Sethoxydim Risk Assessment

Appendix 1: Toxicity of Sethoxydim (NP-55) and Poast to experimental mammals [94-99% a.i. unless 
otherwise specified]. 
Animal 
Dose/Exposure 
Response 
Reference 
Mice, BD, 6 weeks 
0, 40, 120, 360, or 
After 52 weeks: 
Nisso Inst. 
old, males and 
females, 
70/sex/dose group; 
100/sex/control 
group 
1080 ppm NP-55 in 
diet for 104 weeks. 
NB: This is an 
interim report (first 
52 weeks in 104-week 
feeding study). 
No carcinogenicity 
NOEL = 120 ppm 
No clinical signs of toxicity; no treatment 
related mortality; no treatment-related 
hematological effects; no effects on urinalysis; 
Adverse effects included decreased body weight 
gain in both sexes at 360 and 1080 ppm; 
decreased food consumption in males at 360 
and 1080 ppm; decreased blood glucose in 
males at 1080 ppm; decreased A/G ratio in 
males at 360 and 1080 ppm; increased ALP in 
females at 40 and 120 ppm; increased organ 
weights (heart, liver, and spleen) and 
significantly increased ratio of organ ( liver and 
spleen) to body weights in males at 1080 ppm; 
significantly increased liver to body weight 
ratio in females at 360 and 1080 ppm. 
1980b 
EPA/OTS 
88-9200030 
23 
Pathological changes include lesions in lung 
(grayish zone) not otherwise specified; and 
ovarian lesions (cyst) at 40 and 360 ppm 
Histopathological findings include dose-related 
changes in the liver, including swollen liver 
cells and fatty degeneration in males at 360 and 
1080 ppm; and two cystadenomas in 1 female 
at 40 ppm 1 female at 360 ppm. 
Appendix 1 - 7 

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Appendix 1: Toxicity of Sethoxydim (NP-55) and Poast to experimental mammals [94-99% a.i. unless 
otherwise specified]. 
Animal 
Dose/Exposure 
Response 
Reference 
ORAL -chronic (continued) 
Mice, BDF1, 6 
0, 40, 120, 360, or 
weeks old, 
1080 ppm 
70/sex/dose group, 
NP-55(dissolved in 
100/sex/in control 
acetone) in diet for 104 
group 
weeks. 
Mean intakes values 
equal 0, 4.48, 13.77, 
41.16, and 134.6 
mg/kg/day in males 
and 0, 4.85, 14.86, 
44.33, and 142.85 
mg/kg/day in females 
for 104 weeks. 
NOEL = 120 ppm 
No evidence of carcinogenicity, no clinical 
signs of toxicity, no significant change in water 
consumption, no marked effects on hematology, 
no significant change in urinalysis, no 
dose-related changes observed at gross necropsy 
(except for increased liver weight), and no 
evidence of treatment-related tumors in any 
organs, including the liver. 
At 1080 ppm, growth rate was depressed in 
both sexes, food consumption was slightly 
higher in both sexes, GOT and GOT activity 
increased (p<0.001 and p<0.01) in males at 24 
(but not 12) months, liver to body weight ratios 
increased in both sexes at 12 and 24 months. 
Histopathological findings indicate that the 
liver is the target organ for NP-55 exposure 
in mice.  At 360 and 1080 ppm, fatty 
degeneration and swelling of the liver occurred 
frequently in males at 12 months; at 24 months, 
these lesions almost disappeared in the 360 
ppm group but not in the 1080 ppm group. 
Although the incidence of focal granulomatous 
inflammations and hemosiderin depositions 
were highest in the males of the 1080 ppm 
group, these changes were found in the livers of 
all groups. 
Takaori et 
al.  1981 
MRID 
00100527 
Appendix 1 - 8 

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Appendix 1: Toxicity of Sethoxydim (NP-55) and Poast to experimental mammals [94-99% a.i. unless 
otherwise specified]. 
Animal 
Dose/Exposure 
Response 
Reference 
DERMAL 
Rats, 
single topical 
LD
50
 >4000 mg/kg 
BASF 
Sprague-Dawley, 
application to clipped 
1992a 
males (mean wgt 
skin of dorsal and 
No mortality; possible signs of neurotoxicity 
EPA/OTS 
218 g) and females 
lateral parts of trunk 
included excitation, staggering tremors, 
88-9200030 
(mean wgt 182 g), 
(area about 50 cm
2
) of 
twitching, spastic gait, convulsions (rolling 
56 
5/sex/dose group 
Poast
 as 50% aqueous 
tonic and clonic) in non-moribund animals. 
preparation in a dose of 
400 mg/kg and 
undiluted in doses of 
1000, 2000, or 4000 
mg/kg; application site 
occluded for 24 hours; 
observation period of 
14 days 
Rats, Fischer 344, 
topical application of 
LD
50
 >5000 mg/kg in males and females 
Bio-Medical 
6 weeks old, males 
5000 mg/kg NP-55 to 
Research 
(avg bw 145.9 g) 
clipped skin (area of 
No mortality; signs of toxicity included 
Laboratories 
and females (avg 
2x2 cm of cervical and 
decrease of spontaneous movement, depression, 
Co, Ltd. 
bw 109.6 g), 
dorsal parts of trunk); 
and transitory escape reflex. 
1980 
10/sex/dose group 
mice  wore plastic neck 
collars to prevent oral 
No particular changes noted at autopsy. 
EPA/OTS 
exposure to test 
88-9200030 
substance; 14-day 
22 
observation period 
Mice, ICR, 6 
topical application of 
LD
50
 >5000 mg/kg in males and females 
Bio-Medical 
weeks old, males 
5000 mg/kg NP-55 to 
Research 
(avg bw 29.2 g) 
clipped skin (area of 
No mortality; signs of toxicity included slight 
Laboratories 
and females (avg 
2x2 cm of cervical and 
decrease of spontaneous movement in males 
Co, Ltd. 
bw 25.4 g), 
dorsal parts of trunk); 
and females after 24 hours with recovery at 48 
1979 
10/sex/dose group 
mice  wore plastic neck 
hours,  and ptsosis of eyelid in 2 males and 4 
collars to prevent oral 
females after 2 ½ hours, but touch escape was 
EPA/OTS 
exposure to test 
normal. 
88-9200029 
substance; 14-day 
76 
observation period 
Additional notes on Bio-Medical Research Laboratories Co, Ltd 1979:  Study includes acute oral, 
intravenous, subcutaneous, and dermal toxicity data in mice.  Several detailed data tables provided. 
Appendix 1 - 9 

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