicit an allergic response when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was initially accomplished using the local lymph node assay. Since solubility testing indicated that the maximal solubility of AOC in acetone:olive oil was approximately 10%, the highest concentration of AOC used for LLNA was 10%. No significant effect was observed in the LLNA when mice were exposed to AOC at low concentrations (0.625%, 1.25% and 2.5%). However, when AOC was applied at higher concentrations, 5% and 10%, there was a significant increase in the proliferative response when compared to the vehicle control group. In addition, at the 10% concentration, there was greater than a three-fold increase observed as compared to the response of the vehicle animals.

The irritancy assay (IRR) in this study was conducted together with LLNA assay to determine if AOC was an irritant at the concentrations tested using a modified procedure. No positive irritant responses were observed in animals exposed to 0.625-10% concentrations of AOC.

In addition to the LLNA and IRR assays, the Mouse Ear Swelling Test was performed to determine the potential effect of AOC to induce contact hypersensitivity. Two dose levels, 5% and 10%, of AOC were used for sensitization and animals were challenged with a 10% concentration of AOC. In contrast to the LLNA result, AOC did not affect the ear thickness even at the highest soluble concentration (10%).

In summary, the results from LLNA demonstrated that AOC treatment significantly increased the proliferation of the draining lymph node cells at the two high concentrations (5% and 10%). However, AOC did not appear to be an irritant as measured in the IRR assay. Furthermore, AOC did not have significant effects on the percent of mouse ear swelling in MEST. Taken together, the results suggested that AOC is a weak contact sensitizer at the concentrations tested in female BALB/c mice.


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