Adverse Effects:
Body Weight Decrease
Bone
Brain
Cancer: Possible Human Carcinogen - THYROID
Cholesterol
Clastogenicity
CNS
Dermal
Endocrine: Altered Sex Ratio
Endocrine: Pituitary - (disruption in the thyroid-pituitary status)
Endocrine: Suspected Endocrine Disruptor
Endocrine: Testicular
Endocrine: Thyroid
Kidney
Liver
Lung
Reproductive/Developmental
Stomach

Contamination incident:
2001: Crawfish farmers in Louisiana file Class Action against the makers of the fipronil insecticide ICON, Rhone-Poulenc/Aventis, for killing crawfish.
2004: Farmers and landowners in Class Action awarded $45 million.

Environmental
-- Highly toxic to rainbow trout and very highly toxic to bluegill sunfish
-- The sulfone metabolite is 6.3 times more toxic to rainbow trout and 3.3 times more toxic than the parent compound to bluegill sunfish.
-- High toxicity to freshwater aquatic invertebrates. The sulfone metabolite is 6.6 times more toxic and the desulfinyl photodegradate 1.9 times more toxic on an acute basis to freshwater invertebrates than the parent compound.
-- Highly toxic to upland game birds.. The sulfone metabolite is more toxic than the parent compound to certain bird species. This metabolite has shown a very high toxicity toward upland game birds ...
-- Highly toxic to bees, lizards, and gallinaceous birds

2004 - Bayer Crop Science
2003 - Bayer Environmental Science
1996 - Rhone-Poulenc   

FRANCE:
formerly Rhone-Poulenc, Montlucon

FRANCE:
Aventis CropScience SA, AllÕ Chem, Montlucon

FRANCE:
Aventis CropScience SA, Rue de Verdun F-76410, Saint Aubin-les--Elbeuf

• new - Fipronil: Material Safety Data Sheets and Labels

May 28, 2007 - Neonicotinoids, such as Fipronil, a suspect in
honeybee colony collapse disorder.

"... In sublethal doses, however, research has shown that imidacloprid and other neonicotinoids, such as fipronil, can impair honeybees' memory and learning, as well as their motor activity and navigation. When foraging for food and collecting nectar, honeybees memorize the smells of flowers and create a kind of olfactory map for subsequent trips... The possibility that neonicotinoids are at the heart of the bee die-off implies a far more complex problem because of the widespread use of pesticides. Every year these chemicals are applied to hundreds of millions of acres of agricultural lands, gardens, golf courses and public and private lawns across the United States. Their use on major crops nearly tripled between 1964 and 1982, from 233 million pounds to 612 million pounds of active ingredients. And since then, their use has exploded. By 1999, the U.S. Environmental Protection Agency reported 5 billion pounds of pesticides used on U.S. crops, forests, lawns, flowers, homes and buildings..". The Star-Ledger (Newark, N.J.)

May 18, 2005 - Tick box plan kicked out of Nahanton. By Karla Hailer-Fidelman. Newton TAB (MA)

2004. SPECIAL: Louisiana crawfish farmers and landowners who suffered severe losses due to Icon contamination receive $45 million in a Class Action settlement. See:

• A little background on the geneology and events of the insecticide Icon

• Index to some documents and reports pertaining to the Class Action

• News Items related to the settlement

December 2001 - ENVIRONMENTAL FATE OF FIPRONIL by Pete Connelly. Environmental Monitoring Branch, Department of Pesticide Regulation, California Environmental Protection Agency.

August 10, 2004: a North Carolina hockey team (the Hurricanes) accepts sponsorship deal with BASF-Termidor. Termidor is a termite insecticide with fipronil its active ingredient.

US EPA grants public health exemption to New York State Bureau of Pesticides to control vectors for Lyme Disease. MAXFORCE Tick Management System, an unregistered end-use product, containing 0.70% fipronil, manufactured by Bayer Environmental Science, may be used. Applications may be made until December 31, 2003.

June 14, 2001 - Implementation of the Community Strategy for Endocrine Disruptors - a range of substances suspected of interfering with the hormone systems of humans and wildlife. Communication from the Commission to the Council and the European Parliament. Commission of the European Communities, Brussels COM (2001) 262 final. (More information available at: http://europa.eu.int/comm/environment/docum/01262_en.htm )

This document presents a "priority list of substances for further evaluation of their role in endocrine disruption. During 2000, a candidate list of 553 man-made substances and 9 synthetic/natural hormones has been identified." Organofluorine pesticides in this list include:

BASF & IR-4: Pesticide tolerance petitions.

• Fipronil and its sulfone and amide constitute greater than 75% of the identified residues in all studies.
• Reproductive and developmental toxicity. The developmental toxicity NOELs in the rat and rabbit were 20 mg/kg/day (HDT) and 1 mg/kg/day (HDT), respectively. Maternal toxicity was observed in the rat at the HDT as evidenced by decreased body weight gain and food efficiency. In the rabbit, the maternal toxicity NOAEL was less than 0.1 mg/kg/day, based on reduced body weight gain and food efficiency at all dose levels tested. In a two-generation rat study, the NOEL for parental (systemic) toxicity was 3 ppm (0.26 mg/kg/day for both sexes combined), based on increased weight of the thyroid glands and liver in males and females, decreased weight of the pituitary gland in females, and an increased incidence of follicular epithelial hypertrophy in females at 30 ppm. The NOEL for reproductive toxicity was 30 ppm (2.64 mg/kg/day for both sexes combined), based on clinical signs of toxicity in pups, decreased litter size, decreased pup body weights, decreased mating, decreased fertility index, reduced pre- and postnatal survival, and delays in physical development at 300 ppm (26.03 and 28.40 mg/kg/day for males and females, respectively).
• In a developmental neurotoxicity study in the rat, the NOAEL for maternal toxicity was 10 ppm (0.91 mg/kg/day), based on decreased body weights and body weight gain at 200 ppm (HDT; 15 mg/kg/day). Considerable maternal toxicity at the HDT prevented adequate neurotoxicity evaluation of pups at this dose level. There was no evidence of neurotoxicity at 10 ppm (0.91 mg/kg/day), which was the NOAEL for developmental neurotoxicity. The NOAEL for general developmental toxicity was 0.5 ppm (0.05 mg/kg/day), based on systemic effects consisting of decreases in pup weights during lactation and increases in time of preputial separation in males at 10 ppm.
• Subchronic toxicity. The NOAEL for systemic toxicity in rat was 5 ppm (0.35 mg/kg/day for both sexes combined), based on alterations in serum protein values and increased weight of the liver and thyroid at 30 ppm (1.93 and 2.28 mg/kg/day for males and females, respectively). The NOAELs in the dog were 2 and 0.5 mg/kg/day for male and female, respectively, based on clinical signs of toxicity in males at 10 mg/kg/day and clinical signs of toxicity and decreased body weight gain in females at 2 mg/kg/day. The NOAEL for mice was 10 ppm (1.27 and 1.72 mg/kg/day for males and females, respectively), based on a possible decreased body weight gain at 25 ppm (3.2 and 4.53 mg/kg/day for males and females, respectively). A repeated dose dermal study in the rabbit had a systemic NOAEL of 5 mg/kg/day, based on decreased body weight gain and food consumption at 10 mg/kg/day, and a dermal irritation NOEL of 10.0 mg/kg/day (HDT).
• Subchronic neurotoxicity study in rats, the NOEL was 5 ppm (0.301 and 0.351 mg/kg/day for males and females, respectively), based on results of the functional observational battery (FOB) at 150 ppm (8.89 and 10.8 mg/kg/day for males and females, respectively).
• Chronic toxicity. The NOAEL for systemic toxicity in a 1-year feeding study in the dog was 0.3 mg/kg/day in females and 1 mg/kg/day in males, based on clinical signs of neurotoxicity at 1 and 2 mg/kg/day in females and males, respectively. The NOAEL for systemic toxicity in mice was 0.5 ppm (0.06 mg/kg/day) based on decreased body weight gain, decreased food conversion efficiency in males, increased liver weights, and liver histopathology at 10 ppm (1.3 mg/kg/day). Fipronil was not
carcinogenic when administrated to mice at dose levels up to 60 ppm. The NOAEL in a 2-year dietary study in the rat was 0.5 ppm (0.019 and 0.025 mg/kg/day for males and females, respectively) based on clinical signs of toxicity and alterations in clinical chemistry and thyroid parameters at 1.5 ppm (0.059 and 0.078 mg/kg/day for males and females, respectively).
• Cancer. The EPA's Health Effects Division Carcinogenicity Peer Review Committee classified fipronil in Group C - Possible Human Carcinogen, based on thyroid tumors observed in rats at 300 ppm (HDT). Mechanistic data indicate that these tumors are related to a disruption in the thyroid-pituitary status and are specific to the rat. In addition, there was no apparent concern for mutagenic activity. Thus, it was recommended that RfD methodology, i.e. non-linear or threshold, be used for the estimation of human risk.
• Acute neurotoxicity. The NOEL was 2 mg/kg, based on decreases in body weight gain and food consumption in males and females during the week following treatment, decreases in locomotor activity, hind-limb splay and rectal temperature 6-hour post dosing in males and females, and decreases in the proportion of males with an immediate righting reflex on days 7 and 14, at 12 mg/kg/day. In a rat developmental toxicity study, the NOEL was 1 mg/kg/day, based on the slight increase in fetal and litter incidence of reduced ossification of several bones at 2.5 mg/kg/day.
• Subchronic toxicity. The NOAEL in the rat was 3 ppm (0.18 and 0.21 mg/kg/day in males and females, respectively), based on clinical signs of toxicity in both sexes and decreased body weight and body weight gain in males at 10 ppm. The NOEL for the mouse was 0.5 ppm (0.08 mg/kg/day), based on the aggressive and irritable behavior with increased motor activity in males at 2 ppm. The NOEL for the dog was 9.5 ppm (0.29 mg/kg/day), based on behavioral changes in females at 35 ppm (1.05 mg/kg/day).
• The rat chronic/carcinogenicity study was negative for carcinogenicity. The LOAEL for females was 0.5 ppm (0.032 mg/kg/day), based on clinical signs of toxicity. There was no NOEL established. For males, the NOAEL was 2 ppm (0.098 mg/kg/day), based on clinical signs of toxicity, and stomach and lung histopathology at 10 ppm (0.497 mg/kg/day).
• Endocrine disruption. Data from the reproduction/ developmental toxicity and short- and long-term repeated dose toxicity studies with fipronil in the rat, rabbit, mouse, or dog, do not suggest any endocrine disruption activity. This information is based on the absence of any treatment-related effects from the histopathological examination of reproductive organs as well as the absence of possible effects on fertility, reproductive performance, or any other aspect of reproductive function, or on growth and development of the offspring. Evidence of offspring toxicity was observed only in the presence of significant parental toxicity. Fipronil disrupts the thyroid-pituitary axis. However, mechanistic studies have demonstrated that fipronil decreases thyroid hormone levels in long-term studies via increased clearance, rather than a direct effect on the thyroid. Concerns related
to long-term exposure of fipronil are addressed in human risk estimates, as the chronic RfD (0.0002 mg/kg/day) is based on endpoints that include thyroid hormone related effects in rats.
• Drinking Water. A drinking water monitoring study for fipronil and relevant metabolites in surface water from the corn growing regions has been conducted (MRID 45526101). The ground water values model by the EPA when the cotton use was examined will also be used for comparison. The samples were collected on regular intervals between April and August. The water samples wereanalyzed for firponil and metabolites: MB45950, MB46136, and MB46513.
• Post-application exposure of children can occur from three scenarios:
(1) Incidental ingestion of fipronil pellets or granules;
(2) incidental ingestion of soil (hand to mouth) from fipronil treated residential areas; and
(3) incidental ingestion (hand to mouth) of fipronil from treated pets.