Since its inception 25 years ago, EPA [the US Environmental Protection Agency] has applied the same logic to hundreds of other substances, extrapolating from high levels in animal studies to arrive at acceptable levels for humans. But that approach, say scientists both inside and outside the federal government, may no longer be the best way to safeguard public health...EPA's new emphasis on molecular data is based on a growing body of evidence that extrapolations from megadoses can provide a misleading picture of the effects of low-level exposure. Chloroform is a good example. EPA's current strict standards were derived from a study in which mice developed liver tumors after exposure to massive daily doses of chloroform pumped into their stomachs over several months. However, those findings may not be relevant to human exposures, according to a paper picked by the Society of Toxicology as the best published last year in its journal.
|
Extrapolating from one species to another is fraught with uncertainty... For almost all of- the chemicals tested to date, rodent bio-assays have not been cost-effective. They give limited and uncertain information on carcinogenicity, generally give no indication of mechanism of action, and require years to complete.' [They are] 'rarely the best approach for deciding whether to classify a chemical as a human carcinogen.
|
Data from dose-response relationships are sometimes employed to estimate the expected tumour incidence at dose levels very much lower than those which could possibly be employed in conventional [animal] experiments. A number of mathematical models have been employed in such estimates and the results obtained vary considerably. Despite these uncertainties - and the possibly greater ones in extrapolating from animals to man - such models are often employed in some quarters to estimate the likely risk to man.
|
We're building a whole public health strategy based on these drugs, extrapolating a huge amount from a few small studies. How could you say they are efficacious? We don't know. Given that governments are spending millions, it's unconscionable that companies aren't giving more answers.
|
[Regarding tamoxifen, an anti-cancer drug] 'Experimentally, tamoxifen has carcinogenic potential. In some strains of rat, but not mouse or hamster, tamoxifen can cause liver cancers at doses as low as 5mg/kg per day... However, there are doubts about the correlation of [the results] with the risk of malignant disease even in rats, let alone in other rodents, mammals, or human beings. There are many uncertainties in extrapolating these experimental data from rats to women. The effect depends on bioavailability, hepatic [liver] blood flow, and hepatic [liver] metabolism to active genotoxic carcinogens, all of which differ enormously between rat and man.
|