Adverse Effects:

Body Weight Decrease
Blood
Cancer: Likely to be Carcinogenic to Humans: LIVER
Eye
Kidney
Liver

Environmental Effects:

The acid metabolite has a potential for leaching which might require particular attention in vulnerable areas to ensure protection of groundwater.

13 residue tolerances for:
Corn, Cotton, Potato, Soybean 

Pyraflufen-ethyl belongs to the protox inhibitor class of compounds, and chemically is a 3-phenylpyrazole. The herbicidal activity of protox inhibitors is due to the inhibition of protoporphyrinogen IX oxidase.
Ref: US EPA, Federal Register: Nov 20, 2002

E2: 2-chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazole-3yl)-4-fluorophenol
E3: 4-chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl)-5-difluoromethoxy-1-methylpyrazole
E9: 2-chloro-5-(4-chloro-5-difluoromethoxylpyrazole-3yl)-4-fluorophenoxyacetic acid.

Pyraflufen-ethyl was practically completely degraded into E1 metabolite. E1 metabolite was to a large extent degraded into metabolite E2 and to a minor extent into metabolite E9. Metabolite E2 was almost completely degraded into metabolite E3. In the aerobic soil metabolism studies, soil bound residues were formed in percentages ranging from 15-17% and cumulative amounts of CO2 ranged from 2 to 9%. The maximum levels and half-lives of E1, E2 and E3 in laboratory studies with aerobic soils are given in the following table.

The half-lives of E2 and E3 given in this table were measured in studies in which either E2 or E3 was added to the soil. It was not attempted to derive half-lives of E2 and E3 from metabolism studies with the parent compound. However, the results of studies with the parent compound are not consistent with the half-lives of 6-11 days reported above for E2: in studies with the parent compound the percentage E2 after 100 days was 7, 12, 30 and 39% in four different soils.

Nichino America, Inc. Pesticide Petition. PP 7F7190. Proposal to establish a tolerance for residues of the herbicide, pyraflufen-ethyl and its acid metabolite, E-1 (2-chloro-5-(4-chloro-5-difluoromethoxy-(1-methyl-1H- pyrazol-3-yl)-4-fluorophenoxyacetic acid), expressed in terms of the parent in or on food commodities:

Aqueous organic solvent extraction, column clean up, and quantitation by GC is used to measure and evaluate the chemical residues.

Nichino America. Pesticide Tolerance. FINAL RULE.
-- Pyraflufen-ethyl has been classified as a ``likely to be carcinogenic to humans'' by the oral route of exposure. The exposure from pyraflufen-ethyl residues in food results in a cancer risk in the range of 1 in 1 million and is not a concern.
-- Tolerances have been established (40 CFR 180.585) for the combined residues of pyraflufen-ethyl and its acid metabolite, E-1 (2-chloro-5-(4-
chloro-5-difluoromethoxy-1-methyl-1H- pyrazol-3-yl)-
4-fluorophenoxyacetic acid), expressed as the ester equivalent, in or on a variety of raw agricultural commodities.
-- Pyraflufen-ethyl is currently registered for use on the following residential non-dietary sites: Airports, nurseries, ornamental turf, golf courses, roadsides, railroads, noncrop land, and uncultivated agricultural areas.
-- EPA determined that the 10X SF to protect infants and children should be removed and instead, a different additional safety factor of 1X should be used. The FQPA factor is removed because: There is no evidence of increased susceptibility of rat or rabbit fetuses following in utero exposure in the developmental studies with pyraflufen-ethyl; there is no evidence of increased susceptibility of young rats in the reproduction study with pyraflufen-ethyl; there are no residual uncertainties identified in the exposure databases; the dietary food exposure assessment is expected to be conservative, tolerance-level residues and 100 PCT information were used; and dietary drinking water exposure is based on conservative modeling estimates.

May 21, 2003

Nichino America. Pesticide Tolerance. FINAL RULE. This regulation establishes a tolerance for combined residues of pyraflufen and pyraflufen-ethyl in or on
-- Cotton, gin byproduct............ 1.5
-- Cotton, undelinted seed........0.04
-- Cancer Classification: ``Likely to be Carcinogenic to Humans'' by the oral route Q₁* = 3.32 x 10-2 (mg/kg/day)-1
-- Inhalation1 long-term (< 6 months) Oral NOAEL= 20 1X Mouse carcinogenicity. LOAEL = 98 mg/kg/day based on liver toxicity.
-- Inhalation1 intermediate-term (1-6 months) Oral NOAEL= 20 1X Mouse carcinogenicity. LOAEL = 98 mg/kg/day based on liver toxicity at interim sacrifice.
-- Inhalation1 short-term (1-30 days) Oral NOAEL= 20 1X Developmental toxicity- rabbit. LOAEL = 60 mg/kg/day based on decreases in bwt and food consumption, GI observations, and abortions.
-- Chronic dietary. Mouse carcinogenicity. Chronic RfD = 0.20 mg/ kg/day. LOAEL = 98 mg/kg/day. based on liver toxicity.
-- Pyraflufen-ethyl is currently registered for use on the following residential non-dietary sites: Airports, nurseries, ornamental turf, golf courses, roadsides, and railroads.

Nichino America. Pesticide tolerances. FINAL RULE established for combined residues of the herbicide pyraflufen-ethyl (ethyl 2-chloro-5-(4-chloro-5-difluoromethoxy-1- methyl-1H-pyrazol-3-yl)-4-fluorophenoxyacetate) and its acid metabolite, E-1 (2-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-1H- pyrazol-3-yl)-4-fluorophenoxyacetic acid)•, expressed as the ester equivalent in or on

-- Cancer Classification: ``Likely to be Carcinogenic to Humans'' by the oral route.
-- Mouse Carcinogenicity LOAEL = 98 mg/kg/day based on liver toxicty
-- Developmental toxicity- rabbit. LOAEL = 60 mg/kg/day based on decreases in bwt and food consumption, GI observations, and abortions

• -- Note from FAN; this metabolite is Pyraflufen.