PRINCIPLES OF TOXICOLOGY

influx of sodium, followed by an increase in the potassium permeability, causing an outward flow of
potassium. The ionic currents cause a temporary reversal of the membrane potential from negative to
positive resulting in nerve impulse conduction along the nerve fiber. Pyrethroids exert their effect by
slowing the closing of the sodium activation gate. Type I pyrethroids prolong individual channel
currents causing whole cell sodium influx to be prolonged, elevating the after-potential until the
threshold potential is reached and repetitive discharges occur. Examples of type I pyrethroids include
allethrin, cismethrin, permethrin, and resmethrin. Type I pyrethroids, at high levels in animals, have
been reported to cause increased sensitivity to external stimuli, tremors, increased body temperature,
and rigor immediately preceding death. Type II pyrethroids cause an extremely prolonged sodium
current, leading to depolarization of the nerve and impulse conduction block. Type II pyrethroids
include cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, and fenvalerate. Type II pyrethroids cause
behavioral problems early in the intoxication, leading to salivation, miosis, bradycardia, tremor,
decreased startle response to sound, and ataxia.
Like pyrethrins and pyrethrum, the synthetic pyrethroids are rapidly metabolized and excreted in
humans and do not bioaccumulate. In fact, the relatively resistant nature of mammals, including
humans, stems from the ability to metabolize these compounds quickly and efficiently. Synthetic
pyrethroids have greater insecticidal activity and lower mammalian toxicity than the organophosphate,
carbamate, and organochlorine insecticides. Experimental animals that have been treated with high
doses of pyrethroids experience symptoms such as tremors, salivation, and/or convulsions. In general,
animals surviving an acute intoxication to pyrethroids recover within several hours of exposure.
The primary reported reaction to exposure to synthetic pyrethroid insecticides in humans occurs
with exposure to those pyrethroids containing cyano groups (e.g., fenvalerate and cypermethrin). This
reaction consists of paresthesia, typically occurring around the mouth region in workers exposed to
these compounds. This paresthesia is reversible and dissipates usually within 24 h of cessation of
exposure. An occupational study of 199 workers who were involved in dividing and packaging
pyrethroids (fenvalerate, deltamethrin, and cypermethrin) showed that aside from transient paresthesias
occurring in the facial area and sneezing and increased nasal secretions, there were essentially no
adverse health effects attributable to the pyrethroid exposure. Treatment of pyrethrin overexposure
consists of decontamination and supportive treatment.
Rotenone
Rotenone (Noxfish) occurs naturally in several plants species (e.g., the Leguminocae genera) and is
used mainly as an insecticide as well as to eliminate fish in lakes and ponds. The mechanism of action
for rotenone is as a respiratory toxin, blocking electron transport at ubiquinone, preventing oxidation
of NADH. Rotenone seems to have low toxicity in man, and few reports of serious injury appear to
have been reported. Occupational exposure to the powder of the plant that contains rotenone has
reportedly caused dermal and respiratory tract irritation and numbness in mouths of workers. Treatment
of rotenone overexposure consists mainly of decontamination and supportive therapy.
Bacillus thuringiensis
15.3 INSECTICIDES OF BIOLOGICAL ORIGIN 355
Microbial insecticides, such as several strains Bacillus thuringiensis (e.g., Dipel, variety kurstaki),
have been developed as effective insecticides. The endotoxin of Bacillus thuringiensis is insecticidal
in certain sensitive species. Bacillus thuringiensis has not generally been associated with mammalian
or human toxicity; only a few instances of adverse effects in humans have been reported. A group of
18 human volunteers ingesting 1 gram of a B. thuringiensis formulation for 5 days, with 5 of these 18
subjects also inhaling 100 mg of the powder for 5 days, reported no adverse effects. Furthermore, a
group of workers exposed to various processes involved in the formulation of a commercial product
containing the biological insecticide showed no adverse health effects.