Pyrethroids
Background
Pyrethroids are a moderately large and very useful class of insecticides based on naturally
insecticidal compounds found in chrysanthemum species. Ground up flowers of
Pyrethrum cineraraefolium and C coccineum, and occasionally of other chrysanthemum
species, have been used for at least a century as insecticidal preparations. Their
usefulness was severely limited by the rapid degradation of the insecticidally active
components, both by sunlight and by biotransformation. Insects metabolize natural
pyrethrum so quickly that recovery after knockdown is not unusual. In the 1950s, efforts
began to synthesize analogs to the natural pyrethrins that would be more persistent, both
in the environment, and in organisms, without losing the potency or the range of
insecticidal activity of the natural products. These efforts have been spectacularly
successful: synthetic pyrethroids are among the most commonly used insecticides, and
various congeners have proven invaluable in agriculture, in medical entomology, and in
household use.
Natural pyrethrum is a mixture of plant products, consisting of esters of chrysanthemic
acid or pyrethric acid with pyrethrolone, cinerolone and/or jasmololone. The basic
skeleton and its variants are shown in Figure 1. Composition of the major insecticidal
constituents of pyrethrum is shown in Table 1.
Figure 1: Basic structure of natural pyrethrum. R and Rí indicate substituents listed in
lower half of figure. Which substituents are present in specific natural pyrethroids is
shown in Table 1.
Pyrethrum
R R’ % OF FLOWERS
Pyrethrin I
Pyrethrin II
Cinerin I
Cinerin II
Jasmolin I
Jasmolin II
A
B
A
B
A
B
C
C
D
D
E
E
10%
9%
2%
3%
1%
1%
TABLE 1: Structures of components of natural pyrethrum. A, B, C, D, and E refer to
moieties shown in figure 1.
Note that several of the carbon atoms in the pyrethrum skeleton have 4 different
substituents, allowing for the formation of steroisomers or enantiomers. These
stereoisomers have different binding capacity to pyrethrum receptors. For example, the
1R and 1S cis isomers shown in Figure 2 bind competitively to one site on the sodium
channel. The 1R and 1S trans isomers, however, bind noncompetitively to a different
site on the sodium channel. The 1S isomer does not alter channel function; however, it
does prevent binding by the 1R isomer. (Thus, a pyrethrum mix consisting entirely of 1S
isomers would not cause toxicity, but would actually protect against later exposure to
1R.) Only the 1R isomer is toxic in intact mammals. It is possible to use such
stereospecific differences in toxicity to produce pure isomers with remarkably selective
toxicity. Deltamethrin is one such pyrethroid. However, note that the relative absence of
mammalian toxicity is primarily due to the rapid metabolism of pyrethroids to their
inactive alcohol and acid components.
Figure 3: Stereoisomeric configurations of pyrethrum
Contact with the receptor ñ sodium channels in nerve and muscle cells ñ occurs at the
isobutenyl moiety of the acid, the dimethylcyclopropane ring, and the unsaturated side
chain of the keto-alcohol (Figure 4). In synthetic pyrethroids, the cyano[C-triple-bond-N]
moiety appears to confer maximum complementarity between the pyrethroid and the
receptor.
Toxicology
Mechanistically, pyrethroids without the cyano group cause the nerve channels to close
very slowly, producing a prolonged after-potential. In contrast, pyrethroids containing the
cyano group cause a delayed closure of sodium channels, suppressing spontaneous
generation of the after-potential.
Figure 4: Interaction of Pyrethrum with its receptors occurs at 3 points of the structure.
Toxicity
Pyrethroids, like OPs and carbamates, are neurotoxins when administered systemically.
And, like all other insecticides, they affect nerve cell function. They do not kill cells.
Unlike OPs and carbamates, pyrethroids as a class exhibit several different kinds of
toxicity, to some extent depending on route of administration. Topical application
produces a very different syndrome from ingestion. Moreover, systemic toxicity falls into
roughly 2 types ñ which are rather mundanely named Type I and Type II forms of
toxicity.
Type I toxicity is due primarily to action of the pyrethroid on the central nervous system,
notably the brain stem. (The cerebrum and cerebellum do not appear to be involved.)
Symptoms in milder cases include a progressive development of fine whole body tremor
and an exaggerated startle response, which are associated with a large increase in
metabolic rate. In more severe cases, there is uncoordinated twitching of dorsal muscles,
hyperexcitability and hyperthermia. Death results from hyperthermia and/or metabolic
exhaustion.
Type II toxicity is somewhat more complex, since it involves pyrethroid effects on all
levels of the brain, rather than mostly on the brain stem. Salivation may be profuse. A
rolling gait is seen due to increased extensor tone in the hind limbs; incoordination
progresses to a coarse tremor; sensory stimuli produce writhing spasms, tonic seizures,
apnea, and death.
Topical application of natural or synthetic pyrethroids also produces contact dermatitis,
which is not uncommon after household use of natural or synthetic pyrethroids. Pure
synthetic pyrethroids can also produce an irritant effect. that is not associated with
inflammation, lasts up to 24 hours, and may include numbness or parasthesias. It is
characterized as annoying but not disabling and does not appear to cause long-lasting
damage. It is most commonly seen in occupational exposure.
Not often noted in the literature is the potential for allergic reactions to chrysanthemums
and to pyrethroids. These allergic responses include asthma, which can be a lifethreatening disease. Pneumonia is also a possible allergic response to pyrethroid
exposure. It is advisable for people who use pyrethroids (whether occasionally or
frequently) to be aware of their reactions to these otherwise benign insecticides. It is also
advisable for people who recommend pesticides to lay people to be aware that
pyrethroids, while ordinarily considered the least dangerous insecticides for household
use, may be quite hazardous for a subset of the population.
There are no specific antidotes for pyrethroid poisoning. Therapy consists of mitigating
the symptoms: bringing down fever, preventing seizures, etc. Atropine will decrease the
amount of saliva produced, but is not particularly effective against other symptoms.
Ecotoxicology
Pyrethroids are extremely toxic to fish and should not be used in locations or under
conditions that result in their presence in water. Since natural pyrethrum and the early
pyrethroids are so short-lived, this was not a significant problem in pyrethroid use. The
more recent pyrethroids, on the other hand, are sufficiently persistent to allow them to
reach streams or lake after terrestrial use. It is perhaps fortunate that these newer
pyrethroids are also applied at very low levels ñ as little as 1/20th of the lb/A application
rates for OP and carbamate insecticides. The low level of application means less risk of
water contamination.
With the exception of toxicity to fish, the pyrethroids are considered ecologically benign,
since they are not overly persistent and not very toxic to mammals.
Table 2: Selected pyrethroids. (gen) refers to the generation, with later generations being
more persistent in the environment. Generation 4 contain a cyano (CN) group.
Pyrethroid (gen)
Pyrethrum
Barthrin (1)
Phenothrin (2)
Resmethrin (2)
Permethrin (3)
Fenvalerate (3)
Cypermethrin
(4)
Deltamethrin (4)
Flucythrinate (4)
Fluvalinate (4)
LD50 (po, rats) Characteristics
1,500 Rapidly degraded
> 20,000 Rapidly degraded
> 5,000
2,000 Considered very safe
Introduced 1973
1,500 Persistent
450 Introduced 1972
247 Sufficiently persistent
128 Most persistent
53-67
> 3,000
Uses
Home and garden
No longer marketed
No longer marketed
Agriculture: corn, cotton
Field crops, vegetables, fruit
Agriculture; roach control
Broad spectrum of use
General use