Dimetridazole review history and regulatory outcomes

Nomination for review

In 1988 the US EPA announced the withdrawal of approvals for dimetridazole. The EPA found that dimetridazole was a potential mutagen and carcinogen. Dimetridazole is chemically similar to ipronidazole and metronidazole, chemicals which may also be mutagenic and carcinogenic, and its metabolites are also suspected carcinogens. The EPA found that the available data were inadequate to discount the possibility that dimetridazole was a genotoxic carcinogen although it allowed the use of dimetridazole under veterinary prescription, provided it is only used on non-food-producing animals.

In 1995, the EU withdrew dimetridazole as a veterinary medicine over concerns about its potential to act as a carcinogen. In May 2002 the EU banned the use of dimetridazole as a feed additive since insufficient data had been submitted to meet the requirements for re-evaluation.

In 2002, the Joint Expert Committee on Food Additives (JECFA) reported that dimetridazole is mutagenic in vitro but there was insufficient evidence to determine if dimetridazole is mutagenic in animals. JECFA requested that additional studies be done and placed the dimetridazole on the inactive list, pending evaluation of additional human safety data.

In 2002 the APVMA began a review of dimetridazole because of concerns relating to human health risks arising from exposure to residues in chicken, eggs and pork products.

Draft (Preliminary Review Findings) Report

In 2004 the APVMA released the Dimetridazole Draft (Preliminary Review Findings) Report.

The APVMA’s findings at this time were that:

• the toxicological data were insufficient to retain the existing health intake standard (Acceptable Daily Intake or ADI) or to establish new health intake standard for dimetridazole. Because of insufficient data the Office of Chemical Safety indicated that the registration of products currently used in food-producing animals could no longer be supported
• the use of the dimetridazole should be limited to companion animals and non-food producing breeder poultry, breeder game birds, and breeder pigeons for squab production
• the risk to users from acute and repeated exposures is greatest in feed milling processes, on-farm mixing and during transportation
• the risk to users can be reduced by the use of personal protective equipment and the addition of new safety directions on product labels.

Subsequent to the release of the draft report, the Office of Chemical Safety (OCS) withdrew the ADI for dimetridazole.

Final review and outcomes

In 2007 the APVMA released the Dimetridazole Review Report and Regulatory Decision. The APVMA key findings in the final review report were:

• the use of dimetridazole products in food-producing animals according to existing label instructions posed an undue hazard to the safety of people exposed to them during their handling or use
• the use of dimetridazole products in food-producing animals according to existing label instructions could leave residues which might have an effect that is harmful to human beings.

As an outcome of the review, the APVMA:

• cancelled the use of dimetridazole in food-producing-species
• allowed the phase out of cancelled uses of dimetridazole over a 24-month period
• allowed its continued use in caged birded not intended for human consumption
• amended product labels to include amended safety directions and a warning statement indicating that dimetridazole is a ‘possible genotoxic chemical’.

For the duration of the 24-month phase-out period for products which have uses only in food-producing animals, the APVMA further recommended:

• the inclusion of new instructions on product labels on how the cancelled products are to be handled and used
• new temporary MRLs for poultry meat, pig meat, edible offal and poultry eggs
• a withholding period of 28 days for meat and eggs
• a re-treatment interval of 28 days for breeder chickens, breeder turkeys and pigs.

For more information please contact the Chemical Review Program on (02) 6210 4749 or by email to chemrev@apvma.gov.au