signs of cross tolerance to either resistant 
strain. 
An informative example of the effects of 
small changes in chemical structure on re- 
sistance and the detoxifying enzymes is the 
toxicity of malathion to susceptible and re- 
sistant Culex tarsalis mosquito larvae (table 
10), Matsumura and Brown (19) have shown 
that malathion resistance, which is due to a 
single partially dominant gene allele, is (like 
malathion resistance in the mammal, fig. 1) 
largely the result of increased carboxyes- 
terase. This enzyme in Culex tarsalis is also 
susceptible to inhibition by EPN, which acts as 
a synergist for malathion against the resistant 
strain. The malathion resistance could be com- 
pletely reversed by changing the ester group 
from ethyl, asin malathion, to methyl, as shown 
in table 10. These data demonstrate the high 
specificity of the carboxyesterase detoxica- 
tion enzyme, which has a concentration in re- 
sistant larvae of about 13 times that in sus- 
ceptible larvae (20), 
Synergists, such as EPN, that inhibit the 
action of the detoxication enzyme may be used 
to restore the susceptibility of the resistant 
species, N,N-dibutyl-p-chlorobenzenesulfona- 
mide (‘'Anti-Resistant") is a strong inhibitor 
of DDT dehydrochlorinase and, as shown in 
table 9, substantially restores the action of 
DDT to resistant house flies. The hydroxyla- 
tion detoxication mechanism of carbamates, 
previously discussed (fig. 2), is a critical 
factor in determining house fly resistance to 
these insecticides and can be developed to high 
levels by continued selection (10), This enzyme 


is inhibited by piperonyl butoxide and other 
methylenedioxyphenyl compounds, and these 
effectively synergize carbamates against re- 
sistant house flies (table 10). 
ENVIRONMENTAL CONTAMINATION 
AND ECOLOGICAL MAGNIFICATION 
Perhaps the area of greatest concern in the 
present-day use of pesticides is the extreme 
persistence of the widely used chlorinated 
organics, such as DDT and dieldrin, and their 
accumulation and storage in animal lipids. DDT 
is virtually omnipresent in human fat, averag- 
ing in parts per million 3 to 7 in the United 
States, 0.8 in Eskimos, 2.3 in meat abstainers, 
140 in pesticide applicators, and reaching 648 
in a worker in a DDT-formulating plant. Al- 
though no ill effects have been associated with 
any of these levels of DDT storage, its ubiqui- 
tous presence is clearly undesirable. Fortu- 
nately DDT in human fat has a well-defined 
biological half-life and is slowly metabolized 
and excreted in the urine, principally as DDA 
(4,4'-dichlorodiphenylacetic acid), As a con- 
sequence, careful studies by the U.S. Public 
Health Service have shown no increase in 
DDT-storage rates in the U.S, population since 
1950: Average values in parts per million in 
1950 - 5.3, 1955 - 7.4, 1954-56 - 4.9, 1961- 
62 - 3.9 (11). 
The more serious aspect of this lipoid solu- 
bility and biological stability of DDT and re- 
lated compounds is the biological magnifica- 
tion of in vivo storage, which may take place 
Table 10.--Toxicity of malathion analogs to susceptible and 
resistant mosquitoes (Culex tarsalis) 
[Lc50 p.p.m. | 



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