Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors

Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and “doses” of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled “Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors” held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments

Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors

Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and “doses” of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled “Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors” held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments

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

<p></p><p><i>Tris</i>(4-chlorophenyl)methane (TCPME) and <i>tris</i>(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues.</p><p>The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice.</p><p>[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.</p><p>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.</p><p>The disposition of [¹⁴C]TCPMOH was similar to that of [¹⁴C]TCPME.</p><p>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.</p><p>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.</p><p></p> <p><i>Tris</i>(4-chlorophenyl)methane (TCPME) and <i>tris</i>(4-chlorophenyl)methanol (TCPMOH) have been detected in various biota and human tissues.</p> <p>The current studies were undertaken to investigate the disposition and metabolism of TCPME and TCPMOH in rats and mice.</p> <p>[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.</p> <p>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.</p> <p>The disposition of [¹⁴C]TCPMOH was similar to that of [¹⁴C]TCPME.</p> <p>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.</p> <p>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.</p