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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 service 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 the 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 data 
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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 material is expected to be on growing plants for 

metabolism. 

 

 2. Analytical method. 

This petition proposes to establish exemptions from 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) ether is 4.5 mg/ sq. ft. Since 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. / sq. 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 food would not exceed 4.5 mg. However this is 

unrealistic since the surfaces are rinsed prior to food exposure and Polyoxyethylene mono 

(tristyrylphenyl) ether is highly water soluble. 

B. Toxicological Profile

The available toxicity database for the tristyrylphenol ethoxylates was assessed in the 2006 

reassessment document. The Agency has determined that these data are appropriate and adequate to 

characterize the toxicity of Polyoxyethylene mono (tristyrylphenyl) ether. 
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 1. Acute toxicity. 

Study Results 

[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 Reg. 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, including 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] was 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 increase 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 skeletal variations except for an increased incidence 

of all unossified proximal phalanges of the hind limb (skeletal variations) at 1000 mg/kg/day. The 

NOAEL for fetotoxicity was 300 mg/kg/day 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.) (USEPA 

MRID 46405213). 
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 4. Chronic Toxicity 

Rat 

In a 90-day study Sprague-Dawley rats were administered [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 mineralization, thyroid weight changes and 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 intratubular 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 inert 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. population was 12.2% (non-nursing infants were the 

most highly exposed population with the chronic exposure estimate occupying 35.6% of the 

cPAD). It should be noted that this screening level dietary risk assessment is quite 
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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 exposures to the tristyrylphenol ethoxylates as it 

results in exposure estimates orders of magnitude 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 use pattern defined by this petition, these 

assessments 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 mono 

(tristyrylphenyl) Ether is highly water soluble which makes 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 ethoxylate physical/chemical properties (very strong 

sorption to soils/sediment and organic carbon) and 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 (from groundwater sources) at levels of concern 

from indoor uses. 

 2. Non-dietary exposure. 

The primary route of exposure to these chemicals from their use as inert ingredients in pesticide 

products would most likely be through consumption of food to which pesticide products 

containing them have been applied, and possibly through drinking water (from runoff). Dermal and 

inhalation exposures are also possible from residential use of pesticide products containing these 

inert ingredients. However, the quantitative exposure assessment via inhalation and dermal 

routes of exposure was not performed 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 other 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.
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E. Safety Determination

1. U.S. population. 

Based on the use of the screening level inert 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 the proposed postharvest 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. population 

was 12.2% (non-nursing infants were the most highly exposed population with the 

chronic exposure estimate occupying 35.6% of the cPAD). It should be noted that

this screening level dietary risk assessment is quite 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 nonoccupational exposures to the tristyrylphenol ethoxylates as it results in exposure 

estimates orders of magnitude 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 use pattern defined by this petition, these assessments 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 mono 

(tristyrylphenyl) Ether is highly water soluble which makes 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 tristyrylphenol 

ethoxylates for the following reasons: 

1. EPA has sufficient data to assess the toxicity of tristyrylphenol ethoxylates. The data presented

in the assessment on the tristyrylphenol ethoxylates are adequate to characterize the expected behavior 

of the subject chemicals. There are no carcinogenicity studies available on the tristyrylphenol ethoxylates; 

however, the primary toxicity appears to be to the kidney and thyroid in rats and liver in dogs. The 

kidney effects in rats appear to be the most sensitive endpoint. The Agency has considerable knowledge 

of the intratubular mineralization toxic effect to the kidneys and has determined that by preventing the

intratubular mineralization in the kidney, tumor formation is unlikely to occur. Since these kidney

effects are the most sensitive endpoint, protective measures 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

factor for use of subchronic toxicity for long term exposure assessment. The critical effect seen in the 

subchronic study (intratubular mineralization in the kidney) is believed to occur as a result of 

precipitation of a chemical based on its physicochemical properties. Precipitation of a chemical based on 

its physiochemical properties is a function primarily of dose level rather than duration of dosing. 

Thus, once the threshold for precipitation of the chemical is established (as it was in the subchronic

dog study), this threshold level would be considered protective of any short or long term exposure. 

Therefore, the additional safety factor for the lack of long term studies is not warranted.

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2. EPA concluded that there is no evidence of increased 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 (based 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 toxicity 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 parameters 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. Therefore, 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 ethoxylates, 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 chemical 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 

the petition. 

F. International Tolerances 

There are no CODEX or international tolerance exemptions established for the subject inert 

 ingredient at this time.