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The ‘New Maths’ phenomenon: zero plus zero equals something; chemicals hitherto harmless prove toxic in combination with other chemicals; new Pandora’s box for regulators

Posted by gmarkets on 3 September, 2007

According to New Scientist, (01/09/2007, p.46), Earl Gray, an ecotoxicologist at the reproductive toxicology division of the US Environmental Protection Agency’s Health and Environmental Effects Research Laboratory (HEERL) in Research Triangle, North Carolina, and his team while exposing pregnant rats to vinclozolin and procymidone – in order to study the impact of the chemicals to the reproductive capacity – saw no effect when they exposed the animals to the compounds individually, however, when they combined the two, half of the males were born with hypospadia – a phenomenon called by Gray as “the new math – zero plus zero equals something”. Harmful chemicals commonly used: Gray then tried the same experiment with phthalates – the ubiquitous compounds used for softening plastics and thicken lotions, and found in everything from shampoo to vinyl flooring and flexible medical tubing. They also disrupted male development, in this case by stopping the foetus from making testosterone.

Increased risk through value additivity: The mix of two phthalates that Gray used caused many of the same effects on male rat foetuses as a mixture of vinclozolin and procymidone. It makes sense that chemicals targeting the same pathway would have an additive effect. But what about mixtures of chemicals that work via different mechanisms? Surely the individual doses of such chemicals would not be additive in the same way.

Principle does work: In 2004, Gray and his team put this to the test by mixing procymidone with a phthalate at levels that, on their own, would produce no effect. Because the chemicals work via different routes, he expected that the combination wouldn’t have any effect either. But they did.

Wreaking havoc in reproductive system!: Then the team mixed seven compounds – with four independent routes of action – each at a level that did not produce an effect. “We expected nothing to happen, but when we give all [the compounds] together, all the animals are malformed,” Gray said. “We disrupted the androgen receptor signalling pathway by several different mechanisms. It seems the tissue can’t tell the difference and is responding in an additive fashion.”

Time to take cognizance: All of this was throwing up problems for regulatory agencies around the world. Governments generally don’t take into account the additive effects of different chemicals, with the exception of dioxins -which accumulate to dangerous levels and disrupt hormones in the body – and some pesticides.

Easier said than done!: For the most part, risk assessments were done one chemical at a time. Even then, regulation was no simple issue. First you needed to know a chemical’s potency, identify which tissues it harmed and determine whether a certain population might be exposed to other chemicals that might damage the same tissue. Add in the cocktail effect and it would get harder still. “It is a pretty difficult regulatory scenario,” admitted Gray. “At this point the science is easier than implementing the regulatory framework.”

New Scientist, 1/9/2007, p. 46

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