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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [P.V. Shah, 703-308-1846]

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In 

cases where the outline element does not apply, please insert “NA-Remove” and 

maintain the outline. Please do not change the margins, font, or format in your 

pesticide petition. Simply replace the instructions that appear in green, i.e., “[insert 

company name],” with the information specific to your action.

TEMPLATE:

[ISK Biosciences Corporation]

[1E7900]

EPA has received a pesticide petition ([1E7900]) from [ISK Biosciences 

Corporation], [7470 Auburn Road, Suite A, Concord OH 44077] proposing, 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 180.920 to establish an exemption from the requirement 

of a tolerance for [Calcium gluconate (CAS. No. 299-28-5)] [under 40 CFR 180.920 

when used as an inert ingredient as a sequestrant, binder and filler in pesticide 

formulations applied pre-harvest to all raw agricultural commodities]. 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. No specific plant metabolism data is 

available, nor is it required for the establishment of a tolerance exemption.]

2. Analytical method. [NA-Remove based on the fact that this information is 

not required for the establishment of a tolerance exemption.]

3. Magnitude of residues. [[NA-Remove based on the fact that this information 

is not required for the establishment of a tolerance exemption. There is no specific 

crop residue information available for calcium gluconate and this information is 

typically not available nor required for the establishment of a tolerance exemption 

for inert ingredients.]
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B. Toxicological Profile

Gluconic acid and its inorganic salts have been evaluated by the Joint FAO/WHO 

Expert Committee on Food Additives (JECFA), which determined that these 

substances were of very low toxicity and allocated an acceptable daily intake of "not 

specified" (JECFA, 1999). The calcium, magnesium, potassium, and sodium 

gluconates were previously evaluated by JECFA as individual compounds or in 

other group categories as inorganic salts and salts of organic acids. It was concluded

that they are freely ionizable and that it was appropriate to allocate

ADIs on the basis of data on their corresponding anion (gluconic acid). Calcium 

gluconate was added to the CODEX General Standard for Food Additives (GSFA) 

in 1999. Calcium gluconate is included in the Food and Drug Administration (FDA)

list of direct food substances generally recognized as safe (GRAS List) and is 

commonly consumed as a mineral supplement and is used for the treatment of 

hypocalcemia.

1. Acute toxicity. [Toxicological studies considered by JECFA in their 

evaluation of gluconic acid and its inorganic salts included acute oral toxicity studies 

in the rat, mouse, rabbit and hamster with LD50 values ranging from >2000 mg/kg 

to 7850 mg/kg]

2. Genotoxicty. [Gluconic acid and its inorganic salts have been tested in in 

vitro assays which demonstrated that gluconic acid was not mutagenic with or 

without metabolic activation.]

3. Reproductive and developmental toxicity. [No observable adverse effects 

were noted at limit dose levels (i.e., > 1000 mg/kg/day) or at the highest doses tested

4. Subchronic toxicity. [In various subchronic studies evaluated by JECFA, no 

observable adverse effects were noted at limit dose levels (i.e., > 1000 mg/kg/day) or 

at the highest doses tested.

5. Chronic toxicity. [In various, chronic studies evaluated by JECFA, no

observable adverse effects were noted at limit dose levels (i.e., > 1000 mg/kg/day) or 

at the highest doses tested.

6. Animal metabolism. [Calcium gluconate dissociates under normal 

physiologic conditions into gluconic acid, as do all of the inorganic salts of gluconic 

acid. Intraperitoneal administration of calcium gluconate resulted in excretion of 

primarily unchanged gluconate anion in the urine; the remainder was metabolized. 

Twenty percent of a dose of calcium gluconate was absorbed from the intestine.]

7. Metabolite toxicology. NA-remove

8. Endocrine disruption. [There is no information that suggests that

calcium gluconate is an endocrine disrupter.]
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C. Aggregate Exposure

1. Dietary exposure. NA-remove

i. Food. NA-remove

ii. Drinking water. No drinking water exposure is anticipated.

2. Non-dietary exposure. NA-remove

D. Cumulative Effects

EPA has not made a common mechanism of toxicity finding as to calcium gluconate 

and any other substances, and calcium gluconate does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, 

therefore, EPA has not assumed that calcium gluconate has a common mechanism 

of toxicity with other substances.

E. Safety Determination

1. U.S. population. [Calcium gluconate exhibits low acute toxicity. The closely

related compounds, sodium gluconate and gluconic acid, exhibit low sub-chronic 

toxicity and rapid metabolism and excretion. The strong structural similarity of 

calcium gluconate to sodium gluconate and gluconic acid makes it reasonable to 

consider that it will have similar toxicity and metabolism. This metabolism pattern 

is important because it explains why the toxicity of these compounds is low. 

Consequently, it may be stated that there is a reasonable certainty that no harm will 

result to the general population and to infants and children from aggregate 

exposure to residues of calcium gluconate from the proposed use in pesticide 

formulations.

2. Infants and children. [At this time, there is no concern for potential 

sensitivity to infants and children resulting from exposures to calcium gluconate. In 

its evaluation of gluconic acid and sodium gluconate, JECFA reported no 

quantitative or qualitative evidence of increased susceptibility following the prenatal 

exposure to mice, rats, hamsters and rabbits in developmental toxicity studies 

(JECFA, 1999) at doses ranging up to 780 mg/kg/day (the highest dose tested). A 

safety factor analysis has not been used to assess the risk. For these reasons the

additional tenfold safety factor for the protection of infants and children is 

unnecessary.

F. International Tolerances

[There are no known international tolerances for calcium gluconate]
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