Dimetridazole chemical review

In 1988, the United States Environment Protection Autority (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 that 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 used only on non-food-producing animals.

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

In 2002, the Joint Expert Committee on Food Additives reported that dimetridazole is mutagenic in vitro, but there was insufficient evidence to determine whether it is mutagenic in animals. The committee requested that additional studies be done and placed dimetridazole on the inactive list, pending the 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.

In 2004 the APVMA released the Dimetridazole draft (preliminary review findings) report.

The APVMA’s findings at that time were as follows:

• The toxicological data were insufficient to retain the existing health intake standard (the acceptable daily intake) or to establish a new health intake standard for dimetridazole. For that reason, 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, during 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.

After the release of the draft report, the Office of Chemical Safety withdrew the acceptable daily intake for dimetridazole.

In 2007, the APVMA released the Dimetridazole review report and regulatory decision. The key findings in the report were that 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
• could leave residues that 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 dimetridazole’s continued use in caged birds 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’.

To reduce the risk to the public, the APVMA cancelled the use of dimetridazole in food-producing animals and amended the labels of products used in non-food-producing situations to include new safety directions and warning statements.

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

• the inclusion of new instructions on product labels for 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 retreatment interval of 28 days for breeder chickens, breeder turkeys and pigs.