The New Scientist, 15 February 2003, Issue 2382 - Andy Coghlan

Deadly Poisons Reveal their Friendly Side

The New Scientist, 15 February 2003, Issue 2382 - Andy Coghlan

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THE world's most reviled chemicals might actually do you some good in small doses, according to a controversial study.

The US Environmental Protection Agency (EPA) is taking the findings seriously, though it is not abandoning traditional toxicology just yet. "We have scientists thinking about it," says Chon Shoaf, assistant director of the EPA's National Center for Environmental Assessment in Research Triangle Park, North Carolina.

Traditionally, toxicologists assume there is no safe dose for carcinogens, such as dioxins. This is wrong, say Ed Calabrese and Linda Brown, toxicologists at the University of Massachusetts in Amherst, in this week's Nature (vol 421, p691). After analysing large quantities of data on animals from official sources such as the EPA, they conclude that at certain doses, dioxins have protective effects. "At low doses, the animals had profoundly lower tumour risk," says Calabrese.

For non-carcinogens, it has always been assumed that a safe level can be worked out by knowing how excessive doses affect animals. This is also wrong, says Calabrese. Of the thousands of chemicals he has looked at, in a multitude of animals, toxicity always dips before rising, varying along a "J-shaped" curve as dose increases. All chemicals came out as hazardous at very high doses, but there is always a range of low concentrations in the "hook" of the J where the chemicals are beneficial. "We have copious evidence that these agents which have harmful effects at high doses have beneficial effects at low doses," he says.

If Calabrese and Brown's model supplants today's gospel, it could mean a radical shake-up in the way we measure the hazards chemicals pose to humans and the environment, and the way drug doses are worked out. "They're all Jekyll and Hydes," says Calabrese. "People don't want to hear that, and would prefer to say: 'That one's good and that one's bad'."

Calabrese says that although there is no single explanation for the toxic behaviour of chemicals, he believes that at low levels they "exercise" cells' defences against them, making them fitter. Low levels of chemicals that mutate DNA, for example, activate repair enzymes that also rectify additional faults in DNA. Alcohol is another example: beneficial at moderate levels but damaging if abused.

Shoaf says the model is far from baloney. But he adds that its implications, for the EPA at least, are very unclear.

From issue 2382 of New Scientist magazine, 15 February 2003, page 10

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