Fipronil is an insecticide discovered and developed by Rhône-Poulenc
between 1985-87 and placed on the market in 1993. Although effective against a
variety of pests, there are concerns about its environmental and human health
effects. Actively marketed in many industrialised and developing countries its,
worldwide use is increasing.
Fipronil is a member of the phenyl
pyrazole class of pesticides, which are principally chemicals with a herbicidal
effect(1). Fipronil, however, acts as an insecticide with contact and stomach
action. It is sparingly soluble in water(2); is stable at normal temperatures
for one year but not stable in the presence of metal ions and is degraded by
sunlight to produce a variety of metabolites one of which (fipronil-desulfinyl
(MB 46513)) is extremely stable and is more toxic than the parent compound(3).
In 1997, production was around 480 tonnes per annum, and was expected to rise to
800 tonnes by 2000(4). Production takes place at the Rhône-Poulenc Biochimie
plant at Saint-Aubin-Lčs-Elbeuf, France(5), but approval has recently been
gained for another production plant in China which will ensure the synthesis,
formulation and distribution for the insecticide Regent in the Chinese
Between 1987 and 1996 fipronil was evaluated on more than 250 insect pests on 60
crops worldwide(7) and crop protection accounted for about 39% of total fipronil
production in 1997(8).
Fipronil is marketed under the trade
name Regent for use against major lepidopterous and orthopterous pests on a wide
range of field and horticultural crops and against coleopterous larvae in
soils(9). It is also employed for cockroach and ant control(10) under the trade
names Goliath and Nexa including in the US, where it is also used against pests
of field corn, golf courses and commercial turf(11) (trade name Chipco Choice).
It has been used under the trade name Adonis for locust control in Madagascar(12
13 14) and in Kazakhstan(15).
Fipronil also controls termite pests
and was shown to be effective in field trials in Africa(16 17) and
Australia(18). It is marketed under the name Termidor(19).
In 1999, 400,000 hectares were treated
with Regent. It became the leading imported product in the area of rice
insecticides, the second biggest crop protection market after cotton in
Fipronil under the trade name Frontline
or Top Spot is also used to control fleas, ticks and mites on domestic
animals(21 22) and as a pour-on or dip for cattle to control ticks(23). In the
UK, provisional approval for five years has been granted for fipronil use as a
public hygiene insecticide(24).
Mode of action
Fipronil is an extremely active molecule and is a
potent disruptor of the insect central nervous system via the (-aminobutyric
acid (GABA) regulated chloride channel(25). Despite the fact that the GABA
channel is important in nerve transmission in both vertebrate and invertebrate
animals(26), and that fipronil does bind to the GABA receptor in vertebrates,
the binding is ‘less tight” which offers a degree of selectivity(27).
Field persistence is low-moderate in water and soil (half-life 10-130 hours (h)
in water and 45-530 h in soil) with three major degradates formed in soil –
RPA 20076 (amide), MB46513 (fipronil-desulfinyl), and RPA 104615 and two major
metabolites in water, including MB 45950 (sulfide). Under aerobic conditions in
soil several metabolites have been identified, including RPA 200766 and MB 46136
Fipronil’s half-life on treated
vegetation has been determined at 3-7 months, depending on the substrate and the
habitat where it is applied(29).
Laboratory studies show direct and
indirect photolysis, volatilization, and hydrolysis as contributors to fipronil
field dissipation(30). Of the major degradates identified in laboratory studies,
only two (MB 46136 and RPA 200766) were found in field studies at amounts
greater than the limit of detection(31).
Fipronil residues tend to stay in the
upper 15 cm of soil and exhibit low potential to leach to groundwater(32).
In aquatic environments, fipronil
residues rapidly move from the water to the sediment with over 95% of the
residues being found in or on the sediments within one week of application(33).
Metabolic studies showed that there was
a potential for bioaccumulation of the photodegradate MB 46513 in fatty
Fipronil is classed as a WHO Class II moderately hazardous pesticide and has a
rat acute oral LD50 (the dose required to kill half a population of lab animals)
is 97 mg/kg(35). It is less toxic to mammals than to some birds, fish and most
Fipronil has moderate acute toxicity by
the oral and inhalation routes in rats. Dermal absorption in rats is less than
1% after 24 h and toxicity is considered to be low. In contrast, it is of
moderate dermal toxicity to rabbits(36).
The photodegradate MB46513 appears to
have a higher acute toxicity to mammals than fipronil itself by a factor of
Fipronil is neurotoxic in both rats and dogs as shown
in the acute and sub-chronic screening in the rat, developmental neurotoxicity
and chronic carcinogenicity studies in the rat and in two chronic dog
There has been a low incidence of
severe skin reactions to Frontline Spray treatment, Top Spot for Cats and Top
Spot for Dogs, mostly resulting in skin irritation and/or hair loss at the site
of application. There is some suggestion that dogs are more severely affected
Fipronil is carcinogenic to rats at
doses of 300 ppm in males (12.68 mg/kg/day) and females (16.75 mg/kg/day)(40),
causing thyroid cancer related to disruption in the thyroid-pituitary
status(41). However fipronil was not carcinogenic to female mice when
administered at doses of 30 ppm(42 43).
Fipronil is associated with
reproductive effects in rats fed 95.4% fipronil continuously in the diet at 300
ppm based on clinical signs of toxicity, decreased litter size, decreased body
weights, decrease in the percentage of animals mating, reduction in fertility
index, reduced post-implantation survival and offspring postnatal survivability,
and delay in physical development(44).
There have been very few studies undertaken with human subjects, although human
cells have been used in some carcinogenicity studies in which no adverse effects
Fipronil has been classified as a Group
C (Possible Human) Carcinogen based on an increase in thyroid follicular cell
tumours in both sexes of the rat(46). In contrast, thyroid tumours induced by
fipronil in rats are not considered of relevance to human health in the UK(47).
Two Top Spot products were determined
by the New York State Department of Environmental Conservation to pose no
significant exposure risks to workers applying the product. However, concerns
were raised about human exposure to Frontline spray treatment in 1996 leading to
a denial of registration for the spray product. Commercial pet groomers and
veterinarians were considered to be at risk from chronic exposure via inhalation
and dermal absorption during the application of the spray, assuming that they
may have to treat up to 20 large dogs per day(48).
Effects on wildlife
Laboratory toxicity tests
Fipronil is highly toxic to certain groups of gallinaceous birds (Acute LD50 for
Bobwhite quail = 11.3 mg/kg), while being relatively innocuous to passerines
(LD50 for field sparrow = 1120 mg/kg) and wildfowl (LD50for Mallard duck >
The LD50 of fipronil for the fringe-toed lizard (Acanthodactylus
dumerili) [Lacertidae] has been estimated at 30 µg a.i./g body weight in
laboratory tests, indicating that it is highly toxic. Mortality was delayed and
lizards died during the four weeks after treatment(50). Locomotor activity, prey
consumption and body weight remained significantly lower in lizards fed fipronil
treated prey than in the control group for 2-4 weeks after treatment. Data on
other lizard species is not available(51).
Toxicity of fipronil to fish varies
with species. It is very highly toxic to bluegill sunfish (LC50 (Lethal
Concentration) (96 h) = 85 µg/l), highly toxic to rainbow trout (LC50 (96 h) =
248 µg/l) and highly toxic to European carp (LC50 (96 h) = 430 µg/l)(52 53).
It is very highly toxic to one of the African tilapia (Oreochromis niloticus)
(LC50 (96 h) = 42 µg/l)(54). Fipronil affects larval growth in rainbow trout at
concentrations greater than 0.0066 ppm(55).
Fipronil is also toxic to a wide range
of aquatic invertebrates, very highly toxic to shrimps and other crustacea and
very highly toxic to oysters(56 57).
Fipronil is highly toxic to bees(58)
and termites(59). It had the highest acute toxicity for the parasitoid Bracon
hebetor [Hymenoptera: Braconidae] with an LC50 of 0.09 ng/cmŤ, and
the second highest Risk Quotient (RQ) of the seven insecticides tested by the
FAO Locustox study(60). It appears to reduce the longevity and fecundity of
female braconid parasitoids and ‘long term effects on reproduction are to be
foreseen with fipronil’(61). Fipronil was given the highest hazard ranking for
beneficial tenebrionid beetles of six insecticides tested in the Locustox
study(62). It is virtually non-toxic to earthworms(63).
The metabolite MB 461(36) is more toxic
than the parent to avian species tested (very highly toxic to upland game birds
and moderately toxic to waterfowl on an acute oral basis)(64). The metabolite MB
46136 is more toxic than the parent to freshwater fish (6.3 times more toxic to
rainbow trout and 3.3 times more toxic to bluegill sunfish). Metabolites MB
46136 and MB 45950 are more toxic than the parent to freshwater invertebrates
(MB 46136 is 6.6 times more toxic and MB 45950 is 1.9 times more toxic)(65).
Few studies of effects on wildlife have been carried out, but studies of the
non-target impact from emergency applications of fipronil (Adonis 7,5) as
barrier sprays for locust control in Madagascar showed adverse impacts of
fipronil on termites (Coarctotermes spp.), which appear to be very severe
and long-lived. There were also indications of adverse effects in the short-term
on several other invertebrate groups, one species of lizard (Mabuya elegans)
and several species of birds (including the Madagascar bee-eater)(66).
Non-target effects on some insects
(predatory and detritivorous beetles, some parasitic wasps and bees) were also
found in field trials of fipronil for desert locust control in Mauritania(67)
and very low doses (0.6-2.0 g a.i./ha) used against grasshoppers in Niger caused
impacts on non-target insects comparable with those found with other
insecticides used in grasshopper control(68). The implications of this for other
wildlife and ecology of the habitat remain unknown but appear unlikely to be
Grasshopper control in Siberia resulted
in a greater impact on non-target invertebrate wildlife from fipronil than from
There is conflicting evidence over the suitability of
fipronil for use in Integrated Pest Management (IPM), which is generally
recognised as a route towards more ecologically sustainable agriculture. Field
study results range from good selectivity by fipronil for certain beneficial
insects and lower toxicity than (the highly toxic) methyl parathion and
endosulfan(70); through slight and transitory decline in abundance of certain
predators and parasitoids and little difference between fipronil and other
insecticides(71 72 73); to reductions in beneficial arthropods and poorer crop
damage prevention than a comparative insecticide(74).
Trials in Vietnam have suggested that
fipronil use is incompatible with IPM in rice due to disruption of natural
enemies and adverse effects on aquatic organisms(75 76). The study also
questioned whether fipronil acted as a stimulant to plant growth(77). This
finding and the effects on aquatic organisms were disputed by the
manufacturers(78), but the disruption of natural enemies was not.
The Locustox study concluded that
fipronil is relatively toxic to the beneficial invertebrates tested (natural
enemies and soil insects)(79).
There are also potentially negative
impacts for sustainable agricultural practices in rangeland in Madagascar from
fipronil use in locust control, if reduced termite activity affects soil
nutrient cycling and water infiltration into soil. However, further study would
be necessary to confirm this possibility(80).
Developing country problems
There are few issues unique to fipronil in relation to
its use in developing countries – most are relevant to all pesticide use.
However, the following risks are noted in relation to fipronil because of its
specific characteristics and the conditions and situations under which it may be
used in less developed nations:
Climate – due to heat levels frequently
encountered in the tropics, the likelihood of non-use of suitable protective
clothing when applying fipronil or coming in contact with it shortly after
application is increased. Due to possible human health hazards and known
irritant characteristics of certain formulations, this is an area of
Container disposal – pesticide
containers become attractive and valuable assets in materially poor
communities and are frequently taken for use as storage vessels, etc. They
are rarely adequately cleaned beforehand. Due to possible human health
hazards, this is an area of concern.
Illiteracy – problems associated
with inability to read label warnings during use may lead to increased human
Poor ecological knowledge – where
little is known of the ecology of habitats likely to be treated with
fipronil, predictions cannot be made for effects on wildlife nor the
implications for the structure and functioning of the ecosystem.
Unique, unusual and/or poorly known
fauna – the wide differences in toxicity of fipronil to different (even
closely related) animals means that risk assessment for areas with unusual
fauna cannot be predicted without extensive studies on locally occurring
species. The need for incorporation of data on indigenous species in risk
assessment in semi-arid regions, especially temporary ponds has been
Fipronil is a highly effective, broad spectrum
insecticide with potential value for control of a wide range of crop, public
hygiene, amenity and veterinary pests. It can generally be applied at low to
very low dose rates to achieve effective pest control.
Questions have been raised about
fipronil’s suitability for use in IPM and studies suggest that this must be
evaluated on a case by case basis. In certain situations it may disrupt natural
enemy populations, depending on the groups and species involved and the timing
Its acute toxicity varies widely even
in animals within the same groups (see above). This means that the toxicological
findings from results on standard test animals are not necessarily applicable to
animals in the wild. Testing on local species seems particularly important in
determining suitability of fipronil based products for registration in different
countries or habitats and the likely risk to non-target wildlife.
Fipronil use requires careful
consideration where contamination of the aquatic environment is likely, due to
its high toxicity to some fish and aquatic invertebrates.
The dose levels at which fipronil
produces thyroid cancer in rats are very high and unlikely to occur in normal
conditions of use. There is also dispute as to whether this is relevant to human
health risk. However, in developing countries where illiteracy, lack of
protective clothing and use of insecticide drums increase the risk of human
contact with the product at above recommended dose rates, a precautionary
approach may be warranted.
In general, it would appear unwise to
use fipronil-based insecticide without environmental monitoring to accompany its
use, in situations, regions or countries where it has not been used before and
where its use may lead to its introduction into the wider environment or bring
it into contact with people.
The fact sheet was written by staff at
the Natural Resources Institute. An expanded version is available in a Fipronil
Briefing Document from PAN UK.
1. Atelier International Fipronil/lutte antiacridienne, Rhône-Poulenc,
Lyon, 3-5 May 1995.
2. Evaluation on: Fipronil use as a public hygiene insecticide, Issue No.
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Assessment, Chemical 129121, Barcodes D242090, D245656, D245627, &
D241676, Cases 288765, 031271, 060305, & 061662, Submissions S535772,
S541670, S541551, S534929, USEPA Washington DC 20460, US, Office of
Prevention, Pesticides and Toxic Substances, 1998, 90 pp + 3 attachments.
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20. Op. cit. 6.
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25. Op. cit. 9.
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27. Op. cit. 1.
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32. Op. cit. 11.
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37. Op. cit. 3.
38. Op. cit. 2.
39. Op. cit. 3.
40. Op. cit. 11.
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42. Op. cit. 11.
43. Op. cit. 2
44. Op. cit. 11.
45. New York State Dept. of Environment and Conservation, Division of Solid
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47. Op. cit. 2.
48. Op. cit. 3.
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52. Op. cit. 9.
53. Op. cit. 11.
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56. Op. cit. 11.
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78. AL Bostian and ND Long, Rhône-Poulenc Agro position paper on: DANIDA
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[This article first
appeared in Pesticides News No.48, June 2000, p20]