


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

EPA Registration Division contact: P.V. Shah, 703-308-1846

TEMPLATE:

Monsanto Company

[IN-10965]

	EPA has received a pesticide petition (IN-10965) from Monsanto Company, 1300 I Street NW., Suite 450 East, Washington, DC, 20005  requesting, 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 by amending the exemption from the requirement of a tolerance for mono-, di-, and trimethylnapthalenesulfonic acids and napthalenesulfonic acids formaldehyde condensates, ammonium and sodium salts (CAS Reg. Nos. 9008 - 63 - 3, 9069 - 80 - 1, 9084 - 06 - 4, 36290 - 04 - 7, 91078 - 68 - 1, 141959 - 43 - 5, 68425 - 94 - 5) to include the potassium salts (CAS Reg. No. 67828-14-2).  

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 [NA-Remove]

B. Toxicological Profile

	1. Acute toxicity.  Available toxicity data indicates that SAPNFC as a class has low acute oral and inhalation toxicity.  Representatives have an oral LD50 of 3250  -  4300 mg/kg in the rat (CAS Reg. No. 67828-14-2) and greater than 5,000 mg/kg in mice (CAS Reg. No. 91078-68-1), and low inhalation toxicity, with an acute inhalation LC50 of around 50 mg/L. No irritation to the skin was revealed in several rabbit studies and at worst was only slightly irritating to the rabbit eye (CAS Reg. No. 90884-06-4).  Alternate routes of exposure to rats provided an LD50 of460 mg/kg (IP) and 435 mg/kg (IV).  Subacute mouse LD50 is reported to be 1,275 mg/kg. 

	2. Genotoxicty. CAS Reg. No. 9084-06-4 was not mutagenic in an Ames test listed in the IUCLID, indicating the absence of mutagenic potential. IARC, NTP nor OSHA has listed this representative SAPNFC as a carcinogen.

	3. Reproductive and developmental toxicity. Naphthalenesulfonic acid, polymer with formaldehyde sodium salt (CAS Reg. No. 9084-06-4) was tested in an OECD 422 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test. No developmental or reproductive effects were observed at doses of 100,
300, and 1,000 mg/kg/day.  The NOAEL for reproduction/developmental toxicity was considered to be 1000 mg/kg/day.

	4. Subchronic toxicity. Naphthalenesulfonic acid, polymer with formaldehyde sodium salt (CAS RN 9084-06-4) has been tested in an OECD 422 Combined Repeated Dose Toxicity Study with a Reproduction /Developmental Toxicity Screening Test. The general toxicity NOAEL from the OECD 422 Study was 1000 mg/kg body weight/day. In this study male rats received doses of the test substance for 28 days and the females were treated for 14 days prior to pairing, through the pairing and gestation periods until the Fl generation reached day 4 post partum. 

The overall toxicity NOAEL is 1000 mg/kg/day as the only effects observed at this dosage level were transient effects on food consumption and body weight at the beginning of treatment and were not considered adverse because they recovered immediately thereafter, and had no impact on the terminal mean body weight of both males and females treated at the limit dose of 1000 mg/kg/day.]

	5. Chronic toxicity. There are no chronic data available on the SANFC surfactants; however, no structural alerts for cancer were identified in a qualitative structure activity relationship (SAR) database, DEREK Version 11. In addition, there was little concern about any of the postulated metabolites having greater toxicity than the parent compounds.

	6. Animal metabolism. The higher molecular weight (MW) polymeric SANFC surfactants (MW >1,000) are not expected to be readily absorbed or metabolized, and should thus be rapidly excreted (likely in the feces) unchanged. Additionally, lower molecular microsome cytochrome P-450 oxygenases may hydroxylate the naphthalene ring and/or methylene bridge to produce alternative metabolites that should also be readily conjugated and excreted.

	7. Metabolite toxicology. No metabolites having greater toxicity than the parent compounds are expected from SAPNFCs based on the proposed limited animal metabolic pathway.

	8. Endocrine disruption. Naphthalenesulfonate formaldehyde condensates do not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system. CAS Reg. No. 9084-06-4 has been evaluated in repeat dose, developmental, and reproductive studies capable of detecting effects on endocrine mediated events. The results of these studies did not give any indication of a treatment-related effect on the estrogen receptor or endocrine system.

C. Aggregate Exposure

	1. Dietary exposure. EPA assesses potential dietary exposures to inert ingredients used in agricultural pesticide formulations using a screening-level model referred to as "I-DEEM," in which the "I" stands for inerts and "DEEM" is the dietary exposure evaluation model that is used by EPA to assess dietary exposures to active ingredients in pesticide  products. EPA's Inert Ingredients Assessment Branch and residue chemists in the Health Effects Division of the Office of Pesticide Programs jointly developed I-DEEM. 

Based on I-DEEM screening level calculations, the chronic dietary exposures are estimated to be 1.9% of the proposed cPAD for the general U.S. population and 6.2% of the cPAD for children 1-2 years old. These data demonstrate that the I-DEEM screening-level chronic dietary (food and drinking water) exposures are below the cPAD and are therefore below EPA's established level of concern for all U.S. subpopulations. 

On the basis of the OECD 422 repeat dose toxicity study and comparison of I-DEEM exposures to the proposed cPAD, the Petitioner asserts that there is sufficient basis for EPA to grant a tolerance exemption supported by way of this petition.

	i. Food. No hazard was identified for the acute and chronic dietary assessment (food and drinking water). Available data demonstrate that the I-DEEM screening level chronic dietary exposures are well below 100% of the cPAD, and are, therefore, below EPA's established level of concern for all U.S. subpopulations.

	ii. Drinking water.  Drinking water was included in the I-DEEM exposure assessment.  However, exposure to ammonium, potassium and sodium alkyl-naphthalenesulfonate formaldehyde condensates via drinking water is expected to be negligible. 

	2. Non-dietary exposure. Ammonium, potassium and sodium naphthalene-sulfonate formaldehyde condensates surfactants are predominantly used in agricultural formulations. In addition to pesticide formulations, many of the SAPNFC surfactants included in this Petition are used in a wide variety of industrial applications as dispersants for pigments, latex and natural fibers, defoamers in food contact packaging, and emulsifiers in personal care products and cellophane for food packaging. Given the low estimate of dietary exposure, there is ample room in the overall aggregate MOE for non-dietary uses.

D. Cumulative Effects

	There is no evidence that SAPNFCs share a common mechanism of toxicity with any other substances, and SAPNFCs do not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, it is assumed that SANFCs do not have a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. A dietary exposure assessment using current EPA inert screening level methodology (I-DEEM) was conducted. Based on the conservative I-DEEM dietary exposure estimates, there is a reasonable certainty that no harm will result to the U.S. population from the aggregate exposure to ammonium, potassium and sodium naphthalenesulfonate formaldehyde condensates.

	2. Infants and children. FFDCA Section 408 requires an additional tenfold margin of safety for the protection of infants and children in case of threshold effects to account for prenatal and postnatal toxicity, and an inadequate toxicity database. Where an adequate and reliable database is available and there is a lack of evidence for increased susceptibility, the FQPA safety factor may be reduced or removed. An evaluation of susceptibility and uncertainty issues associated with SAPNFC surfactants has been performed. Based on the points summarized below, it is proposed that the FQPA safety factor be reduced from the default 10X to 1X. Additionally, under these circumstances the chronic Population Adjusted Dose, cPAD, is the same as the Chronic Reference Dose cited above, cPAD =cRID =10 mg/kg/day. 

 A scientifically sound mammalian toxicology database, which includes acute, repeat dose, reproductive, and developmental toxicity study data indicate no adverse effects to sensitive populations.
 The surfactants in this cluster do not belong to a class of chemicals known or suspected to having adverse effects on the estrogen receptor or endocrine system.
 OECD 422 testing indicates no reproductive and no developmental effects in offspring at the limit dose of 1000 mg/kg/day.
 There was no evidence of effects on the nervous system in the acute, repeat dose, or reproduction studies. 
 No evidence of mutagenicity in the Ames test


F. International Tolerances

	The Agency is not aware of any country requiring a tolerance for the SAPNFCs nor have any CODEX Maximum Residue Levels been established for any food crops at this time.




