15 Substrate Specificity of Mouse-Liver Microsomal Enzymes in Pyrethroid Metabolism DAVID M. SODERLUND and JOHN E. CASIDA 1
Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, University of California, Berkeley, Calif. 94720
Rapid detoxification contributes to the low acute and chronic toxicity to mammals of the pyrethrins and other chrysanthemates ( 1 , 2 ) . Increased insecticidal potency in the newer synthetic pyrethroids has been achieved by replacing some of the biodegradable groupings by substituent s that retain overall insecticidal configurations but are more refractory to metabolism (3). Currently important pyrethroids include 9 acid moieties [A-I; shown as 1R,trans (A-F) or most insecticidal isomer (G, I] and 9 alcohol moieties [ a - i ; the most insecticidal isomer of a-c and is shown] as follows (Figure l ) : h
acid
A: C: D: E:
R R R R
= = = =
moieties
CHF ' CI Br H alcohol
I
H
moieties
Figure 1
in
cyclo
Figure
relationship
3-phenoxybenzyl
(R =Cl
molecular
chain at
CH^ >
esters
Br).
is
164
SYNTHETIC
yy^LioR >
^^^^ΐΓ^)
=
HYDROLYSIS
Ρ
^JLXor
R
PYRETHROIDS
-y^ioR * RHXAOR
>
R' = CI > F > CH> Br 326 300 166 128 40 [1RS]
R all substituents /=
3
1500 >1500 >1000 >1500
1°
tt
50
trans
Τ.ΤΊ
Toxicity
no t r a n s / c i s
with
and
alcohol
Acid
Intraperitoneal
^trans-ester
[lR]
available;
[ l R , c i s ] - e s t e r
data
S-3206 s-5602 [ R S 3
[1RS]
lk9
NRDC
Cyanophenothrin
Allethrin
Ethanoresmethrin
[1R]
Phenothrin
^ 0
Mouse
configuration
and
I.
Resmethrin
acid
Compound
Table
I—»
3
ο
η
o'
15.
SODERLUND A N D CASIDA
Table
II.
Resmethrin
Ester
Enzyme
Metabolites
and -Permethrin, Acid and
Compound Resmethrin Permethrin
Substrate
of
Specificity in Pyrethroids
[lR,trans]-
Rat
in
[lR,cis]-
vivo
Ester
alcohol
metabolites,^
moieties
trans
Af
and
171