Report Date: July 2010
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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
Tert-butyl hydroperoxide is widely used for cationic emulsion and suspension polymerization of ethylene, vinylacetate, acrylates, poly vinyl chloride and unsaturated polyesters. TBH has found usage in bleaching, waste treatment and disinfectants (Chemical land, 2006; Sanchez and Myers, 1995). TBH may enter the environment via industrial spills. Occupational exposure may occur through dermal contact or inhalation of TBH. In occupational exposures, the peak concentration of TBH in the workplace (limited access area) was estimated to be 6 ppm in one study, and the authors' "worst case" expected human exposure was estimated to be 1.44 mg/m3 (0.39 ppm) with an average human exposure of 0.37 mg/m3 (0.1 ppm) (OECD, 1993). In the general population exposure may occur from the uses of TBH as a component of bleaching or deodorizing agents.
The following studies were conducted to determine the sensitizing potential for TBH when applied dermally to female BALB/c mice. The local lymph node assay was initially performed to measure the sensitization potential of TBH at concentrations of 0.5%, 1%, 2.5%, 5%, 10% and 25% in vehicle acetone: olive oil (4:1). TBH at concentrations of 1.0% and above increased the draining lymph node cell proliferation; however, a statistically significant increase in lymph node cell proliferation (DPM/mouse) was only observed at TBH concentrations of 2.5% and 25% when compared to the vehicle control. None of the doses administered resulted in a Stimulation Index of three or greater.
The irritant potential of TBH was evaluated using the irritancy) assay. TBH at concentrations of 2.5% and above significantly increased the percent ear swelling at 24 hours following the last exposure. Slight increases in ear thickness were also observed in mice treated with 0.5%-1% TBH; however, these changes did not reach the level of statistical significance.
To clarify whether the positive response in the LLNA assay was due to irritancy or if TBH was a contact sensitizer, the Mouse Ear Swelling Test was performed. In the sensitization phase, four concentrations of TBH (1%, 2.5%, 5%, and 25%) were used, and the concentration of 25% was applied during the challenge phase. At the 24 hours time point, a dose related increase in ear swelling was observed, however the increase did not reach the level of statistical significance for any dose group. TBH at concentrations of 2.5% and above significantly increased the ear thickness at 48 hours post-challenge. Of note is the fact that a singe application of TBH to the ear (irritancy control group) resulted in a significant increase in ear swelling when compared to the vehicle control group at both 24 and 48 hours post-challenge.
In conclusion, under the experimental conditions utilized in this study of female BALB/c mice, TBH was positive in the irritancy assay, positive in the LLNA and positive in the MEST.