Factors Determining the Toxicity of Organic Pollutants to Animals and Plants - Organic Pollutants: An Ecotoxicological Perspective - page 64

taBLe 2.9
Synergism due to Inhibition of detoxication

detoxifying
enzyme

Synergistic
ratio organism Insecticide Inhibitor (Synergist)

Insect strains resistant
to pyrethroids (e.g.,
H. virescens )

Cypermethrin Monooxygenase Piperonyl butoxide (PBO) <200

Insects Carbaryl Monooxygenase PBO and other

methylenedioxyphenyls

<400

Mammals and some
malathion-resistant
insects

Malathion Carboxylesterase Some OPs other than

malathion

<200

Note: Synergistic ratio = toxicity without synergist/toxicity with synergist.
Sources: Kuhr and Dorough 1976, McCaffery et al. 1991, Walker and Oesch 1983.

honeybees by EBI fungicides, due to inhibition of detoxication by monooxygenases
(Chapter 12); the increased toxicity of the carbamate insecticide carbaryl to red-
legged partridges ( Alectoris rufa) caused by the OP malathion due to inhibition of
detoxication by monooxygenases (Johnston et al. 1994; Chapter 10); the enhanced
toxicity of malathion to birds by EBI fungicides as a consequence of induction of
monooxygenase and increased activation (Chapter 10); and the enhanced activa-
tion of mutagenic PAHs due to induction of monooxygenases by coplanar PCBs and
dioxins (Chapter 9).

2.7 Summary
The toxicity of an organic chemical depends on the operation of toxicokinetic and
toxicodynamic processes within living organisms, and selectivity between species,
strains, sexes, and age groups is the outcome of the differential operation of these
processes between such contrasting groups. A model is presented that describes the
fate of lipophilic organic compounds within living organisms, seen from a toxicolog-
ical point of view. After uptake, the chemical is distributed to sites of action, metabo-
lism, storage, and excretion. Toxicokinetics encompasses all of those processes that
occur before the arrival of a toxic compound (original compound or active metabo-
lite) at the site of action—processes that determine how much of the toxic compound
reaches the site of action. Toxicodynamics is concerned with the interaction of the
toxic compound with the site of action and consequent toxic effects.
Emphasis is given to the critical role of metabolism, both detoxication and activa-
tion, in determining toxicity. The principal enzymes involved are described, includ-
ing monooxygenases, esterases, epoxide hydrolases, glutathione- S -transferases, and
glucuronyl transferases. Attention is given to the influence of enzyme induction and
enzyme inhibition on toxicity.