of cationic compounds to produce peripheral 
effects in insects suggests along with other 
very limited data that insect myoneural junc- 
tions are not cholinergic. Thus, the cationic 
carbamates represent the converse of selec- 
tive insecticides--selective mammalicides. 
Some of the carbamates developed as in- 
secticides, such as Isolan (l-isopropyl-3- 
methyl-5-pyrazolyl N,N,-dimethylcarbamate) 
and 2-methyl-2-methylthiopropionaldehyde 
oxime N-methylcarbamate, are highly toxic to 
both mammals and insects (table 8), However, 
many of the newer N-methylcarbamate in- 
secticides not only are of low or moderate oral 
toxicity to mammals but also are virtually 
nontoxic by cutaneous application. Carbaryl 
(Sevin), one of the safest of the groups, has 
passed all tests as a dusting powder for body 
lice, where it is used in conjunction with 
piperonyl butoxide synergist. 
In regard to chronic toxicity, the carbamates 
are particularly suitable. These esters are 
very labile and are readily detoxified and ex- 
creted as conjugated aryl sulfates and glu- 
curonate. Carbaryl, for example, has been fed 
to rats at 200 p.p.m. without any effect or any 
tissue storage. When residues are ingested by 
dairy cattle, carbaryl is not concentrated and 
secreted in butter fat as is DDT. The metabo- 
lism of carbaryl, as shown in figure 2, is an 
excellent example of desirable pesticide bio- 
degradability. The principal metabolic path- 
ways are hydroxylation of ring and N-methyl 
groups by microsomal oxidases andhydrolysis 
by aliesterase action. These detoxication path- 
ways account for the often unexpected selective 
0 
i) 
OCNHCH»OH 
~ 
action of the carbamate insecticides to insects. 
Examples are shown in table 8. 
Unfortunately the honey bee and other Hy- 
menoptera are extremely susceptible to car- 
baryl and other carbamates and appear to lack 
the microsomal oxidases that are abundant in 
the house fly, for example. These detoxifying 
enzymes are very susceptible to inhibition by 
the methylenedioxyphenyl compounds, such as 
piperonyl butoxide, which synergizes carbaryl 
as much as 400-fold in the female house fly. 
One of the newest carbamate synergists is 
2,3-methylene-dioxynaphthalene, which gives 
appreciable synergism with carbaryl when 
present at one one-hundredth part (Metcalf, 
R, L., unpublished data), 
INSECT RESISTANCE TO 
INSECTICIDES 
Acquired resistance of insects to insecti- 
cides is another manifestation of selective 
toxicity. The resistance arising through na- 
tural selection depends in most cases on en- 
hanced ability of the organism to detoxify the 
insecticide, and the biochemical defense mech- 
anisms are exactly the same sort that afford 
protection to higher animals. Although re- 
sistance is a natural consequence of the ability 
of organisms to detoxify an almost unlimited 
variety of chemical compounds present in their 
food and environment, its occurrence poses 
challenging problems in the development of in- 
secticides of the future. The ability to develop 
resistance to insecticides is not shared equally 
Oo .¢) Oo 
conjugates “OO OCNHCH, OCNHCH OCNHCH, OH 
me 4 Z —»conjugates 
——= (10) ae OO: 
f S S OH 
\ OH 
(9) HO H HO H 
oO 
+ HCH + NH30H 
Figure 2,--Metabolic pathways of carbaryl (Sevin) in insects and vertebrates, 
18 
