


EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [insert name and telephone number with area code]

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:

[Dow AgroSciences L.L.C.]

[IN-11012]

	EPA has received a pesticide petition (IN-11012) from [Dow AgroSciences], [9330 Zionsville Road, Indianapolis, IN 46268] 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.

(Options (pick one)
   

	2. to establish an exemption from the requirement of a tolerance for

	[nicotinamide (CAS 98-92-0) when used as an inert ingredient as a corrosion inhibitor at up to 5% within a pesticidal product].  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

 [Because an exemption from the requirement of a tolerance is requested, no field residue studies are required.]

B. Toxicological Profile

	1. Acute toxicity.  [Nicotinamide has low acute toxicity in lab animals with oral LD50 values >2200 mg/kg body weight (bw) and dermal LD50 values >2000 mg/kg bw.]

	2. Genotoxicty. [Nicotinamide was negative in the Ames assay, the in vitro chromosomal aberration assay, and the in vivo mouse micronucleus assay.]

	3. Reproductive and developmental toxicity. [In a rat developmental toxicity assay, no teratogenic effects were observed at doses up to the high dose of 1000 mg/kg/day.  Fetotoxicity (decreased fetal weight) was observed only at the maternally toxic dose of 1000 mg/kg/dy.]

	4. Subchronic toxicity. [In a 28-day oral toxicity study in rats, the NOAEL was considered to be 215 mg/kg bw/day based on spleen effects in females at 1000 mg/kg bw/day.  Rabbits and guinea pigs fed nicotinamide at 2% in the diet showed no adverse effects.  Side effects such as headaches, nausea, vomiting, itching, and insomnia are reported in humans consuming therapeutic doses of greater than 6 g/day.]

	5. Chronic toxicity. [There was no increase in tumor incidence in Swiss mice fed 1% nicotinamide in the diet (~2600 mg/kg bw/day for females and ~3300 mg/kg bw/day for males).]

	6. Animal metabolism. [Nicotinamide is a vitamin required for lipid metabolism, tissue respiration, and glycogenolysis.  It is rapidly absorbed and incorporated into the body as NAD or is excreted in the urine, primarily as N-methyl-nicotinamide or N-methyl-2-pyridone-5-carboxamide.]

	7. Metabolite toxicology. [No specific information was identified on toxicity of nicotinamide metabolites.  However, nicotinamide is a normal part of the human diet.  It is rapidly metabolized, and metabolite toxicity would be represented in the effects observed following human or animal ingestion.  Overall, metabolite toxicity is considered to be low.]

	8. Endocrine disruption. [Nicotinamide does not belong to a class of chemicals known or suspected to have adverse effects on the estrogen receptor or endocrine system.]

C. Aggregate Exposure

	1. Dietary exposure. [Nicotinamide is a natural part of the human diet and may be consumed as a dietary supplement.  A recommended daily allowance (RDA) for niacin has been established at not less than 16 mg/day for an adult male.  An upper limit (UL) was set for niacin at 35 mg/day based on flushing, a very sensitive effect associated with nicotinic acid, but not nicotinamide exposures.  Therefore, a UL for nicotinamide could theoretically be established based on the next most sensitive effect (ocular effects) at 1 g/day for adults.]

	i. Food. [An assessment based on the general results of the EPA screening-level dietary exposure model I-DEEM is provided.  I-DEEM is based on a screening level dietary assessment of 57 of the most "significant" active ingredients used as surrogates for inerts within the Dietary Exposure Evaluation Model software with food Commodity Intake Database (DEEM-FCID, Version 3.16).  Exposures were compared to the RDA and UL for nicotinamide mentioned above.  All exposures were below the RDA and less than 0.5% of the UL.]

	ii. Drinking water. [Drinking water estimates have been included in the I-DEEM model and are included in the conclusion of a passing dietary risk assessment as discussed above.]

	2. Non-dietary exposure. [No uses of nicotinamide in pesticidal products for non-crop uses are indicated in publically available databases.  Non-dietary consumer exposures to nicotinamide are possible due to its use in personal care products such as cleansers and lotions.  There is a history of safe human use of such products and as such, no quantitative risk assessment has been conducted.  Furthermore, as dietary exposures are well below established limits and levels regularly safely consumed as dietary supplements, a reasonable certainty of no harm can be concluded for aggregate exposures based on a history of safe use.  The use of nicotinamide in pesticidal products is not expected to appreciably change human exposures.]

D. Cumulative Effects

	[Unlike for pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, for nicotinamide EPA has not made a common mechanism of toxicity finding.  Consideration of a common mode of toxicity is not appropriate given that there is no information available that indicates potential toxic effects, if any, would be cumulative with any other compounds.]

E. Safety Determination

	1. U.S. population. [A reasonable certainty of no harm has been established for the general population for the proposed use of nicotinamide as an inert ingredient in pesticide formulations.  This use is not expected to appreciably increase current exposures from other exposure sources.]

	2. Infants and children. [The available information does not indicate any qualitative or quantitative evidence of increased susceptibility to infants and children for nicotinamide.  Assessment of the various child subpopulations is included in the I-DEEM analysis and for all subpopulations, exposures are below the RDA and UL for nicotinamide and are not expected to significantly alter current exposure levels.  A reasonable certainty of no harm has been established for children as well.]

F. International Tolerances

	[No international tolerances have been established for nicotinamide.]




