Sethoxydim Risk Assessment

scenario for acute exposure, as defined in Worksheet D03 and one scenario for longer-term 
exposure, as defined in Worksheet D04.  In both scenarios, the concentration of sethoxydim on 
contaminated vegetation is estimated using the empirical relationships between application rate 
and concentration on vegetation developed by Fletcher et al. (1994) which is in turn based on a 
re-analysis of data from Hoerger and Kenaga (1972).  These relationships are defined in 
worksheet A04.  For the acute exposure scenario, the estimated residue level is taken as the 
product of the application rate and the residue rate (Worksheet D03). 
For the longer-term exposure scenario (D04), a duration of 90 days is used and the dissipation on 
the vegetation is estimated using a foliar half-time.  Although the duration of exposure of 90 days 
is somewhat arbitrarily chosen, this duration is intended to represent the consumption of 
contaminated fruit that might be available over one season.  Longer durations could be used for 
certain kinds of vegetation but would lower the estimated dose (i.e., would result in a less 
conservative exposure assessment). 
For the longer-term exposure scenarios, the time-weighted average concentration on fruit is 
calculated from the equation for first-order dissipation.  Assuming a first-order decrease in 
concentrations in contaminated vegetation, the concentration in the vegetation at time t after 
spray, C
t
, can be calculated based on the initial concentration, C
0
, as: 
C
t
 = C
0
 × e
-kt 
where k is the first-order decay coefficient [k=ln(2)÷t
50
].  Time-weighted average concentration 
(C
TWA
) over time t can be calculated as the integral of C
t
 (De Sapio 1976, p. p. 97 ff) divided by 
the duration (t): 
C
TWA
 = C
0
 (1 - e
-k  t
) ÷ (k t). 
For the acute exposure scenario, it is assumed that a woman consumes 1 lb (0.4536 kg) of 
contaminated fruit.  Based on statistics summarized in U.S. EPA/ORD (1996) and presented in 
worksheet D04, this consumption rate is approximately the mid-range between the mean and 
upper 95% confidence interval for the total daily vegetable intake for a 64 kg woman.  The range 
of exposures presented in Table 3-2 is based on the range of concentrations on fruit and the range 
of application rates for sethoxydim.  The longer-term exposure scenario is constructed in a similar 
way, except that the estimated exposures include the range of fruit consumption (Worksheet A03) 
as well as the range of concentrations on fruit and the range of application rates for sethoxydim. 
When applied to nursery plots, there will typically be a 300 foot buffer between the application 
site and any vegetation that might be consumed by the general public – i.e., farm crops, home 
gardens or bushes containing edible berries that the general public might access.  Based on the 
AGDRIFT model using low boom ground applications, the proportion of drift estimated at 300 
feet off-site is 0.0024 (Worksheet A06).  In other words, at the highest  application rate that 
would be used by the Forest Service, 0.375 lb/acre,  the “functional application rate” at 300 feet 
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offsite would be 0.0009 lbs/acre [0.375 lb/acre × 0.0024 = 0.0009 lb/acre].  For this risk 
assessment, the effects of the buffer is not considered quantitatively and the assumption is made 
that the vegetation is accidentally sprayed at the nominal application rate (Worksheet D03).  As 
detailed further in Section 3.4, this approach is adopted for sethoxydim because the direct spray 
scenario leads to estimates of risk that are far below a level of concern.  Thus, considering spray 
drift and a buffer zone quantitatively would have no impact on the characterization of risk. 
3.3. DOSE-RESPONSE ASSESSMENT 
3.3.1. Overview. 
The Office of Pesticide Programs of the U.S. EPA has derived both an acute and chronic RfD for 
sethoxydim.  The chronic RfD of 0.09 mg/kg/day based on a NOAEL of 9 mg/kg/day for a 1-year 
feed study in dogs and an uncertainty factor of 100.  This uncertainty factor includes 10 for 
extrapolating from animals to humans and 10 for extrapolating to sensitive individuals within the 
human population.  The acute RfD is 0.6 mg/kg/day based on a NOAEL in rabbits of 180 
mg/kg/day and an uncertainty factor of 300.  The uncertainty factor for the acute RfD includes the 
same two components as the uncertainty factor for the chronic RfD as well as an FQPA (Food 
Quality Protection Act) uncertainty factor of 3 for the possible increased sensitivity of children to 
sethoxydim. 
3.3.2.  Existing Guidelines.  U.S. EPA’s Office of Pesticide Programs (U.S. EPA/OPP 1998a) 
has derived a chronic RfD of 0.09 mg/kg/day for sethoxydim.  This RfD is based on a 1-year 
dietary exposure study using dogs (IRDC 1984, detailed in Appendix 1).  In this study, the dogs 
were given sethoxydim in the diet at concentrations of 0 (control), 300, 600, and 3600 ppm for1 
year.  Based on measured food consumption in male/female dogs, these dietary concentrations 
corresponded to average daily doses of 0, 8.86/9.41, 17.5/19.9, and 110/129 mg/kg/day.  Signs of 
toxicity in dogs were noted in the liver (increased weights and slight hepatocellular cytoplasmic 
changes) and blood (decreased erythrocyte counts, hemoglobin and hematocrit) at 600, and 3600 
ppm but not at 300 ppm.  Thus, the U.S. EPA identified the NOAEL, rounded to one significant 
digit, as 9 mg/kg/day.  In deriving the chronic RfD, the U.S. EPA/OPP (1998a) used an 
uncertainty factor of 100, consisting of two components: a factor of 10 for extrapolating from 
animals to humans and a factor of 10 for extrapolating to sensitive individuals within the human 
population.  This is identical to the chronic RfD on IRIS (U.S. EPA/IRIS 1989). 
3.3.3.  Dose-Severity-Duration Relationships.  For acute dietary exposure, the U.S. EPA/OPP 
(1998a) uses a short-term NOAEL of 180 mg/kg/day from a reproductive toxicity study in 
rabbits.  This NOAEL was not found in the studies identified in the CBI search on sethoxydim but 
is very similar to the 160 mg/kg/day NOAEL in the rabbit reproduction study by IRDC (1980a) 
that is also discussed in IRIS (U.S. EPA/IRIS 1989).  As with the chronic RfD, the EPA used 
uncertainty factors of 10 for extrapolating from animals to humans and an additional factor of 10 
for extrapolating to sensitive individuals within the human population.  In addition, the U.S. 
EPA/OPP (1998a) used an FQPA (Food Quality Protection Act) uncertainty factor of 3 for the 
possible increased sensitivity of children.  Thus, the acute RfD is (180 mg/kg/day ÷ (10×10×3) = 
0.6 mg/kg/day).  This acute RfD is a factor of about 7 above the chronic RfD and will be used in 
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