Document ID: EPA-HQ-OPP-2016-0252-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2016-07-20T04:00Z

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-10888

	EPA has received a pesticide petition (IN-10888) from [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 180.910 to establish an exemption from the requirement of a tolerance for residues of titanium dioxide (CAS Reg. No. 13463-67-7) in honey as a result of its use as an inert ingredient (colorant) at a concentration of not more than 0.1% in pesticide formulations intended for varroa mite control around bee hives.  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.  [Titanium dioxide is low in toxicity following acute exposure, with a reported oral LD50 in rats of greater than 5,000 mg/kg body weight.  An acute inhalation exposure study in rats to titanium dioxide at a concentration of 3.43 mg/L caused no deaths.  No acute dermal toxicity studies have been identified for titanium dioxide.  Two separate dermal irritation studies in rabbits reported that titanium dioxide is not a dermal or eye irritant. Titanium dioxide is not a sensitizing agent. ]

	2. Genotoxicty. [A variety of genotoxicity studies have been conducted on titanium dioxide, including sister chromatid exchange assays, in vitro and in vivo micronucleus assays, comet assays, reverse mutation tests and chromosome aberration tests.  These various reports produced mixed results but overall support the determination that titanium dioxide is not mutagenic.  ]

	3. Reproductive and developmental toxicity. [There was no effect of titanium dioxide dosing on reproductive toxicity in parental animals or developmental toxicity in the offspring. The NOAEL for both reproductive and developmental toxicity was 1,000 mg/kg bw/day.]

	4. Subchronic toxicity. [The potential effects of repeated oral exposure to titanium dioxide were evaluated in rats in a 28-day toxicity test conducted according to OECD 407. No effects of treatment were considered to be toxicologically significant and the No-Observed-Adverse-Effect-Level (NOAEL) was considered to be 1,000 mg/kg bw/day. ]

	5. Chronic toxicity. [Titanium dioxide has been tested for potential carcinogenicity in laboratory animals exposed by the oral route, by the inhalation route and via intratracheal administration.  Oral exposure is the route of primary interest for consideration of an exemption from the requirement of a tolerance for exposure from the proposed use.  Groups of 50 male and 50 female mice were fed diets that contained 0, 2.5% or 5% titanium dioxide for 103 weeks.  No significant differences in tumor incidences or body weights were observed between treated and control groups of mice.  Titanium dioxide was shown not to be carcinogenic following chronic dietary exposure.]

	6. Animal metabolism. [The data available indicate that titanium dioxide is not absorbed by mammalian systems and consequently, is not metabolized.]

	7. Metabolite toxicology. [The data available indicate that titanium dioxide is not absorbed by mammalian systems and consequently, is not metabolized.   ]

	8. Endocrine disruption. [Toxicity related to endocrine disruption was not observed in the titanium dioxide database.    ]

C. Aggregate Exposure

	1. Dietary exposure. [No dietary exposure assessment is necessary to support an exemption from the requirement of a tolerance for titanium dioxide use as a colorant in plastic pesticide strips.  The conclusion in the 2012 EPA assessment that no dietary exposure assessment was warranted for titanium dioxide for the proposed uses holds true for the proposed new use of titanium dioxide.]

	i. Food. [The potential exposure to titanium dioxide via food from the proposed new inert use is very low, and titanium dioxide is low in toxicity.]

	ii. Drinking water. [No drinking water exposure from the use of titanium dioxide as a colorant in a plastic pesticide formulation is expected.]

	2. Non-dietary exposure. [Titanium dioxide is an approved food additive and also ingredient in personal care products that are intentionally applied to the skin, including make-up, deodorant, and sunscreens.  Any additional exposure to titanium dioxide from use as a colorant in a plastic pesticide formulation will be very low in comparison.]

D. Cumulative Effects

	[To our knowledge there are no available data or other reliable information that suggest any effects produced by titanium dioxide would be cumulative with those of any other chemical compounds. ]

E. Safety Determination

	1. U.S. population. [The low toxicity of titanium dioxide and the lack of potential exposure from the proposed use suggest that the total aggregate exposures will be well below an acceptable exposure.  Thus, a safety finding for titanium dioxide can be concluded for aggregate exposures from dietary and non-dietary uses.]

	2. Infants and children. [The low toxicity of titanium dioxide 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 titanium dioxide can be concluded for infant and child exposures from dietary uses.]

F. International Tolerances

	[There are no international tolerances for titanium dioxide.  Codex general standards for food additives (GSFA) for titanium dioxide have been developed for a variety of foods, including dairy-based drinks, condensed milk, cream analogues, a variety of cheeses, sherbet and sorbet, and processed fruit and vegetables.]