Sethoxydim Risk Assessment

Table 2-3: Labeled Application Rates for Poast. 
Poast 
1.5 
lbs a.i./gallon 
Pints Poast 
/acre
1 
Gallons Poast/acre 
lbs 
a.i./acre 
Typical 
1 
0.125 
0.1875 
Minimum 
0.5 
0.0625 
0.09375 
Maximum 
2 
0.25 
0.375 
Conversions: 
8 pints/gallon 
1
 Values from BASF (2000) 
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Figure 2-1: Statistics on the agricultural uses of sethoxydim (USGS 1992). 
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3.  HUMAN HEALTH RISK ASSESSMENT  
3.1. HAZARD IDENTIFICATION  
3.1.1.  Overview.  Reported gavage LD
50
 values for sethoxydim range from about 3000 to 6000 
mg/kg in rats and 5600 to 6500 mg/kg in mice.  The oral LD
50
 in dogs is 2500-5000 mg/kg but 
the method of administration involved capsules rather gavage exposures and thus the results 
cannot be directly compared to those in rats and mice.  The acute oral LD
50
 of the formulated 
product, Poast, is comparable to that of sethoxydim – i.e., 4390 to 5000 mg Poast/kg.  For both 
sethoxydim and Poast, the primary signs of acute poisoning in  mice, rats, and dogs are consistent 
with neurological effects: lacrimation, salivation, incontinence,  ataxia, tremors, and convulsions. 
The available data on sethoxydim are sufficient to define NOAELs for systemic toxic effects from 
both acute and chronic exposures.  Sethoxydim has been tested for and does not appear to cause 
carcinogenicity, birth defects, or other reproductive effects. 
Poast contains a substantial amount of petroleum solvent (74%) that includes naphthalene (7% of 
the solvent).  The primary effect of naphthalene and petroleum solvents involves CNS depression 
and other signs of neurotoxicity that are similar to the effects seen in animals exposed to Poast as 
well as sethoxydim.  While sethoxydim is rapidly degraded in the environment, some of the 
degradation products are much more persistent and this pattern is quantitatively considered in the 
risk assessment. 
Based on standard studies required for pesticide registration, Poast may cause skin and eye 
irritation. Concentrations of sethoxydim in the air that would be much higher than any plausible 
concentrations in human exposure scenarios have been associated with lung congestion in rats. 
The potential inhalation toxicity of sethoxydim is not of substantial concern to this risk assessment 
because of the implausibility of inhalation exposure involving  high concentrations of this 
compound. 
3.1.2.  Acute Toxicity.  Acute toxicity studies on sethoxydim have been conducted as part of the 
FIFRA pesticide registration process (BASF 1982; Kirsch and Hildebrand 1983; Nishibe et al. 
1980,1981,1984).  In addition, several unpublished studies have been submitted to the U.S. EPA 
under requirements of the Toxic Substances Control Act (BASF 1980; Bio-Medical Research 
Laboratories Co. Ltd. 1979,1980; Nisso Inst. 1980a,b). Both groups of studies are summarized in 
Appendix 1. 
The most common measure of acute oral (gavage) toxicity is the LD
50
, the estimate of a dose that 
is most likely to cause 50% mortality in the test species after a single oral dose.  As summarized in 
Appendix 1, the acute oral LD
50
 values for sethoxydim in rats range from 2676 mg/kg 
(Bio-Medical Research Laboratories Co. Ltd. 1980) to 5573 mg/kg (Nishibe et al. 1980).  Mice 
may be somewhat less sensitive than rats, with acute LD
50
 values in the range of 5600 to 6500 
mg/kg (BASF 1982; Bio-Medical Research Laboratories Co. Ltd. 1980). 
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While the differences between the sensitivities of mice and rats to sethoxydim are not substantial, 
they are consistent with the general observation that larger mammals are more sensitive to many 
toxic agents than are smaller mammals.  This observation is incorporated into the dose-response 
assessment for sethoxydim by the use of an uncertainty factor in extrapolating results from 
experimental mammals to humans (Section 3.3).  Based on the administration of sethoxydim in 
gelatin capsules rather than gavage, the oral LD
50
 in dogs is 2500-5000 mg/kg (Nisso Inst. 
1980a).  Because of the difference in the dosing method (gavage vs. capsules), these results in 
dogs cannot be directly compared to those in rodents to further assess patterns in species 
differences in sensitivity to sethoxydim. 
One study in rats (Bio-Medical Research Laboratories Co Ltd.  1979) involved the formulated 
product (Poast) rather than the active ingredient alone (sethoxydim) and this study reports LD
50 
values that are in the higher region of the range of sethoxydim LD
50
 values for rats – i.e., 4390 to 
5000 mg Poast/kg.  The LD
50
 values expressed as sethoxydim equivalents are 790 to 900 mg 
sethoxydim/kg bw, below the LD
50
 values for technical grade sethoxydim. 
The primary signs of acute poisoning in  mice, rats, and dogs are consistent with neurological 
effects: lacrimation, salivation, incontinence,  ataxia, tremors, and convulsions (Appendix 1). 
Other than inferences that might be made from these gross signs of toxicity, the mechanism of the 
acute toxicity of sethoxydim is unclear.  One mechanistic study (Yamano and Morita 1995) 
reports that sethoxydim uncouples mitochondrial oxidative phosphorylation, at least in vitro. 
Oxidative phosphorylation is an important biochemical process in mammals and the uncoupling of 
oxidative phosphorylation can lead to increased body temperature and weight loss (Gregus and 
Klaassen 1996).  In vivo, sethoxydim has been shown to cause a decrease rather than increase in 
body temperature (Nishibe et al.  1980). 
3.1.3.  Subchronic or Chronic Systemic Toxic Effects.  No studies have been published on the 
subchronic or chronic toxicity of sethoxydim to humans or mammals.  As summarized in 
Appendix 1, standard chronic (2-year) toxicity studies have been conducted in rats (Burdock et al. 
1981) and mice (Nisso Inst. 1980b; Takaori et al.  1981).  All of these studies are unpublished and 
were submitted to the U.S. EPA in support of the registration of sethoxydim.  In the rat study 
(Burdock et al.  1981), dietary concentrations up to 360 ppm resulted in no observed effects. 
Two additional chronic toxicity studies have been summarized in U.S. EPA/OPP (1998a).  In one 
study, dietary concentrations of 0, 360, and 1,080 ppm (equivalent to 18.2/23.0, and 55.9/71.8 
mg/kg/day in males/females) failed to induce any signs of toxicity.  In the other study, a dietary 
concentration of 3,000 ppm led to changes in food consumption and body weight as well as liver 
pathology (U.S. EPA/OPP 1998a). 
Mice appear to be somewhat more sensitive to chronic exposure to sethoxydim than rats.  In the 
chronic mouse feeding study (Nisso Inst. 1980b; Takaori et al.  1981 summarized in Appendix 1), 
a dietary concentration of 1080 ppm resulted in decreased growth rate in both sexes accompanied 
by a slight increase in food consumption in both sexes, as well as toxic effects to the liver.  At 
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