more than 100 times as suceptible on a weight 
basis, 
The data in table 4 show that the remarkable 
selectivity to the bee is confined to the diisop- 
ropyl phosphorothioate ester. Biochemical 
investigations have shown that this selectivity 
is the net result of the inability of the bee to 
readily accomplish the lethal synthesis of 
diisopropyl p-nitrophenyl phosphate from the 
phosphorothioate (a microsomal oxidation) 
coupled with the lower affinity of the phos- 
phate metabolite for bee cholinesterase. The 
conjunction of these two variances in reaction 
rates suffices to provide a difference of ap- 
proximately 1,000-fold in the ultimate rates 
of diisopropyl phosphorylation between the fly 
enzyme and bee enzyme. Field trials of 
isopropyl parathion to ascertain the extent of 
its selective action would seem to be warranted. 
Selectivity of Malathion and Related 
Compounds 
The development in 1950 of malathion (0,0- 
dimethyl S-(1,2-dicarbethoxyethyl) phosphoro- 
dithioate) was an important milestone in the 
emergence of the selective toxicity of the 
organophosphorus insecticides (14). An inter- 
esting comparison between the ‘selectivity of 
malathion and the nonselectivity of parathion 
is shown in table 2. Since that time the com- 
parative use of millions of pounds of both ma- 
terials on a worldwide basis has indicated that 
malathion can be applied without appreciable 
hazard to human or animal health, whereas 
parathion, unless carefully handled by trained 
personnel, may cause illness and even death. 
Therefore, although parathion is from 2 to 20 
times more active to insects than malathion, 
the latter has had increasingly widespread 
application as a general-purpose insecticide 
for use by the general public (38). 
Inquiry into the biochemical basis for the 
selectivity of malathion should provide a 
rationale for the development of other selec- 
tive insecticides. Animals poisoned by mala- 
thion show symptoms of anticholinesterase 
activity, yet purified malathion is not an anti- 
cholinesterase. It is apparent that malathion 
(P=S) is oxidized in vivo into mala-oxon(P=O), 
which is about 1,000 times as active as an 
anticholinesterase. The oxidizing enzyme sys- 
tem is found in the microsomal fraction of 
mouse liver and in cockroach midgut and fat 
Table 4,--Selectivity of parathion derivatives to house fly and honey bee (24) 













Parathion derivative 
OONC GHAOP.(S)/( OMe) 9 cteteleeys steerer ecrele 
OONC GHAOR(S) CORE) samen eee cee 
OONC GHAOPS)I( OPT) O% cere cic cisioiera- 
OONCGHAOR (SOP io ss ce. crececiereree 
OoNCgH4OP(S)(OBu)9...........000- 
DONG GHAOR(O) (OMe) ony ae see eerie 
OONC GHAOP (0) (OED)IO\ veicrs crelelelereiere enals 
OONCEHAOP(O) NOPD) Os stycccietiaes «versie 
ONC GHAOP((O)(O1Pr) oj emecetie cee ee 
OoNCgH40P(0)(OBu)Q......-....000e 
Topical LD59 yper gram 

Selectivity ratio 
bee/fly 
> 240 
