Citation for this Web Page: Lois Swirsky Gold, Bruce N. Ames, Thomas H. Slone. Animal Cancer Tests and Human Cancer Risk: A Broad Perspective. MOE.html, September 2008.

Margin of Exposure: The Big Picture
(See Graphic on Right and Popup Table with Details on Each Chemical Exposure)

(   Carcinogenic Dose for 10% of Rodents (mg/kg/day)   )/ Average Human Exposure (mg/kg/day)

For example, a value of 1 means that the human exposure level is the same as the dose that gave tumors in rodent experiments. In a few unusual cases at the top of the graphic, the MOE is less than 1, which indicates that human exposures were so high that the rodent carcinogenic dose was actually lower than the exposures to humans (e.g., occupational exposure to Vinyl chloride in the 1950’s, MOE=0.01). A value of 300 indicates that the rodent carcinogenic dose is 300 times greater than the human intake (e.g., the naturally occurring chemical Safrole in spices in the total diet). A value of 7,000,000 indicates that the rodent carcinogenic dose is 7 million times greater than the human exposure (e.g., the synthetic pesticide Lindane in the total diet in 1990).

A table in a popup window reports details on human exposure, rodent cancer dose and reference for each exposure in the graphic.

“Rodent carcinogens” as defined by high dose tests are ubiquitous. Public concern about cancer from the low human exposures to synthetic pesticide residues or pollutants does not seem warranted by the science.

Gold, L. S. et al. Misconceptions About the Causes of Cancer. Vancouver, Canada: Fraser Institute (2002). Gold, L. S., et al. Pesticide Residues in Food and Cancer Risk: A Critical Analysis. In: Handbook of Pesticide Toxicology, Second Edition (R. Krieger, ed.), Academic Press, pp. 799-843 (2001). Gold, L. S. et al. Drug Metab. Rev. 30: 203-225 (1998). Ames, B. N. and Gold, L. S. Science 249: 970-971 (1990). Ames, B. N., et al. Proc. Natl. Acad. Sci. USA 87: 7777-7781 (1990). Full text of all publications of the Carcinogenic Potency Project are available at .

Cancer Risk Assessment Methods, 1960’s-1990’s
Proportion Of Chemicals That Are Carcinogenic in High Dose Rodent Experiments
% (   N Positive   )/ N Tested

Chemicals tested in both rats and mice 59% 405/688
Naturally-occurring chemicals 57% 98/171
Synthetic chemicals 59% 307/517
Chemicals tested in rats or mice 52% 786/1523
Natural pesticides 53% 43/81
Commercial pesticides 40% 82/206
Mold toxins 59% 16/27
Natural chemicals in roasted coffee 72% 23/32
Mutagens 75% 294/393
Non-mutagens 48% 217/455
FDA database of drug submissions 44% 125/282

More than 50% of chemicals tested in rodents at the Maximum Tolerated Dose (a near-toxic dose) cause tumors.

Natural chemicals are positive as often as synthetic, industrial chemicals. More than 99% of the human intake of chemicals is from naturally occurring chemicals.

Natural pesticides (the chemicals that plants produce to defend themselves against predators and are present in all the fruits and vegetables we eat) are as often positive as commercial pesticides.

What may account for the high positivity rate?
  1. High dose effects that are not relevant to low human exposures.

  2. Carcinogenic processes in rodents that are not plausible in humans.

  3. Bias in picking chemicals to test that were expected to be positive. Our research indicates that bias is a minor factor for several reasons, including:

New Risk Assessment Paradigm
Human Relevance Framework
Human Relevance Framework Examples
Chemicals That Do Not Damage DNA:
[Participants in the new human relevance paradigm include International Life Sciences Institute, Health Canada, US EPA, International Programme on Chemical Safety]

References for Human Relevance Framework
Cohen, S. M., et al., Toxicol. Sci. 78: 181-186 (2004). Klaunig, J. E., et al., Crit. Rev. Toxicol. 33: 655-780 (2003). Meek, M. E., et al., Crit. Rev. Toxicol. 33: 591-653 (2003).

Lois Swirsky Gold, Bruce N. Ames, Thomas H. Slone Carcinogenic Potency Project

This web page was supported by the Department of Energy, Low Dose Radiation Research Program. From 1980-2008 the Carcinogenic Potency Project has been supported by Department of Energy (DOE); National Institute of Environmental Health Sciences (NIEHS); National Toxicology Program (NTP); National Cancer Institute (NCI); Environmental Protection Agency (EPA); University of California, Berkeley, Dean’s Office of the College of Letters and Science.

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