Synergist - November 2011

ancy in counts is largely due to IARC’s listing of many forms of radiation, specific polynuclear aromatic compounds and medicinal agents, which NTP and NIOSH group together. The OSHA cancer policy requires a list, 3 but after 1980 the agency announced it would not compile the list. The California Proposition 65 list includes 548 chemicals. The EPA and ACGIH classifications are not published in summary form, and GHS has not yet been implemented in the U.S.

Classification Criteria and Terminology

Classification criteria are roughly parallel but contain some differences. Agents, which include various industrial processes, are classified as known to be carcinogenic to humans only if multiple studies find associations. That is, a big enough group of people must be exposed, at levels high enough and long enough to generate a statistically significant excess above population levels, with enough employment, exposure and mortality data collected. These studies can’t be conducted without proper funding and access to the data (mostly controlled by management). The most potent carcinogen in the world won’t be “known” if it hasn’t been studied. A cancer hazard is very high if an epidemiologist has found it.

IARC and NTP formally characterize the evidence in people as “sufficient,” “limited” and “inadequate.” Inadequate includes no studies at all or studies “ considered” too weak to conclude an association. “Considered” means a group of experts reviewed the data and, possibly, voted. After studies in people and the laboratory are considered, an overall evaluation is made and summary term (sufficient, limited, or inadequate) applied.

The major battle centers on laboratory
data, which is generated almost exclu-
sively by two-year bioassays in rats and
mice. (Note that these studies don’t in-
clude in utero and perinatal exposure,
and ignore tumors that appear late in life
because the animals are sacrificed at re-
tirement age, not old age.) The IARC
considers two independent studies find-
ing increased incidence of tumors to be
“sufficient,” and only one to be “lim-
ited.” In 2006, IARC clarified that a
study in one gender of rat or mouse con-
ducted in the same laboratory was a
study independent of the other gender.
This change was important because im-
portant agents were bioassayed only
once. The NTP-ROC rules emphasize
studies in two species or by two routes,
although the text includes some weasel
words. One species, even repeated, is
“limited.” Both sets of rules allow con-
sideration of “mechanism,” which per-
mits Houdini risk assessment hypotheses
that erase laboratory findings, but also
permits reclassification.

“not suspected.” Older versions of the TLV® book gave specific dose criteria for discounting laboratory studies. These criteria would have excluded cigarette smoke as carcinogenic (in the absence of overwhelming epidemiology); perhaps that’s why the numbers were withdrawn. The ACGIH criteria are the only ones I’m aware of that use dose to exclude associations. However, there’s no clarity that carcinogenic potency is evaluated or used in setting TLVs.

EPA classifies substances as “ carcinogenic to humans,” “likely to be carcinogenic,” “suggestive evidence of carcinogenic potential,” “inadequate information,” and “not likely to be carcinogenic to humans.” A huge guidance document governs application of these terms. It appears that “likely” and “ suggestive” are equivalent to IARC’s “ probably” and “possibly.” The GHS rules are unclear; Category 1A seems to equate to known carcinogens, and Category 1B includes probably and possibly. GHS Category 2 includes many chemicals that are unclassified by IARC but would be considered potential occupational carcinogens by OSHA and NIOSH.

My next article will discuss how these terms are applied to individual substances.

Franklin Mirer, PhD, CIH, is a professor at the Hunter College School of Health Sciences in New York. He can be reached at (212) 481-7651 or fmirer@humter. cuny.edu. Please send feedback on this article to synergist@aiha.org.

References

1. Harris, Gardiner: “Government Says 2 Common Materials Pose Risk of Cancer.” New York Times, June 10, 2011. [Online] Available at www.ny times.com/2011/06/11/health/11ca ncer.html.

2. Grosse, Yann, et al.: “Carcinogenicity of chemicals in industrial and consumer products, food contaminants and flavourings, and water chlorination byproducts.” The Lancet Oncology 12:4:328–329 (2011).