Penoxsulam
CAS No. 219714-96-2
 
 

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ACTIVITY: Herbicide (triazolopyrimidine)

CAS Name: 2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-
yl)-6-(trifluoromethyl)benzenesulfonamide

Structure:

Adverse Effects:

Bladder
Body Weight Decrease
Cancer:
classified as Suggestive Evidence of Carcinogenicity (Mononuclear cell leukemia)
Endocrine: Testicular
Kidney
Leukemia
Liver
Skin
Environmental:
Penoxsulam is expected to be very mobile in the environment with six degradation products of toxicological concern to be even more mobile than the parent compound.
Data are not available to fully characterize these degradates and their respective degradation pathways.
Potential to leach to ground water

Regulatory Information
(only comprehensive for the US)
US EPA Registered: Yes
US EPA PC Code: 119031  
US Tolerances: 180.605
US Maximum Residue Levels permitted in food commodities

• On September 24, 2004, EPA issued its first-time tolerances for residues of Penoxsulam on food.

Rice, grain
Rice, straw

Other Information
Molecular Formula: C16H14 F5 N5O5S 
Manufacturers: Dow AgroSciences 
Logo for Grasp  
Other Names: Granite GR
Grasp SC
DE-638
XDE-638
XR-638
X-638177
 
Logo for Grasp
Of special interest:
PAN Data  

June 18, 2007 - Penoxsulam. Human Health Risk Assessment for Proposed Uses on Fish and Shellfish. Docket: EPA-HQ-OPP-2006-0076-0004. USEPA.

Notes from FAN:
• This 84 page EPA document, which we have downloaded for public access, has been deliberately "locked" and can neither be searched nor sentences copied.
• EPA reported a finding in the rat developmental toxicity study as Cutis laxis (pp 22-23), which we can only assume is as rare a term as the condition itself. If EPA persists in using terms that are not commonly used, then they should provide a definition. An accessible definition of Cutis Laxa was online: It is a rare disorder of connective tissue that causes the skin to stretch easily and hang in loose folds... Sometimes only the skin is affected, but connective tissues throughout the body can be affected.

2005 - Summary of Toxicology Data for Penoxsulam. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised 3/17/05.
October 2005 - Brazil - WTO.
September 2004 - US EPA Fact Sheet on Penoxsulam
August 25, 2003. Dow AgroSciences announces plans to manufacture penoxsulam, a new rice herbicide, at a brownfield site at their Michigan operations. Press Release.

Penoxsulam degradation products identified by EPA as being of toxicological concern. These toxic residues are:

BSTCA: 3-[[[2-(2.2-difluoroethoxy)-6-(trifluoromethyl)phenyl]-sulfnyl]animo]-1H-1,2,4-triazole-5-carboxylic acid

2-animo TCA: 2-animo-1,2,4-triazole carboxylic acid
(Synonym: Polars)

5-OH-XDE-638: 2-(2,2-difluoroethoxy)-N-(5,6-dihydro-8-methoxy-5-oxo[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-

SFA: 2-(2,2-difluoroethoxy)-N-(iminomethyl)-6-(trifluoromethyl)-benzenesulfonamide

sulfonamide: 2-(2,2,-difluoroethoxy)-6-(trifluormethyl)-benzenesulfonamide

5,8-diOH: 2-(2,2,-Difluoroethoxy)-t-trifluoromethyl-N-(5,8-dihydroxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide
Ref: (pages 81-82
) June 18, 2007 - Penoxsulam. Human Health Risk Assessment for Proposed Uses on Fish and Shellfish. Docket: EPA-HQ-OPP-2006-0076-0004. USEPA.

Penoxsulam: Breakdown products.
From Pesticide Action Network
Data Chemical Identity US EPA PC Code
PAN 2-(2,2-Difluoroethoxy)-N-(5,6-dihydro-8-methoxy-5-oxo-[1,2,4]triazolo [1, Breakdown product 619031
PAN 3-[[[2-(2,2-Difluoroethoxy)-6-(trifluoromethyl)phenyl]sulfonyl]amino]-1H-1,2,4- Breakdown product 619032
PAN 2-Amino-8-methoxy[1,2,4]triazolo[1,5-c]pyrimidin-5-ol Metabolite of Penoxsulam / breakdown product 619033
PAN 2(2,2-Difluoroethoxy)-6-(trifluoromethyl)benzenesulfonic acid Metabolite of Penoxsulam / breakdown product 619034
PAN 5,8-Dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-amine Metabolite of Penoxsulam / breakdown product 619035
PAN 2-(2,2-Difluoroethoxy)-N-1H-1,2,4-triazol-3-yl-6 (trifluoromethyl)- Breakdown product 619036
PAN (5,8-Dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)sulfamic acid,triethylamine salt Breakdown product 619037

US Federal Register 
Date Published Docket Identification Number Details
July 25, 2007 EPA-HQ-OPP-2006-0076

Dow AgroSciences. Pesticide tolerance. FINAL RULE. This regulation establishes a tolerance for combined residues or residues of penoxsulam (2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfonamide) in or on

Commodity

Parts per million
Fish 0.01
Fish, shellfish, mollusc 0.02
Fish, shellfish, crustacean 0.01

Document available with this Final Rule: Penoxsulam. Human Health Risk Assessment for Proposed Uses on Fish and Shellfish. June 18, 2007. Docket: EPA-HQ-OPP-2006-0076-0004.

Notes from FAN:
• This 84 page EPA document, which we have downloaded for public access, has been deliberately "locked" by EPA and can neither be searched nor sentences copied.
• EPA reported a finding in the rat developmental toxicity study as Cutis laxis (pp 22-23), which we can only assume is as rare a term as the condition itself. If EPA persists in using terms that are not commonly used, then they should provide a definition. An accessible definition of Cutis Laxa was online: It is a rare disorder of connective tissue that causes the skin to stretch easily and hang in loose folds... Sometimes only the skin is affected, but connective tissues throughout the body can be affected.

• (page 44) HED has reviewed the available data, and finds that it does not support the petitioner's request for tolerance exemptions on shellfish and finfish, resulting from the proposed aquatic uses. The studies show real residues of penoxsulam at both the 10X rate and the 1X rate. At 1x the application rate (0.15 mg ai/L) the maximum penoxsulam residues in catfish were 4.16 ppb (0.004 ppm) and in clams were up to 18.3 ppb (0.018 ppm). In bluegills at 1X, the maximum TRR were 11.4 ppb (0.0114 ppm). If these results are multiplied by 34% of the TRR to estimate penoxsulam, per se, the estimated concentration of parent only becomes 3.9 ppb (0.004 ppm). Based upon the crustacean study using rice treatment rates, and assuming linerarity, TRR in crayfish inwater treated at 0.15 mg ai/L are estimated to be about 4.9 ppb (0.005 ppm). At 10X (1.5 mg ai/L) the maximum application rate residues of penoxsulam were found in catfish up to 56 ppb (0.6 ppm) and in clams up to 141 ppb (0.14 ppm). Based upon the data as submitted, residues in bluegills at 10X were up to 39 ppb (0.04 ppm). As extrapolated from the rice field study, TRR in crayfish are expected to be up to 48 ppb (0.05 ppm). Tolerances are therefore required for fish... In general, from the bluefish study, 5-hydroxypenoxsulam is present in penoxsulam residues at about 40% of the parent penoxsulam. Thus, residues of concern in fish (finfish, mollusc and crustacean) for risk assessment based upon these studies should be penoxsulam plus 5-hydroxy penoxsulam...

• (page 7): The proposed use is an aquatic herbicide in the water of lakes, ponds, canals, and reservoirs. Typical application rates of penoxsulam will be 10-20 ppb in an initial application with additional 'bump' applications of 5-10 ppb to keep the water concentrations at 5-10 ppb for 45-90 days. There is a season maximum of all applications of 150 ppb. Although typical multiple application rates are proposed at 5-20 ppb, a single in-water application is alllowed at up to the maximum rate of 150 ppb.

• (page 8): Penoxsulam is expected to be very mobile in the environment with the degradation products of toxicological concern to be even more mobile than the parent compound.

• (page 10): Aggregate penoxsulam exposures can result from the aquatic and turf use scenarios. Since HED considers the swimmer dermal and oral MOEs to be over estimates of the actual risk and does not recommend that these MOEs be used when aggregating risk, the swimming exposure assessment will not be used in calculating the short- and intermediate-term aggregate risk and only the exposures resulting from the turf use will be considered.

• (page 11): In regard to aquatic scenarios, postapplication exposure is expected to occur to only non-occupational individuals swimming in treated areas. Therefore an occupational postapplication exposure assessment is not requried for the proposed use.

• (page 11): Based on information provided in the proposed turf labels; handler exposure is anticipated to only be short-term in duration. Therefore, neither a dermal nor inhalation intermediate-term handler exposure assessment was performed for turf uses.

• Although an intermediate-term dermal endpoint was selected, intermediate-term dermal postapplication exposure is expected to be neglibible based on information on the proposed turn fables and chemical specific turf tansfer residue studies. Therefore, a dermal postapplication exposure assessment for turf was not performed.

April 14, 2006 EPA-HQ-OPP-2006-0076 Dow AgroSciences. Petition for New Exemption from Tolerance: Pesticide Petition 5F7012.
Proposal to establish an exemption from the requirement of a tolerance for residues of the herbicide penoxsulam, in or on fish and shellfish, resulting from the use of penoxsulam as an aquatic herbicide. Because this petition is a request for an exemption from the requirement of a tolerance without numerical limitations, no analytical method is required.
Sept 24, 2004 OPP-2004-0286

Dow AgroSciences. Pesticide tolerance. FINAL RULE.

-- Carcinogenicity: Evidence of carcinogenicity in male rats based on possibly treatment related increase incidence of Large Granular Lymphocyte (LGL) Leukemia at 5, 50, & 250 mg/kg/day. Also increase severity at 250 mg/kg/day. Female rats - negative for carcinogenicity, but dosing was only marginally adequate.
-- Carcinogenicity-mice: In males, negative for carcinogenicity at doses tested. Dosing inadequate.
-- The Agency has classified penoxsulam as Suggestive Evidence of Carcinogenicity, But not sufficient to assess human carcinogenic potential and, therefore, quantification of human cancer risk is not required. The weight-of-the-evidence for this classification is as follows: a. Evidence of carcinogenicity (mononuclear cell leukemia (MNCL)) was seen in one sex (males) of one species (rat).b. There was an increased incidence of MNCL at all dose levels with all incidences exceeding the laboratory historical control, however, the dose-response was flat over a wide range of doses. c. Although MNCL is recognized as a common neoplasm in Fischer rats, the mechanism of producing MNCL is not completely understood. Therefore, the significance of MNCL and its biological relevance for human cancer risk remains uncertain and cannot be discounted ...
--
EPA determined that the 10X safety factor (SF) to protect infants and children should be removed...
-- Significant dose-related effects in the two-generation
reproduction study were limited to the delay in preputial separation. No other endpoints of reproductive toxicity or offspring growth and survival were affected by treatment.

Commodity
Parts per million
Rice, grain. 0.02
Rice, straw 0.50
Rice hull, bran No tolerances were necessary for the rice process commodities, rice hulls, bran, or
polished rice, because residues will not exceed the established tolerance in rice, grain.
 
Polished rice
 
Aug 6, 2003 OPP-2003-0261

Dow AgroSciences. Pesticide tolerance petition. This is the first time Penoxsulam will be considered by EPA. Tolerances requested are in or on the rice raw agricultural commodities (RACS) and rice processed products

rice grain 0.01 ppm
rice straw 0.05 ppm
rice hull 0.01 ppm
rice bran 0.01 ppm
polished rice 0.01 ppm

-- Reproductive and developmental toxicity... At the highest dosage tested (HDT) (300 mg/kg/day), body weights and weight gains in both males and females were depressed, liver and/or kidney weights were increased, and histologic changes were noted in the liver (males) and kidneys (females). At 100 mg/kg/day, increased liver weights were recorded in males, with no histologic correlate, and histologic changes noted in the kidneys of females. Transient decreases in pup body weights were seen at the HDT,
-- Subchronic toxicity. Dietary exposure to penoxsulam identified the liver and/or urinary tract (kidneys and bladder) as target organs in rats, mice, and dogs following a 4-week and 13-week administration. Effects on the liver were reflected in increased liver weights and hepatocellular hypertrophy... Effects noted in the kidneys included crystal deposition, most likely from precipitation of penoxsulam from the urine, with resultant irritation, inflammation, and hyperplasia of renal pelvic transitional epithelium.
-- Chronic toxicity. Following long-term exposure in rats, the kidneys and urinary bladder were the primary target organs. Histologic changes seen at the end of 2 years of exposure consisted of inflammation and hyperplasia of the renal pelvic transitional epithelium, crystal deposition in the kidneys and urinary bladder, and hyperplasia of the mucosa of the urinary bladder. In the mouse, the liver was the primary target organ, and histologic changes consisted of hepatocellular hypertrophy. The incidence of mononuclear cell leukemia (Fischer rat leukemia) was increased in all groups of treated male rats compared to the concurrent controls...

Cumulative Effects. Currently, no methodologies are available to resolve the complex scientific issues concerning common mechanism of toxicity and cumulative exposure and risk. EPA has begun a pilot process to study this issue further through the examination of particular classes of pesticides. Thus, Dow AgroSciences LLC believes it is appropriate to consider only the potential risks of penoxsulam in its exposure assessment.

 
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