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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 prep aring the pesticid e 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:

[Clariant Corporation, 4000 Monr oe Road, Char lotte, NC 28205]

EPA has received a pesticide petition (IN 10630] from Clariant Corporation (EPA Company Number 8340, 4000 Monroe Road Charlotte, NC 28205] requesting, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (F FDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 to establish an exem ption from the requirement of a tolerance for [the use of Secondary Alkane (C 13 -C 17 ) Sulfonates (C 13 -C 17 SAS) as pesticide inert ingredients (as surfactants) for use in food crops in accordance with 40 CFR §180.920 (preharvest) for seed treatment and foliar app lications pursuant to S ection 408(d)(1) of the Federal Food, Drug, and Cosmetic Act (FFDCA). There are currently no approved nonfood uses or food use tolerance exemptions for C 13 -C 17 SAS as a pesticide inert ingredient.] EPA has determined that the pet ition 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.

[The SAS surfactant compounds are mixtures of sulfonated C 13 -C 17 linear alkanes in

which the sulfonate sodium sa lt is distributed an d mainly located on the secondary carbon atoms in the linear alkyl chain. The followi ng CAS RNs are supported by way of this petition].

Secondary Alkane (C 13 -C 17 ) Sulfonates

CAS R e g istry Numbe r (CAS R N) Name

85711-69-9 Sulfonic Acids, C 13 -C 17 sec- a lk a ne 97489-15-1 Sulfonic Acids, C 14 -C 17 sec- a lk a ne,2

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

B. Toxicological Profile

The C 13 -C 17 SAS surfactants have been generally te sted as aqueous solutions (60%-30%), because this represents how the commerci al products are generally available for formulation and manufacturing purposes both in the EU and US. Overall, the testing results may reflect the different commercial grades of C 13 -C 17 SAS in a dose dependent

manner that is consistent with the test concentration of C 13 -C 17 of the SAS surfactant. The specific concentration of C 13 -C 17 SAS in the test material was identified whenever possible. On the basis of the chemical identity analysis that toxicology data reported for CAS RN 85711-69-9 Sulfonic Acids, C 13 -C 17 sec-alkane can be bridged to CAS RN

97489-15-1 Sulfonic Acids, C 14 -C 17 sec-alkane.

1. Acute toxicity. [The C 13 -C 17 SAS surfactants demonstrate the following acute toxicity data: OECD 401 (rat acute oral) data that range LD 50 = 2,000 to 500 mg/kg/day (EPA IV - III); OECD 402 (acute dermal) not acutely toxic in mice; OECD 404 (skin irritant irritation), non-irritat ing; OECD 405 (rabbit acute eye irritation) eye irritant; and OECD 406 (guinea pig Buehler Assay) non-sensitizing.]

2. Genotoxicty. [The C 13 -C 17 SAS surfactants do not display mutagenic activity in the following assays: AMES bacterial (OECD 471) assay with and without metabolic activation; In Vitro Evaluation: Mammalian Cell Gene Mutation (Similar OECD 476) was negative with and without metabolic ac tivation. Mouse Micronucleus Chromosome Aberration study (similar to OECD 474) was ne gative for genotoxic effects in male and female rats.]

3. Reproductive and developmental toxicity. [C 13 -C 17 SAS surfactants (as a 60% aqueous solution) was assessed over two generations in CD ra ts (25/sex/dose). The test compound was administered in the diet in bot h the F0 and F1 generations at dose levels3

of 0 (vehicle cont rol), 1000, 3000, or 10000 ppm. Treatme nt was given continuously to both sexes for 60 days prior to mating and throughout three successive pregnancies (F1A, F1B, F1C, F2A, F2B and F2C). Food intake , hematological parameters, absolute and relative organ weights as well as histopat hological evaluation of tissues showed no

adverse treatment-related effects. In the F0 generation, a slight but not statistical significant depression of body weight gain was observe d. During the three subsequent pregnancies, some fluctuation in body weight gain was recorded in treated females, but no significant inter-group va riation was observed. In both generations, estrous cycles, mating performance and conception rate s were unaffected by treatment.

Macroscopic examination, absolute and relati ve organ weights, and histopathological evaluation of F0 and F1 parent animals showed no adverse treatment-related effects. It

was concluded from these i nvestigations that continuous treatment with sec-alkane

The NOAEL for maternal toxicity, as well as for fertility, was 10,000 ppm in the diet corresponding to about 500 mg/kg bw/day. Sulfonate-sodium salts SAS (as a 60% aqueous solution) at a concentration level of 10,000 ppm was indicative of only slight, unspecific maternal toxicity.

Developmental Toxicity The 2-generation rat reproduction study al so included a Segment II phase for developmental toxicity. C 13 - C 17 SAS surfactant (as a 60% aq ueous solution) was tested for reproductive function and in tra-uterine development in CD rats (25/sex/dose) by treatment to females only during the organogenesis stage (days 6-15 of gestation). The

female test animals received the test material at dose levels of 0 (v ehicle control), 1000, 3000 or 10,000 ppm in the diet. No treatment -related adverse effect s were observed in any of the groups treated during organoge nesis. There were no indications for an embryotoxic or teratogenic eff ect related to treatment in any dose groups. There was no

treatment related effects and no indication of fetotoxicity were observed in any of the dose groups throughout the study. Teratogeni c effects were also not observed. The NOAEL with regard to developmental eff ects was considered to be 10,000 ppm in the diet corresponding to about 500 mg/kg bw/day.

DEREK Structure Activity Relationship (S AR) modeling was conduc ted to identify structural alerts for mammalian toxicology . There were no structural alerts for developmental (teratogenicity) or reproductive toxicity.]

4. Subchronic toxicity. [C 13 -C 17 SAS surfactants (as a 60% aqueous solution) were tested for systemic subchronic toxicity using both, the oral (in rats) and dermal (in mice) routes of exposure. Both studi es provide sufficient documentation to afford a credible

evaluation of subchronic oral and dermal exposures. Subc hronic inhalation testing is not available, but this is not a relevant route of exposure.4

Rat Subchronic Dietary Testing In a feeding study, CD Sprague-Dawley rats (30/sex/dose) received C 13 -C 17 SAS (tested as 60% aqueous solution) for a peri od of 52 weeks at concentrations of 0% (vehicle control), 0.08%, 0.40% and 2.0% via the di et. All rats were obs erved daily for clinical signs and mortality. Food consumption was ca lculated weekly. Bodyweight was recorded weekly for the first 13 weeks, then monthl y thereafter. Ophthalm oscoopic examination was performed prior to the st art of the study, and at 26 and 52 weeks of treatment. Hematology (10 rats/sex/dose), clinical chemistry (5 rats/sex/dose) and urinalysis (5 rats/sex/dose) were evaluate d at 26 and 52 weeks. Organ weight histopathological examination was performed. At 2%, impaired grooming activity was reported in both males and females, when compared with th e vehicle control group. Food intake was reduced (approximately 10%) in males at 2% over the first 19 weeks, when compared to the vehicle control group. No eff ect was reported in females at 2% or any other dose level. Decreased body weight gain was reported in males and females at 2% when compared with the vehicle control group. At the end of 52 weeks, male s were 80% of the control group mean weight and female were 77% of the control group mean weight (statistical significance not reported). In males, absolu te body weight at 52 weeks was decreased by 13% and females at 52 weeks body weight was decreased by 18% when compared with the vehicle control group body weight mean (statistic al significance not reported). No other treatment-related effects were reported in the study.

Based on the study results, the no observable ad verse effect level (NOAEL) in this study was conservatively placed at 0.40% (approxim ately 200 mg/kg bw/day) and the lowest

observable adverse effect levels was 2.0% (20,000 ppm, approximately 1000 mg/kg bw/day) based on the decrease in body weight. At the highes t level of 2% approximately 1000 mg/kg bw/day) in the diet only body we ight changes were noted and the NOAEL could be assigned as 4000 ppm, or approximately 200 mg/kg bw/day.

Mouse Dermal Subchronic Testing A 60% aqueous formulation of C 13 -C 17 SAS was administered to the intact skin of groups

of 25 female mice at concentr ations of 0, 0.1, 0.5 (increasi ng to 8.0 and finally to 16.0) and 1.0% w/v (increasing to 2.0 and finally 32.0) over periods of four or five weeks. A

constant dose of 0.1 mL / mouse was used on five days per week of treatment. Encrustation, skin thickening, erythema and sl ight sloughing were observed at the treated

site in all mice administered 32 % w/v. Mice given 16% showed slight skin thickening after one week of treatment. Weight loss, without concomitant re duction of food intake, was seen in all mice receiving 32%. There was a return to norma l growth during the second week at this dose level. Necropsy fi ndings were confined to the application site

and consisted of skin thicke ning, erythema, edema, sloughing and pus at 32%, and skin thickening at 16%. Mice treat ed with solutions containing 8% w/v and below were unaffected by treatment.]5

5. Chronic toxicity. [C 13 -C 17 SAS (as 60% aqueous solution) was tested for potential chronic and carcinogenic effects by the oral and de rmal routes of exposure in rats and mice respectively. Although these st udies do not adhere to current guidelines or GLP standards, these studies were performed according to scientific standards at the time of performance and of acceptable validity based on current standards. Reliability declarations regarding procedures and perfor mance are available. Both studies provide sufficient documentation to afford a credible evaluation of carcinogenicity and systemic chronic toxicity through both the or al and dermal routes of exposure.

Rat Oral Carcinogenicity Testing

C 13 -C 17 SAS as 60% aqueous solution) was tested for potential carcinogenicity in CD Sprague-Dawley rats (50/sex/dose) at concen trations of 0% (veh icle control), 0.08%, 0.4%, or 2.0% via the di et over a period of 2 years. Anim als were observed for clinical signs of toxicity or mortality at least once a day; physical examin ations were made at least weekly. Food intake wa ke calculated weekly. Bodywe ight was recorded weekly for the first 13 weeks, every four weeks from weeks 14-85, and then every two weeks thereafter. Hematology parameters and urinalysis were measured at 26, 52 and 72 weeks (10/sex/dose) and 104 weeks in all su rviving animals. Gross pathology and histopathological examination was performed on all animals. The results of the study

indicate that administration of the test com pound up to 2% (w/w) in the diet resulted in both the non-neoplastic as well as neoplastic pathology wi thin normal limits. Initially a temporary impaired grooming in rats receiving the highest dietary concentration of 2.0% (w/w) was noted. No other finding wa s recorded in respect to appearance, general health condition, beha vior and locomotor function. Survival was not affected.

The cellular and chemical characteristics of blood and urine were also undisturbed by treatment. Macroscopic and histopathological investigations revealed no indications of nonneoplastic and/or ne oplastic changes.

The NOAEL was set at 2% (w/w) in the diet corresponding to approximately 1000 mg/kg bw/day. Based on these study re sults, there was no evidence that C 13 -C 17 SAS demonstrated carcinogenic effects by the oral route of exposure.

Dermal Mouse Carcinogenicity Testing CD-1 Mice (100/sex/dose) were treated derm ally at concentrations of 0% (vehicle control), 0 % (untreated), 0.1%, 0.5% or 1% (w/w) C 13 -C 17 SAS (as 60% aqueous solution) three times each week over a sche duled period of 80 week s that was followed by an observation period lasting 24 weeks. A ll animals were observed for clinical signs and mortality daily. Body weights were measured every 4 weeks, food and water consumption was not recorded. Gross pat hology and histopatholog y was performed on all animals that died on study and those th at survived until the end of the treatment period. Mortality was extremely high in th is study with 982/1000 mice (496 males and 486 females) found dead or killed in extremis. During the first six weeks of the study, animals that died were replaced. The morta lity was distributed among all the test groups

and not considered to be treatment related.6

No signs of treatment related effects were re corded at any time during the total 104 week period. Histopathological exam ination of skin samples re vealed that there were no

treatment-related dermal abnormalities. Based on these study results, there was no

evidence that C 13 -C 17 SAS demonstrated carcinogenic e ffects by the dermal route of exposure at up to 1% (w/w).

Summary Repeat Dose Risk Analysis A NOAEL of 200 mg/kg bw/day is proposed fo r oral repeat dose risk assessment for

both for CAS RN 85711-69- 9 Sulfonic Acids, C 13 -C 17 sec-alkane that can be bridged to

CAS RN 97489-15-1 Sulfonic Acids, C 14 -C 17 sec-alkane.

. Additionally body weight changes were report ed at dietary levels of up to 2% (w/w) corresponding to about 1000 mg/kg body weight per day after 90-days of exposure, the NOAEL is 0.4% (calculated as 200 mg/kg bw/day ). The subacute dermal toxicity study in mice, performed with a 60% aqueous solution of C 13 -C 17 SAS revealed no indications of toxicity after dermal treatment at 8% (w/v ) for 4 or 5 consecutiv e weeks. Based on the
results of this test, the NOAEL for local ef fects was calculated with approximately 500 mg / kg body per day. At higher test concentrat ions signs of irritation / inflammation at the

treated skin sites were revealed. Adverse systemic toxicity effects were not observed.

Oral:

 NOAEL (chronic): 200 mg/kg bw/day (60% aqueous)

 NOAEL (subchronic): 0.4% (wt/wt) (200 mg/kg bw/day)

Dermal:

 NOAEL (subchronic): estimated to be 500 mg/kg bw/day

DEREK Modeling did not indicate structural alerts for carcinogenicity, genotoxicity, liver, thyroid and kidney toxicity, irritation, sensitization, or repr oductive toxicity. The modeling report supports the findings of the subchronic and chronic toxicology database previously summarized.]

6. Animal metabolism. Pseudomonas sp . can metabolize primary n-alkanesulfonates to bisulfite and the corresponding aldehyde metabol ite. By analogy it can thus be postulated

that the C13- C 17 SAS should be initially oxidized to generate bisulfite and the corresponding alkyl ketone metabolite. The al kyl ketone metabolite may then be further metabolized through oxidative degradation to presumably to alkyl acetate ester metabolites. Follow-on ester cleavage would yield acetate and alkyl alcohol metabolites which should be further metabolized by ß-ox idation fatty acid processes to ultimately generate carbon dioxide and water

.

Toxicokinetic Studies

SAS Surfactants, rat toxicoki netic data substant iated the likelihood of a ß-oxidation pathway since excretion of radiolabeled CO 2 was observed and that there is rapid

excretion with the absence of bioaccumulation.7

 14 C radiolabeled C 13 -C 17 SAS administered by gavage to male rats at concentrations of 0.5, 5.3 or 51 mg/kg was excreted according to a biphasic elimination with a biological half-life of 11 hours to 65 hours. Up to 17% of the administered radioactivity was exhaled as CO 2 , approximately 30% was excreted

via urine and about 45% with feces. In total more than 90% of the applied radioactivity was excreted within the fi rst 24 hours after appl ication. There was

no indication of bioaccumu lation as demonstrated by very low residual radioactivity (< 1 ppm) in organs after 7 days. Metabolites were not identified.

 Dermal application to male rats dem onstrated low penetr ation potential of 14 Cradiolabled C 13 -C 17 SAS. Elimination half-life av eraged about 41 hours (15%

elimination in air 18% in urine and about 31% in feces. About 2.2% of the radioactivity was found in the treated skin and 35% in the band age used to cover

the treated area all of which indicate a low potential fo r dermal absorption (calculated 1%).]

7. Metabolite toxicology

. [No Reported Data]

8. Endocrine disruption

. [C 13 -C 17 (SAS) surfactants do not belong to a class of chemicals known or suspected of having adverse effects on the estrogen receptor or endocrine system.]

C. Aggregate Exposure

1. Dietary exposure. [Clariant is proposing that the C 13 -C 17 SAS surfactants be exempt from the requirement of a toleranc e when used in seed treatment and foliar applications under 40 CFR §180.920. While no speci fic food use residue information is

available for C 13 -C 17 SAS surfactant on the basis of the physical chemical and environmental properties analysis crop residues are not like ly. As a minor component in

seed treatment formulat ions, the amount of C 13 -C 17 SAS applied to seeds would be small and by the time seeds germinate, any residual C 13 -C 17 SAS surfactant would be absorbed/bound to the soil (as indicated by Fugacity estimates and Koc) and should undergo rapid degradation. Thus, it is unlikely th at the SAS surfactant s could be available for uptake by plants.

Dietary Risk Assessment

EPA assesses potential dietary exposures to iner t ingredients used in agricultural pesticide formulations using a screening-level model re ferred to as “I-DEEM,” in which the “I” stands for inerts and “DEEM” is the dietary ex posure 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 chemis ts in the Health Effects Division of the Office of Pesticide Programs jointly develope d I-DEEM. The model, as developed by EPA, uses crop-specific residue data (i.e., maximum tolerances ) for 57 active ingredients as surrogates for potential inert ingredient residue levels. I-DEEM assumes that inert ingredients are used on all crops, and that 100 percent of all crops are assumed to be “treated” with the inert ingredient(s). I-DEEM also assumes that the inert is present at a8

concentration of 50% in all the pesticide form ulations. In addition, EPA includes potential residues of 100 ppb in water for potential dr inking water exposures. Using these assumptions the chronic dietar y exposure is estimated to be 0.189 mg/kg/d for the general U.S. population and 0.706 mg/kg/d for children 1-2 years of age (i.e., the most highly exposed subpopulation).

The dietary (food plus drinking water) exposur es are expressed as a percentage of the
proposed cPAD, The % cPAD for the general U.S. population and children 1-2 years old,
the subpopulation with the highest potential exposures.

Reproductive/Developmental Toxi city, a no-observable-adverse -effect-level (NOAEL) for

C 13 -C 17 SAS should be assigned as 200 mg/kg bw/day based on chronic testing.

The chronic reference dose (cRf D) proposed for CAS RN 97489-15-1 Sulfonic Acids,

C 14 -C 17 sec-alkane. is therefore 2.0 mg/kg/day.

 cRfD = 200 mg/kg bw/day /100

 cRfD/cPAD = 2 mg/kg bw/day

The data provided herein and us e pattern of soil application support that the FQPA safety

factor for C 13 -C 17 SAS should be reduced from 10X to 1X . Therefore, only the 10X factors for intra- and inter- species variability shou ld be included in calculating the chronic reference dose (cRfD) and the chr onic population adjusted dose (cPAD).

Thus, based on I-DEEM screening level calcul ations, the chronic di etary exposures are

estimated to be 9.5% of the cPAD for the general U.S. population and 35.3% of the cPAD
for children 1-2 years old. These data demonstrate that the I-DEEM screening-level
chronic dietary (food and drinking water) expo sures are below the cP AD and are therefore

below EPA’s established level of concern for all U.S. subpopulations.]

i. Food. [The chronic dietary ex posures estimated using the conservative IDEEM screening level model (food and dri nking water) are well below 100% of the cPAD, and are therefore be low the level of concern for all U.S. subpopulations.]

ii. Drinking water. [Drinking water is included in the I-DEEM exposure assessment and base d on anticipated concentrations expected to be negligible.]

2. Non-dietary exposure : None (no residential uses are proposed)

D. Cumulative Effects

[It has not been determined that the C 13 -C 17 surfactants will have a common mechanism of toxicity with other substances.]9

E. Safety Determination

1. U.S. population. [Based on the conservative ex posure estimates, there is a reasonable certainty that no harm will result to the U.S. population from the aggregate exposure to C 13 -C 17 surfactants formulations in 40 CFR § 180.920 preharvest seed treatment and foliar applic ations with chronic dietary exposure estimated to be 9.5 mg/kg/day (0.095%. PAD) for the general US population.]

2. Infants and children

. [The FFDCA Section 408 requires an additional tenfold margin of safety for the protection of infants and ch ildren 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 safe ty factor may be reduced or removed.

Based on available informati on discussed herein, Clariant , Inc. believes the FQPA safety factor should be reduced to 1X.The cRfD is therefor e equivalent to the chronic population adjusted dose (cPAD).]

 An evaluation of susceptibility and uncertai nty issues associated with the use of C 13 - C 17 SAS surfactants in I-DEEM estimated ch ronic dietary exposures to children 1-2 years of age (the potentially most ex posed population) provided an estimated chronic exposure of 35.3 % PAD.

 The availability of a scientifically sound mammalian toxicology database that includes acute, subchronic, and genotoxicity data. These test data, did not result in adverse developmental, reproductive and neurological endpoints or genotoxic

effects.

 The DEREK modeling results did not indicate any structural alerts for carcinogenicity, genotoxicity, liver, thyroid and kidney toxicity, irritation, sensitization, or reproductive toxicity.

 Physicochemical/environmental propertie s data indicate that crop residues and resultant dietary exposures to sensitive populations are unlikely.

 C 13 -C 17 SAS surfactants do not belong to a cl ass of chemicals known or suspected of having adverse effects on the estr ogen receptor or endocrine system.]

F. International Tolerances

[There are no known intern ational tolerances for C 13 -C 17 SAS Surfactants.]