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Abstracts

Activity: Insecticide, Acaricide (pyrethroid)
Structure:

Adverse Effects:
Ataxia
Bladder
Body Weight Decrease
Cancer: Possible Human Carcinogen URINARY BLADDER, LIVER, LUNG
Endocrine: Ovary/Estrus
Endocrine: Suspected Disruptor
Endocrine: Thyroid
Liver
Lung
Tremors/Convulsions
Environmental

A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks... Ataxia was noted in 4 dogs/sex at 8.84 and 17.7 mg/kg/ day and in one female at 4.42 mg/kg/day. Languidness occurred primarily at 17.7 mg/kg/day in both sexes, but also occasionally at 8.84 mg/kg/ day. All of these symptoms occurred more frequently during the last 3 weeks of the study. Other dose-related clinical signs included blinking, mydriasis, nystagmus, lacrimation, and polypnea.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule. http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Bladder (click on for all fluorinated pesticides)

A chronic/carcinogenicity study in mice fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or 30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females). Chronic LOEL is 10 mg/kg/day based on the incidence of tremors in both sexes. Chronic NOEL is 2.5 mg/kg/day. Carcinogenic potential was evidenced by a statistically significant increased trend for hemangiopericytomas in the urinary bladders of males, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females.
Carcinogenicity. Using its Guidelines for Carcinogen Risk Assessment published September 24, 1986 (51 FR 33992) the Carcinogenicity Peer Review Committee (CPRC) has classified bifenthrin as a Group C chemical, possible human carcinogen, based on urinary bladder tumors in mice, but did not recommend assignment of a cancer potency factor Q* (Q star) for a linear quantitative cancer risk assessment, instead, the CPRC recommended the RfD approach. Based on CPRC's recommendation that the RfD approach be used to assess dietary cancer risk, a quantitative linear dietary cancer risk assessment was not performed. Human health risk concerns due to long term consumption of bifenthrin residues are adequately addressed by the dietary risk evaluation chronic exposure analysis using the RfD.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Abstract: Bifenthrin, a synthetic pyrethroid insecticide/miticide, has been fed to male and female Swiss Webster mice at levels of 0, 50, 200, 500, and 600 ppm in the diet for between 604 and 644 days. Tumors of the urinary bladder were observed and initially reported as leiomyosarcomas. Subsequently, the bladders were reviewed and the tumors showed a pattern of both epithelioid cells and spindle cells forming irregular vascular channels. The tumors appeared to arise from the trigone of the bladder and, in some cases, invaded the bladder wall. No metastases were recorded. The tumor is usually considered rare; however, in this study, it was commonly observed in all groups but predominantly in males. The histogenesis of the tumor is uncertain, but from its pleomorphic histological features, including smooth muscle and vascularity, it is probably derived from vascular mesenchyme.
Ref: Mesenchymal tumors of the mouse urinary bladder with vascular and smooth muscle differentiation; by Butler WH, Cohen SH, Squire RA. Toxicol Pathol. 1997 May-Jun;25(3):268-74.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9210258&dopt=Abstract

... In a rat teratology study, an increased incidence of hydroureter (without hydronephrosis) was noted in fetuses at 2 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. EPA believes that there is sufficient evidence for listing bifenthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological and developmental toxicity data.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

Body Weight Decrease (click on for all fluorinated pesticides)

Reproductive toxicity study. In the rat reproduction study, parental toxicity occurred as decreased body weight at 5.0 mg/kg/day with a NOEL of 3.0 mg/kg/day. There were no developmental (pup) or reproductive effects up to 5.0 mg/kg/day (highest dose tested).
Ref: Federal Register: September 5, 1997. Bifenthrin; Pesticide Tolerances for Emergency Exemptions.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Sept.5.1997.htm

A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks... A non-statistically significant, but possibly treatment- related reduction in body weight (bwt) gain was noted in females at 17.7 mg/kg/day (0.6 kilogram (kg)) relative to the controls (1.3 kg). None of the females at 8.84 or 17.7 mg/kg/day showed cyclic activity or signs of estrus, but cyclic activity was observed in 2, 2, and 1 female at 0, 2.21, and 4.42 mg/kg/day, respectively and \4/5\ showed signs of estrus. The lowest observed effect level (LOEL) for this 13-week study is 4.42 mg/kg/day based on the increased incidence of tremors in both sexes. The NOEL is 2.21 mg/kg/day.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Cancer: Possible Human Carcinogen URINARY BLADDER & LIVER (click on for all fluorinated pesticides)

Group C -- Possible Human Carcinogen. Hemangiopericytomas in the urinary bladder; Hepatocellular carcinomas & combined hepatocellular adenomas & carcinomas; Swiss Webster mice (M)
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs.
From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Group C -- Possible Human Carcinogen. Hemangiopericytomas in the urinary bladder; Hepatocellular carcinomas & combined hepatocellular adenomas & carcinomas; Swiss Webster mice (M)
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs.
From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Group C--Possible Human Carcinogen. Reviewed 4/ 29/ 92.
Ref: List of Chemicals Evaluated for Carcinogenic Potential. Science Information Management Branch, Health Effects Division, Office of Pesticide Programs, U. S. Environmental Protection Agency. March 15, 2002.
http://www.biomuncie.org/chemicals_evaluated_for_carcinog.htm

Abstract: The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen [fluoridated] and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.
Ref: Tumor-promoting activity and mutagenicity of 5 termiticide compounds; by Goto S, Asada S, Fushiwaki Y, Mori Y, Tanaka N, Umeda M, Nakajima D, Takeda K. J UOEH. 2004 Dec 1;26(4):423-30.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15624354&query_hl=11

"Bifenthrin. Withdrawn. Indication of carcinogenic effects. 1992."
Definition: "Withdrawn. A substance which the manufacturer has either withdrawn from the market, or for which he has withdrawn his application for registration, approval, or renewed approval and when it is clear that these measures were undertaken due to the health or environmental properties of the substance."
Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

A chronic/carcinogenicity study in mice fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or 30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females). Chronic LOEL is 10 mg/kg/day based on the incidence of tremors in both sexes. Chronic NOEL is 2.5 mg/kg/day. Carcinogenic potential was evidenced by a statistically significant increased trend for hemangiopericytomas in the urinary bladders of males, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females.
Carcinogenicity. Using its Guidelines for Carcinogen Risk Assessment published September 24, 1986 (51 FR 33992) the Carcinogenicity Peer Review Committee (CPRC) has classified bifenthrin as a Group C chemical, possible human carcinogen, based on urinary bladder tumors in mice, but did not recommend assignment of a cancer potency factor Q* (Q star) for a linear quantitative cancer risk assessment, instead, the CPRC recommended the RfD approach. Based on CPRC's recommendation that the RfD approach be used to assess dietary cancer risk, a quantitative linear dietary cancer risk assessment was not performed. Human health risk concerns due to long term consumption of bifenthrin residues are adequately addressed by the dietary risk evaluation chronic exposure analysis using the RfD.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Carcinogenic Effects: There was no evidence of cancer in a 2-year study of rats who ate as much as 10 mg/kg/day of bifenthrin. However, an 87 week feeding study of mice with doses of 7, 29, 71, and 86 mg/kg showed a significantly higher, dose related trend of increased tumor incidence in the male urinary bladder (63, 67). The incidence was significantly increased at 86 mg/kg/day. Also, females had higher incidences of lung cancer than the controls at doses of 7 mg/kg and higher (67). The EPA has classified bifenthrin as a class C carcinogen, a possible human carcinogen (11, 63).
Ref: EXTOXNET Pesticide Information Profile. 1995.
http://ace.ace.orst.edu/info/extoxnet/pips/bifenthr.htm

Abstract: The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.
Ref: J UOEH. 2004 Dec 1;26(4):423-30. Tumor-promoting activity and mutagenicity of 5 termiticide compounds.Goto S, Asada S, Fushiwaki Y, Mori Y, Tanaka N, Umeda M, Nakajima D, Takeda K.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15624354

Endocrine: Ovary / Estrus  (click on for all fluorinated pesticides)

REPRODUCTION, RAT. 50429-065 - 50429-070; 42427-42432; "Multigeneration Reproduction Study with FMC 54800 (Biphenate) Technical in Rats"; 834; FMC Toxicology Laboratory; 1/31/86; Bifenthrin technical (FMC 54800), 88.35% a.i., 98% cis, 2% trans; 100, 60, 30 and 0 ppm in the feed for 8 weeks prior to F0 mating through F2b weaning; 25/sex/dose; no fertility or reproductive effects, other effects include tremors during lactation, ovary weight reduction in adults; NOEL = 100 ppm (reproductive/fertility), NOEL = 60 ppm (tremors), NOEL = 30 ppm (ovary weight reduction); No Adverse Effects Indicated; Study Acceptable. (Martz, 1/5/87; Updated 5/8/89, Morgan)
Ref: Summary of toxicology data: Bifenthrin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Original date: August 26, 1987 Revised dates: 7/9/90, 9/19/94, 4/4/00.
http://www.cdpr.ca.gov/docs/toxsums/pdfs/2300.pdf

A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks. There was no mortality during the study... A non-statistically significant, but possibly treatment- related reduction in body weight (bwt) gain was noted in females at 17.7 mg/kg/day (0.6 kilogram (kg)) relative to the controls (1.3 kg). None of the females at 8.84 or 17.7 mg/kg/day showed cyclic activity or signs of estrus, but cyclic activity was observed in 2, 2, and 1 female at 0, 2.21, and 4.42 mg/kg/day, respectively and \4/5\ showed signs of estrus. The lowest observed effect level (LOEL) for this 13-week study is 4.42 mg/kg/day based on the increased incidence of tremors in both sexes. The NOEL is 2.21 mg/kg/day.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Endocrine: Suspected Disruptor (click on for all fluorinated pesticides)

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Endocrine: Thyroid (click on for all fluorinated pesticides)

Limited data were available regarding endocrine effects in animals following oral exposure to pyrethroids. Serum levels of the thyroid hormones T3 and T4 were significantly decreased in mice administered fenvalerate at a dose level of 120 mg/kg/day for 15 days (Maiti and Kar 1998). Akhtar et al. (1996) reported similar effects in rats administered bifenthrin or lambda-cyhalothrin at daily oral dose levels of 0.5 mg/rat (approximately 0.75 mg/kg/day) and 0.2 mg/rat (approximately 2 mg/kg/day), respectively, for 21 days. Lambda-cyhalothrin treated rats also exhibited a significantly decreased serum T3/T4 ratio, relative to controls. In addition, both bifenthrin and lambda-cyhalothrin treatment resulted in significantly increased serum TSH levels, compared with control rats (p 39)
Ref: September 2001. Draft Toxicological Profile for Pyrethrins and Pyrethroids. US Department of Health and Human Services. Public Health Service Agency for Toxic Substances and Disease Registry.

Endocrine Disruption. EPA is required to develop a screening program to determine whether certain substances (including all pesticides and inerts) ``may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or such other endocrine effect....'' The Agency is currently working with interested stakeholders, including other government agencies, public interest groups, industry and research scientists in developing a screening and testing program and a priority setting scheme to implement this program. Congress has allowed 3 years from the passage of FQPA (August 3, 1999) to implement this program. At that time, EPA may require further testing of this active ingredient and end use products for endocrine disrupter effects.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Liver (click on for all fluorinated pesticides)

A chronic/carcinogenicity study in mice fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or 30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females). Chronic LOEL is 10 mg/kg/day based on the incidence of tremors in both sexes. Chronic NOEL is 2.5 mg/kg/day. Carcinogenic potential was evidenced by a statistically significant increased trend for hemangiopericytomas in the urinary bladders of males, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

-- Category C (possible human) carcinogen, primarily on the basis of the mouse carcinogenicity study in which the high-dose males (81.3 mg/kg/day) showed a highly significant increased incidence of urinary bladder tumors. Other findings in the mouse study included a dose-related trend of increased combined incidences of adenoma and adenocarcinoma of the liver (males only), and increased incidences of bronchioalveolar adenomas and adenocarcinomas of the lung in females at some, but not all, doses relative to their controls.
Ref. Federal Register. April 30, 2003. Bifenthrin; Pesticide Tolerance.
http://www.fluorideaction.org/pesticides/bifenthrin.fr.apr.30.2003.htm

Lung (click on for all fluorinated pesticides)

A chronic/carcinogenicity study in mice fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or 30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females). Chronic LOEL is 10 mg/kg/day based on the incidence of tremors in both sexes. Chronic NOEL is 2.5 mg/kg/day. Carcinogenic potential was evidenced by a statistically significant increased trend for hemangiopericytomas in the urinary bladders of males, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Carcinogenic Effects: There was no evidence of cancer in a 2-year study of rats who ate as much as 10 mg/kg/day of bifenthrin. However, an 87 week feeding study of mice with doses of 7, 29, 71, and 86 mg/kg showed a significantly higher, dose related trend of increased tumor incidence in the male urinary bladder (63, 67). The incidence was significantly increased at 86 mg/kg/day. Also, females had higher incidences of lung cancer than the controls at doses of 7 mg/kg and higher (67). The EPA has classified bifenthrin as a class C carcinogen, a possible human carcinogen (11, 63).
Ref: EXTOXNET Pesticide Information Profile. 1995.
http://ace.ace.orst.edu/info/extoxnet/pips/bifenthr.htm

Tremors/Convulsions (click on for all fluorinated pesticides)

For the inhalation endpoint, no appropriate studies were available. EPA determined that the risk assessment should be inclusive of oral and inhalation exposure components assuming 100 percent absorption via the inhalation route. An aggregate oral and inhalation risk assessment is appropriate due to the similarity in the toxicity endpoint (neurotoxicity) seen in rats via these routes. The inhalation study used for comparison purposes was an acute toxicity study in rats on the 25.1 percent formulation where tremors, convulsions, and loss of hindlimb motor control was observed among other clinical signs of toxicity.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

-- Acute dietary general population including infants and children: Developmental toxicity, Rats - tremors in dams during & post dosing
-- Chronic dietary all populations: Chronic oral, dogs - tremors in both sexes
-- Short-term dermal (1 to 7 days) (Occupational/Residential): Developmental toxicity, Rats - tremors in dams during & post dosing
-- Intermediate-term dermal (1 week to several months) (Occupational/Residential): Developmental toxicity, Rats - tremors in dams during & post dosing
-- Chronic dermal (several months to lifetime) (Occupational/Residential): Chronic oral, dogs - tremors in both sexes
-- All time periods: Inhalation (Occupational/Residential): Development toxicity, Rats - tremors in dams during & post dosing (No appropriate inhalation studies available)
Ref: Federal Register: September 27, 2001. Bifenthrin; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Sept.27.2001.htm

1996: A chronic dietary exposure/risk assessment has been performed for bifenthrin using a Reference Dose (RfD) of 0.015 mg/kg of bwt/day. The RfD was based on a No Observed Effect Level (NOEL) of 1.5 mg/kg/day from the 1-year study in dogs and a safety factor of 100. The endpoint effect of concern was intermittent tremors in test animals at the lowest effect level.
Ref: Federal Register: June 12, 1996. Bifenthrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.Fr.June.12.1996.htm

Nov. 26, 1997:
A 13-week feeding study in dogs (by capsule) of doses at nominal dose levels of 0, 2.5, 5, 10, or 20 milligram/kilogram/day (mg/kg/day) (equivalent to 2.21, 4.42, 8.84, and 17.7 mg/kg/day, based on percent active ingredient (a.i.)) for 13 weeks... Tremors were noted in 3 dogs/sex at 4.42 mg/kg/day and in 4 dogs/sex at 8.84 and 17.7 mg/kg/day.
A 90-day feeding study in rats fed at doses of 0, 12, 50, 100, and 200 ppm (0, 0.6, 2.5, 5, or 10 mg/kg/day) with a NOEL of 2.5 mg/kg/ day and LOEL of 5 mg/kg/day based on the increased incidence of tremors in both sexes.
A 1-year chronic/carcinogenicity study in dogs was administered in the diet at dose levels of 0, 0.75, 1.5, 3, or 5 mg/kg/day... Tremors were noted in all males and females at 5 mg/kg/day during weeks 15-29 and in \1/4\ males and \2/4\ females at 3 mg/kg/day during weeks 16-23... The LOEL for this 52- week study is 3 mg/kg/day based on the increased incidence of tremors in both sexes. The NOEL is 1.5 mg/kg/day.
A chronic/carcinogenicity study in mice fed at doses of 0, 50, 200, 500, or 600 ppm (0, 2.5, 10, 25, or 30 mg/kg/day) in the diet for 87 weeks (males) or 92 weeks (females). Chronic LOEL is 10 mg/kg/day based on the incidence of tremors in both sexes.
Chronic/carcinogenicity study in rats was administered for in the diet at doses of 0, 12, 50, 100, or 200 ppm (0, 0.6, 2.5, 5, or 10 mg/kg/day). Chronic LOEL is 5 mg/kg/day based on the increased incidence of tremors in both sexes and possible increases in organ-to- body weight ratios in males. Chronic NOEL is 2.5 mg/kg/day.
In a pilot developmental study in rats bifenthrin was administered in the diet at dose levels of 0, 0.5, 1.0, 2.0, or 2.5 mg/ kg/day during days 6-15 of gestation. Three of 10 rats at 2.5 mg/kg/day died on days 14-15. Tremors were noted in all 10 rats at 2.5 mg/kg/day and in \9/10\ at 2.0 mg/kg/day... The maternal LOEL is 2.0 mg/kg/day based on sporadic tremors (gestation days 7-18) and 30 percent mortality at 2.5 mg/kg/day. The maternal NOEL is 1.0 mg/kg/day. The developmental LOEL and NOEL were not determined; fetuses were not examined.
A developmental study in rats given gavage doses of 0, 0.5, 1.0, or 2.0 mg/kg/day was administered... Maternal toxicity NOEL was 1.0 mg/kg/day based on tremors at LOEL of 2.0 mg/kg/day.
A developmental study in rabbits given gavage doses of 0, 2.67, 4.0, or 8.0 mg/kg/day or with 3.0 gram/kilogram/day (g/kg/day) resulted in no developmental toxicity observed under the conditions of the study. The maternal NOEL is 2.67 mg/kg/day, based on head and forelimb twitching at LOEL of 4.0 mg/kg/day. The developmental NOEL is 8.0 mg/kg/day, the highest dose tested.
A 2-generation reproduction study in rats fed diets containing doses of 0, 30, 60, or 100 ppm (0, 1.5, 3 or 5 mg/kg/day). Systemic LOEL is 5 mg/kg/day based on the incidence of tremors and marginally lower bwts in P and F1 generation females during gestation and lactation. Systemic NOEL is 3 mg/kg/day.
For the inhalation endpoint, no appropriate studies were available. EPA determined that the risk assessment should be inclusive of oral and inhalation exposure components assuming 100 percent absorption via the inhalation route. An aggregate oral and inhalation risk assessment is appropriate due to the similarity in the toxicity endpoint (neurotoxicity) seen in rats via these routes. The inhalation study used for comparison purposes was an acute toxicity study in rats on the 25.1 percent formulation where tremors, convulsions, and loss of hindlimb motor control was observed among other clinical signs of toxicity.
Ref: Federal Register: November 26, 1997. Bifenthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Bifenthrin.FR.Nov.1997.htm

Environmental (click on for all fluorinated pesticides) Aquatic acute toxicity values for bifenthrin include a bluegill 96- hour LC 50 of 0.35 ppb, a rainbow trout 96-hour LC 50 of 0.15 ppb, a sheepshead minnow LC 50 of 17.5 ppb, and a daphnid 48-hour EC 50 of 1.6 ppb. EPA believes that there is sufficient evidence for listing bifenthrin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the available environmental toxicity data. Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule. Fish -- Sheepshead minnow (Cyprinodon variegatus) - Very Highly Toxic -- Gizzard shad (Dorosoma cepedianum) - Very Highly Toxic Ref: Acute Aquatic Ecotoxicity Summaries for Bifenthrin on All Taxa Groups. PAN Pesticides Database - Chemical Toxicity Studies on Aquatic Organisms. http://www.pesticideinfo.org/List_AquireAcuteSum.jsp?Rec_Id=PC32863 Fish -- Sheepshead minnow Cyprinodon variegatus - - Very Highly Toxic -- Bluegill (Lepomis macrochirus) - Very Highly Toxic -- Rainbow trout,donaldson trout Oncorhynchus mykiss - Very Highly Toxic Ref: PAN Pesticides Database - Chemical Toxicity Studies on Aquatic Organisms. Toxicity Studies for Bifenthrin on All Organism Groups - Toxicology studies on aquatic organisms from science journals. http://www.pesticideinfo.org/List_AquireAll.jsp?Rec_Id=PC32863 Persistence in sediment Abstract: Pyrethroids are commonly used insecticides in both agricultural and urban environments. Recent studies showed that surface runoff facilitated transport of pyrethroids to surface streams, probably by sediment movement. Sediment contamination by pyrethroids is of concern due to their wide-spectrum aquatic toxicity. In this study, we characterized the spatial distribution and persistence of bifenthrin [BF; (2-methyl(1,1'-biphenyl)-3-yl)methyl 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate] and permethrin [PM; 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester] in the sediment along a 260-m runoff path. Residues of BF and PM were significantly enriched in the eroded sediment, and the magnitude of enrichment was proportional to the downstream distance. At 145 m from the sedimentation pond, BF was enriched by >25 times, while PM isomers were enriched by >3.5 times. Pesticide enrichment along the runoff path coincided with enrichment of organic carbon and clay fractions in the sediment, as well as increases in adsorption coefficient K(d), suggesting that the runoff flow caused selective transport of organic matter and chemical-rich fine particles. Long persistence was observed for BF under both aerobic and anaerobic conditions, and the half-life ranged from 8 to 17 mo at 20 degrees C. The long persistence was probably caused by the strong pesticide adsorption to the solid phase. The significant enrichment, along with the prolonged persistence, suggests that movement of pyrethroids to the surface water may be caused predominantly by the chemically rich fine particles. It is therefore important to understand the fate of sediment-borne pyrethroids and devise mitigation strategies to reduce offsite movement of fine sediment. Ref: Distribution and persistence of pyrethroids in runoff sediments; by Gan J, Lee SJ, Liu WP, Haver DL, Kabashima JN. J Environ Qual. 2005 Apr 20;34(3):836-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15843646&query_hl=11 Abstract: The use of pyrethroid insecticides is increasing for agriculture, commercial pest control, and residential consumer use. In addition, there is a trend toward the use of newer and more potent compounds. Little is known about the toxicity of sediment-associated pyrethroid residues to aquatic organisms, yet recent work has shown they commonly are found in aquatic sediments in the heavily agricultural Central Valley of California, USA. Minimal data exist on the sensitivity of standard sediment toxicity testing species to pyrethroids, despite two or more decades of agricultural use of these compounds. Sediment concentrations causing acute toxicity and growth impairment to the amphipod Hyalella azteca were determined for six pyrethroids in three sediments, ranging from 1.1 to 6.5% organic carbon (OC). In order of decreasing toxicity of sediment-associated residues, the compounds tested were bifenthrin (average 10-d median lethal concentration [LC50] = 0.18 microg/g OC), lambda-cyhalothrin (0.45 microg/g OC), deltamethrin (0.79 microg/g OC), esfenvalerate (0.89 microg/g OC), cyfluthrin (1.08 microg/g OC), and permethrin (4.87 microg/g OC). In a sediment containing about 1% OC, most pyrethroids, except permethrin, would be acutely toxic to H. azteca at concentrations of 2 to 10 ng/g dry weight, a concentration only slightly above current analytical detection limits. Growth typically was inhibited at concentrations below the LC50; animal biomass on average was 38% below controls when exposed to pyrethroid concentrations roughly one-third to one-half the LC50. Survival data are consistent with current theory that exposure occurs primarily via the interstitial water rather than the particulate phase. A reanalysis of previously reported field data using these toxicity data confirms that the compounds are exceeding concentrations acutely toxic to sensitive species in many agriculture-dominated water bodies. Ref: Use and toxicity of pyrethroid pesticides in the Central Valley, California, USA. Amweg EL, Weston DP, Ureda NM. Environ Toxicol Chem. 2005 Apr;24(4):966-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15839572&query_hl=11 Abstract: The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied. The results showed that 24 h-EC50, 48 h-LC50 and 96 h-LC50 of bifenthrin on D. magna were 3.24, 12.40 and 1.40 microg/L respectively. And the LOEC and NOEC of bifenthrin were 0.02 and 0.004 microg/L respectively. The recovery test of bifenthrin on Daphnia magna was presented. Daphnia magna (F0 generation) were exposed during 21 d to different bifenthrin concentrations. Offspring (animals from the first and third brood: F1 (1st) and F1 (3rd), respectively) were transferred to a free pesticide medium during a 21 d recovery period. In this recovery study, survival, growth, reproduction (mean total young per female, onset of reproduction and number broods per female) and the intrinsic rate of natural increase (r) were assessed as parameters. Reproduction such as number of young per female as well as length was still reduced in F1 (1st) generation daphnids from parentals (F0) exposed to the bifenthrin. However F, (3rd) individuals from parentals exposed to pesticide concentrations were able to restore reproduction when a recovery period of 21 d was allowed, but the length of F, (3rd) from parentals exposed to the 0.5 and 0.75 microg/L bifenthrin concentration was still significantly effected (P < 0.05). Ref: Effects of bifenthrin on Daphnia magna during chronic toxicity test and the recovery test; by Ye WH, Wen YZ, Liu WP, Wang ZQ. J Environ Sci (China). 2004;16(5):843-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15559825&query_hl=11 Abstract: Recent studies showed that synthetic pyrethroids (SPs) can move via surface runoff into aquatic systems. Fifty-six of SP-degrading bacteria strains were isolated from contaminated sediments, of which six were evaluated for their ability to transform bifenthrin and permethrin in the aqueous phase and bifenthrin in the sediment phase. In the aqueous phase, bifenthrin was rapidly degraded by strains of Stenotrophomonas acidaminiphila, and the half-life (t1/2) was reduced from >700 h to 30 to 131 h. Permethrin isomers were degraded by Aeromonas sobria, Erwinia carotovora, and Yersinia frederiksenii. Similar to bifenthrin, the t1/2 of cis- and trans-permethrin was reduced by approximately 10-fold after bacteria inoculation. However, bifenthrin degradation by S. acidaminiphila was significantly inhibited in the presence of sediment, and the effect was likely caused by strong adsorption to the solid phase. Bifenthrin t1/2 was 343 to 466 h for a field sediment, and increased to 980 to 1200 h for a creek sediment. Bifenthrin degradation in the inoculated slurry treatments was not greatly enhanced when compared with the noninoculated system. Therefore, although SP-degrading bacteria may be widespread in aquatic systems, adsorption to sediment could render SPs unavailable to the degraders, thus prolonging their persistence. Ref: Microbial transformation of pyrethroid insecticides in aqueous and sediment phases; by Lee S, Gan J, Kim JS, Kabashima JN, Crowley DE. Environ Toxicol Chem. 2004 Jan;23(1):1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14768859&query_hl=11