EPA ANTIMICROBIALS DIVISION COMPANY NOTICE OF FILING FOR 

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Antimicrobials Division contact: Jacqueline Hardy 703-308-6416

EPA has received a pesticide petition #4F8324 from Cupron Inc, 800 East Leigh 

St., Richmond VA 23219 requesting, pursuant to section 408(d) of the Federal Food, 

Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend the tolerance exemption 

in 40 CFR part 180.1021 for cuprous oxide in/on meat, milk, poultry, eggs, fish, shellfish, 

and irrigated crops by including the use of cuprous oxide embedded in polymer emitter 

heads used in irrigation systems for agricultural crops or residential food commodities for 

algaecidal or root incursion prevention.

EPA has determined that the petition contains data and 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. Copper is an essential nutrient in plant development and 

nutrition

2. Analytical method. Since the request is for an exemption from tolerance, no 

analytical method has been supplied.

3. Magnitude of residues. NA-Remove

B. Toxicological Profile

1. Acute toxicity. Copper generally has moderate to low toxicity (Toxicity 

Category II, III and IV) based on acute oral, dermal and inhalation studies in animals. 

The toxicity categories for cuprous oxide are:

Acute Toxicology: Category III LD50 greater than 500 mg/kg and less than 5000 mg/kg

Acute Dermal: Category IV LD50 greater than 5000 mg/kg

Acute Inhalation: Category IV LD50 greater than 5000 mg/kg

Primary Eye Irritation: Cat III LD50 greater than 500 mg/kg and less than 5000 mg/kg

Dermal Irritation: Category IV LD50 greater than 5000 mg/kg

Dermal Sensitization: Not a Sensitizer
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2. Genotoxicity. Copper and cuprous oxide are considered essential nutrients,

there is no evidence of genotoxicity from exposure.

3. Reproductive and developmental toxicity. As discussed in the Agency’s 

reregistration document for cuprous oxide, available reproductive and developmental 

studies by the oral route of exposure generally indicate that the main concern in animals 

for reproductive and teratogenic effects of copper has usually been associated with the 

deficiency rather than the excess of copper.

4. Subchronic toxicity. According to the Agency’s reregistration document for 

Cuprous Oxide, based on available data, there is no evidence that warrants determining 

any dietary, oral, dermal or inhalation endpoints to quantify sub-chronic toxicity.

5. Chronic toxicity. According to the Agency’s reregistration document for 

Cuprous Oxide, based on available data, there is no evidence that warrants determining 

any dietary, oral, dermal or inhalation endpoints to quantify chronic toxicity.

6. Animal metabolism. Although the metabolism pathways are not clearly known, 

the mechanisms for regulating total copper in the body appear to be efficient in maintaining a 

generally consistent level of copper needed for homeostasis. The efficiency of copper 

absorption varies greatly, depending on dietary intake. When dietary copper is high and more 

copper is absorbed, mainly through the gastrointestinal tract, excretion of copper from the 

body increases, protecting against excess accumulation of copper in the body. Depending on 

the copper status in the body at the time, approximately 20 to 60% of dietary copper may be 

absorbed. Copper absorption is also affected by other factors such as species, age, chemical 

form, and pregnancy. When copper intake is low, little copper is excreted from the body, 

protecting against copper depletion. Generally, current available data and literature studies 

indicate that there is a greater risk from the deficiency of copper intake than from excess 

intake. A deficiency of copper or a defect in copper carrying proteins may result in symptoms 

such as anemia, defective blood vessel development, or connective tissue symptoms.

7. Metabolite toxicology. NA- Remove

8. Endocrine disruption. Copper and Cuprous Oxide are not endocrine disruptors.

C. Aggregate Exposure

1. Dietary exposure. Copper is a ubiquitous, naturally occurring metal that is 

essential to human health, found naturally at low levels in a variety of food products as 

well as in drinking water from copper plumbing pipes. According to the EPA reregistration 

document for Cuprous Oxide, based on available studies and literature, there are no human 

health aggregate risks of concern resulting from aggregate dietary and residential 

exposures

i. Food. NA-Remove

ii. Drinking water. NA-Remove
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2. Non-dietary exposure. NA-Remove

D. Cumulative Effects

There are no cumulative effects from chronic exposure to cuprous oxide.

E. Safety Determination

1. U.S. population. NA-Remove

2. Infants and children. FFDCA, as amended by FQPA, directs the Agency 

to use an additional 10X safety factor (SF), to account for potential pre- and postnatal toxicity 

and completeness of the data with respect to exposure and toxicity to infants and children. 

FQPA authorizes the Agency to modify the 10X FQPA SF only if reliable data demonstrate 

that the resulting level of exposure would be safe for infants and children. In humans, there 

does not appear to be any reports in the literature of teratogenesis induced by exposure to 

excess copper. The only teratogenic effects observed in available animal studies occurred 

after exposure with copper salts at high doses which were likely maternally toxic. Moreover, 

there is no evidence to suggest susceptibility in infants and children. Since copper is an 

essential trace element, with copper deficiency more common in humans than toxicity from 

the excess, and since the dietary (food and drinking water) contribution of copper to the total 

diet is low, endpoints to quantitatively assess dietary risk were not selected. EPA has low 

concerns and no residual uncertainties with regard to pre- or postnatal toxicity from copper 

exposures. Since a qualitative assessment was conducted for potential human health exposure 

to copper, the 10X FQPA SF was not retained.

F. International Tolerances

NA-Remove