Disposition of tris(4-chlorophenyl)methanol and tris(4-chlorophenyl)methane in male and female Harlan Sprague Dawley rats and B6C3F1/N mice following oral and intravenous administration

Abstract

1. Tris(4-chlorophenyl)methane (TCPME) and tris(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues.

2. The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice.

3. [¹⁴C]TCPME was well absorbed (≥66%) in male rats and mice following a single oral administration of 1, 10, or 100 mg/kg. The excretion of [¹⁴C]TCPME-derived radioactivity in urine (≤2.5%) and feces (≤18%) was low. The administered dose was retained in tissues (≥ 64%) with adipose containing the highest concentrations. The metabolism of TCPME was minimal. The disposition and metabolism of [¹⁴C]TCPME in females was similar to males.

4. The time to reach maximum concentration was ≤7 h, the plasma elimination half-life was ≥31 h, and the bioavailability was ≥82% following a 10 mg/kg oral dose of [¹⁴C]TCPME in male rats and mice.

5. The disposition of [¹⁴C]TCPMOH was similar to that of [¹⁴C]TCPME.

6. Following an intravenous administration of [¹⁴C]TCPME or [¹⁴C]TCPMOH in male rats and mice, the pattern of disposition was similar to that of oral administration.

7. In conclusion, both TCPME and TCPMOH are readily absorbed and highly bioavailable following a single oral administration pointing to importance of assessing the toxicity of these chemicals.

Keywords:

• Tris(4-chlorophenyl)methanol
• tris(4-chlorophenyl)methane
• disposition
• oral absorption
• bioavailability
• metabolism

Acknowledgements

The authors are grateful to Mr. Brad Collins and Dr. Troy Hubbard for their review of this manuscript. This work was performed for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. N01-ES-75563 (HHSN29120077563).

Disclosure statement

No potential conflict of interest was reported by the authors.