Document ID: EPA-HQ-OPP-2015-0858-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2016-03-16T04:00Z

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]

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:

 Baker Petrolite LLC

IN-10889

EPA has received a pesticide petition ([N-10889) from Baker Petrolite LLC, (12645 West Airport Boulevard, Sugar Land, TX 77478) 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, 40 CFR part 180.920, 40 CFR part 180.930, 40 CFR part 180.940(a), and 40 CFR part 180.960 to establish an exemption from the requirement of a tolerance for Alcohols, C>14, ethoxylated with CAS Number 251553-55-6 in or on growing crops or to the raw agricultural commodity and to animals.  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. [Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients.]

	2. Analytical method. [Not applicable/Not required for the establishment of a tolerance exemption for inert ingredients.] 

	3. Magnitude of residues. [There is no specific crop residue information available for AAA and this information is typically neither available nor required for the establishment of a tolerance exemption for inert ingredients.] 

B. Toxicological Profile

1. Acute toxicity.  [Human exposure from the use of AAAs as pesticide inert ingredients will primarily occur via the oral route through the consumption of food or drinking water. As a class AAA surfactants are not volatile. Thus, post-application inhalation exposure is unlikely. The AAAs show low to moderate acute toxicity by the oral route of exposure and the limited data available for dermal exposure also indicate low to moderate toxicity, especially for the diluted formulations. Irritation has been reported in animal laboratory studies. The AAAs did not cause skin sensitization when they were tested as diluted formulations. The acute oral LD50 values for rats range from 600 mg/kg to 10,000 mg/kg (HERA 2007). Talmage (1994) reported LD50 values ranging from 544 mg/kg to > 25,000 mg/kg. Undiluted AAA compounds can be moderate to severe irritants to the skin; diluted products are not of concern and not expected to be irritating to the skin.]
 
 2. Genotoxicty. [AAAs were not genotoxic or mutagenic in bacterial or mammalian in vitro cell systems (HERA 2007). Neither IARC, NTP nor OSHA listed AAA surfactants as a carcinogen.] 
3. Reproductive and developmental toxicity. [Two AAA literature reviews (HERA 2007, Talmage 1994) show that reproductive/developmental studies with oral exposure for C14-15EO7 with relatively low toxicity reported NOELs of 250 mg/kg/day for reproduction and 50 mg/kg/day for maternal toxicity. A dermal exposure reproductive study with C9-11EO6 also reported a low toxicity NOAEL of 250 mg/kg/day for both reproductive and systemic toxicity.
OECD 421 Reproduction/Developmental Toxicity Screening Test of Secondary Alcohol Ethoxylate (CAS RN 84133-50-6) shows the reproductive/developmental NOEL is greater than 470 mg/kg/day as no effects on mating and fertility as well as on Fl generation up to day 4 post partum were observed at the highest dosage tested.
OECD 422 Oral (Gavage) Combined Repeated Dose Toxicity Study with a Reproduction/Developmental Toxicity Screening Test of CAS RN 9004-98-2 shows the NOEL for reproduction and developmental toxicity was 242 mg/kg/day, the highest dose tested.
OECD 4220ra1 (Gavage) Combined Repeated Dose Toxicity Study with a Reproduction/Developmental Toxicity Screening Test of CAS RN 103818-93-5 shows the NOEL for reproduction and developmental toxicity was 300 mg/kg/day, the highest dosage level tested.]
 
4. Subchronic toxicity. [Based on the Federal Register Notice (August 9, 2006, Volume 71, Number 153, pages 45415-45424), the Agency stated that the preferred test for repeat-dose toxicity is the "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 422)." AAAs (CAS RN 9004-98-2, and CAS RN 103818-93-5) have been tested in repeat dose studies (OECD 422 Combined Repeated Dose Toxicity Study with a Reproduction/Developmental Toxicity Screening Test) and an OECD 421 Oral (Gavage) Reproduction/Developmental Toxicity Screening Test of Secondary Alcohol Ethoxylate was conducted with CAS RN 84133-50-6. The paternal and maternal NOAEL for CAS RN 84133-50-6 was 60 mg/kg/day. The paternal and maternal NOAEL for CAS RN 9004-98-2 was 110 mg/kg/day. The paternal and maternal NOAEL for CAS RN 103818-93-5 was 48 mg/kg/day.]

5. Chronic toxicity. Based on the Federal Register Notice (August 9, 2006, Volume 71, Number 153, pages 45415-45424), the Agency stated that the preferred test for repeat-dose toxicity is the "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 422)."
Chronic dietary studies with rats showed no incidence of cancer and no effects at the concentrations tested (lowest dose tested was ca 50 mg/kg/day).]
 
6. Animal metabolism. [The metabolism of the AAA surfactant initially occurs by hydrolysis of the ether linkage to the corresponding long chain alkyl alcohol and polyalkoxylate, which subsequently undergo oxidative degradation and/or excretion. The higher molecular weight substances and highly polar (highly polyalkoxylated) AAA surfactants are not readily absorbed and metabolized.

Various oxidative pathways for aliphatic alcohol metabolism would work in concert with each other. Linear saturated and unsaturated alcohols are oxidized successively to their corresponding aldehydes and carboxylic acids, which then enter the fatty acid beta-oxidation pathway. Branched-chain aliphatic alcohols are converted by similar oxidation reactions to their corresponding carboxylic acid, which then undergoes metabolism via beta-oxidation and cleavage to yield carbon dioxide in the amino acid pathways, the fatty acid pathways, and the tricarboxylic acid pathways. Alternatively, alcohols having steric hindrance could undergo beta and gamma oxidative pathways and/or conjugation elimination pathways. 

7. Metabolite toxicology. [No metabolites of toxicological concern are expected based on the proposed animal metabolic pathway.] 

8. Endocrine disruption. [The AAA surfactants do not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system. AAAs have been evaluated in acute, repeated 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. [The dietary (food plus drinking water) exposures for AAA surfactants are expressed as a percentage of the proposed chronic population adjusted dose (cPAD) for the general US population and children 1-2 years old, the subpopulation with the highest potential exposures.
Based on I-DEEM screening level calculations, the chronic dietary exposures for the AAA are estimated to be 25.4% of the cPAD for the general U.S. population and 88.5% 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 for both the AAAPD and AAASD are well below 100% of 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 1-DEEM exposures to the proposed cPAD, the applicant asserts that there is sufficient basis for EPA to grant a tolerance exemption for AAA surfactants.
 Chronic Dietary Safety Assessment, % cPAD

         Study
                               Chronic 
Systemic
                                   NOAEL[1]
                                 mg/kg 
bw/day
                                    cPAD[2]
                                 mg/kg 
bw/day
                                    Percent
                           cPAD 
Children 
1-2 years
                                    of age 
                                    Percent
                                     cPAD
                              U.S. Gen
Population
 CASRN 103818-93-5

 Repeated Dose Toxicity with

 Reproduction/Developmen tal Toxicity Screening in
                                      48
                                     0.48
                                     88.5
                                     25.4
 Rats- (OECD 422) CRL

 Study number UPU00006 (Lech, J. 2009c)

 Note:
 [1]NOAEL  -  No observed adverse effect level
 [2]cPAD  --  Chronic population adjusted dose, defined as: 
                                           chronic NOAEL / (safety factor x FQPA factor)]

	i. Food. [The available data demonstrate that the I-DEEM screening level chronic dietary (food and drinking water) 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 is included in the I-DEEM exposure assessment. Exposure to AAA via drinking water is expected to be negligible.] 

	2. Non-dietary exposure. [AAA surfactants are used in agricultural formulations as well as in non-pesticidal uses such as personal care products. Given the low estimate of dietary exposure, there is ample room in the overall aggregate MOE for non-dietary uses.] 

D. Cumulative Effects
 [For the purpose of the tolerance exemption actions cited herein, the applicant has assumed that the AAA will not have a common mechanism of toxicity with other surfactant substances. It is therefore appropriate to consider only the potential risks of the compounds included in CST 1 in the exposure assessment.]
 
E. Safety Determination

 U.S. population. 
[A dietary exposure assessment using current EPA inert screening level methodology (1-DEEM) was conducted. Based on the conservative I-DEEM dietary exposure estimates, there is a reasonable certainty that no harm will result to the US population from the aggregate exposure to AAA.] 
	2. Infants and children. 
[The 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 the Alkyl Alcohol Alkoxylates has been performed, and the applicant recommends that the FQPA safety factor be reduced to 1X for the following reasons:
          The availability of a substantial and scientifically sound mammalian toxicology database that includes acute, subchronic and chronic repeat dose, reproduction, developmental and carcinogenicity toxicity data for the CST 1 AAAs, including CAS RN 84133-50-6, CAS RN 9004-98-2 and CAS RN 103818-93-5.
          OECD 421/422 testing of CAS RI' 84133-50-6, CAS RN 9004-98-2 and CAS RN 103818-93-5 indicate that there were no reproductive effects and no evidence of malformations in the developing offspring.
          There was no evidence of effects on the nervous system in the acute, repeat dose or reproduction studies for the CST 1 supported surfactants.

There is no evidence of endocrine disruption for the AAA surfactants. The AAA surfactants do not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system. AAAs have been evaluated in acute, repeated dose (subchronic and chronic), 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.] 

F. International Tolerances
[There are no known international tolerances for Alkyl Alcohol Alkoxylates.]