application of toxicological risk assessment principles to the chemical constituents of cigarette smoke

Introduction:
This article reviews the chemical constituents of cigarette smoke and provides an analysis of the relative contribution of each constituent to health risks, based on published hazard and constituent content values. The study aims to inform prevention efforts using harm reduction by prioritizing the hazards in cigarette smoke using toxicological risk assessment principles.

Key Points:

* The study identifies 158 compounds in cigarette smoke, of which 45 are known or suspected human carcinogens.
* Cancer potency factors were available for 40 of these compounds and reference exposure levels (RELs) for non-cancer effects were found for 17.
* a cancer risk index (CRI) and non-cancer risk index (NCRI) were calculated by multiplying yield levels with CPFs and dividing yield levels with RELs, respectively.
* Gas phase constituents dominate both CRI and NCRI for cigarette smoke.
* The contribution of 1,3-butadiene (BDE) to CRI was more than twice that of the next highest contributing carcinogen (acrylonitrile) using potencies from the State of California EPa.
* a comparison of CRI estimates with estimates of smoking-related cancer deaths in the USa showed that the CRI underestimates the observed cancer rates by about fivefold using ISO yields in the exposure estimate.
* The study highlights the need for constant re-evaluation of the bases for these priorities as new toxicology information emerges.

Main Message:
The application of toxicological risk assessment methods to cigarette smoke provides a plausible and objective framework for the prioritization of carcinogens and other toxicant hazards in cigarette smoke. however, this framework does not enable the prediction of actual cancer risk for several reasons, and the lack of toxicology data on cardiovascular endpoints for specific chemicals makes the use of this framework less useful for cardiovascular toxicity. Therefore, it is crucial to constantly re-evaluate the bases for these priorities as new toxicology information emerges.

Fowles, J, and E Dybing. “application of Toxicological Risk assessment Principles to the Chemical Constituents of Cigarette Smoke.” Tobacco Control 12, no. 4 (December 2003): 424–30. https://doi.org/10.1136/tc.12.4.424.