[ 28 February 2000 ]

DEHP confirmed as non-carcinogenic

International Agency for Research on Cancer (IARC) reclassifies DEHP as Non-Carcinogenic to Humans

The most commonly used phthalate plasticiser, di(2-ethylhexyl) phthalate (DEHP), has been confirmed as non-carcinogenic to humans by the world’s leading international authority on cancer.

The International Agency for Research on Cancer (IARC), which is part of the World Health Organisation (WHO), has reclassified DEHP as “not classifiable as to carcinogenicity to humans.”

DEHP, which is used extensively to soften PVC products, including many life-saving medical devices, PVC flooring, wire and cable sheathing and car interiors, has been recognised as being non-carcinogenic to humans by most international authorities, including the European Commission, for several years. IARC however, had previously classified it as “possibly carcinogenic to humans” based on some early research studies carried out on rodents.

IARC has concluded that more recent and more extensive research has since shown that the effects seen in rats and mice are not relevant to humans.

The IARC decision, which was taken by a group of 28 experts from 12 countries meeting in Lyon, France last week, has been welcomed by the plasticiser industry. “Allegations that DEHP causes cancer have received considerable media coverage and have unduly alarmed consumers,” said Dr David Cadogan, Director of the European Council for Plasticisers and Intermediates (ECPI).

“This is a very clear ruling by the world’s leading authority: phthalate plasticisers, which have been used for more than four decades without a single known case of anyone having been harmed, do not cause cancer,” he said.

Technical Note

DEHP belongs to a structurally diverse group of compounds that induce peroxisome proliferation in the liver in mice and rats, but not in other rodent and non-rodent species that have been tested and not in human liver tissue. DEHP causes tumours of the liver in mice and rats, but at no other site, and had previously been classified by IARC as possibly carcinogenic to humans (Group 2B).

The IARC report says that the working group considered that in light of a large body of other relevant data, including evidence from genetically engineered mice, DEHP met criteria previously established for evaluation of such substances (IARC Technical Report No. 24, 1995; Consensus Report available on the IARC website: DEHP was downgraded from Group 2B to Group 3, not classifiable as to carcinogenicity to humans. In making its overall evaluation of the possible carcinogenicity to humans of DEHP, the working group took into consideration that (a) DEHP produces liver tumours in rats and mice by a non-DNA-reactive mechanism involving peroxisome proliferation; (b) peroxisome proliferation and hepatocellular proliferation have been demonstrated under the conditions of the carcinogenicity studies of DEHP in mice and rats; and (c) peroxisome proliferation has not been documented in human hepatocyte cultures exposed to DEHP nor in the livers of exposed non-human primates. Therefore, the mechanism by which DEHP increases the incidence of hepatocellular tumours in rats and mice is not relevant to humans.

While di(2-ethylhexyl) adipate (DEHA) also causes peroxisome proliferation in the liver in mice and rats, evidence that this compound is carcinogenic in experimental animals is less than sufficient. Thus considerations of mechanism or mode of action of this compound played no role in its classification by this working group, says the IARC report.

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Tim Edgar
Deputy Director
European Council for Plasticisers and Intermediates (ECPI)
Brussels, Belgium

Tel: 0032 2 676 7363
Fax: 0032 2 676 7392
e-mail: ted@cefic.be