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BLOG: October 2009

 Smoking health hazards: no dose-response

Some things we just know: for instance, a few cigarettes a day hardly can do any harm. Nothing to worry about. But a recent study on cardiovascular mortality and cigarette smoke begs to differ. Its data show that dose-response relationship matters little when it comes to smoking health hazards.

The study (Pope et al, Cardiovascular Mortality and Exposure to Airborne Fine Particulate Matter and Cigarette Smoke, 2009) started out as an attempt to find explanation for puzzling data associating secondhand smoke with significantly higher risk of cardiovascular mortality than what a simple linear extrapolation indicates vs. active smoking.

So the authors went out to analyze data for over million adults, collected by the American Cancer Society as part of the Cancer Prevention Study II.

After adjusting data for numerous relevant factors, including education, marital status, body mass, alcohol consumption, occupational exposures, and diet, mortality figures were plotted against estimated exposure level to fine particulate matter from smoking. The result was surprising, but not quite unexpected.

The risk of cardiovascular mortality was substantially higher even for active smoking with only a few cigarettes a day. It was not insignificant for secondhand smoke exposure as well, but the apparent discrepancy vs. active smoking exposure was gone.

Specifically, study data indicates that smoking 18-22 cigarettes a day doubles the risk of cardiovascular mortality, while

as few as 3 cigarettes a day increase the risk by 65%.

Significantly higher exposure of 8-12 cigarettes a day added only 14% to this figure, rising the excess risk to 79%.

Even those exposed only to second hand smoke equivalent to less than a single cigarette had 20-30% increased mortality risk. This is still significantly higher than the official CDC (Centers for Disease Control) estimate of 7% of cardiovascular deaths attributable to secondhand smoke, but the difference is smaller when the mortality risk figure from the study is adjusted for the group of avid and heavy smokers, with over 100% higher risk.

The overall conclusion is that the risk of cardiovascular mortality has very sharp increase at low-level exposures to cigarette smoke, gradually becoming more linear in the more common range for active smokers of 1-2 packs a day. Similar, non-linear risk increase was established for the exposure to fine particulate matter in the polluted air, which was also included in the study.

The moral of the story is that, when it comes to toxic exposures,

it is not safe to assume the conventional dose-response effect,

still prevalent in toxicology, as well as in official assessments of toxicity. It is based on the assumption that the effect of toxin between its minimum effective dose and saturation (after which there is no appreciable change in effect with increase in dose) changes nearly in proportion with the dose.

There are actually three assumptions to the dose-response rule, the second being that there is a point below which toxin becomes harmless, and the third that at some point it reaches saturation effect-wise. Such a simple rule cannot possibly reflect effect of a myriad of toxic substances on incredibly complex biochemistry of the human body.

Wide individual differences are only a part of it. Dose-response is already recognized as generally not applicable for allergic reaction, where toxic element acts indirectly, by triggering body's own chemical response, which in effect does the harm. The trigger-dose can vary greatly for any given level of damage caused by it.

Also, some toxins act in non-linear manner, some have no low or high threshold, or both, some produce different effects at low vs. high doses, and yet others have no dose-related gradient, being either causing full effect, or none at all.

Some toxins - like bisphenol A - have multiple thresholds, with different toxic effects within different exposures range, and no effect in intermediate dosages. Similar pattern of harmful effects is established for non-ionizing electromagnetic radiation, from power field to cell phone radiation.

To sum it up: steer clear of anything known to be toxic, as much as you can. Little is not necessarily harmless, be it cigarette smoke, or something else. Keep it safe.