Report on the Immunotoxicity of Phenol in Female B6C3F1 Mice (CAS No. 108-95-2)
Report Date: August 2012
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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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.
Phenol is a contaminant found in drinking water. A study by Hsieh et al. (1992) suggested that the immune system may be a target for PNL. A number of regulatory agencies have established limits for the levels of phenol in the water supply and have considered immune effects in the risk assessment process. The National Institute of Environmental Health Sciences and the National Toxicology Program elected to do a comprehensive evaluation of the potential of phenol to modulate immune function. In conducting the evaluation, assays established by these agencies, which are known to be capable of detecting immunomodulatory compounds, were utilized.
These studies were conducted in female B6C3F1 mice. The animals were exposed to phenol based on the concentration of the test substance in the drinking water. Phenol solutions were prepared fresh 3 times weekly and stored between 2-8°C.
Phenol was administered in the drinking water for 28 days for the majority of the studies at doses of 5, 20, and 100 mg/L. There was no statistically significant difference in drinking water consumption between animals exposed to phenol and the tap water controls. Exposure to phenol did not produce any signs of overt toxicity. There was no significant difference in body weight and body weight change between the exposed and control animals during the experimental period. No gross pathological lesions were observed in phenol-exposed animals; furthermore, there were no differences observed in the weights of liver, spleen, lungs, thymus, or kidneys when the data were expressed as either an absolute or a percent value, with the exception of relative liver weights at the 5 and 100 mg/L doses. Overall, the erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, the percentage of reticulocytes, total leukocyte count, and counts of leukocyte differentials were unaffected by phenol.
Exposure to phenol produced no significant effects in the majority of immunological parameters. There were no changes in the percentage and number of B cells, total T cells, (cluster of differentiation) CD4+ T cells, CD8+ T cells, natural killer cells, or macrophages. The effects of phenol on the activity of splenic T cells and NK cells were evaluated using the one-way mixed leukocyte response and by measuring cytotoxicity to YAC-1 tumor cells, respectively. There was no alteration in either MLR or NK activity after exposure to phenol. Furthermore, exposure to phenol did not produce a consistent effect on the Immunoglobulin M antibody-forming cell responses to sheep red blood cells or on serum IgM anti-sRBC antibody titers. The initial AFC studies that were conducted demonstrated a phenol-related suppression of the IgM AFC response to sRBC. Follow-up studies were unable to replicate the suppression of the IgM AFC response to sRBCs using the original lot of phenol or several alternate lots. Additional studies were also conducted to examine the serum IgM antibody titers to sRBCs. Phenol did not affect this measure of the antibody response. Based on the results of the multiple plaque assays conducted and the lack of effect on the sRBC enzyme-linked immunosorbent assay, the weight of evidence suggests that phenol does not suppress the humoral response to the T-dependent antigen sRBC.
In conclusion, under the conditions of this study, phenol administered for 28 days in the drinking water at doses from 5 to 100 mg/L, produced only minimal toxicological and immunomodulatory effects in female B6C3F1 mice.
Hsieh G.C., Sharma R.P., Parker, R.D., & Coulombe, R.A. Jr. (1992). Immunological and neurobiochemical alterations induced by repeated oral exposure of phenol in mice. Euro. J. Pharm. 228:107-114.