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COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION

EPA Registration Division contact: Richard Gebken 703-305-6701

LG Life Sciences

Petition Number #LGLS02

EPA has received an inert ingredient petition # LGLS02 from Ag-Chem Consulting (12208 Quinque Lane, Clifton VA 21024) on behalf of LG Life Science (910 Sylvan Avenue, Englewood Cliffs, NJ 07632) 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 to establish an exemption from the requirement of a tolerance for postharvest crops for the surfactant
Polyoxyethylene mono (tristyrylphenyl) ether , CAS# 99734-09-5 , under 180.910 when applied to

food areas and food contact surfaces in food servi ce and food handling establishments such as ( but not limited to) : Restaurants Meat Processing Plants Grocery Stores Bakeries Food Manufacturing Establishments Food Processing Establishments Food Warehousing Establishments

It is used as a formulation surfactant. It is contained in the formulation at a maximum concentration of 8.0 %. This petition is for use as a surfactant in pesticide formulations. Polyoxyethylene mono (tristyrylphenyl) ether (CAS Reg. No. 99734-09-5) is currently used as an inert in pesticide formulations applied to growing crops and for post harvest uses on citrus crop group applications. In 2006, EPA reassessed the tolerance exemptions under 40CFR 180.920 for the tristyrylphenol ethoxylates when used as inert ingredients at not more than 15% in pesticide formulations applied to growing crops. As stated in the 2006 reassessment document, a Structure Activity Relationship (SAR) assessment for the tristyrylphenol ethoxylates was performed by the Agency’s Office of Pollution Prevention and Toxics (OPPT) Structure Activity Team (SAT); and it was determined that the data presented in the assessment on the tristyrylphenol ethoxylates are adequate to characterize the expected behavior of the subject chemical (CAS Reg. No. 99734-09-5). The Agency also approved the post-harvest use on citrus under 40CFR 180.1288 in March of 2009. The additional post harvest uses proposed in this petition will not significantly increase the dietary and exposure burden analyzed in the tolerance reassessment and the previous petition to add post-harvest use to citrus.

EPA has determined that th e petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; 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 data2

may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism

. This petition is for use on food contact surfaces. No ma terial is expected to be on growing plants for

metabolism.

2. Analytical method

. This petition proposes to establish exemptions fr om the requirement of a tolerance without any numerical limitation; therefore no analytical method has been submitted.

3. Magnitude of residues

. Since Polyoxyethylene mono (tristyrylphenyl) ether is 8% of the product, the maximum incidental residue of Polyoxyethylene mono (tristyrylphenyl) et her is 4.5 mg/ sq. ft. Si nce a portion of food is unlikely to exceed this physical dimension the worse case is ingestion of 4.5 mg.

The maximum potential surface residue is 4.5 mg. / s q. foot. Assuming all residue was adsorbed to

food it came into contact it is reasonable to assume that such food would be under 1 sq. ft. or the portion eaten by a single person would be equal to or less than this surface concentration. Therefore maximum exposure from incidental residues on f ood would not exceed 4.5 mg. However this is unrealistic since the surfaces are rinsed pr ior to food exposure and Polyoxyethylene mono (tristyrylphenyl) ether is highly water soluble.

B. Toxicological Profile The available toxicity database for the tris tyrylphenol ethoxylates was assessed in the 2006 reassessment document. The Agency has determined th at these data are appropriate and adequate to characterize the toxicity of Polyoxyethylene mono (tristyrylphenyl) ether.3

1. Acute toxicity

.

Results

Study

[CAS Reg. No. 105362-40- 1](analog) (USEPA MRID 46587704) [CAS Reg. No. 90093-37-1] (USEPA MRID 46587705)

Oral (rat) Not toxic at 4750 mg/kg. No abnormal symptom was noted in the treated animals, autopsy showed no lesion, weight gain was similar to

controls. Not toxic at 7150 mg/kg. No abnormal symptom was noted in the treated animals, autopsy showed no lesion, weight gain was

similar to controls

Eye
irritation (rabbit) Slight irritant slight to moderate irritant

Skin (rabbit) Slight irritant Slight irritant

2. Genotoxicity and Carcinogenicity

.

In an Ames genetic toxicity study, [CAS Re g. No. 105362-40-1] (analog chemical) showed no mutagenic activity to Salmonella typhimurium strains TA 1535, 1537, 1538, 98, or 100, both with and without activation (USEPA MRID 46587703).

Results of acceptable mutagenicity studies, incl uding a chromosomal aberration assay in Chinese hamster ovary cells (CHO) and a test for unscheduled DNA synthesis in rat primary hepatocyte cultures were negative (USEPA, 2006).

Based on the results of the above studies, the Agency concluded that the subject tristyrylphenol ethoxylates are not likely to be mutagenic.

3. Reproductive and developmental toxicity

. In a developmental study, [CAS Reg. No. 119432-41-6] wa s administered by gavage to pregnant SpragueDawley rats at dosages of 0, 100, 300, or 1000 mg/kg/day.

The maternal NOAEL is 300 mg/kg/day based on reduced body weights and incr ease in liver weights and loose feces seen at the LOAEL of 1000 mg/kg/day. There were no significant differences

between treated and control fetuses for external and sk eletal variations except for an increased incidence of all unossified proximal phalanges of the hind lim b (skeletal variations) at 1000 mg/kg/day. The NOAEL for fetotoxicity was 300 mg/kg/day based on increased skeletal variations (incr eased incidence of all unossified proximal phalanges of the hind limb seen at the LOAEL of 1000 mg/kg/day.) (USEPA MRID 46405213).4

4. Chronic Toxicity

Rat In a 90-day study Sprague-Dawley rats were administ ered [CAS Reg. No. 105362-40-1] (analog chemical) by gavage at dosages of 0, 500, 1500, or 4000 mg/kg/day. The NOAEL was 500 mg/kg/day based on thyroid effects seen at the LOAEL of 1500 mg/kg/day and decrease in hematological parameters and histopthological changes in the pituitary seen at 4000 mg/kg/day.

In a 90-day subchronic oral gavage study, Sprague-Dawley rats were administered [CAS Reg. No. 119432-41- 6] at concentrations of 0, 100, 500, or 2500 mg/kg/day five days per week. When the results of the above study and the second study (see below) were combined, the NOAEL was 100 mg/kg/day based on intratubular minera lization, thyroid weight changes a nd histopathological findings in the thyroid seen at the LOAEL of 500 mg/kg/day.

In a study to further evaluate kidney toxicity, male Sprague-Dawley rats were administered [CAS Reg. No. 119432-41-6) by gavage at dosages of 1, 10, 30, or 100 mg/kg/day for 5 days/week for 13 weeks.

The no observable effect level (NOEL) for renal intr atubular mineralization in this strain of rats under the conditions of this study is considered to be at least 30 mg/kg/day . When the results of this study and the previous study are combined, the NOAEL was 100 mg/kg/day.

Dog In a 90-day study, beagle dogs were orally administered [CAS Reg. No. 105362-40-1] (analog chemical) by gelatin capsule at dosages of 0, 50, 500, or 1000 mg/kg/day (reduced to 750 mg/kg/day on day 43 due to six deaths). The NOAEL was 50 mg/kg/day based on the increase in liver weights and the increase in alkaline phosphatase seen at the LOAEL of 500 mg/kg/day in males. For females, the NOAEL was 500 mg/kg/day based on the mortality, hyperemia of the stomach and intestines, liver pathology and changes in liver enzymes seen at the LOAEL of 750 mg/kg/day.

5. Endocrine disruption

. The Agency has no information that suggests Polyoxyethylene mono (tristyrylphenyl) ether in general will have an effect on the immune or endocrine system.

C. Aggregate Exposure

1. Dietary exposure

.

i. Food Based on the use of the screening level in ert ingredient dietary exposure model and the selected chronic dietary exposure toxicity endpoint for the tristyrylphenol ethoxylates,

there are no concerns for risks associated with chronic dietary exposures to tristyrlphenol ethoxylates for the existing pre-harvest uses and post-harvest use on citrus crops. The resulting exposure estimates were less than IIAB’s level of concern (<100% cPAD). The chronic dietary estimate for the U.S. popula tion was 12.2% (non-nursing infants were the most highly exposed population with the chr onic exposure estimate occupying 35.6% of the cPAD). It should be noted that this screen ing level dietary risk assessment is quite5

conservative in nature and likely to greatly exceed actual dietary exposure to the tristyrlphenol ethoxylates. In addition, this highly conservative exposure assessment is protective of any possible non-occupational exposur es to the tristyrylphenol ethoxylates as it results in exposure estimates orders of ma gnitude greater than the high-end exposure estimates for residential uses of pesticides routinely used by the Office of Pesticides Programs.

Given the small potential additional amounts of polyoxyethylene mono (tristyrylphenyl) ether residues on post-harvest commodities resulting from incidental exposure from the proposed food surface us e pattern defined by this petition, these assessments are not expected to be altered by th is additional use. The surfaces are likely to

contact little actual food and will have been previously washed. Polyoxyethylene mono (tristyrylphenyl) Ether is highly water soluble which ma kes the likelihood of appreciable surface residues at all unlikely.

ii. Drinking water

. Tristyrylphenol ethoxylate is used as an inert ingredient in pesticide products applied to growing crops. Tristyrylphenol ethoxylat e physical/chemical properties (very strong sorption to soils/sediment and organic carbon) a nd the effects of biodegradation in soil make it unlikely that tristyrylphenol ethoxylate will migrate to ground water sources; therefore, they are not likely to reach drinking waters (f rom groundwater sources) at levels of concern

from indoor uses.

2. Non-dietary exposure

. The primary route of exposure to these chemicals fr om their use as inert ingredients in pesticide products would most likely be through consumption of food to which pesticide pr oducts containing them have been applied, and possibly through drinking water (from runoff). Dermal and inhalation exposures are also possible from reside ntial use of pesticide products containing these inert ingredients. However, the quantitative exposure assessment via inhalation and dermal routes of exposure was not perf ormed because negligible inhalation and dermal absorption is expected based on its physicochemical properties of the compounds.

D. Cumulative Effects Unlike other pesticide ingredients for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to tristyrylphenol ethoxylates and any ot her substances and tristyrylphenol ethoxylates do not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has not assumed that tristyrylphenol ethoxylates have a common mechanism of toxicity with other substances.6

E. Safety Determination

1. U.S. population. Based on the use of the screening level inert ingredient dietary exposure m odel and

t h e s e l e c t e d chronic dietary exposure toxicity endpoint for the tristyrylphenol ethoxylates, there are no c o n c e r n s f o rr i s k s a s s o c i a t e d w i t h c h r o n i c d i e t a r y e xposures to tristyrlphenol ethoxylates for the e x i s t i n g p r e

- h a r v e s t u s e s a n d t h e p r oposed posth a r v e s t u s e o n c i t r u s c r o p s

. T h e r e s u l t i n g exposure estim ates were less than IIAB’s

l e ve l of c onc e r n ( < 100% c P AD) . The c h r oni c di e t a r y estim ate f o r the U

. S

. population was 12.2% (non-nursing infants were the m o st highly exposed population with the chronic exposure estim ate occupying 35.6% of the cPAD). It should be n o t e d t h a t this screening level dietary risk assessm ent is quite conservative in nature and likely to greatly exceed actual dietary exposure to the tristyrlphenol ethoxylates. In addition, this

h i g h l y conservative exposure assessm ent is protective of any possible nonoccupational exposures to the tristyrylphenol ethoxylates as it results in exposure

estim ates orders of m a gnitude greater than the high-end exposure estim ates for residential uses of pesticides routinely used by the Office of Pesticides Program s.

Given the sm all potential additional am ounts of polyoxyethylene m ono (tristyrylphenyl) ether residues on post-harvest com m odities resulting from incidental exposure from the proposed food surface use pattern defined by this petition, these assessm ents are not expected to be altered by this additional use. The surfaces are likely to contact little actual food and will have been previously washed. Polyoxyethylene m ono (tristyrylphenyl) Ether is highly water soluble which m a kes the likelihood of appreciable surface residues at all unlikely.

2. Infants and Children.

EPA concluded that the FQPA safety factor can be reduced to lx for tristy ry lphenol ethoxy lates for the following reasons:

1. EPA has sufficient data to assess the toxicity of tristy ry lphenol ethoxy lates. The data p r e s e n t e d

in the assessm ent on the tristy ry lphenol ethoxy lates are adequate to characterize the expected behavior of the subject chem icals. There are no carcinogenicity studies available on the t r i s t y r y l p h e n o l e t hoxy lates;

h o w ev er, th e p r imary to x i city ap p ears to b e to th e k i d n e y an d th y r o i d in rats and liver in dogs. The kidney effects in rats appear to be the m o st sen sitive endpoint. The Agency has considerable knowledge

of the intratubular m i neralization toxic effect to the kidney s a n d h a s d e t e r m i n e d t h a t b y p r e v e n t i n g t h e intratubular m i neralization in the kidney

, tum o r fo rmatio n is u n lik ely to o ccu r. Sin ce th ese k i d n e y effects are the m o st sensitive endpoint, p r o t e c t i v e m easures for kidney toxicity will be protective of

any other long term effects. Further, EPA concluded that there is no need for the additional FQPA safety

f a c t o r f o r u s e o f s u b c h r o n i c toxicity for long term exposure assessm ent. The critical effect seen in the

su b c h r o n i c stu d y (intratubular m i neralization in th e kidney ) is believed to occur as a result of

p r e c i p i t a t i o n o f a chem ical based on its phy sicochem i cal properties. Precipitation of a chem ical based on

i t s phy siochem i cal properties is a function prim arily of dose level rather than duration of dosing. Thus, once the threshold for precipitation of the chem ical is established (as it was in the s u b c h r o n i c dog study ), this threshold level w ould be considered protective of any short or long term exposure. Therefore, the additional safety factor for the lack of long term studies is not w a r r a n t e d

.

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7 2. EPA concluded that there is no evidence of in creased susceptibility to infants and children. The developmental toxicity study in which rats were administered (CAS Reg. No. 119432-41-6) resulted in a NOAEL of 300 mg/kg/day for maternal toxicity (b ased on reduced body weights and increase in liver weights and loose feces seen at the LOAEL of 1000 mg/kg/day) and a NOAEL of 300 mg/kg/day for developmental toxicity based on increased skeletal variations (increased incidence of all unossified proximal phalanges of the hind limb seen at the LOAEL of 1000 mg/kg/day). Fetal effects were seen only at the limit dose and in the presence of maternal toxicity.

3. No rabbit developmental study or reproductive toxi city studies are available for these chemicals, however, the developmental toxicity study in rats indicates no robust developmental toxicity at the limit dose and none of the reproductive para meters were affected in the rat developmental study at the limit dose of 1000 mg/kg/day. This endpoint in the developmental study is considered conservative since the incidence of skeletal variations seen at 1000 mg/kg/day was marginal.

4. There is no indication in the database that the tristyrylphenol ethoxylates are neurotoxic chemicals and there is no evidence of increased susceptibility. Th erefore, there is no need for a developmental neurotoxicity study.

5. There are no residual uncertainties identified in the exposure databases. In the absence of actual exposure data on tristyrylphenol ethoxylate s, a highly conservative dietary exposure assessment would not underestimate the risk to infants and children. Based on overall weight of evidence, the FQPA

factor of 10X was reduced to 1X.

It is proposed that, in amending 40 CFR part 180.910, to establish the exemptions as proposed, there is a reasonable certainty that no harm to the general population, including infants and children, will result from aggregate exposure to the other ingredient chemi cal residues of the subject inert, when used as a preservative in pesticide products applied to food contact surfaces at this level in the manner described in he petition. t

F. International Tolerances

There are no CODEX or international tolerance exemptions established for the subject inert ingredient at this time.