Meeting Title: Aldicarb Comparative Cholinesterase Study: Adult Dose
Selection

Minutes	August 27, 2009	2:30 – 3:00p,	Conference Call



Attendees	Anna Lowit – Environmental Protection Agency (EPA), Health
Effects Division (HED)

Ginger Moser – EPA, Office of Research and Development

Linda Taylor -- EPA HED

Joy Schnackenbeck – EPA SRRD

Anne Blacker – Bayer CropScience





Purpose	To discuss and agree upon doses for the adult rats in the
aldicarb CCA study.

background	Pursuant to the aldicarb reregistration eligibility decision
(RED) data call-in (DCI) Bayer CropScience is conducting a comparative
cholinesterase inhibition study similar in design to those submitted for
other N-methyl carbamates (NMC) recently.  In the human health
assessments for the aldicarb RED, EPA referred to a 1999 comparative
cholinesterase inhibition study, which demonstrated that rat post-natal
day 17 (PND 17) pups were approximately two times more sensitive than
adult rats at comparable doses based on inhibition of brain
acetylcholinesterase.  Relying on this study and results from other
developmental and reproduction studies, EPA believed that the 1999
comparative cholinesterase inhibition study accounted for all potential
postnatal toxicity and applied a 2x Food Quality Protection Act (FQPA)
safety factor to take into account the potential for pre and postnatal
toxicity.  However, since the RED, comparative cholinesterase inhibition
study results from other NMCs have become available and suggest PND 11
pups are generally more sensitive than PND 17 pups.  Therefore, Bayer
CropScience is conducting a new CCA study for aldicarb using PND 11 pups
and including a time course component to assess the time to peak effect,
the time to recovery and a dose-response component evaluating brain and
red blood cell acetylcholinesterase inhibition along with clinical
observation.  Upon receipt of an acceptable study, EPA will refine the
aldicarb FQPA factor in both the single chemical and NMC cumulative risk
assessments, as appropriate.      

Discussion	EPA and Bayer CropScience discussed doses for the adult rats
in the aldicarb CCA study.

Conclusions	The doses chose for the adult rats were: 0.03, 0.05, 0.065,
0.08, 0.15, 0.3

These doses will result in approximately four doses that will result in
red blood cell inhibition before saturation and four doses, which will
result in brain inhibition.

Action items

The time course study for the PND11 pups will run on September 21.  EPA
and Bayer CropScience will need to meet the week of September 28 to
agree on doses for the PND 11 pups.







