Document ID: EPA-HQ-OPP-2022-0841-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-11-17T05:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: 

Ingredion Incorporated

	EPA has received a pesticide petition IN-11715 from Ingredion Incorporated, 5 Westbrook Corporate Center, Westchester, IL 60154, United States requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180

  to establish an exemption from the requirement of a tolerance for

      Amylopectin, 2-hydroxypropyl ether, acid-hydrolyzed (CASRN: 2756130-86-4) in or on raw agricultural commodities pre-harvest as a seed treatment (40 CFR 180.920).  EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. NA Remove

	2. Analytical method. NA Remove

	3. Magnitude of residues. NA Remove

B. Toxicological Profile

Toxicity data are not available for Amylopectin, 2-hydroxypropyl ether, acid-hydrolyzed.  The data presented are from a re-evaluation of modified starches in food additives conducted by the European Food Safety Authority (EFSA) Panel on Food Additives and Nutrient Sources added to Food (EFSA, 2017).  2-Hydroxypropyl starch (CAS number 9049-76-7), a chemically similar starch, is one of the modified starches considered in this article.  Given the structural, physicochemical, and biological similarities, the EFSA panel concluded that it is possible to read-across between all the modified starches considered and relevant findings for all modified starches are therefore summarized.  

 Acute toxicity.  

      Acute Oral Toxicity
      
      LD50 values between 7 to 35 g/kg bw were observed in acute oral toxicity studies using distarch phosphate with mice, rats, guinea pigs, rabbits, and cats.  No histopathological abnormalities were observed in the livers and kidneys of guinea pigs, rabbits, and cats (Hodge, 1954, 1956; cited in EFSA, 2017).
      
      Based on these LD50 values, the modified starches discussed here would not present an acute oral toxicity hazard to humans when used as an inert ingredient in seed-applied pesticides.
      
	2. Genotoxicty. NA Remove

	3. Reproductive and developmental toxicity. NA Remove

	4. Subchronic toxicity

      Relevant toxicity data for all starches reviewed by the EFSA panel are summarized in Table 1 (EFSA, 2017). 
      
Table 1	Summary of Short-Term and Subchronic Toxicity Data for Modified Starches 
Modified Starch
Reference in EFSA, 2017
Animal
Dose 
Result
Oxidised starch
Garton & Sons Co. Ltd., 1967
Rat
63,000 mg/kg bw per day for 10 weeks
No toxic effects.
Oxidised starch
Documentation provided to EFSA n. 20
Rat
450, 9,000, and 22,500 mg/kg bw per day for 90 days
No adverse effects.
Distarch phosphate
Documentation provided to EFSA n. 21
Rat
4,500, 13,500, and 40,500 mg/kg bw per day for 3 months
No treatment-related changes from control.
Distarch phosphate
Documentation provided to EFSA n. 22
Dog
50, 250, and 1,250 mg/kg bw per day for 90 days
No adverse effects.
Distarch phosphate
Anderson et al., 1973a
Pig
Diet containing 5.6% of the test substance for 25 days
No treatment-related changes from control.
Phosphated distarch phosphate
Documentation provided to EFSA n. 23
Rat
22,500 or 45,000 mg/kg bw per day for 8 weeks
No detectable adverse effects on body weight.
Phosphated distarch phosphate
Documentation provided to EFSA n. 22
Dog
50, 250 or 1,250 mg/kg bw per day for 90 days
No adverse effects.
Phosphated distarch phosphate
Anderson et al., 1973a
Pig
Diet containing 5.6% of the test substance for 25 days
No treatment-related changes from control.
Acetylated distarch phosphate
Documentation provided to EFSA n. 23
Rat
30,000 or 60,000 mg/kg bw per day for 7 days
Slight body weight reduction and mild diarrhoea occurred at the highest dietary level. No hair loss was noted.
Acetylated distarch phosphate
Documentation provided to EFSA n. 23
Rat
22,500 or 45,000 mg/kg bw per day for 8 weeks
Body weights of males at the highest dietary level were slightly decreased.
Acetylated distarch phosphate
Shillam et al., 1971
Pig
1,250, 2,500, or 6,250 mg/kg bw per day for 14 weeks
No effect on growth, food, consumption, haematology, or biochemistry was observed.
Acetylated distarch phosphate
Documentation provided to EFSA n. 26
Hamster
Diet containing 30% of the test substance for 30 days
Slightly lower daily intake was observed. No other treatment-related effects were observed.
Acetylated starch
Documentation provided to EFSA n. 23
Rat
30,000 or 60,000 mg/kg bw per day for 7 days
Slight body weight reduction and mild diarrhoea occurred at the highest dietary level. No hair loss was noted.
Acetylated starch
Documentation provided to EFSA n. 16
Rat
Diet containing 60% of the test substance for 28 days
For starches with more than 2% acetylation: weight gain was reduced, diarrohea occurred and there was noticeable caecal enlargement.
Acetylated starch
Documentation provided to EFSA n. 23
Rat
22,500 or 45,000 mg/kg bw per day for 8 weeks
No effects on growth or body weight. Caecal weight and caecal enlargement occurred in a dose-related manner. 
Acetylated starch
Documentation provided to EFSA n. 27
Rat
4,500, 13,500, or 40,500 mg/kg bw per day for 13 weeks
Growth rates and haematological findings were not significantly affected. Caecal weights were slightly higher in treated animals than the control.
Acetylated distarch adipate
Documentation provided to EFSA n. 28
Rat
36,000 mg/kg bw per day for 30 days 
No treatment-related effects other than enlargement of the caecum.
Acetylated distarch adipate
Documentation provided to EFSA n. 29
Rat
45,000 mg/kg bw per day for 90 days 
Treated males showed a significantly reduced growth rate (20%). Relative weights of caeca were higher in both sexes of the test group compared with the control. Female rats on the test diet experienced alkaline urine. 
Acetylated distarch adipate
Documentation provided to EFSA n. 26
Hamster
Diet containing 30% of the test substance for 30 days
Slightly lower daily intake was observed. No other treatment-related effects were observed.
Hydroxypropyl starch
Kay and Calandra, 1961
Rat
1,800, 4,500, 9,000, or 22,500 mg/kg bw per day for 90 days
No systemic toxicity noted. Slight reduction in growth rate and mild diarrhoea at the highest dietary level. 
Hydroxypropyl starch
Documentation provided to EFSA n. 31
Rat
4,500, 13,500, or 40,500 mg/kg bw per day for 90 days
Caecal enlargement and moderate diarrhoea were observed at the highest dietary level. 
Hydroxypropyl starch
Leegwater et al., 1974
Rat
9,000 or 36,000 mg/kg bw per day for 10 days  -  3 months
The severity of diarrhoea and relative caecal weights increased with increases in the dietary level of the test substance. 
Hydroxypropyl distarch phosphate
Documentation provided to EFSA n. 32
Rat
30,000, 60,000, 90,000, or 120,000 mg/kg bw per day for 28 days
At the highest levels tested, growth and body weights were reduced compared to the control. 
Hydroxypropyl distarch phosphate
Documentation provided to EFSA n. 33
Rat
4,500, 9,000 or 22,500 mg/kg bw per day for 90 days
Caecal weights were increased at the highest dietary level. Macroscopically, no compound-related differences were observed amongst the various groups.
Starch sodium octenyl succinate
Documentation provided to EFSA n. 34
Rat
Diet containing 35% of the test substance for 8 weeks
A slightly slower growth rate was observed I the test group.
Starch sodium octenyl succinate
Buttolph and Newberne, 1980
Rat
Diet containing 6%, 12%, or 30% of the test substance for 30-90 days
No significant effect on growth rate. 
Starch sodium octenyl succinate
Unilever, 1984
Rat
37,000 mg/kg bw per day for 90 days
No adverse effects.
Acetylated oxidized starch
Documentation provided to EFSA n. 35
Rat
5,000, 15,000 or 25,000 mg/kg bw per day for 14 days
Caecal weights were increased at the two highest dietary levels. 
Acetylated oxidized starch
Documentation provided to EFSA n. 35
Rat
3,000, 5,900, or 18,000 mg/kg bw per day for 90 days
The NOAEL level was determined to be 5,900 mg/kg bw per day, on the basis of microscopic changes in the kidney and urinary bladder epithelium
Starch aluminum octenyl succinate
FDRL, 1961
Rat
1.5 g or 3.0 g per day for 4 weeks
Weight gain, behavior and growth were comparable among test and control rats
Starch aluminum octenyl succinate
Documentation provided to EFSA n. 34
Rat
Diets containing 1% or 10% of the test substance for 8 weeks. The 1% diet was increased to 25% after the first 4 weeks.
Haematology (complete blood counts and blood sugar and nonprotein nitrogen) was similar between the treatment and the control group. No other treatment-related effects were observed.

      The most common results of the subchronic and short-term toxicity tests using these modified starches are an increase in caecal weight and mild to moderate diarrhoea.  Based on these results, the modified starches discussed here would not present a subchronic or short-term toxicity hazard to humans when used as an inert ingredient for seed-applied pesticides.

      The EFSA panel also concluded there is no safety concern for the use of modified starches as food additives and there is no need to assign a numerical acceptable daily intake (ADI) for these substances (EFSA, 2017). 

	5. Chronic toxicity. NA Remove

	6. Animal metabolism. NA Remove

	7. Metabolite toxicology. NA Remove

	8. Endocrine disruption. NA Remove

C. Aggregate Exposure

	1. Dietary exposure. NA Remove

	i. Food. NA Remove

	ii. Drinking water. NA Remove

	2. Non-dietary exposure. NA Remove

D. Cumulative Effects

	NA Remove

E. Safety Determination

	1. U.S. population. NA Remove

 Infants and children. NA Remove
         
F. International Tolerances

	NA Remove