Sethoxydim Risk Assessment

oral exposure, probably because the rate of dermal absorption is less than the rate of oral 
absorption. 
The kinetics of dermal absorption of sethoxydim are not documented in the open literature and no 
studies on the kinetics of dermal absorption have been submitted to U.S. EPA.  Such studies are 
not required for pesticide registration. 
Dermal exposure scenarios involving immersion or prolonged contact with chemical solutions use 
Fick's first law and require an estimate of the permeability coefficient, K
p
, expressed in cm/hour. 
Using the method recommended by U.S. EPA/ORD (1992), the estimated dermal permeability 
coefficient for sethoxydim is 0.0002667 cm/hour with a 95% confidence interval of 0.0001686 to 
0.0004217 cm/hour.  The details of the U.S. EPA/ORD (1992) method for estimating K
p
 based 
on the molecular weight and octanol-water partition coefficient  are given in Worksheet A07b. 
The application of this method to sethoxydim is detailed in Worksheet B04. The estimated K
p
 is 
used in all exposure assessments in this document that are based on Fick’s first law. 
For exposure scenarios like direct sprays or accidental spills, which involve deposition of the 
compound on the skin’s surface, dermal absorption rates (proportion of the deposited dose per 
unit time) rather than dermal permeability rates are used in the exposure assessment.  Using the 
methods detailed in SERA (2000), the estimated first-order dermal absorption coefficient is 
0.00109 hour
-1
 with 95% confidence intervals of 0.00047 to 0.0025 hour
-1
.  The details of the 
method specified in SERA (2000) for estimating the first-order dermal absorption coefficient 
based on the molecular weight and octanol-water partition coefficient  are given in worksheet 
A07a. The application of this method to sethoxydim is detailed in worksheet B03. 
The lack of experimental data regarding the dermal absorption of sethoxydim adds uncertainty to 
this risk assessment.  Nonetheless, uncertainties in the rates of dermal absorption, although they 
are substantial, can be estimated quantitatively and are incorporated in the human health exposure 
assessment (Section 3.2). 
3.1.8.  Inhalation Exposure.  As summarized in Appendix 1, there is one acute inhalation 
toxicity study on sethoxydim (Gamer 1991), one acute inhalation toxicity study on Poast (BASF 
1980) and one subchronic inhalation study on sethoxydim (Gamer 1993). 
Both acute studies follow a relatively standard protocol involving acute (4-hour) exposure of rats 
to relatively high concentrations in which the animals were exposed only through the head and 
nose - i.e., the rest of the animals body was protected from exposure to rule out dermal 
absorption as a significant route of exposure.  No effects were observed in the acute study with 
sethoxydim at concentrations up to 5,600 mg/m
3
 (Gamer 1991).  In the study using Poast, 
however, neurotoxicity (ataxia) was observed at a concentration of 7,640 mg/m
3
 and abnormal 
behavior (crouching posture) persisted for 6 days after exposure (BASF 1980a). 
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In the subchronic study with sethoxydim, animals were exposed (head-nose only) to 0, 40, 300, or 
2,400 mg/m
3
 for 6 hours/day for 1 month (21 exposures).  While no effects were seen in the 
lowest exposure group, mild nasal irritation was observed at 300 mg/m
3
 and irritation to the upper 
respiratory tract and oral cavity as well as signs of liver toxicity were observed at 2,400 mg/m
3 
(Gamer 1993).  No evidence of neurologic effects were seen in any of the exposed groups. 
While somewhat speculative, the neurologic effects observed after exposure to Poast are 
consistent with the possible role of the petroleum solvent in Poast as a CNS depressant (Section 
3.1.9.3) 
3.1.9.  Impurities, Metabolites, and Formulation Additives. 
3.1.9.1.  Impurities -- There is no published information regarding the impurities in technical 
grade sethoxydim or any of its commercial formulations.  No information on the identity of 
impurities in technical grade sethoxydim or Poast was been encountered in a search of the 
EPA/FIFRA files.  This lack of information does add uncertainty to the hazard identification. 
Nonetheless, all of the toxicology studies on sethoxydim involve technical sethoxydim, which is 
presumed to be the same as or comparable to the active ingredient in the formulation used by the 
Forest Service.  Thus, if toxic impurities are present in technical sethoxydim in substantial and 
toxicologically significant amounts, they are likely to be encompassed by the available toxicity 
studies using technical grade sethoxydim. 
3.1.9.2.  Metabolites -- There are two major mammalian metabolites of sethoxydim, referred to 
as M1-SO and M2-SO.  The toxicity of these compounds is comparable to that of technical grade 
sethoxydim: acute oral LD
50
 (95% confidence interval) values of 3,080 (2,953 to 3,175) mg/kg 
for M1-SO and 5,573 (4,942 to 7,435) mg/kg for M2-SO.  In addition, the signs of toxicity for 
these two compounds are similar to that of sethoxydim: lacrimation, salivation, ataxia, sedation, 
urinary incontinence, and a decrease in body temperature.  In addition, M2-SO was associated 
with irritation and hemorrhage of the intestinal tract (Nishibe et al.  1980; Nishibe et al.  1981). 
Another metabolite, 2-[1-(ethoxyimino)butyl]5-[2-(ethylsulfonyl) propyl]-3,5-dihydroxy-2­
cyclohexen-1-one, has an acute oral LD
50
 of >5,000 mg/kg (Nishibe et al.  1981). 
In assessing the potential hazards of exposures to both sethoxydim and metabolites of 
sethoxydim, the U.S. EPA/OPP (1998a) combines residues of metabolites with residues of 
sethoxydim in establishing pesticide tolerances for this compound.  In other words, the 
concentrations of sethoxydim and all sethoxydim metabolites are added and the mixture is treated 
as if it consisted entirely of sethoxydim.  Based on the comparable toxicities of the metabolites 
with the toxicity of sethoxydim, both in terms of acute toxic potency and signs of toxicity, this 
approach appears to be reasonable. 
For the current risk assessment, the metabolites of sethoxydim are important in the application of 
environmental fate models.  As detailed further in Section 3.2.3, GLEAMS is used to estimate 
runoff and percolation of sethoxydim from soil and these estimates are used further to estimate 
concentrations of sethoxydim that may be present in ambient water.  The selection of parameters 
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