Toxicology


An extensive database of toxicology studies on pyrethrum has been generated by the Pyrethrin Joint Venture of which MGK is a member.  The U.S. Environmental Protection Agency ("EPA") reviewed the studies and determined that the database was acceptable to re-register pyrethrins in 2006 when the Reregistration Eligibility Decision (RED) for pyrethrins was issued. The database consists of a long list of studies including:

 

  • Acute toxicity studies
  • Acute and chronic dietary studies
  • Short and intermediate term oral studies
  • Short and intermediate term inhalation studies
  • Reproductive and fertility studies
  • Genotoxicity studies
  • Developmental toxicity studies
  • Neurotoxicity studies
  • Dermal absorption study 

Pyrethrins are relatively low in toxicity to humans and mammals with the toxicity to rats being 4000 times lower than pyrethrins toxicity to the house fly.  There were no reproductive, genetic, or mutagenic effects from pyrethrins in these studies.

The Pyrethrin Joint Venture conducted a series of studies looking at the mode of action of pyrethrins on the liver following EPA guidelines.  In 2008, the EPA’s Cancer Assessment Review Committee ("CARC") classified pyrethrins as “Not Likely to be Carcinogenic to Humans” at doses that do not cause a mitogenic response in the liver/cell proliferation.  This is based on a weak liver tumor response seen in female rats only at the high dose.  No tumors were seen in male or female mice.  The weight of evidence supports a non-genotoxic mitogenic mode of action for liver tumors.

As the EPA and the industry investigated exposure modeling and conducted risk assessments, the dermal absorption became a key factor.  The PJV decided to conduct a human dermal absorption study on pyrethrins due to the EPA’s use of a 20% dermal absorption as a default factor.  The dermal absorption study was conducted in Europe under clinical conditions with male volunteers and found a dermal absorption value of 0.21% or two orders of magnitude less than the EPA’s default value.  This value was helpful in showing the low levels of exposure to pyrethrins in the use of our products.  

The EPA has identified neurobehavioral effects and thyroid effects as critical toxicological effects of pyrethrins and has required additional studies to better understand these affects.  The neurobehavioral effects will be evaluated by conducting either a developmental neurotoxicity study or alternative studies that the EPA and the pyrethrin/pyrethroid industry have been discussing.  The thyroid effects will be evaluated by conducting a comparative thyroid study.  These studies are expected to be started in 2011.  It is expected that pyrethrins caused the formation of tumors in the thyroid through dose-related secondary proliferative stimulation of thyroid follicular cells.  The tumor formation is clearly based upon a dose-threshold by non-genotoxic mechanisms that are unlikely to occur in humans.

The EPA has concerns with adverse affects from pyrethrin containing products involving dermal or inhalation exposures.  The PJV initiated a Stewardship Program in 2010 that will track all adverse affect reports from products containing pyrethrins and conduct follow-ups to better understand these events.  The Stewardship Program will be conducted for five years and yearly reports will be prepared for the EPA to summarize the findings from the previous year.

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