TELEPHONE HUDSON 3-6126

Manufacturing Chemists' Association, Inc.
(FOUNDED 1S721

1825 Connecticut Avenue, N. W,
Washington, D. C. 20009
August 21,

TO:

Members of the Food, Drug,
Committee

SUBJECT:

1967

and Cosmetic Chemicals

Report of the Panel on Potentiation of the
FDA Advisory Committee
\

Gentlemen:
At the June 13 meeting of the FDCC Committee,
ashed to obtain the subject report dated March 16,

1 was
1967

for your information.
Enclosed is a copy.
Sincerely yours,

Morgan M. Hoover
MMB:sjg
Enclosure

ASI 00002118

FOOD AND DRUG ADMINISTRATION

ADVISORY COMMITTEE ON PROTOCOLS FOR SAFETY EVALUATIONS

Report of tin Panel on Potentiation on
Testing for Potentiation between Anticholinesterase Pesticides

March 16, 1067

Committoe Members:
Norton Nelson, Chairman
Julius M. Coon
' Loo Friedman
Robert E. Gossc!.in
Calvin M. Kunin
Tod A. Loomis
Philippe Shubik
James L. Whittcnbeigor
James 0. Wilson

Panel onPotentiation Members:
Julius 11. Coon, Chairman
Kenneth P. PtOois (consultant)
John P. Frawley (consultant)
Robert E. Gosselin
Tod A, Loom!s

FT»A Liaison Representative to the Panel on Potentiation;
Joseph L. Svirbely

Executive Secretary:.
Charles J, Kokoski

ASI

00002119

Report: of the Panel on P tentlation on
Testing for Potentiation between Anticholinesterase Pesticides

In 1957, it was found that EPN exerted a narked potentiation of the
toxicity of malathlon under certain experimental conditions.

Since that

time numerous exatnplos of important toxicological interactions have come
to light, not only between other anticholinesterase pesticides, but also
between these agents and other environmental chemicals, as well as drugs.
There has been a continuing and growing concern about these toxicological
interactions.
This panel was assigned the specific task of considering the usefulness
of the FDA requirement (F.R. par. 120.35) that each new anticholinesterase
pesticide be tested for toxicity In combination with each of the other
anticholinesterase pesticides for which a tolerance has been set.

In

>

regard to this requirement and the design of the tests that have been run
to meet it,this panel has two recommendations to make:
1.

The present requirement as set forth in the Federal Regulations

(par, 120.35) should be abandoned since it has failed to serve any useful
purpose.

This recommendation is based on two considerations.

Firstly, no single, practical experimental design has been developed
by which it is possiblo to detect all cases of potentiation between pairs
of anticholinesterase pesticides.
Secondly, even in cases where the current test procedure has shown
the existence of potentiation, the results do not supply Information
pertinent to the safety evaluation of pesticide residues on agricultural
conmodltfes.

None of the established potentiative pairs, when fed subacutoly

to experimental animals at or near the minimal effect levels, has shown

ASI 00002120

-3establish the optimal procedur

Cor detecting anti-allesterase activity.

In the meantime, the panel urges the FDA to accumulate data that would
contribute to our knowledge of the general toxicologic and physiologic
significance of the aliesterases.

Dr.
Dr.
Dr.
Dr.
Dr.
Dr.

J.
K.
J.
R.
T,
J.

L.
P.
P.
E.
A.
H.

Svirbely (FDA Represent;tive)
DuBois (consultant)
Frawley (consultant)
Gosselin
Loomis
Coon (chairman)

March 16, 1967

ASI 00002122