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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: [PV 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:

[Bayer HealthCare LLC, Animal Health Division]

[IN-10884]

EPA has received a pesticide petition (IN-10884) from Technology Sciences 

Group Inc. (1150 18th Street, N.W. Suite 1000, Washington, D.C. 20036) on behalf of 

Bayer HealthCare, LLC, Animal Health Division, (P.O Box 390 Shawnee Mission, 

KS 66201) 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 to establish an 

exemption from the requirement of a tolerance for iron oxide yellow (CAS # 20344-49-

4)] in or on the raw agricultural commodity [honey]. 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

1. Acute toxicity. Iron oxides are an inorganic source of iron, and iron is an 

essential element required by all forms of life. Iron is a critical component of the 

heme proteins: hemoglobin, myoglobin and cytochromes, as well as iron-sulfur 

enzymes, iron storage and transport proteins, and other iron-containing or iron-
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activated enzymes. Data from laboratory animal studies in dogs and cats indicated 

that high levels of iron oxide in the diet (up to 10 g/kg) did not cause adverse effects.

2. Genotoxicty. Iron oxide yellow is an inorganic the essential element, iron 

that is required by all forms of life. It is not necessary to evaluate the potential 

genotoxicity of this simple source of the essential element, given the natural 

occurrence of iron oxides in food. 

3. Reproductive and developmental toxicity. No adverse effects on reproduction 

were reported in rats that consumed more than 50 mg/kg/day iron oxide for 8-

generations.

4. Subchronic toxicity. The National Academy of Sciences (NAS) Institute of 

Medicine published a detailed report that included derivation of a Tolerable Upper 

Intake Level (UL) for iron of 40 mg/day for children (2 to 13 years of age), and a UL 

of 45 mg/day for adolescents and adults (14 years of age and older). The US Food 

and Drug Administration (FDA) accepted these ULs as the highest levels of iron that 

pose no risk of an adverse effect when the nutrient is consumed over long periods of 

time. 

5. Chronic toxicity. The NAS-derived Tolerable Upper Intake Levels (ULs) for 

iron of 40 mg/day for children (2 to 13 years of age), and 45 mg/day for adolescents 

and adults (14 years of age and older) are suitable for chronic exposure assessment. 

The US FDA accepts these ULs as the highest levels of iron that pose no risk of an 

adverse effect when the nutrient is consumed over long periods of time, and this 

indicates the ULs are suitable for evaluation of chronic exposure. 

6. Animal metabolism. Elemental iron is the key metabolite of iron oxide in the 

body. A key biological function of iron is transfer of oxygen from the environment 

to the tissues. Oxygen binds to the iron-containing porphyrin ring of hemoglobin 

where it is transported within the erythrocytes to the tissues, and it may be 

transferred to myoglobin which facilitates oxygen diffusion through the muscle 

tissues. Iron is also an important component of cytochrome heme proteins that are 

active in the mitochondrial respiratory systems.

7. Metabolite toxicology. The iron oxide metabolite of interest is elemental 

iron, which is an essential element. 

8. Endocrine disruption. Toxicity related to endocrine disruption was not 

observed in the iron oxide yellow database. 

C. Aggregate Exposure

1. Dietary exposure. The estimated chronic dietary exposure to iron oxide 

yellow was determined using the Dietary Exposure Evaluation Model (DEEM) 

software with the Food Commodity Intake Database. The assessment assumes that: 

1) the inert ingredient is used on only honey from bee hives, 2) 100% of hives are 
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treated with the inert, and 3) 100% of the inert is transferred to the honey. The 

maximum exposure was 0.0% of the Population Adjusted dose.

i. Food. The food commodities included in the assessment were honey, and 

honey, baby food.

ii. Drinking water. No drinking water exposure from the use of iron oxide 

yellow in honey bee hives to control varroa mites is expected.

2. Non-dietary exposure. The only non-dietary exposure to iron oxide yellow

from use of the bee hive strips possible would be dermal exposure to workers that 

apply the strips to the hives if they do not wear gloves.

D. Cumulative Effects

Iron oxide yellow has been used for many years in food, drugs and cosmetics. 

The additional exposure to 0.0% of the Population Adjusted Dose of iron oxide is 

not expected to increase the current exposures significantly.

E. Safety Determination

1. U.S. population. The low toxicity of iron oxide yellow and the lack of 

potential exposure from the proposed use suggest that the total aggregate exposures 

to iron will be well below the acceptable exposure. Thus, a safety finding for iron 

oxide yellow can be concluded for aggregate exposures from dietary and nondietary uses.

2. Infants and children. The low toxicity of iron oxide and the lack of potential

dietary exposure suggest that the total aggregate exposures for infants and children 

will be well below the acceptable exposure. Thus, a safety finding for iron oxide 

yellow can be concluded for infant and child exposures from dietary uses.

F. International Tolerances

There are no international tolerances for iron oxide yellow. Codex general 

standards for food additives (GSFA) for iron oxides have been developed for more 

than a dozen foods, including breakfast cereals (75 mg/kg), chewing gum (10,000 

mg/kg), and jams, jellies and marmalades (200 mg/kg) to name a few.]