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 request ing, pursua nt 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 u se 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. Analy tical 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

Ca tegory 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 grea ter than 5000 mg/kg

Acute Inhalation: Category IV LD50 greater than 5000 mg/kg Primary Eye Irritation: Cat III LD50 greater th an 500 mg/kg and less than 5000 mg/kg

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

Dermal Sensitization: Not a Se nsitizer2

2. Genotoxic i ty. Copper and cuprous oxide are considered essential nutrients, there is no evidence of genotox icity from exposure.

3. Reproductive and developmental toxicity. As discussed in the Agency’ s reregistr ation document for cuprous oxi de, a vailable 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 r eregistration document for Cupro us Oxide, b ased on available data, there is no evidence that warrants determining any dietary, oral, dermal or inhalation endpoints to quantify sub

- chronic tox icity.

5. Chronic toxicity. According to the Agency’s r eregistration document for Cupro us Oxide, b ased on available data, there is no evidence that warrants determining any dietary, oral, dermal or inhalation endpoi nts 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, lit tle 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 o r 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 d isruptors.

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, b ased 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

- Remove3

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 b y 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 th e 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 onl y 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

esse ntial 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 selec ted. 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. Inter national Tolerances

NA

- Remove