### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 2 of 85 Table of Contents 1.0 Executive S ummary .......................................................................................................... 4 Regulatory Recommendation .................................................................................................. 6

2.0 Background ....................................................................................................................... 6

3.0 Ingredient Profile .............................................................................................................. 7 3.1 Summary of Proposed Uses .......................................................................................... 7 3.2 Structural I nformation ................................................................................................. 7 3.3 Physical an d Chemical Properties ............................................................................... 8

4.0 Haz ard Characterization/Assessment ............................................................................. 9 4.1 Database Summary ....................................................................................................... 9 4.2 Toxicological Effects and Metabolism ........................................................................ 9 4.3 Dermal Absorption ..................................................................................................... 13 4.4 Mutagenicity ................................................................................................................ 13 4.5 Carcinogenic Potential ................................................................................................ 15 4.6 FQPA Considerations ................................................................................................. 16 4.7 Toxicity En dpoint Selection and Levels of Concern ................................................ 18 4.8 Endocrine Disruption ................................................................................................. 20

5.0 Dietary Exposure/Risk Characterization ..................................................................... 21 5.1 Residues of Concern ................................................................................................... 21 5.2 Drinking Water Residue Profile ................................................................................ 22 5.3 Food Residue Profile ................................................................................................... 22 5.4 Analytical Methodology .............................................................................................. 24 5.5 Dietary (Food and Water) Exposure and Risk ......................................................... 24 5.5.1 Acute Dieta ry Exposure and Risk ..................................................................... 24 5.5.2 Chronic Dietary Exposure and Risk ................................................................. 24 5.5.3 Cancer Dietary Exposure and Risk ................................................................... 25 5.5.4 Summary o f Dietary Exposure and Risk Assessment Results ........................ 25

6.0 Residential (Non-Occu pational) Exposure/Risk Characterization ............................ 25 6.1 Residential Handler Exposure ................................................................................... 26 6.2 Residential Postapplication Exposure ....................................................................... 31

7.0 Aggregate Risk Assessments and Risk Characteriz ation ............................................ 36 7.1 Acute Aggregate Ris k ................................................................................................. 36 7.2 Short-Term/Intermedia te-Term Aggregate Risk ..................................................... 36 7.3 Long-Term Aggregate Risk ....................................................................................... 38 7.4 Cancer Risk ................................................................................................................. 38

8.0 Occupation al Exposure/Risk Pathway .......................................................................... 38 8.1 Handler Risk ................................................................................................................ 38 8.2 Occupation al Postapplication Risk ........................................................................... 45

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 3 of 85 9.0 Environmental Justice .................................................................................................... 46

10.0 Human Studies ................................................................................................................ 46

APPENDIX A. Toxicity Data .................................................................................................... 48

APPENDIX B. Structure-Activity Relationship (SAR) Discussion ....................................... 62

APPENDIX C. Drinking Water Surrogate Analysis .............................................................. 63

APPENDIX D. Detailed Dietary Exposure and Risk Information ........................................ 66 D.1. Input File for Acute and Ch ronic Dietary Exposure Assessment ............................. 66 D.2. Results File for Acute Dietary Assessment .................................................................. 84 D.3. Results File for Chronic Dietary Assessment .............................................................. 85

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 4 of 85 1.0 Executive Summary

The Joint Inert Task Force (JITF) Cluster S upport Team Number 5 (CST 5) has submitted a petition proposing to establish an exemption from the requireme nt of a tolerance under 40 CFR §180.910 for the alkylphenol ethoxylates (APEs). A pproval of the request would permit use of these inert ingredients in pesticide pr oducts applied pre- and post-harvest.

The toxicology database is adequate to assess risk for the APEs when used as inert ingredients in pesticide formulations. The avai lable toxicity data indicate that the APE inerts have low to moderate acute oral and dermal toxicity, are a mild to moderate skin irritant, and an eye irritant. In the OECD Test Guideline 422 study with th e APE parent compound, there was no evidence of increased susceptibility. Add itionally, there was no evidence of neurotoxicity, developmental toxicity or reproductive toxicity in the OECD 422 study. The Agen cy has identified octylphenol as a potential metabolite/degradate of concern. The Agency considered available toxicity data on octylphenol as well as toxicity data on the structurally rela ted nonylphenol when assessing the hazard for this potential degradate. The major e ffects seen in the metabolite/degradate databases are consistent with potential dist urbances in estrogenic activity, but a complete mode of action analysis has not been conducted. These effect s are the most sensitive endpoints for both metabolites and were considered the key findings for regulatory purposes. The Agency has used available data on the nonylphenol and octylpheno l metabolites, which specifically look at these effects, to establish dietary endpoints for bot h the parent compound and the degradates of concern. The Agency considers the toxicity da tabase to be sufficien t to address potential hazards, and the Agency is regulating on the mo st sensitive endpoints seen in the database; effects which are well characterized with clea r NOAELs. Further, the Agency has conducted a highly conservative exposure asse ssment that is not likely to unde restimate risk; therefore, it is appropriate to reduce the FQPA sa fety factor to 1X for the dietary risk assessments. Endpoints for residential risk assessments were sele cted from the OECD 422 Test Guideline study conducted on the parent compound. However, si nce the study was not designed to detect specific perturbations to estroge nic activity that are the most sensitive effects seen for the metabolites, the Agency has retained the FQPA 10X safety factor for the residential risk assessments. Endpoints for worker risk assessments were also selected from the OECD 422 Test Guideline study conducted on the parent compound.

An acute dietary endpoint for risk assessment was selected for the parent compound and octylphenol from a study conducted with oc tylphenol and is based on increased postimplantation loss. A chronic dietary endpoint for risk assessment was se lected for octylphenol from two literature studies on nonylphenol, which were considered co-cri tical, a 2-generation reproduction study in rats and a 3-generation re production study in rats. The effects observed included significant increases in pituitary weight in parental males and decreases in ovary weight in parental females, significant acceleration of vaginal opening in the pups and decreases in the number of implants and live pups . Endpoints for residential a nd occupational risk assessments for the parent compound for all exposure durations and incidental oral an d inhalation routes of exposure were selected from the OECD 422 Te st Guideline study on the parent compound. The effects observed included clinical signs, decreased body weight ga in in both sexes, decreased thymus weight in females, and increased live r weight and liver hypertrophy in males, and decreased pup body weight in both sexes. Since there was no assessment of specific estrogenic

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 5 of 85 effects determined to be most sensitive for metabolites in the OECD 422 study on the parent compound, the FQPA safety factor was retained to protect infants and children (residential exposures to the parent compound). Quantitative dermal risk assessments were not performed for occupational or residential exposures. When pot ential endpoints are consid ered in light of an estimated conservative dermal absorption value of 1%, effect levels would be at or above the limit dose. Therefore the Agency concludes that a quantitative dermal risk assessment is not required for the APEs. The Agency has concluded, based on weight of the evidence, that there is not sufficient evidence to warrant a quantitative cancer assessment.

Uncertainty in the mutagenicity database must be addressed. Assu ming activation and/or in vivo metabolism will take into account potential me tabolites, the Agency is recommending a tiered approach to required data for the parent com pound. The following confirmatory data for the parent compound are required, a new Ames assay and a mouse lymphoma assay (Tier 1), a bone marrow assay (Tier 2), and a two-year cancer bioa ssay in rats and mice (Tier 3). At any point should a tier yield negative findi ngs, no additional data from the next tier will be required.

Sufficient data were provided on the chemical identity of the APEs; however, limited data are available on the metabolism and environmental degradation of this compound. The Agency relied collectively on the submitted physicochemical data, structure-activity relationship information, as well as information on other su rfactants and chemicals of similar size and functionality to determine the re sidues of concern for this inert ingredient. The Agency has concluded that the residues of concern in food and drinking water are the parent APE compounds, their partially de-et hoxylated degradation products, as well as the degradation product p- t -octylphenol.

No residue data were provided for the APE iner ts. In the absence of data, the Agency has developed an approach that uses surrogate in formation to derive upper bound exposure estimates for the subject inert ingredient. Provided that th e concentration of the APE inerts is limited to no more than 7% by weight in the end-use product, acute and chronic dietar y (food and water) risks are not of concern.

A screening level residential exposure and risk assessment was completed for products containing the APEs as inert ingr edients. Provided the APEs are limited to no more than 7% by weight in the final formulation for outdoor pr oducts, and 3% for indoor products, residential risks are not of concern for the U.S. populati on and all subpopulations, including children 1 – 2 years of age, the most highly exposed subgroup. Further, provided the limits noted above are imposed, there are no aggregate risks of concern.

HED has completed an occupational exposure an d risk assessment for the APE inerts. Occupational handler risks are not of concern fo r all scenarios. Occ upational postapplication exposures were not assessed for the APEs because no dermal hazard was identified.

Potential areas of environmental ju stice concerns, to the extent possi ble, were considered in this human health risk assessment, in accordance w ith U.S. Executive Order 12898, "Federal Actions to Address Environmental Just ice in Minority Populations an d Low-Income Populations," http://www.eh.doe.gov/oepa/ guidance/justice/eo12898.pdf ).

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 6 of 85 This assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide. These studies have re ceived the appropriate ethical review for use in risk assessment.

Regulatory Recommendation

Provided the amount of the APE inert is limited to no more than 7% by wei ght in final pesticide formulations for agricultural and outdoor residential products, and 3% for indoor residential products, there are no human health risk considerations that woul d preclude the establishment of one-year time limited exemptions from the requirement of a tolerance as follows:

Under 40CFR 180.910:

α -[p-(1,1 ,3,3-tetram ethylbutyl)phenyl]- ω -hydroxypoly (oxyethylene) produced by the condensation of 1 mole of p -(l,1,3,3- tetramethylbutyl)phenol with a range of 1-14 or 30- 70 moles of ethylene oxide: if a blend of products is used, the average range number of moles of ethylene oxide reacted to produce a ny product that is a component of the blend shall be in the range of 1-14

Given concerns raised in the lite rature for potential mutagenicity, c onfirmatory toxicity testing is required prior to establishing permanent exempti ons from the requirement of a tolerance for these inert ingredients. A tie red approach to the c onfirmatory data is proposed. The testing scheme is as follows: Tier 1: A new Ames and a mouse lymphoma assay Tier 2: A bone marrow assay Tier 3: Two-year cancer bioa ssays in the mouse and the rat

Note: The petitioner has requested an ex emption under 180.910 only (pre- and post-harvest uses). HED has determined that the conclusions in this memorandum also support an exemption with the limitations noted above under 180.920 for direct application to livestock.

2.0 Background

Inert ingredients are those ingr edients that are added to end use products that are not active ingredients. The terms "active ingredient" and "inert ingredie nt" are defined under the Federal Insecticide, Fungicide, and Roden ticide Act (FIFRA). An active in gredient is one that prevents, destroys, repels or mitigates a pest, or is a plant regulator, defoliant, desiccant or nitrogen stabilizer. The statute defines th e term "inert ingredient" as an ingredient that is not active.

As mandated by the Food Quality Protect ion Act (FQPA) of 1996, EPA conducted a reassessment of tolerances and exemptions fr om the requirement of tolerances for inert ingredients used in pesticide products to determ ine if they met FFDCA’s revised standard of safety. As a result of that reassessment, the Ag ency published a final rule in the Federal Register

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 7 of 85 (FR Notice Volume 71, No. 153, p. 45422, Aug 9, 2006) proposing revocation of specific exemptions from the requirement of a tolerance due to insufficient data.

In response to the proposed revoca tion, the Joint Inerts Task For ce (JITF) Cluster Support Team (CST) 5 submitted a petition dated October 31, 2008 and supplement dated April 15, 2009 proposing to establish an exemption from the requi rement of a tolerance to support pre- and postharvest uses of a group of inerts known collectively as the “alkylphenol ethoxyl ates” or APEs as follows under 40CFR 180.910:

α -[p-(1,1 ,3,3-tetram ethylbutyl)phenyl]- ω -hydroxypoly (oxyethylene) produced by the condensation of 1 mole of p -(l,1,3,3- tetramethylbutyl)phenol with a range of 1-14 or 30- 70 moles of ethylene oxide: if a blend of products is used, the average range number of moles of ethylene oxide reacted to produce a ny product that is a component of the blend shall be in the range of 1-14 with the percen t in pesticide formulation not to exceed 5.0%

The Agency reviewed the submitted information a nd concluded that a safety finding could not be made to support the requested exemptions fr om the requirement of tolerance (D366012, D. Davis, 7/9/09). Subsequent to the issuance of the July memorandum, the petitioner submitted additional citations and data to address concerns raised by th e Agency in the supplemental submission from Exponent dated August 21, 2009. Th is risk assessment considers all data and literature citations submitted to the Agency as of the issuance date of this memorandum.

3.0 Ingredient Profile

3.1 Summary of Proposed Uses

The alkyphenol ethoxylates are used as surfactants in pesticide fo rmulations. In addition to uses in formulations applied in agricultural settings, the APEs are used in household products such as floor cleaners, detergent sanitizers and waterless hand cleaners, as well as in industrial settings. EPA’s search of products which contain the APEs has indicated that these inerts may be present in pesticide products applie d to companion animals.

3.2 Structural Information

The akylphenol ethoxylates as described in the submitted exemption request are t -octylphenols with one or more ethylene oxide molecules attached at the phenol. The number of ethylene oxide groups can range from 1-14 or 30-70. The structure, descriptor , and CAS numbers for these groups are provided in Table 3.2, below.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 8 of 85 Table 3.2. Alkyl Phenol Ethoxylates (APE) Chemical Information

Chemical Structure 1

Common name Alkyl Phenol Ethoxylates (APE)

CAS Numbers CAS RN 9036-19-5: Poly (oxy-l, 2-ethanediyl), alpha- [4-(1,1,3,3-tetramethylbutyl)phenyl]- omega-hydroxyCAS RN 9002-93-1: Poly (oxy-l, 2-ethanediyl), alpha- [4-(1,1,3,3-tetramethylbutyl)phenyl]- omega-hydroxyDescriptor [alpha]-[p-(1,1 ,3,3-Tetramethylbutyl)phenyl]-[ omega]-hydroxypoly (oxyethylene) produced by the condensation of 1 mole of p-(l,1,3,3- tetramethylbutyl)phenol with a range of 1-14 or 30-70 moles of ethylene oxide: if a blend of products is used, the average range number of moles of ethylene oxide reacted to produce any product that is a component of the blend shall be in the range of 1-14 or 30-70

1 Figure excerpted from petition, “ Petition Proposing An Exempti on From The Requirement Of A Tolerance For Residues Of Joint Inerts Task Force Cluster 5: "Al kyl Phenol Ethoxylates" In Or On Raw Agricultural Products And Food Products” ; page 6 dated October 31, 2008.



### 3.3 Physical and Chemical Properties

Physicochemical data were estimated for the APE cluster using publicly available Estimation Program Interface suite (EPI SuiteTM) modeling ( http://www.epa.gov/opptintr /exposure/pubs/episuite.htm and are provided in Table 3.3. The basis for the estimated Estimation Program Interface suite (EPI SuiteTM) modeling physicochemical calculations and model capabilities are describe d in the EPA document titled The Use of Structure-Activity Relationships (SAR) in the High Production Volume Chemicals Challenge Program (EPA 1999). The EPA EP I SuiteTM 3.2 model calculations for water solubility are based on K OW 

### (WSKOWWIN model) and mol ecular fragments (WATERNT model). EPA has cautioned in the publicati on OPPTS Pollution Prevention P2 Network (EPA, 2005), that EPI SuiteTM 3.2 water solubility calc ulations are not reliable for dispersible compounds such as surfactants.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 9 of 85 Table 3.3. Physicochemical Properties of Re presentative Alkyl Phenol Ethoxylates (APE) 1

CAS No. Descriptor MW Log
K OW Melting Point (°C) Boiling Point (°C) Vapor Pressure (mm Hg) Water Solubility 2

(mg/L)

9002-93-1 Moles POE
n = 1 250.38 4.86 95.66 334.45 6.99 2.54 10.9

9002-93-1 Moles POE n = 9 602.81 2.67 267.22 616.94 9.4 x 10 -17 2.63 1040

9036-19-5 Moles POE
n = 5 426.6 3.77 191.94 475.9 1.79 x 10 -11 4.12 117

9036-19-5 Moles POE
n = 14 823.08 1.3 349.58 793.25 1.65 x 10 -23 1.33 14,400

9036-19-5 Moles POE n = 30 1527.9 4 -3.09 349.84 1357.44 5.55 x 10 -43 0.102 1,000,000
1 Table values taken from petition submission.

2 The EPI SuiteTM model calculates water solubility based on the octanol-water partition coefficient (K
ow ) (WSKOWWIN) and molecular fragment s (WATERNT). The first value re flects the WSKOWWIN calculation and the second value reflects the WATERNT calculation.



### 4.0 Hazard Characterization/Assessment

4.1 Database Summary

The existing toxicology database for the APE in erts consists of one OECD Test Guideline 422 combined repeated dose toxicity study with the reproduction/ de velopmental toxicity screening test in rats on octylphe noxy poly(ethyleneoxy)ethanol, branched (CAS 9002-93-1). Additionally, toxicity data are av ailable for the potential metabo lite, octylphenol. These data include acute data and several studies from the scientific literature [a two-generation reproduction study in rats, a female pubertal assay, mutagenicity studies, and several short-term studies]. Further, to supplement the octylphenol database, additional data from the open scientific literature on nonylphenol (a chemical that differs by only one carbon from octylphenol) was also considered.

The OECD Test Guideline 422 study conducted on the parent compound provides information on the possible health hazards like ly to arise from repeated ex posure. The method comprises the basic repeated dose toxicity study as well as a reproduction/developmental toxicity-screening test and also places emphasis on neurol ogical effects as a specific e ndpoint. Therefore, the study can provide information on general toxicity as well as possible developmental, reproductive, and neurological effects. It can also provid e basic indications of immunological effects.

4.2 Toxicological Effects and Metabolism

Toxicological Effects

Octylphenol Ethoxylates (Parent Compounds) The available toxicity data indicate that APE iner ts have low to moderate acute oral and dermal toxicity, are a mild to moderate skin irritant, and an eye irritant . Based on the analysis of the

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 10 of 85 studies in the open literature, there is both positive and nega tive evidence that ethoxylated octylphenol (CAS 9036-19-5) is mutagenic in bacteria ( Salmonella typhimurium ) and mammalian (CHO, mouse lymphoma) cells.

In the OECD 422 study on a representative parent compound (CAS 9002-93-1) , parental toxicity manifested as clinical signs (pushing head th rough bedding after dosing) , decreased body-weight gain in both sexes during the premating period, d ecreased thymus weight in females, increased liver weight in males, and increased incidence of centrilobular hepatocy te hypertrophy in males at the same dose levels where the offspring sh owed decreased pup body weight in both sexes. There was no evidence of increased susceptibi lity. There was no evidence of reproductive toxicity or neurotoxicity in the parental animals.

In a study referenced in th e petition (Hazelden and Wilson, 1986), skeletal abnormalities (supernumerary ribs) were observed following dietary expos ure of dams to the surfactant Triton X-100 (CAS # 9036-19-5) during gest ation days 6-17 at both dose levels tested. The OECD 422 study did not include an examination for skeletal anomalies of the offspring.

The Agency has concern with respect to impact s on estrogenic activity seen in studies conducted on a potential degradate, octylphenol. The OECD 422 study on the parent compound does not assess certain endpoints related to the estrogenic activity that were the most sensitive effects observed in studies on the degradate.

In a screening literature searc h, several studies were found that suggest mutagenic potential. Ethoxylated octylphenol was shown to be mutageni c in bacteria (Salmonella typhimurium) and mammalian (CHO, mouse lymphoma) cells with and without metabolic activation. In other Ames Salmonella/ microsome plate test s (tester strains TA98, TA100, TA1535, TA1537, TA1538), the parent compound did not exhibit mutagenic activity with or without metabolic activation.

Octylphenol (Metabolite/Degradate) The major effects seen in the metabolite/degradate octylphenol database appe ar to be related to potential disturbances in estr ogenic activity. Given the limited database for octylphenol, the Agency is also considering data on nonylphenol, a chemical that differs by only one carbon from octylphenol. The estrogenic activity effects appear to be the most sensitive endpoints for nonylphenol and were considered the key findi ngs for regulatory purposes. In a screening literature search, several studies were found describing similar effects following octylphenol exposure that are consistent with estrogenic activity, including acceler ation of the vaginal opening. These studies on octylphenol are described below.

In the published two-generation reproduction study by Tyl et al. (1999) on octylphenol, no effects were reported on reproduc tive function, testes, prostate, or ovary weights or morphology, on sperm counts, motility, morphology, pr oduction, or on estrous cyclicity ; however, a significant reduction ( ↓ 18-20%) in uterine weight was obser ved in the F0 females at the high dose. Decreased pup body weight was observed duri ng the latter part of l actation (LD 14 and 21;
F1 ↓ 13-16%**; ↓ F2 6-8%). There was a slight delay in acquisition of vaginal patency and preputial separation at the high dose in both generations, which was accompanied by minimal

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 11 of 85 decreases in body weight ( ↓ 6%). The delays in sexual maturation are statistically significant, although not very large. The delays in male sexu al maturation would be consistent with impacts on estrogenic activity; however, one would exp ect the vaginal opening to be advanced, not delayed (as observed in Laws, et al. 2000). The NOAEL from this study is 10 mg/kg/day and the LOAEL , based on decreased body weights in adults and during the latter portion of lactation in offspring and minor delays in acquisition prep utial separation , is 111 mg/kg/day.

In the open literature, 4-tert-octylphenol (OP) is shown to have estrogen-like action in in vitro and in vivo assays. This is based on changes in uterin e weight, estrus cyclicity and the afternoon surge of FSH, LH, and prolacti n, as well as interference with sexual receptive behavior. Neonatal exposures to OP and exposures of fema le rats during infancy cause premature vaginal opening, induction of persistent estrus, abnormal development of uteri, and disruption of the cyclic release of LH, FSH, and prolactin. Decl ine in serum FSH and LH levels has also been reported in 14-day old female rats neonatally ex posed to 4-tert-octylphenol. Although in many of the studies, the route of exposure is by subcut aneous administration, in studies comparing the subcutaneous and oral (gavage) routes of exposure to OP, e ffects on uterine weight were reported after both routes of exposure, with the magnitude of the effects being greater following subcutaneous injection. Vagina l opening was significantly acceler ated following gavage dosing in a female rat pubertal assay.

In a screening literature search, several stud ies were found that suggest mutagenic potential. Octylphenol induced a high incidence of sist er chromosome exchange (SCE) and caused DNA migration in one comet assay and tail length and tail moment were significantly different in an in vivo (comet) assay. In the His+ re vertant assay in bacteria ( Salmonella typhimurium ), octylphenol was mutagenic in TA98 and TA 100 strains without metabolic activation. Octylphenol did not exhibit mutagenic activity in three Ames Salmonella/microsome plate tests and was negative in chromosomal aberration/Chin ese hamster lung (CHL) cells with and without S9. Structural chromosomal aberration and pol yploidy cells were not induced in Chinese hamster lung (CHL/IU) cells.

Nonylphenol (Structurally Related Compound) There are several multigeneration reproductive toxicity studies in rats on nonylphenol that demonstrate no adverse effects on reproducti ve function. Two of the multigeneration reproduction studies in the open li terature on nonylphenol demonstrat e an acceleration of vaginal opening (VO). Additionally, there are several pu bertal onset assays on nonylphenol in which acceleration of vaginal opening, de lay of preputial separation, and estrous cycle changes have been demonstrated in the rat. These are described below:

In a published three-generation reproduction study in rats (Tyl et al., 1999) on branched pnonylphenol, no effects were reported on reproduc tive parameters, testes and epididymides weight or morphology, on sperm counts , motility, morphology, production; however, a significant reduction in ovarian we ight was observed in the F0 ( ↓ 32%) and F1 ( ↓ 20%) females at the high dose. Decreased pup body weights and body- weight gains were observed in both sexes during the latter part of lactation (LD 21; F1 ↓ 16%; ↓ F2 11%; ↓ F3 8%). Kidney toxicity was reported in males at 650 and 2000 ppm, as evid enced by increased kidney weights and kidney histopathology (medullary cysts, mineralizati on of corticomedullary junction, and tubular

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 12 of 85 nephropathy). A NOAEL of 200 ppm ( ≈ 15 mg/kg/day) for kidney effects was reported. Anogenital distance was not measured, and ac quisition of vaginal pa tency and preputial separation were not assessed in th is study following nonylphenol exposure.

In another published 2-generation reproduction st udy in rats (Nagao, et al., 2001) on nonylphenol (2, 10, 50 mg/kg/day), parental effects included increased liver, ki dney, and pituitary weights in males, decreased thymus weight ( ↓ 24%) in males, decreased ovary weight ( ↓ 18%) in F0 and F1 females, increase in TSH levels (males), and centrilobular hepatocyte hypertrophy in both sexes at the high dose. There was a significant decreas e in the number of implantation sites (F2). Developmental effects included decreased numbe r of live pups, decreased pup viability (PND 0- 4), increase in serum FSH level and decrease in T3 level for males, decreases in LH and TSH levels, and an increase in T3 levels for fema les at 50 mg/kg/day. The timing of vaginal opening was accelerated (F1) at 50 mg/kg/day, but no effect was observed on the timing of preputial separation. No adverse changes in behavior or learning in of fspring were reported. The NOAEL is 10 mg/kg/day.

In a multigeneration reproduction study in rats with the branched nonylphenol (Chapin, et al., 1999), small increases in estrus length (F 1 14%; F2 18%) were observed at 2000 ppm (100 mg/kg/day), and vaginal opening was accelerated by ≈ 2 days at 650 ppm (30 mg/kg/day) and ≈ 6 days at 2000 ppm (100 mg/kg/day) in F1, F2, F3 generations. Uterine weights at PND 21 were increased in 650 ppm (14%) and 2000 ppm (50%) F1 females. The NOAEL was 200 ppm (9 mg/kg/day).

The age of vaginal opening was advanced follo wing oral exposure to branched p-nonylphenol (50 and 100 mg/kg/day; 5.3 and 6.8 days) from po stnatal days 21-35 (Laws, et al., 2000). The NOAEL was demonstrated at 25 mg/kg/day. Estr ous cycle changes and accelerated vaginal opening were observed following 20-day postnat al exposure (100 mg/kg/day; 6.7 days) to branched p-nonylphenol (Kim, et al., 2002). The NOAEL was 10 mg/kg/day. The age of preputial separation was delayed following or al exposure to nonylphe nol (100 mg/kg/day).

Metabolism The registrant has not provided metabolism studies for the parent, but di d cite a study for the potential degradate octylphenol, CAS 140- 66-9 (p- (1,1,3,3-tetramethylbutyl)phenol). There are a few literature studi es available for the nonylphenol ethoxylates (NPEs), which are structurally similar to the octy lphenol ethoxylates. One study wh ere the NPEs were labeled in the ethoxylate chain indicated that excretion of the NPEs in urine was nearly complete in 2 days, and excretion of radiolabeled carbon via the urinary and pulmonary pathways decreased and fecal excretion increased as the ethoxylate chain length increased, indicating decreased gastrointestinal absorption as polyethoxylation increases. A study where the NPEs were labeled in the phenyl ring showed no 14 

### CO 2 

### in the expired air. These studies also showed that the ethoxylate chain moiety was absorbed from th e digestive tract following oral exposure and metabolized less completely as the chain length increased. The principle urinary metabolites were identified as the carboxylic acids of polyethylene glycols a nd glucuronic acid conjugates of nonylphenol.

Based on this information, the Agency concludes that the registrant has proposed a reasonable

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 13 of 85 description of the metabolic path way in mammals. By extrapolat ion from the NPE studies, it is likely that the octylphenol alkoxylate (POE) chai n is cleaved to octyl phenol and the carboxylic acids of the polyethylene glycols. Octylphenol is subjected to glucuronic acid conjugation and can be excreted. The carboxylic acids can be further conjugated or excreted directly.

Octylphenol Metabolism The registrant cited a literature study, Certa, et al., (1996), which showed that in the rat, tOP was rapidly excreted (single i. v. dos e of 5 mg/kg; half-life 5 hours in males; >36 hours in females) by first-pass hepatic metabolism via glucuronide conjugation. Follo wing an oral dose (50 or 200 mg/kg), enterohepatic circulation was suggested, with detectable le vels of tOP in the blood at 48 hours. Following repeated exposure, a dose of 200 mg/kg/day saturates metabolic capacity of the rat for clearance. Studies with the nonylphe nol degradate indicated that it is readily conjugated, particularly to the glucuroni de conjugate, facilitating excretion.

4.3 Dermal Absorption

There are no dermal absorption data on the APE inerts or on the octylphenol metabolite/ degradate. The JITF CST 5 submitted dermal absorption information on the closely related compounds nonylphenol and nonylphenol etthoxylates, which indicate that dermal absorption of 1% would be a reasonable conservative assumpti on for the range of compounds in CST 5. The Agency has reviewed the submitted information a nd concurs that a dermal absorption value of 1% is a conservative estimate. Quantitative dermal risk assessments will not be performed for occupational or residential exposures.

4.4 Mutagenicity

Oxtylphenol Ethoxylates (Parent Compound) The Agency conducted a literature search to look for mutagenicity data in the open literature. There is both positive and negative evidence th at ethoxylated octylphenol is mutagenic in bacteria (Salmonella typhimurium) and mamm alian (CHO, mouse lymp homa) cells. Positive findings: (1) caused reproducible positive increases in the mean number of TA1535 revertants per plate in both presence (3.7 and 4.4-fold ) and absence (5.0 and 2.9-fold) of S-9 (Lawlor/Haworth, 1989); (2) exhibited genetic activ ity in strains TA-1535 and TA-100 with and without S9 and was considered mutagenic (DeGraff/Brusick, 1981). (3) an in vitro cytogenicity assay measuring chromosome aberration freque ncies in Chinese hamster ovary (CHO) cells (with and without S9), CAS 9036-19-5 was consid ered clearly positive, causing significant increases in chromosome aberra tions both with and without meta bolic activation. (4) in a mouse lymphoma forward mutation assay (L5178Y TK+/-), CAS 9036-19-5 induced significant increases in the mutant freque ncy at the TK locus in L5178Y mouse lymphoma cells with and without metabolic activation. (5) was positive in in vitro HeLa cell assay (CST 5 reference). Negative findings: (1) did not cause a positive increase in the number of histidine revertants per plate of any of the test er strains with or wit hout S9 (Lawlor, et al., 1989); (2) did not exhibit mutagenic activity in Ames Salmonella/microso me reverse mutation assay (tester strains TA98, TA100, TA1535, TA1537, TA1538) with and without ±S9 (Jagannath/Myhr; 1986); (3) did not exhibit mutagenic activity in Ames assay in any tester strains with and without ±S9

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Page 14 of 85 (Jagannath/Brusick; 1981); (4) di d not exhibit mutagenic activity in Ames microsome spot test (DeGraff/Brusick; 1983).

Octylphenol (Metabolite/Degradate) Based on the analysis of the studies in the ope n literature, there is both positive and negative evidence that octylphenol is mutagenic. Positive findings: (1) mutagenicity was observed in TA98 and TA100 strains without metabolic activati on in the His+ revertant assay in bacteria (Salmonella typhimurium), Boyacioglu, et al., 2007; (2) tail length and ta il moment significantly different in an in vivo (comet) assay (Ulutas, et al., 2009); (3) caused DNA migration in comet assay and induced high incidence of sister ch romosome exchange (SCE); Tayama, et al., 2008. Negative findings: (1) three stud ies (OECD SIDS) in bacteria (Salmonella typhimurium) were negative in all tester strain (±S9); (2) in chromosomal abe rration/Chinese hamster lung (CHL) cells were not induced with and without S9 (OECD SIDS); (3) structural chromosomal aberration and polyploidy cells were not induced in Chinese hamster lung (CHL/IU) cells (Kusakabe, et al., 2002); (4) di d not result in chromosome ab erration (Tayama, et al., 2008).

Additionally, based on the analysis of studies in the open li terature, there is both positive and negative evidence that nonylphenol is mutagenic. Positive findings: (1) caused DNA migration in comet assay and induced high incidence of si ster chromosome exchange (SCE); Tayama, et al., 2008; (2) in vitro cytogenicity assay for si ster chromatid exchange in Chinese hamster ovary (CHO) cells, nonylphenol was positive for inducing sister chromatid exchange without S9 and negative with S9 (Murli, et al., 1986); (3) in mouse lymphoma forward mutation assay (L5178Y TK+/-), nonylphenol was mutagenic with activation and non-mutagenic without S9 (Cifone/Myhr, 1985); (4) nonylphenol induced micr onuclei in peripheral blood and bone marrow reticulocytes (Kim, et al., 2006; in Polish). Additionally, nonylphenol induced apoptosis of Jurkat cells by caspase-8 dependent mechanisms (inhibited the proliferat ion and induced loss of mitochondrial membrane potential, caspase-8 ac tivation, internucleosomal DNA fragmentation), Yao, et al., 2007. Negative findings: (1) in an Ames Salmonella microsome reverse mutation assay (strains TA98, TA100, TA1535, TA1537, TA1538), Jagannath/Myhr, 1985; (2) in an in vitro transformation of BALB/C-3T3 cells assay, nonylphenol did not induce a significant increase in the frequency of transformed foc i; (3) did not result in chromosome aberration (Tayama, et al., 2008); (4) in vitro cytogenicity assay in Chinese hamster ovary (CHO) cells, nonylphenol was negative for inducing sister chroma tid exchange with S9 (Murli, et al., 1986); (5) in mouse lymphoma forward mutation assay (L5178Y TK+/-), nonylphenol was nonmutagenic without S9 (Cifone/Myhr, 1985).

Though equivocal, the findings in th e literature need to be ad dressed; therefore, HED is requesting confirmatory data to speak to the concern raised by the positive mutagenicity findings. A proposed tiered approach to addr essing this concern is described as follows.

The following studies are required for the parent compound, assuming activation and/or in vivo metabolism will take into account potential me tabolites. The Agency recommends a tiered approach to the confirmato ry toxicity testing.

Tier 1: A new Ames assay (870.5100 – Bacteria l reverse mutation test) and a mouse lymphoma assay (870.5300 – In vitro mammalian cell gene mutation test)

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Page 15 of 85 Tier 2: A bone marrow assay (870.5395 – Ma mmalian erythrocyte micronucleus test)

Tier 3: Two-year cancer bioa ssays in the mouse and rat ( 870.4200 – Carcinogenicity (mouse) and 870.4300 – combined Chronic Toxicity/Carci nogenicity (rat))

If the Tier 1 tests are negative, then the Tier 2 an d Tier 3 tests would not be required. Further, if there are positive findings in Tier 1, but the Tier 2 test is negative, the Ti er 3 study will not be required. The Agency notes, that if the petitioner wishes to assume that the Tier 1 assays will be positive based on literature study data, they ma y move directly to the Tier 2 testing.

4.5 Carcinogenic Potential

There are no chronic toxicity studi es available for the APE inerts. The Agency used a qualitative structure activity relationship (SAR) database, DEREK Version 11, to determine if there were structural alerts suggestive of carci nogenicity. No struct ural alerts were identified for the parent APE compounds.

No chronic toxicity studies are available for the tert-octylphen ol metabolite/degradate. The Agency used a qualitative struct ure activity relationship (SAR) database, DEREK Version 11, to determine if there were structural alerts sugges tive of carcinogenicity. While there were alerts for the degradate, including the estrogenic effects noted in the literature, as well as concern for chromosome damage, no structural alerts specific to carcinogenicity were noted.

The structurally related nonylphenol has been shown to act as a tumor promotor. Several studies demonstrate effects on tumor development follo wing nonylphenol exposure. These include (1) in a two-stage transformation of BALB/C-3T3 cells, nonylphenol markedly enhanced transformation of cells pretreated with sub- threshold dose of carcinogen (MCA) in promotion phase (nonylphenol acts as a pure promoter); may cause enhancement of carcinogenesis in vivo (Sakai, 2001); (2) in a multi-o rgan carcinogenesis model in rats, nonylphenol significantly increased the total incidence of adenomas and carcinomas in l ungs; possible role for oxidative damage in nonylphenol-induced lung tumors was s uggested (Seike, et al., 2003); (3) significant promotion of mammary tumor development in DMBA-induced female transgenic rats and acceleration of induction in non-transgenic females (enhancing effects on tumorigenesis in vivo); nonylphenol caused proliferation of MCF-7 cells at high dose levels (10-6 – 10-5 M) (Fukamachi, et al., (2004); (4) nonylphenol in creased mammary cancer formation in MMTVneu mice; (5) nonylphenol transactivated the endogenous estrogen receptor (ER) alpha in a direct fashion; using steroid-receptor-ne gative HeLa cells engineered to express ERalpha and ERbeta and the hormone-binding domains of both ER alpha and ERbeta, nonylphenol confirmed the direct transcriptional activity; significantly stimulated the pr oliferation of MCF-7 and T47D breast cancer cell lines Vivacqua, et al., 2004; (6) FVB/NTgN (MMTVneu) 202Mul mice, susceptible to mammary cancer were fed nonylphe nol for 32 weeks; nonylphenol increased both tumor incidence and latency at 45 mg/kg/day.

The Agency has carefully considered the weight of the evidence with resp ect to carcinogenicity for both the parent compound and for the octyl phenol degradate. There were no structural alerts

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Page 16 of 85 specifically for carcinogenicity and there were equi vocal mutagenicity findings in the literature studies. HED does not believe at this time that there is sufficient evidence to warrant a quantitative cancer risk assessment.

4.6 FQPA Considerations

In the case of the parent compounds, there was no in creased susceptibility to the offspring of rats following pre- and post-natal exposure in the OE CD 422 combined repeated dose toxicity study with the reproduction/developmenta l toxicity screening test. The offspring effects (decreased body weight in male and female offspring) oc curred at 300 mg/kg/day in the presence of maternal toxicity, which was manifested as clin ical signs, decreased body-weight gain, increased liver weight and liver hypertr ophy in males, and decr eased thymus weight in females at 300 mg/kg/day. However, a study referenced in th e petition (Hazelden and Wilson, 1986) suggests more severe developmental effects (supernum erary rib) following gestational exposure via the diet during gestation days 6-17. The OECD study did not include a skeletal examination of the offspring. Since the OECD study with APE did not assess its impact on the estrogen system, it cannot be used alone to properly assess the most sensitive endpoint. However, selecting the point of departure from the OECD 422 study, which is based on a NOAEL of 150 mg/kg/day and decreased body-weight gain in both sexes during the premating period, decreased thymus weight in females, and increased liver weight and liver hypertrophy in male s at the LOAEL of 300 mg/kg/day, and retaining the FQPA safety factor of 10X is comparable to using the point of departure from the reproduction studies on the most toxicologically potent compound (nonylphenol) that assessed estr ogenic activity (endpoin t: accelerated vagina l opening; point of departure: 10 mg/kg/day). The endpoint (accele rated vaginal opening) and point of departure (10 mg/kg/day) are considered heal th protective of effects not as sessed in the OECD 422 studies on the parent compounds.

For the octyl phenol metabolite, the two-generati on reproduction study in rats showed a delay in the acquisition of preputial sepa ration in both the F1 and F2 pups, and the timing of vaginal opening was accelerated in a study in prepubertal female rats

. For the nonylphenol metabolite, two of the multigeneration reproducti on studies in rats and two studies in prepubertal female rats showed acceleration in the acquisition of vagina l patency. A delay in preputial separation was observed in male rats in a pubertal onset assa y. The combined toxicology databases currently available on octylphenol and nonylphenol identif y accelerated vaginal opening as the most consistent and sensitive endpoi nt, and a clear NOAEL of 10 mg/ kg/day has been demonstrated.

In a developmental toxicity study with the parent compound, developmental toxicity was demonstrated, as evidenced by the increased inci dence of supernumerary ribs following exposure to the dams during gestation days 6-17. Howe ver, the low pregnancy rate among all groups (56%-70%) in this study makes interpretation of the results difficult. Additionally, the OECD 422 study did not include a skeletal examination of the offspring. A developmental toxicity study was identified in the octylphenol databa se, and a clear NOAE L of 15.6 mg/kg/day (postimplantation loss) was established. The point of de parture for octylphenol was selected from this study for the acute dietary (females 13+) exposur e. This study is cons idered appropriate and health protective of effects observed in the developmental toxicity study with the parent compound.

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Page 17 of 85 Since the rat reproduction studies on the most toxicologically potent compound (nonylphenol) identified a clear NOAEL of 10 mg/kg/day for th e most sensitive endpoint (accelerated vaginal opening), and the selected point of departure of 10 mg/kg/day (NOAEL for accelerated vaginal opening) for the dietary risk asse ssment is protective of offspri ng effects, there are no residual

concerns.

The FQPA safety factor can be reduced to 1X for the metabolite upon which the dietary assessment is based for the following reasons:

• The most sensitive endpoint from the most toxicologically potent compound (nonylphenol) was selected for risk assessment and is considered health protective. The database for nonylphenol is protective of oc tylphenol, which has a limited database. There are several studies on nonylphenol (2 multigeneration reproduction studies, pubertal onset assays, uterotrophic assays), which demonstrate acceleration of vaginal opening (VO) in the rat. Accelerated VO is the most consistent and sensitive endpoint identified. Clear NOAELs for this endpoint ha ve been identified following exposure to nonylphenol.

• While endpoints were not selected from the OECD 422 screening test in rats following pre- and post-natal exposure to the parent compound based on concerns that the study did not look for impacts on the estrogen system , the Agency does note that no increased susceptibility was demonstrated in the offspr ing in the OECD 422 screening test in rats following pre- and post-natal exposure to the parent compound.

• Although a developmental toxicity study was id entified in the open literature for the parent compound, a study on octylphenol demons trated an increase in post-implantation loss following exposure to the dams from gestation day 0-8. A clear NOAEL of 15.6 mg/kg/day was established for th e offspring effects. Since the point of departure selected from that study for acute dietary exposu re to the octylphenol metabolite is 15.6 mg/kg/day, this value is considered health pr otective of offspring effects that might be found following octylphenol exposure.

• There is a two-generation repr oduction study in rats on octyl phenol that demonstrates no adverse effects on reproductive function.

• Although the available mammalian toxicity database does not include any chronic toxicity data, there is one 2-generation reproduction study on octylphenol and several multigeneration reproduction studies on the mo st toxicologically potent compound in the risk assessment, nonylphenol, in which test an imals were dosed for extended periods of time and across generations.

• The exposure assessments used in this risk assessment are considered to be highly conservative. In the absence of substan tial information on environmental degradation, the Agency has conducted an assessment which assumes that 100% of the parent compound is degradated to the more toxic degradate, octylphenol. Further, the assessment assumed residues of octylphenol w ill be present in all foods consumed at levels consistent with the highest established pesticide tolerance, and in drinking water at a high-end estimated level of 100 ppb. The Agen cy anticipates that this assessment will overestimate risk.

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Page 18 of 85 The FQPA safety factor is re tained (10X) for the parent compound upon which the residential assessment is based for the following reasons:

• Although endpoints from the OECD 422 screening tests in rats following pre- and postnatal exposure to the parent compound were se lected for the residential and occupational exposure risk assessments, there are concerns that the study did not look for the most sensitive endpoints for the estrogen system.

• The Agency does note that no increased suscepti bility was demonstrated in the offspring in the OECD 422 screening test in rats follo wing pre- and post-n atal exposure to the parent compound.

4.7 Toxicity Endpoint Selection and Levels of Concern

A summary of the points of de parture (PoD) for risk assessment may be found in Tables 4.6.1 and 4.6.2, below.

Endpoints selected are those to be used for th e parent compound and the octylphenol metabolite risk assessments. The acute and chronic dietary assessment endpoints were selected from the available octylphenol and nonylphenol metabolite databases

. The residential and occupational assessment endpoints were selected from the OECD 422 study on the parent compound. Since the study with the parent compound did not look for certain potential effects on the estrogenic system, which were observed to be most sensitive for the metabolites, the FQPA safety factor of 10X is retained for the residential risk assessments for the parent compound.

For the general population, no toxic effects we re identified resulting from a single day’s exposure. Therefore, an acute dietary risk assess ment for the general populat ion is not required.

For females 13+, increased post-implantation loss was observed following exposure of dams to octylphenol during gestation days 0 to 8. This endpoint is considered appropriate as an effect that could result from a single day’s e xposure. Therefore, an acute diet ary risk assessment for females 13+ is required.

Endpoints for the chronic dietary assessment were selected from two literature studies on nonylphenol, which were considered co-critical. In a 2-generation reproduction study in rats (Nagao, 2001) effects observed at the LOAEL of 50 mg/kg/day were signi ficant increases in pituitary weight in parental males and decreases in ovary weight in parental females. Effects found in the pups were significant acceleration of vaginal opening and decreases in the number of implants and live pups. The NOAEL for the pa rental and pup effects was 10 mg/kg/day. In a 3-generation reproduction study in rats (Chapin, 1999) , vaginal opening was also accelerated at a LOAEL of 30 mg/kg/day; the NOAEL was appr oximately 9 mg/kg/day. A 100X uncertainty factor was applied to account for the 10X interspecies and 10X intr aspecies uncertainty factors, resulting in a chronic reference dose (cRfD) of 0.10 mg/kg/day. Since the 10X FQPA safety factor was removed, the chronic population adjust ed dose (cPAD) is the same as the cRfD (0.10 mg/kg/day).

Endpoints for the residential (sho rt- and intermediate-term incide ntal oral and inhalation) and

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Page 19 of 85 occupational (short- and intermediate-term inhala tion) exposures were se lected from the OECD 422 study in the rat on the pare nt compound with a NOAEL of 150 mg/kg/day. Effects observed at the LOAEL of 300 mg/kg/day were clinical si gns, decreased body-weight gain in both sexes during the premating period, decreased thymus weight in fema les, increased liver weight in males, and increased incidence of centrilobular hepatocyte hypertrophy in males. Since studies with the parent compound did not look for certa in potential effects on the estrogenic system, which were observed to be most sensitive for th e metabolites, the FQPA safety factor of 10X was retained.

Quantitative dermal risk assessments will not be performed for occupational or residential exposures. When potential endpoints are considered in light of an estimated conservative dermal absorption value of 1%, effect le vels would be at or above the limit dose. Therefore the Agency concludes that a quanitative dermal risk assessment is not required for the APEs.

Although the available mammalian toxi city database does not include any chronic toxicity data, there are several multigeneration reproduction studies on the most toxicologically potent compound in this risk assessment, as well as a 2-generation reproduction study in rats on octylphenol. Based on the very conservative expo sure assessment, the 10X interspecies and 10X intraspecies uncertainty factors would be ade quately protective, and no additional uncertainty factor is needed for extrapolating from subchronic to chronic exposure.

The level of concern (LOC) is fo r margins of exposures (MOEs) that are less than 1000 and is based on 10x for interspecies extr apolation animals to humans and 10x for variation in sensitivity among humans. The FQPA safety factor was retained (10X).

These LOCs are applicable to all non-occupational populations, including individuals exposed in a residential setting. Risks from oral and inhala tion routes of exposure should be combined since common endpoints (same study) were selected for these routes. The LOC for occupationally exposed workers is 100.

Table 4.6.2 Summary of Toxicological Doses and Endpoints for Alkylpheno l Ethoxylates (APE) and their Metabolites (including octylphenol) for Use in Human Health Risk Assessments

Exposure/ Scenario Point of Departure Uncertainty Factors RfD, PAD, Level of Concern for Risk Assessment Study and Toxicological Effects Acute Dietary (general population) An endpoint attributable to a single exposure was not seen in the database; therefore a point of departure was not selected.

Acute Dietary (females 13+) NOAEL = 15.6 mg/kg/day UF A = 10x
UF H =10x FQPA SF = 1X aRfD = 0.156 mg/kg/day

aPAD= 0.156 mg/kg/day initiation and maintenance of pregnancy in rats (Harazone and Ema, 2001) LOAEL = 31.3 mg/kg/day, based on increased % post-implantation loss following exposure of dams during gestation days 0-8.

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Page 20 of 85 Table 4.6.2 Summary of Toxicological Doses and Endpoints for Alkylpheno l Ethoxylates (APE) and their Metabolites (including octylphenol) for Use in Human Health Risk Assessments

Exposure/ Scenario Point of Departure Uncertainty
Factors RfD, PAD, Level of Concern for Risk Assessment Study and Toxicological Effects

Chronic Dietary (All Populations) NOAEL = 10 mg/kg/day UF A = 10x UF H =10x FQPA SF = 1X cRfD = 0.1 mg/kg/day

cPAD= 0.1 mg/kg/day 2-generation reproduction study in rats (Nagao, et al., 2001), LOAEL = 50 mg/kg/day, based on significant increases in pituitary weight ( ↑ 12%, males), decreases in ovary weight ( ↓ 18%) in F0 animals; timing of vaginal opening significantly accelerated in F1 females; decreases in the numbers of implants and live F2 pups born were observed (NOAEL 10 mg/kg/day). 3-generation reproduction study in rats (Chapin, et al.

, 1999). LOAEL = 30 mg/kg/day, based on vaginal opening was accelerated by ≈ 2 days and ≈ 6 days in F1, F2, and F3 generations following dietary exposure at 30 and 100 mg/kg/day respectively (NOAEL ≈ 9 mg/kg/day)

Incidental Oral and Inhalation(Short- and IntermediateTerm) NOAEL = 150 mg/kg/day

Inhalation toxicity is assumed to be equivalent to oral toxicity

Dermal absorption of 1%

Dermal equivalent dose = 10000 mg/kg/day UF A = 10x UF H =10x FQPA SF = 10x Residential LOC for MOE = 1000

Occupational LOC for MOE= 100 OECD Test Guideline 422 study (MRID 47585801) (octylphenoxy poly(ethyleneoxy)eth anol, branched) Parental systemic LOAEL = 300 mg/kg/day, based on clinical signs (pushing head through bedding after dosing), decreased body-weight gain in both sexes during the premating period, decreased thymus weight in females, increased liver weight in males, and increased incidence of centrilobular hepatocyte hypertrophy in males

Cancer (oral, dermal, inhalation) Classification: not classified; no alerts identified in SAR with respect to carcinogenicity; potential mutagenicity concern identified in open literature for parent compound and metabolite. Wei ght of the evidence determination that there is no sufficient evidence to warrant a quantitative cancer risk assessment. Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associ ated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = ac ute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicable.



### 4.8 Endocrine Disruption

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to

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Page 21 of 85 interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients. This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-applic ation agricultural scenarios. This list should not be construed as a lis t of known or likely endocrine disruptors.

APE and its octylphenol metabolite are not among th e group of 9 inert ingredients on the initial list to be screened under the EDSP. Under FFD CA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all pesticide active ingredients and inerts.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, pleas e visit our website: http://www.epa.gov/endo/.

5.0 Dietary Exposure/Risk Characterization

5.1 Residues of Concern

The Agency considered whether the selected repr esentative chemicals for toxicity testing from the APE cluster were representative of the entire cluster. Based on the representative chemical structures, the generic cluster structures, th e submitted physicochemical EPI SuiteTM information as well as the structure-activity relationship analys is detailed in Appendix D of this review, the Agency concurs that the cluster grouping is appropriate.

Very limited information is available for the Al kyl Phenol Ethoxylates (APE) with respect to plant and livestock metabolism. There is extensive information in the literature on environmental degradation 1 

### , and some information on bacterial and mammalian metabolism, all of which indicate similar degradation of the APE compounds. The ethoxylate moiety is degraded by sequential removal of the et hoxylate groups, eventually degrading to p- t

octylphenol. The structure and other identifiers for p- t -octylphenol are presented in Table 5.1.1. There are studies in the literatur e cited in Klecka (2005) that sugge sts plants have the ability to take up the APE residues from treated soil. Th erefore, the Agency has concluded that the residues of concern in food and drinking water ar e the parent APE compo unds, their partially deethoxylated degradation products, as well as the degradation product p- t -octylphenol.

1 

### Klecka, G.M., Staples, C.A., Losey, B.S. and Woodburn, K.B., “Assessment Of The Persistence And Bioaccumulation Potential For Nonylphenol, Octylphenol, And Their Ethoxylates For Categorization A nd Screening of The Canadian Domestic Substance List”. Prepared for the Alkylphenols a nd ethoxylates Research Council 2005.

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Page 22 of 85 Table 5.1.1. p- t -Octylphenol Chemical Information

Chemical Structure 1

O

Common name p- tert -octyl phenol

CAS Numbers 140-66-9

CAS Name 4-(1,1,3,3-tetramethylbutyl)-phenol



### 5.2 Drinking Water Residue Profile

Selected alkylphenol ethoxylates and p- t -octylphenol have been found in many different water monitoring studies. In a re view article, Ying et al 2 

### state that the APEs and their metabolites are ubiquitous in the environment because of their wide use patterns ̧ and have been detected in air, water, sediment, soil and biot a. The APEs and metabolites have been found in ground and surface waters. Furthermore, they are not comple tely degraded by wastewater treatment plants, and have been found in plant effluents. The APEs and their metabolites have been found in surface water in monitoring studies by the United States Geological Survey (USGS). In addition, a screening literature search revealed numer ous monitoring studies by the states and other entities where selected APEs and p- t -octylphenol were found in ground and surface water. Many of these studies cannot distinguish the source of these compounds, which could have been from consumer, industrial, and/or agricultural uses of the APEs. A study of groundwater in Spain in an agricultural area 3 

### found the highest levels of p- t -octylphenol in an agricultural area, as compared to the urban and industrial areas sampled.

In a supplement to the CST5 petition, the registrant s reported the results of the National Health and Nutrition Examination Surveys (NHANES) for 2003-2004 4 

### , which indicated measureable quantities of the p- t- octyl phenol (tOP) metabolite, in the ur ine of the general US population for all ages 6-60 years. The octyl phenol was detected in 57.4% of samp les at total con centrations of 0.2 μ g/L–20.6 μ g/L. Currently, there is no way to determine the source of the tOP found in urine, as it may have been result of exposure to personal care products ̧ contamination of water from manufacturing or agricultura l sources, detergents, and/or residues in food from use as an inert ingredient.

5.3 Food Residue Profile

2 Ying et al. / (2002) Environment International 28 (2002) 215– 226

3 LaTorre et al., “Presence of nonylphenol, octyphenol and bisphenol a in two aquifers close to agricultural, industrial and urban areas”. Chromatographia 2003, 57, January (No. 1/2) pp. 111-116

4 Calafat AM, Ye X, Wong L-Y, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4- tertiary-octylphenol: 2003–2004. Environ Health Perspect. 2008b;116:39–44.

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Page 23 of 85 No residue data were submitted for the APE inert ingredients or for the octylphenol metabolite/degradate. Nonylphenols (NPs), compounds very similar to the octylphenol degradate have been found in food 5 

### in Germany. The highest level found was 19 ppb in apples. Again, there could be multiple sources of th e NPs, but the authors do mention nonylphenol ethoxylate surfactants as a potenti al source for the nonylphenols found.

In the absence of extensive data, the Agency ha s developed an approach which uses surrogate information to derive upper bound exposure es timates for inert ingredients and their metabolites/degradates, as appropriate. The upper bound exposure estimates are based on the highest tolerance for a given commodity from a lis t of 57 high use insecticides (22), herbicides (20), and fungicides (17). The 57 pesticides were selected based on an overall ranking scheme that included consideration of the 1999 data for active ingredients us e. All herbicides at greater than 5 million lbs/yr and all fungicides and insect icides at greater than 1 million lbs/yr were included as candidate su rrogate chemicals.

OPP assumed that the residue level of the inert ingredient would be no higher than the highest tolerance for a given commodity. Implicit in this assumption is that there would be similar rates of degradation between the active an d inert ingredient (if any) and that the concentration of inert ingredient in the scenarios leading to these hi ghest of tolerances woul d be no higher than the concentration of the active ingredient.

To summarize, the Agency believes the assumptions used to estimate dietary exposures lead to a very conservative assessment of diet ary risk for the following reasons:

• the highest tolerance level from the surroga te pesticides for every food is used;

• 100% crop treated (%CT) is assumed for all cr ops (every food eaten by a person each day has tolerance-level residues);

• many of these high tolerances are based on very short pre-harvest intervals where there is little time for degradation, whereas actual pesticide applications occur throughout the growing season;

• no consideration was given to potential de gradation between harvest and consumption (use of tolerance level residues which are typi cally one to two orders of magnitude higher than actual residues foun d in monitoring data);

• residue values were assigned to every co mmodity in DEEMTM with no consideration given to potential reduction in re sidues from washing or cooking.

Although sufficient information to quantify actual re sidue levels in food is not available, the compounding of these conservative assumptions will lead to a significant exaggeration of actual exposures. OPP does not believe that this appr oach underestimates expos ure in the absence of residue data.

5 Guenther et al, “Endocrine Disrupting Nonylphenols Are Ubiquitous in Food”. Environmental Science & Technology 2002 36 (8), 1676-1680

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 24 of 85 5.4 Analytical Methodology

Since this request is for an exemption from the requirement of a tolerance, an analytical method for enforcement purposes is not re quired to support this action.

5.5 Dietary (Food and Water) Exposure and Risk

The model and inputs used for the alkylphenol ethoxylate inert ingredients dietary risk assessments are described briefly in Section 5.3 and below. A complete description of the dietary exposure and risk assessment is provi ded in the memorandum for a different inert ingredient cluster entitled “Alkyl Amines Polyalkoxylates (Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water) Dietary Exposure and Risk Assessments for the Inerts.” (D361707, S. Piper, 2/25/09).

Chronic aggregate dietary (food and drinking water) exposure and risk assessments were conducted using the Dietary Exposure Evaluati on Model DEEM-FCIDTM, Version 2.03 which uses food consumption data from the U.S. Depa rtment of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998.

5.5.1. Acute Dietary Exposure and Risk

A hazard endpoint for acute exposure to the sulfate and phosphate derivatives of the APE inert ingredients was identified only for females ag es 13-49; no hazard endpoints for acute exposure were identified for any other population group. A conservative screening level assessment was conducted for acute (one-day) dietary (food a nd drinking water) exposure using the highest tolerance level residue for al l food forms, including meat, milk, poultry and eggs, default processing factors for dried commodities and 100% CT. In addition, a defa ult concentration of 100 ppb was assumed for inert ingredient residues in drinking water.

Provided the maximum concentration of the inert i ngredient in the final pesticide formulation is limited to no more than 7% by weight, the ch ronic dietary exposure estimates for food and drinking water are below HED’s level of con cern (<100% cPAD). When limited to no more than 7% of the end-use product, the phosphate and sulfate derivatives of APE inert dietary exposure for food and drinking water is 37% of the cPAD for the females ages 13-49. See Table 5.5.4 below for a summary of results.

5.5.2 Chronic Dietary Exposure and Risk

A conservative screening level assessment was conducted for chronic di etary (food and drinking water) exposure using the highest tolerance leve l residue for all food fo rms, including meat, milk, poultry and eggs, default processing fact ors for dried commodities and 100% CT. In addition, a default concentration of 100 ppb was assumed for inert ingredient residues in drinking water.

Provided the maximum concentration of the inert i ngredient in the final pesticide formulation is limited to no more than 7% by weight, the ch ronic dietary exposure estimates for food and

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 25 of 85 drinking water are below HED’s level of concer n (<100% cPAD) for the U.S. population and all population subgroups. When limited to no more than 7% of the end-use pr oduct, the sulfate and phosphate derivatives of the APE inert dietary exposure for food and drinking water is 29% of the cPAD for the U.S. population and 90% of the cPAD for children 1-2 yrs old, the most highly exposed population subgroup. See Tabl e 5.4.4, below for a summary of results.

5.5.3 Cancer Dietary Exposure and Risk

HED has determined that a quantitative cancer ri sk assessment is not warranted for the APEs; therefore, a cancer dietary expos ure assessment was not performed.

5.5.4. Summary of Dietary Exposure and Risk Assessment Results

The results of the chronic dietary risk assessmen t are shown in the summary table, below. The residue input files and th e dietary exposure detailed results ar e contained in Appendix D of this memorandum.

Table 5.5.4. Summary of Dietary (Food and Drinki ng Water) Exposure and Ri sk for the Alkylphenol Ethoxylates (APE)

Acute Dietary

(95 th Percentile) Chronic Dietary

Population Subgroup Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population 0.02862 29

All Infants (< 1 year old) 0.06153 62

Children 1-2 years old 0.09005 90

Children 3-5 years old 0.06719 67

Children 6-12 years old 0.03748 38

Youth 13-19 years old 0.02149 22

Adults 20-49 years old 0.02191 22

Adults 50+ years old No acute endpoint selected

0.02307 23

Females 13-49 years old 0.05791 37 0.02204 22
The most highly exposed subgroup is bolded

.



### 6.0 Residential (Non-Occupational) Exposure/Risk Characterization

A screening level residential exposure and risk assessment was completed for products containing APE inert ingredients. Details of the assumptions in forming the residential exposure and risk assessment can be found in “ JITF Inert Ingredients. Residential and Occupational Exposure Assessment Algorithms and Assumpti ons Appendix for the Human Health Risk

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 26 of 85 Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, D364751, 5/7/09. A summary of the residential exposure and risk assessme nt is presented below.

The level of concern (LOC) for these risk assessments is an MOE of 1000 based on the standard 10X inter-species and 10X intra-species extrapola tion safety factors, as well as the database uncertainty factor of 10X.

6.1 Residential Handler Exposure

Exposure Scenarios The Agency selected representative scenarios, based on end-use product application methods and labeled application rates. The APE inerts are used in pesticide formulation that may be used in and around the home. These residential pesticide pr oducts are typically formulated as liquids in concentrates or as wettable powde rs. In addition, these inerts ma y be used in pesticide products applied to pets and companion animals as a dust fo rmulation. Lastly, thes e inerts may be present in consumer-type cleaning products used in and around the home. HED conducted an assessment to represent worst-case residential expos ure by assessing:

• APE in pesticide formulations (fungicides/inse cticides/herbicides); (Outdoor Scenarios)

• APE in disinfectant-type uses; (Indoor Scenarios)

• APE in dust pet products; (Pet Product Scenarios)

Based on information provided by the Registration Divison (RD), the APE inerts can be present in cosmetics, personal care products, and consum er cleaning products. Therefore, HED assessed the disinfectant-type products containing the APE inerts using exposure scenarios used by OPP’s Antimicrobials Division to represent wors t-case residential handler exposure.

Mixer/Loader/Applicator High Exposure Outdoor Scenarios : The mixer/loader/applicator high exposure outdoor scenarios use data from the Outdoor Residential Exposure Task Force to represent high exposure ou tdoor residential scenarios:

• Liquid products: Low Pressure Handwand (ORETF data)

• Liquid products: Hose End Sprayer (ORETF data)

• Ready to Use (RTU): Trigger Pump Sprayer Applications (ORETF data)

Exposure Data and Assumptions: A series of assumptions and exposure factors serv ed as the basis for completing the residential handler risk assessments for the APE inerts. Each assumption and factor is detailed below. In addition to these factors, unit exposures were used to calculate risk estimates.

The Agency used assumptions based on the Re sidential Exposure A ssessment Standard Operating Procedures (Residential SOPs). Key assumptions used in this assessment are summarized below.

• The maximum application rate for the inert based on its use in a class of pesticide (herbicide/insecticide/fungicide ) has been assessed for the short-term exposure duration.

• Residential risk assessments are based on high- end estimates of what residential handlers

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 27 of 85 5 gallons formulated pesticide solution*(9 lbs/gallon)*(7% AP E)*(1 part product concentrate/ 10 parts water) = 0.315 lbs APE in formulated pesticide solutions per day 

### (i.e., homeowners) would typically treat. Per HED’s Residential SOPs (1997 & 2001 revision), residential pesticide handlers ar e assumed to mix and apply a volume of 5 gallons of product per day.

• For outdoor pesticide applicati ons, residential handlers are assumed to use a total of 0.315 lbs APE per day. This estimate is based on the following assumptions:

o Five (5) gallons of formulated pesticide solution are assumed to be used per day by a residential handler (Revised Resi dential SOPs Area Treated, February, 2001). Consistent with HED’s residentia l SOPs, the density of the formulated pesticide solution is assumed to be 9 lbs/gallon. The upper bound to the amount of APE iner in the pesticide products is 7%. Therefore, residential exposure assessment assumes 7% APE in any pesticide product formulation. Product concentrates are assumed to be dilu ted at a 1 to 10 ratio with water.

• Residential exposure is assesse d assuming clothing consisting of a short-sleeved shirt, short pants and no gloves or resp iratory protection. This is considered to be typical clothing for a residential pesticide applicator.

• No dermal endpoint was selected from the hazard database for APE; therefore quantitative dermal exposure as sessment was not assessed.

HED believes the duration of exposure for most homeowner applications of home garden and lawn care products is best represented by the shor t-term duration (1 to 30 days). These exposure scenarios include the app lication of herbicides to lawns and insecticides/fungicides to gardens, ornamental plants, or lawns. While these type s of applications may be applied on consecutive days, they are not likely to exceed 30 consecutive application days.

Mixer/Loader/Applicator High Exposure Indoor Scenarios: The mixer/loader/applicator high exposure outd oor scenarios use data from the proprietary Chemical Manufacturers Association (CMA) anti microbial exposure study , and the Pesticide Handlers Exposure Database to represent hi gh exposure indoor resi dential scenarios:

• Liquid Products: Mopping Use (CMA data)

• Liquids Products: Wiping Use (CMA data)

• Aerosol Spray/Trigger pump/Air Deodorization Use (PHED data)

The Agency used assumptions based on met hodology developed by the Anti-Microbial Division (AD) of the Office of Pesticide Programs and th e Residential SOPs to assess exposure and risk from indoor use of household cleaning produc ts containing the APE inerts. Based on information from OPP’s Registration Division (RD), the Agency assumed that the maximum percentage by weight in indoor products would be 3% APE.

Unit Exposure Values : Unit exposure values were taken from the proprietary Chemical Manufacturers Association (CMA) antimicrobial exposure study (USEPA, 1999: DP Barcode D247642) or from the PHED data presented in HED’s Residential SOPs (USEPA, 1997).

“ JITF Inert Ingredients. Residential and Occupational Exposure Assessment Algorithms and

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 28 of 85 1 gallon formulated pesticide solution*(8.34 lbs/gallon)*(3% APE)*(2 oz/ 128 oz dilution factor) = 0.004 lbs APE in formulated pesticide solutions per day

0.13 gallon formulated pesticide solution*(8.34 lbs/gallon)*(3% APE) = 0.033 lbs APE in form ulated pesticide solutions per day 

### Assumptions Appendix for the Human Health Risk Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, D364751, 5/7/09 contains additional information about the disinfectant-type exposure scenarios assessed in this document.

The following key assumptions were used in this assessment:

• For the mopping scenario, the CMA dermal and inhalation unit exposure values for ungloved mopping were used (71.6 mg/lb inert. and 2.38 mg/lb inert, respectively). These values are based on data collected from six replicates moppi ng floors and receiving exposure via contact mopping activites.

• For the wiping scenario, the CMA dermal and inhalation unit exposure values for ungloved wiping were used (2,870 mg/lb inert an d 67.3 mg/lb inert, respectively). These values are based on data collected from six re plicates (dental technicians) who used a finger pump sprayer to apply the product and then wiped surfaces (e.g., fixtures, etc.) with a cloth.

• For aerosol spray, trigger pump and air deodo rization scenarios, the PHED dermal and inhalation unit exposure values are 220 mg/lb in ert and 2.4 mg/lb inert, respectively. The values are based on homeowners applying an aerosol insecticide to baseboards in kitchens and are representative of a handler wearing short pants and a short sleeve shirt, with no gloves.

The quantities handled/treated were estimated based on information from various sources and assumptions.

• For the mopping scenarios, it was assumed that 1 gallon of diluted solution is used by residential handlers. HED assumes that i ndoor products are assumed to have the same density as water (8.34 lbs/gall on). While typical product con centrate directions indicate that 1 oz concentrated pr oduct per 1 gallon of water should be used, HED followed OPP’s Antimicrobial Division’s (AD’s) SOP and assumed a dilution factor of 2 oz concentrated product/128 oz (1 gallon) of water for the residential handler risk assessment to represent heavy-duty cleaning formulations. Based on information from RD, HED assumed that the maximum percentage by weight of APE in indoor products is 3%.

• For the wiping and trigger pump spray scenarios, it was assumed that 0.5 liter (0.13 gal) of ready-to-use (RTU) soluti on is used. For consumer-type products, HED assumed that the maximum percentage by weight of APE in indoor products is 3%.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 29 of 85 • For the aerosol foam spray and air deodorizatio n scenarios, HED assumed that one can of product is used. For the aeros ol spray/trigger pump/air deodorization scenario, HED assumed that a 12 oz net weight product is used (0.094 gallons). HED assumed that the maximum percentage by weight of APE in indoor products is 3%.

Quantitative dermal risk assessments will not be performed for the APE inerts. When potential dermal endpoints are considered in light of an es timated conservative dermal absorption value of 1%, effect levels would be at or above the limit dose. Therefore the Agency concludes that a quantitative dermal risk assessment is not required for the APE inerts.

HED believes the duration of exposure for most homeowner applications of indoor cleaning products is believed to be best represented by th e short-term duration (1 to 30 days) because the different scenarios (i.e. methods of application) are assumed to be episodic, not daily. In addition, residential handlers are assumed to us e different cleaning produ cts with varying active and inert ingredients.

Mixer/Loader/Applicator High Exposure Pet Product Scenarios:

• Pet Dust scenario (Dust application to pets)

According to information provided by RD, produc ts intended for use on pets contain less than 1% APE in the formulation. The relevant products for direct application to pets and companion animals are dust-based. For the residential ha ndler exposure assessment, HED assumed that products associated with the pet use scenarios co ntained 1% APE in products applied directly to pets.

The following key assumptions were used in this assessment:

• For the pet dust scenario, ten percent (0.1) of the inert applied to the pet is available for residential dermal and inhalation exposure during the application process. This assumption is based on the professional judgm ent of the OPP/HED staff and assumed to be an upper-percentile value.

The quantities handled/treated were estimated based on information from various sources and assumptions.

• For the pet dust scenario, it is assumed that the product application rate is 1/3 ounce per 10 pounds of pet treated. The residentia l SOPs specify a 30 pound dog is treated; therefore 1 oz of dust produc t is assumed to be applied to the treated pet.

• HED assumed that the upper bound percentage of APE inert in dust-based pet product is 1%.

No dermal endpoint was selected from the h azard database for APE; therefore quantitative dermal exposure assessment was not assessed.

The duration of exposure for most homeowner applica tions of pet products is believed to be best represented by the short-term duration (1 to 30 days) because typical direct pet treatment products indicate episodic , not daily use.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 30 of 85 Risk Summary For all residential handler scenarios, risk estimat es are not of concern (i .e., MOEs are all greater than 100) for the inhalation route-specific asse ssment. A summary of the results are provided below in Tables 6.1.1, below.

The Agency believes that the handler scenario s assessed represent worse-case exposures and risks resulting from use of indoor and outdoor pesticide products, cleaning products, and pet products containing the APE inerts in residential environments.

Table 6.1.1. Short-term Exposure and Risks for APE Residential Handlers

Exposure Scenario (Formulation/ Application) Application
Rate 1 (lb

inert/ gallon) Quantity Handled/ Treated per day 2 Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure (mg/ lb inert) 3 Dermal
Dose (mg/kg /day) 4 Inhalation
Dose (mg/kg/

day) 5 Baseline Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8

Outdoor Products
Liquids/ Low
Pressure Handwand (ST) (ORETF data) 0.063 lb/gal 5 gallons 38 0.003 NA 0.000014 NA 11,000,000 NA

Liquids/ Hose End Sprayer, Lawn (ST) (ORETF data) 0.063 lb/gal 5 gallons 11 0.017 NA 0.000077 NA 2,000,000 NA

Liquids/ Trigger Sprayer/ Home Garden (ST) (ORETF data) 0.063 lb/gal 5 gallons 54 0.0019 NA 0.0000086 NA 18,000,000 NA

Indoor Products

Indoor hard surface, Mopping (ST) (CMA data) 0.004 lb/gal 1 gallon 71.6 2.38 NA 0.00013 NA 1,100,000 NA

Indoor hard surface, Wiping (ST) (CMA data) 0.25 lb/gal 0.13 gallons 2870 67.3 NA 0.0313 NA 4,800 NA

Indoor hard surface, Aerosol spray (ST) (PHED data) 0.25 lb/gal 0.094 gallons (12 oz) 220 2.4 NA 0.00081 NA 190,000 NA

1 Application rates are based on maximum application rates of products contai ning APE inerts multiplied by 7% for outdoor products and 3% for indoor products to convert from product application rate to inert application rate.

2 Quantity treated daily values are back-cal culated from 5 gallons of product used per day (Revised Residential SOPs 2001) for outdoor products. Indoor products are assumed to be used at 1 ga llon of solution for the mopping scenario, 0.5 L of solution fo r the wiping scenario, and a 12 oz can of spray fo r the aerosol spray/air deodorization scenario.

3 Unit Exposure data sources are identified in the exposure scenario column. All e xposure scenarios assess exposure reflecting applicators wearing short-sleeved shirts an d shorts and no respiratory protection.

4 Daily Dermal Dose = NA

5 Daily Inhalation Dose = (Inhalation Unit Exposure (mg inert / lb inert) * Appli cation Rate (lb /gal) * Quantity handled (gallons/day)) / Body Weight (70 kg)

6 Dermal MOE = NA

7 Inhalation MOE = PoD (NOAEL of 150 mg/kg/ day) / Daily inhalation dose (mg/kg/day)

8 Total MOE = NA; no quantitative dermal exposure assessment.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 31 of 85 Table 6.1.2. Short-term Exposure and Risks fo r APE Residential Handlers for Pet Dust
Products

Exposure Scenario (Formulation) Application
Rate 1 (mg/day) Fraction (F) product available

for exposure Dermal
Dose (mg/kg /day) 2 Daily Inhalation

Dose (mg/kg/day) 3 Baseline Dermal MOE 4 Baseline Inhalation

MOE 5 Total MOE 6

Pet Products

Pet Dust Product (ST) (HED Residential Pet SOP) 284 mg/day 0.1 NA 0.00405 NA 37,000 NA

1 Application rate based on 1 oz app lied, 1% inert in dust formulation.

2 Daily Dermal Dose = NA

3 Daily Inhalation Dose = (Application Rate (mg /day) * F))/ Body Weight (70 kg)

4 Dermal MOE = NA

5 Inhalation MOE = PoD (NOAEL of 150 mg/kg/ day) / Daily inhalation dose (mg/kg/day)

6 Total MOE = NA; no quantitative dermal exposure assessment.



### 6.2 Residential Postapplication Exposure

Exposure Scenarios Residential postapplication exposures result when bystanders, such as children come in contact with the APE inerts in areas where end-use prod ucts have recently been applied (e.g., treated lawns, gardens or recently cleaned surfaces). The Agency selected representative scenarios, based on end-use product applica tion methods and labeled applica tion rates. HED conducted an assessment to represent worst-ca se residential exposure by asse ssing post application exposures and risks from:

• APE in pesticide formulations (fungicides/ inse cticides/ herbicides); (Outdoor Scenarios)

• APE in disinfectant-type uses; (Indoor Scenarios)

• APE in dust pet treatments; (Pet Product Scenarios)

The Agency considers incidental oral (children only ) the primary exposure routes for the APE inerts. The Agency typically also assesses dermal exposure (adults and children) but no quantitative dermal exposure assessment is re quired for APEs since no dermal endpoint was selected from the hazard database. Inhalati on exposures are not typically calculated for postapplication scenarios because inhalation e xposures generally account for a negligible percentage of the overall body bur den for most pesticide chemi cals. Any inhalation exposure through the postapplication route will be less than the inhalation exposures assessed by residential handlers above in sec tion 6.1 which are not of concern.

For all postapplication exposure sc enarios, exposures are assessed at short- and intermediateterm exposure durations because residues may be present on treated lawns, indoor treated surfaces, or on treated pets for lengths of time consistent with short- and intermediate-term exposure. Additionally, residential postapplica tion exposure can occur in commercially treated environments (e.g., schools, child care facilities, hospitals). If the products are used on a routine basis (i.e., daily), exposures may occur over an intermediate-term time duration (30 days – 6 months).

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 32 of 85 Postapplication High End Outdoor Exposure Scenarios

• Hand-to-Mouth activity for toddler s on treated lawns (children)

• Object-to-Mouth activity for toddlers on treated lawns (children)

• Soil ingestion from treated soil (children)

The exposures from these routes and scenarios we re considered individually and were also added together, where appropriate, to determine a total dose for children exposure to treated lawns. Residential postapplication exposure is assessed on the day of applic ation, typically referred to as Day 0.

Exposure Data and Assumptions A series of assumptions and exposure factors serv ed as the basis for completing the residential postapplication risk assessments. The assumptions and factors used in the risk calculations are consistent with current HED policy for comp leting residential exposure assessments (i.e., SOPs for Residential Exposure Asse ssment [1997 and 2001 revision] ).

Exposures to adults/children after contact with treated lawns have been addressed using the latest approaches for this scenario including:

• For child exposure, the mean of median values for male and female 3 year olds was used to estimate exposure (15 kg).

• Based on HED’s Residential SOPs, it was assu med that the surface area used for each hand-to-mouth event is 20 cm 2 

### (based on the surface area of three fingers of a toddler’s hand). For short-term exposures, it is assu med that there were 20 events per hour (90 th 

### percentile, according to the SOP) and for intermediate-term exposures, it was assumed that there were 9.5 event/hour (mean value).

• The exposure time used is 4 hours a day (USEPA, 2000 and 2001).

• The saliva extraction efficiency used is 50% (USEPA, 2000 and 2001).

• Pesticidal products are assumed to contain a maximum of 7% APE by weight in the end use products.

• The relevant application rates for APE contai ning products are derived above in Section 6.1

Postapplication High End Indoor Exposure Scenarios

Standard methodologies base d on HED’s Residential SOPs were used to assess residential postapplication exposure to consumer-type products (e.g., hard surface cleaners).

Based on information provided by RD, HED assumed that the maximum percentage by weight in indoor products would be 3% APE. Based on an ove rall query of products that contain APE, this reflects a high-end concentration.

HED believes the duration of exposure for most homeowner applications of indoor cleaning products is believed to be best represented by th e short-term duration (1 to 30 days) because the different scenarios (i.e. methods of application) are assumed to be episodic, not daily. In addition, homeowners are assumed to use differe nt cleaning products with varying active and inert ingredients. However, intermediate-t erm exposure is assessed for children because

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 33 of 85 disinfectant products are used frequently in sc hools and day care center s where children can spend significant amounts of time. In those en vironments, cleaning products can be used on a daily basis. Also, residues may persist on surfaces to which children can be exposed.

The Agency used assumptions based on the Residential SOPs. The following key assumptions were used in this assessment:

• Toddlers (3 years old) were used to represent the 1 to 6 year old age group and are assumed to weigh 15 kg, the mean of median values for male and female toddlers (USEPA, 2000 and 2001).

• Based on HED’s Residential SOPs, it was assu med that the surface area used for each hand-to-mouth event is 20 cm 2 

### (based on the surface area of three fingers of a toddler’s hand). For short-term exposures, it is assu med that there were 20 events per hour (90 th 

### percentile, according to the SOP) and for intermediate-term exposures, it was assumed that there were 9.5 event/hour (mean value).

• The exposure time was 4 hours a day (USEPA, 2000 and 2001).

• The saliva extraction efficiency was 50% (USEPA, 2000 and 2001).

• No label information was available to represen t the volume of disinfect ant to be used for cleaning surfaces such as floors. It was a ssumed that the diluted treatment solution was applied at a rate of 1 gallon per 1,000 sq. ft.

• The maximum application rate on the product labe ls for application to hard surfaces is 8.34 lbs product/gal, based on the density of water. The amount of product used is assumed to be 0.5 gallons per day at a rate of 1 gallon/1000 ft 2 

### , (i.e., 0.5 gallons for 500 ft 2 

### ). Therefore, the application rate used for the hard surface cleaner scenario in the post application scenario was 3.9x10 -6 

### lbs inert/ft 2 

### [(1 gallon of product used * 8.34 lbs/gallon)/1000 ft 2 

### cleaned = 0.008 lb product/ft 2 

### ); (0.008 lb product/ ft 2 

### * 3% inert in a given disinfectant formulation * 2 oz/128 oz dilution factor= 3.9x10 -6 

### lb/ft 2 

### /per day)] (See Table 6.2: Indoor Cleaning Products).

• No data is available regarding the quantity of solution residue le ft on the floor after treatment. As a conservative measure, it was assumed that 25% of the cleaner remains after the final mopping. This assumption has been used by the AD for other Office of Pesticide Program risk assessments.

• No transferable residue data were available th at could be used to estimate the transfer factor from the floor to skin. Therefore, it is assumed that 10% of the deposition rate is available for dermal transfer (USEPA, 2000 and 2001).

No dermal endpoint was selected from the hazard database for APE inerts; therefore quantitative dermal exposure assessment was not assessed.

Postapplication High End Pet Product Exposure Scenarios Standard methodologies base d on HED’s Residential SOPs were used to assess residential postapplication exposure to pestic idal products used on pets.

Based on information from RD, HED assumed that the upper bound percentage of APE inert in dust-based pet product is 1%.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 34 of 85 Our assessment assumes 28,400 mg of product applie d in each application (1 ounce of dust). For the pet dust scenario, it is assumed that the application rate is 1/ 3 ounce per 10 pounds of pet treated. The residential SOPs specify a 30 pound dog is treated; therefore 1 oz of dust product is assumed to be used.

The residue of pesticidal dust treatments on pets is expected to remain available for transfer and exposures are expected to occur over a short- and intermediate-term time duration (1- 30 days, 30 days – 6 months, respectively).

The Agency used assumptions based on the Residential SOPs. The following key assumptions were used in this assessment:

• Toddlers (3 years old) were used to represent the 1 to 6 year old age group and are assumed to weigh 15 kg, the median for male and female toddlers (USEPA, 2000 and 2001).

• For the pet dust scenario, it is assumed that the application rate is 1/3 ounce per 10 pounds of pet treated. The residential SOPs specify a 30 pound dog is tr eated; therefore 1 oz of dust product is assumed to be used.

• It is assumed that one pet is contacted per day.

• On the day of application, it may be assumed that 20% (0.2) of the maximum application rate is available on the pet’s body and transf erred to the adult/toddler as a dislodgeable residue. This value is believed to be an upper-percentile as sumption (US EPA, 1999 SAP).

• Postapplication activities are assed on the same day that the pesticide is applied because it is assumed that individuals could come in contact with the pe t immediately after application.

• The surface animal of a dog is determined us ing a representative (average) animal, or a medium-sized (30 lb) dog. Estimated risks are based on an even loading of residues across the entire surface of a 30 lb dog, where Surface area (cm 2 

### ) = ((12.3 * (BW (lb)*454)^0.65)) = 2490 cm 2 

### from HED’s 1993 Wildlife Exposure Factors Handbook.

Pet Product Postapplication HTM Exposure Assumptions:

• Based on HED’s Residential SOPs, it was assu med that the surface area used for each hand-to-mouth event is 20 cm 2 

### , representing the surface area of the child’s hands entering the mouth (assumed to be 3 fingers).

• Saliva extraction efficiency is assumed to be 50% (i.e. every time the hand goes in the mouth approximately half of the residues on the hand are removed).

• The approach used to address the hand-to-mouth exposure pathway has been modified since 1999 Draft Policy 13, “Postapplication Exposure Assessment for Children from Treated Pets.” In the revised approach, th e frequency term has been modified to an equilibrium approach analogous to the dermal exposure component (i.e., the frequency = 1 event/day). This approach was revised si nce the data from which the transferable residues concentrations were determined rely on a con tinuous contact (grooming) technique that would lead to concentrations on the hands which are anticipated to be significantly higher than would result from petting/hugging.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 35 of 85 Risks were calculated using the Margin of Exposure (MOE) approach, which compares a toxicological PoD to an exposure estimate. E xposure algorithms and additional information on calculating the risk estimates for residential pos tapplication exposure (ex cept for the residential postapplication hand-to-mouth exposures from pe t dusts described above) can be found in “ JITF Inert Ingredients. Residential and Occupational E xposure Assessment Algorithms and Assumptions Appendix for the Human Health Risk Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, D364751,” 5/7/09.

Risk Summary A summary of the residential pos tapplication exposure and risk estimates are presented in Table 6.2, below. Short- and intermediate-term post a pplication risks for children are not of concern (i.e., the MOEs for the assessed scenarios are greater than 100) fo r both the short- and intermediate-term exposure durations.

Risk Characterization At this time, residue dissipation data or reliable use pattern data are not available, including the frequency and duration of use of antimicrobial products in the re sidential setting. The Agency does not believe that the use patt erns of many residential products result in intermediate-term exposure. However, the Agency notes that inte rmediate-term exposure to children may occur in areas where disinfecting products are used more frequently (i.e., schools and day care centers).

Table 6.2. Residential Postapplication Short- and Intermediate-term Exposures and Risks for APE Exposure Scenario Application Rate 1 

### Exposed Population &

Exposure Duration 2 

### Daily Dose (mg/kg/day) 3 

### MOE 4



### Outdoor Lawn Products
Adult ST NA NA Adult IT NA NA Child ST NA NA Dermal Exposure to Treated Lawns
Child IT NA NA Child ST 0.00471 32,000 Hand-to-Mouth from Treated Lawn Child IT 0.00224 67,000 Child ST Object-to-Mouth from Treated Lawn Child IT 0.00118 130,000

Child ST Soil Ingestion Child IT 1.58E-5 9,500,000

Child ST NA NA Total Lawn Combined Exposures* 0.315 lb/day

Child IT NA NA 

### Indoor Cleaning Product
Child ST Dermal Exposure to Treated Indoor Surface Child IT NA NA

Child ST 0.00255 59,000 Hand-to-Mouth from Treated Indoor Surface 3.9E-6 lb/ft 2

Child IT 0.0012 120,000

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 36 of 85 Table 6.2. Residential Postapplication Short- and Intermediate-term Exposures and Risks for APE Exposure Scenario Application Rate 1 

### Exposed Population &

Exposure Duration 2 

### Daily Dose (mg/kg/day) 3 

### MOE 4

Child ST NA NA Total Surface Combined Exposures* Child IT NA NA



### Pet Product

Adult ST Adult IT NA NA

Child ST Dermal Exposure to Treated Pet
Child IT NA NA

Child ST Hand-to-Mouth from Treated Pet Child IT 0.00632 24,000

Child ST Total Pet Combined Exposures* 284 mg/day

Child IT NA NA

1 Application rates for outdoor products are derived in Section 6. 1 Application rates for indoor and pet products are derived in Section 6.2.

2 ST and IT indicate short- or in termediate-term exposure durations

3 Daily Dose = Daily Dose algorithms for various residential postapplication scenarios outlined in “ JITF Inert Ingredients. Residential and Occupa tional Exposure Assessment Algorithms and Assump tions Appendix for the Human Health Risk Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, D364751, 5/7/09.

4 MOE = PoD (NOAEL of 150 mg/kg/day)/ Daily dose (mg/kg/day)

5 Total Combined Exposures = NA; no qua ntitative derm al exposure assessment.



### 7.0 Aggregate Risk Assessments and Risk Characterization

7.1 Acute Aggregate Risk

Acute aggregate risk includes risks from food an d water only. As shown in Section 5.5.1, acute aggregate risks are not of concern.

7.2 Short-Term/Intermediate- Term Aggregate Risk

Short-term and intermediate-term aggregate ri sk assessments for the APE inert ingredients combine high end residential short- or interm ediate-term exposures with average food and drinking water exposures, and comp are this total to a short- or intermediate term PoD.

The point of departure for the dietary risk asse ssment is 10 mg/kg/day and the LOC is 100 for the APEs. The point of departure for the resident ial risk assessment is 150 mg/kg/day and the LOC is 1000 for the APEs. For the purpose of a ggregating risks from di etary and residential exposure, the Agency is using the ARI (Aggregat e Risk Index) approach for aggregate risk assessment. This approach allows for combining exposures which must be compared to different NOAELs and different LOCs. Potential risks of con cerns are identified by an ARI of less than 1.

Short- and intermediate term residentia l exposures are summarized in Table 7.2.1.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 37 of 85 Table 7.2.1. Short- and Intermediate-Term Resi dential Exposures for the APE Aggregate Risk Calculations

Population Handler MOE 1 

### Postapplication MOE 2 

### Residential Total MOE
Short-Term

Adult Male 4,800
Source: Table 6.1 Indoor hard surface, Wiping (ST) N/A 4,800

Adult Female 4,800
Source: Table 6.1 Indoor hard surface, Wiping (ST) N/A 4,800

Child N/A 24,000
Source: Table 6.2 Pet Product HTM Exposure (IT) 24,000



### Intermediate-Term

Adult Male N/A N/A N/A

Adult Female N/A N/A N/A

Child N/A 24,000
Source: Table 6.2 Pet Product HTM Exposure (IT) 24,000

1 – Handler MOE represents high end inhalation handler expos ure, where the exposure duration is appropriate to assess 2 – Postapplication MOE represents high end incidental oral exposure to outdoor la wn products or indoor cleaning products for the relevant exposure duration



### Short- and intermediate-term aggregate risk s are summarized in Table 7.2.2. Short- and intermediate-term aggregate risks are not of concern for adults or children.

Table 7.2.2 Short-Term and/or Intermediate-T erm Aggregate Risk Calculations for APE 1

Short- or Intermediate-Term Scenario

Population Food &
Water MOE Dietary LOC ARI food &

water Residential MOE Residential LOC ARI Residential Aggregate ARI 2

Short-Term

Adult Male 430 100 4.3 4,800 1,000 4.8 2.3

Adult Female 430 100 4.3 4,800 1,000 4.8 2.3

Child 110 100 1.1 24,000 1,000 24 1.0

Intermediate-Term

Adult Male 430 100 4.3 NA 1,000 N/A 4.3

Adult Female 430 100 4.3 NA 1,000 N/A 4.3

Child 110 100 1.1 24,000 1,000 24 1.0

1 ARI = [MOE CALCULATED /LOC] Aggregate risks of concern are identifiefy by an ARI less than 1. Residential MOEs used in aggregate assessment found in Table 7.2.1. Dietary MOEs = NOAEL/ exposure values in Table 5.5.4.

2 Aggregate ARI = 1/

 [ [(1/

 ARI food & water) + (1

 /ARI residential)]]

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 38 of 85 7.3 Long-Term Aggregate Risk

Long-term aggregate risk includes risks from food and water only. As shown in Section 5.5.2, long-term aggregate risks are not of concern.

7.4 Cancer Risk

The Agency has determined that a quantitative cancer assessment is not required for the APE inert ingredients; therefore, a cancer dietary aggregate exposu re assessment was not performed.

8.0 Occupational Exposure/Risk Pathway

Based on examination of product labels which ma y contain the APE as inert ingredients, HED has determined that exposure to handlers can oc cur in a variety of occupational environments. Details of the occupational e xposure assessment for the APE iner ts can be found in the document

“ JITF Inert Ingredients. Residential and Occupational Exposure Assessment Algorithms and Assumptions Appendix for the Human Health Risk Assessments to Support Proposed Exemption from the Requirement of a Tolerance When Used as Inert Ingredients in Pesticide Formulations”, D364751,” 5/7/09.

The representative occupational scenarios selected by the Agency for assessment were evaluated based on likely maximum application rates for products which may contain the APE inerts for the short-term exposure assessment, and average application rates fo r products likely to contain APE as inerts for the intermediate- and long- term exposure durations. Active ingredient application rates were corrected for the maxi mum amount of APE likely to be in the final formulations to determine exposure a nd risk from exposure to APE grouped by fungicide/insecticide or herbicid e. A summary of the occupati onal assessment is presented below.

The level of concern (LOC) for these risk assessments is an MOE of 100 based on the standard 10X inter and 10X intra species un certainty safety factors.

8.1 Handler Risk

Exposure Scenarios Exposure to pesticide handlers is likely during the occupational us e of pesticides containing the APE inert ingredients. Inhalation exposure wa s estimated using PHED and ORETF data. The quantitative exposure/risk assessment develo ped for occupational handlers to support the requested exemption from the requirement of a tolerance for the APE is based on the following scenarios. HED notes that these scenarios were selected to represent the scenarios with the highest potential exposure.

Mixer/Loader/Applicators: 1) Mixer/Loader for aerial application- high acreage field crops (liquids)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 39 of 85 2) Mixer/Loader for airblast application- tr ee nuts crops (both liquid and wettable powder) 3) Mixer/Loader for groundboom application- hi gh acreage field crops and turf (liquids and wettable powder) 4) Applicators for aerial application- high acreage field crops (liquid) 5) Applicators for airblast- tree nut crops 6) Applicators for groundboom- high acreage field crops and turf 7) Mixer/Loader/Applicator- low pressure ha ndwand (liquids and wettable powders)* 8) High pressure handwand- gr eenhouse (wettable powders) 9) Flagging- high acreage field crops (liquids) * Uses ORETF unit exposure data . All others use PHED data.

Risk estimates were calculated using the Marg in of Exposure (MOE) wh ich is a ratio of the toxicological PoD to the daily dose. Daily dose values are ca lculated by first calculating exposures by considering application parameters (i.e., rate and area tr eated) along with unit exposures. Exposures are then no rmalized by body weight to calculate dose levels. Inhalation short- and intermediate-term exposure is comp ared to the inhalation PoD of 100 mg/kg/day (same PoD for short- and intermediate-term expo sure durations). No dermal endpoint was selected from the hazard database for APE; therefore quantitative dermal exposure assessment was not assessed. To assess handler risks, the Agency used surrogate unit exposure data from the Pesticide Handlers Exposure Data base (PHED), and ORETF data.

The following assumptions and factors were used in order to complete the exposure and risk assessment for occupational handlers/applicators:

• All worker scenarios were assumed to be short- and intermediate-term in exposure durations (i.e., 1-30 days and 1-6 months) except the greenhouse/ hothouse scenario.

• For scenarios where greenhouse/ hothouse applications are pos sible, long-term exposure (6+ months) was assessed. The greenhouse/hothouse scen arios are the non-turf "ornamental" scenarios in Tables 8.1.1, 8.1.2, and 8.1.3

• The exposure assessment assumes an 8 hour work day.

• The maximum application rate per pesticide group (herbicide/insec ticide/fungicide) has been assessed for the short-term exposure duration.

• The average application rate per pesticid e group (herbicide/insect icide/fungicide) has been assessed for the intermediate-term exposure duration.

• A body weight of 70 kg was assumed because th e relevant toxicological PoDs were not gender specific.

• The baseline clothing level for occupational exposure scenarios is c onsidered to be an individual wearing long pants, a long-sleeved shirt, shoes, socks, no chemical-resistant gloves, and no respiratory protection.

• The upper bound to the amount of APE inert in the pesticide pr oducts is 7%. Therefore, the occupational exposure assessment assumes 7% APE in any pesticidal product formulation

Risk Characterization: HED initially assessed handler exposure and risks fo r the APE inerts in fungicides, herbicides and insecticides at baseline PPE (long pants, a long-sleeved shirt, shoes, socks, no chemical-

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 40 of 85 resistant gloves, and no respirator y protection) which HED consider s to be standard agricultural worker clothing.

When handlers are wearing standard worker clothing (i.e., baseline PPE and no respiratory protection) no occupational handler scen ario indicates a risk of concern.

For the mixer/loader/applicator scenarios describe d in the occupational ha ndler tables (below), the ORETF handler studies have no data for ba seline dermal exposure be cause the handlers in the study wore gloves and no resp iratory protection. HED believes baseline exposure is relevant to assess for these exposure scen arios (i.e., baseline dermal PPE and no respiratory protection). Therefore, both ORETF and PHED scenarios are shown in the mixe r/loader/applicator section of the occupational handler tables. Baseline inhala tion MOEs are reported “as is” because ORETF study participants did not wear respiratory pr otection. Additional explanation of the ORETF studies is available in “ JITF Inert Ingredients. Residential and Occupational Exposure Assessment Algorithms and Assumptions Appendix for the Human Health Risk Assessments to Support Proposed Exemption from the Requireme nt of a Tolerance When Used as Inert Ingredients in Pesticide Fo rmulations”, D364751,” 5/7/09.

Table 8.1.1. Exposure and Risks for Occupational Handlers of APE in Herbicide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8



### Mixer/Loader Scenarios

Liquids/ Aerial Application/ High Acreage Crops (ST) 0.728 NA 0.015 NA 10,000 NA

Liquids/ Aerial Application/ High Acreage Crops (IT) 0.14 1200 NA 0.0029 NA 52,000 NA

Liquids/ Airblast/ Nut Tree (ST) 0.504 NA 0.00035 NA 430,000 NA

Liquids/ Airblast/ Nut Tree (IT) 0.224 40 NA 0.00015 NA 980,000 NA

Liquids/ Groundboom/ High Acreage Crops (ST) 0.728 NA 0.0025 NA 60,000 NA

Liquids/ Groundboom/ High Acreage Crops (IT) 0.14 200 NA 0.00048 NA 310,000 NA

Liquids/ Groundboom/ Turf (ST) 0.728 NA 0.0005 NA 300,000 NA

Liquids/ Groundboom/ Turf (IT) 0.14 40 NA 0.0001 NA 1,600,000 NA

Liquids/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.00004 NA 3,500,000 NA

Liquids/ Low Pressure Handwand/ Turf (IT) 0.504 5 2.9 1.2

NA 0.00004 NA 3,500,000 NA

Wettable Powder/ Airblast/ Nut Tree (ST) 0.112 NA 0.00275 NA 55,000 NA

Wettable Powder/ Airblast/ Nut Tree (IT) 0.112 40 NA 0.00275 NA 55,000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (ST) 0.112 NA 0.01376 NA 11,000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (IT) 0.07 200 NA 0.0086 NA 17,000 NA

Wettable Powder/ Groundboom/ Turf (ST) 0.112 NA 0.00275 NA 55,000 NA

Wettable Powder/ Groundboom/ Turf (IT) 0.07 40 3.7 43

NA 0.00172 NA 87,000 NA

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 41 of 85 Table 8.1.1. Exposure and Risks for Occupational Handlers of APE in Herbicide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8

Wettable powder/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.00155 NA 97,000 NA

Wettable powder/ Low Pressure Handwand/ Turf (IT) 0.504 5 NA 0.00155 NA 97,000 NA 

### Applicator Scenarios

Liquid/ Aerial Application/ High Acreage Crops (ST) 9 0.728 NA 0.0008 NA 180,000 NA

Liquid/ Aerial Application/ High Acreage Crops (IT) 9 0.14 1200 Eng control only: 0.0055 Eng control only: 0.068 NA 0.0002 NA 920,000 NA

Airblast/ Nut Tree (ST) 0.112 NA 0.00029 NA 520,000 NA

Airblast/ Nut Tree (IT) 0.112 40 0.36 4.5 NA 0.00029 NA 520,000 NA

Groundboom/ High Acreage Crops (ST) 0.728 NA 0.0015 NA 97,000 NA

Groundboom/ High Acreage Crops (IT) 0.14 200 NA 0.0003 NA 510,000 NA

Groundboom/ Turf (ST) 0.728 NA 0.00031 NA 490,000 NA

Groundboom/ Turf (IT) 0.14 40 0.014 0.74

NA 0.00006 NA 2,500,000 NA 

### Mixer/Loader/Applicator Scenarios

Low Pressure Handwand/ Turf (ORETF data) (ST) 10 0.504 NA 0.00024 NA 630,000 NA

Low Pressure Handwand/ Turf (ORETF data) (IT) 10 0.504 5 No Data 6.6 NA 0.00024 NA 630,000 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (ST) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (IT) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (LT) 10 0.504 5 No Data 1100

NA 0.0396 NA 3,800 NA

Liquid/ Low Pressure Handwand/ Ornamentals (ST) 0.504 NA 0.0011 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (IT) 0.504 NA 0.0011 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (LT) 0.504 5 100 30

NA 0.0011 NA 140,000 NA 

### Flagger Scenarios

Liquid/ Flagger/ High Acreage Crops (ST) 0.728 NA 0.0044 NA 180,000 NA

Liquid/ Flagger/ High Acreage Crops (IT) 0.14 1200 0.011 0.35 NA 0.00084 NA 34,000 NA

1 Application rates are based on maximum application rates of produc ts containing inerts in APE multiplied by 7% to convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 7% in ert APE). Application rat es for Short-term (ST) exposure risk estimates are based on maximu m application rates. Application rates for Intermediate-term (IT) and long-term (LT) exposures are based on average applicati on rates. Baseline Dermal PPE is single layer clothing, no gloves.

2 Area treated daily values are from the EP A HED estimates of acreage tr eated in a single day for each exposure scenario of

concern. 3 Unit Exposure values are reported in PHED Surrogate Exposure Guide dated August 1998 or fro m ORETF data. All exposure scenarios assess baseline dermal PPE plus baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with engineering controls.

4 Daily Dermal Dose = NA

5 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate (lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 42 of 85 6 Dermal MOE = NA

7 ST Inhalation MOE = PoD (NOAEL of 150 mg/kg/ day) / Daily inhala tion dose (mg/kg/day)

8 Total Combined MOE = NA; no quant itative dermal exposure assessment

9 Aerial applicators do not have baseline exposure: only engineerin g control exposure can be assessed.

10 These scenarios have baseline inhalation unit exposures , but not baseline dermal unit expos ures. The M/L/A scenario assessed has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves derma l

exposure.



### Table 8.1.2. Exposure and Risks for Occupational Handlers of APE in Insecticide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8



### Mixer/Loader Scenarios

Liquids/ Aerial Application/ High Acreage Crops (ST) 0.14 NA 0.00288 NA 52,000 NA

Liquids/ Aerial Application/ High Acreage Crops (IT) 0.049 1200 NA 0.001 NA 150,000 NA

Liquids/ Airblast/ Nut Tree (ST) 0.63 NA 0.00043 NA 350,000 NA

Liquids/ Airblast/ Nut Tree (IT) 0.175 40 NA 0.00012 NA 1,300,000 NA

Liquids/ Groundboom/ High Acreage Crops (ST) 0.14 NA 0.00048 NA 310,000 NA

Liquids/ Groundboom/ High Acreage Crops (IT) 0.049 200 NA 0.00017 NA 890,000 NA

Liquids/ Groundboom/ Turf (ST) 0.14 NA 0.0001 NA 1,600,000 NA

Liquids/ Groundboom/ Turf (IT) 0.049 40 NA 0.00003 NA 4,500,000 NA

Liquids/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.00004 NA 3,500,000 NA

Liquids/ Low Pressure Handwand/ Turf (IT) 0.504 5 2.9 1.2

NA 0.00004 NA 3,500,000 NA

Wettable Powder/ Airblast/ Nut Tree (ST) 0.42 NA 0.0103 NA 15,000 NA

Wettable Powder/ Airblast/ Nut Tree (IT) 0.21 40 NA 0.0052 NA 29,000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (ST) 0.112 NA 0.0138 NA 11,000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (IT) 0.049 200 NA 0.006 NA 25,000 NA

Wettable Powder/ Groundboom/ Turf (ST) 0.112 NA 0.0023 NA 55,000 NA

Wettable Powder/ Groundboom/ Turf (IT) 0.049 40 NA 0.0012 NA 120,000 NA

Wettable powder/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.0016 NA 97,000 NA

Wettable powder/ Low Pressure Handwand/ Turf (IT) 0.504 5 3.7 43

NA 0.0016 NA 97,000 NA 

### Applicator Scenarios

Liquid/ Aerial Application/ High Acreage Crops (ST) 9 0.14 NA 0.0002 NA 920,000 NA

Liquid/ Aerial Application/ High Acreage Crops (IT) 9 0.049 1200 Eng control only: 0.0055 Eng control only: 0.068 NA 0.0001 NA 2,600,000 NA

Airblast/ Nut Tree (ST) 0.63 NA 0.0016 NA 93,000 NA

Airblast/ Nut Tree (IT) 0.175 40 0.36 4.5 NA 0.00045 NA 330,000 NA

Groundboom/ High Acreage Crops (ST) 0.14 200 0.014 0.74 NA 0.0003 NA 510,000 NA

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 43 of 85 Table 8.1.2. Exposure and Risks for Occupational Handlers of APE in Insecticide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8

Groundboom/ High Acreage Crops (IT) 0.049 NA 0.0001 NA 1,400,000 NA

Groundboom/ Turf (ST) 0.14 NA 0.00006 NA 2,500,000 NA

Groundboom/ Turf (IT) 0.049 40 NA 0.00002 NA 7,200,000 NA 

### Mixer/Loader/Applicator Scenarios

Low Pressure Handwand/ Turf (ORETF data) (ST) 10 0.504 NA 0.00024 NA 630,000 NA

Low Pressure Handwand/ Turf (ORETF data) (IT) 10 0.504 5 NA 6.6 NA 0.00024 NA 630,000 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (ST) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (IT) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (LT) 10 0.504 5 NA 1100

NA 0.0396 NA 3,800 NA

Liquid/ Low Pressure Handwand/ Ornamentals (ST) 0.504 NA 0.0011 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (IT) 0.504 NA 0.0011 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (LT) 0.504 5 100 30

NA 0.0011 NA 140,000 NA 

### Flagger Scenarios

Liquid/ Flagger/ High Acreage Crops (ST) 0.14 NA 0.00084 NA 180,000 NA

Liquid/ Flagger/ High Acreage Crops (IT) 0.049 1200 0.011 0.35 NA 0.00029 NA 510,000 NA

1 Application rates are based on maximum application rates of produc ts containing inerts in APE multiplied by 7% to convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 7% in ert APE). Application rat es for Short-term (ST) exposure risk estimates are based on maximu m application rates. Application rates for Intermediate-term (IT) and long-term (LT) exposures are based on average applicati on rates. Baseline Dermal PPE is single layer clothing, no gloves.

2 Area treated daily values are from the EP A HED estimates of acreage tr eated in a single day for each exposure scenario of

concern. 3 Unit Exposure values are reported in PHED Surrogate Exposure Guide dated August 1998 or fro m ORETF data. All exposure scenarios assess baseline dermal PPE plus baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with engineering controls.

4 Daily Dermal Dose = NA

5 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate (lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg)

6 Dermal MOE = NA

7 ST Inhalation MOE = PoD (NOAEL of 150 mg/kg/ day) / Daily inhala tion dose (mg/kg/day)

8 Total Combined MOE = NA; no quantitative dermal exposure assessment

9 Aerial applicators do not have baseline exposure: only engineerin g control exposure can be assessed.

10 These scenarios have baseline inhalation unit exposures , but not baseline dermal unit expos ures. The M/L/A scenario assessed has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves derma l

exposure.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 44 of 85 Table 8.1.3. Exposure and Risks for Occupational Handlers of APE in Fungicide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8



### Mixer/Loader Scenarios

Liquids/ Aerial Application/ High Acreage Crops (ST) 0.35 NA 0.0072 NA 21,000 NA

Liquids/ Aerial Application/ High Acreage Crops (IT) 0.049 1200 NA 0.001 NA 150,000 NA

Liquids/ Airblast/ Nut Tree (ST) 0.77 NA 0.00053 NA 280,000 NA

Liquids/ Airblast/ Nut Tree (IT) 0.21 40 NA 0.00014 NA 1,000,000 NA

Liquids/ Groundboom/ High Acreage Crops (ST) 0.35 NA 0.0012 NA 130,000 NA

Liquids/ Groundboom/ High Acreage Crops (IT) 0.049 200 NA 0.00017 NA 890,000 NA

Liquids/ Groundboom/ Turf (ST) 0.35 NA 0.00024 NA 630,000 NA

Liquids/ Groundboom/ Turf (IT) 0.049 40 NA 0.00003 NA 4,500,000 NA

Liquids/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.00004 NA 3,500,000 NA

Liquids/ Low Pressure Handwand/ Turf (IT) 0.504 5 2.9 1.2

NA 0.00004 NA 3,500,000 NA

Wettable Powder/ Airblast/ Nut Tree (ST) 0.49 NA 0.012 NA 12,000 NA

Wettable Powder/ Airblast/ Nut Tree (IT) 0.14 40 NA 0.0034 NA 44,000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (ST) 0.07 NA 0.0086 NA 1,7000 NA

Wettable Powder/ Groundboom/ High Acreage Crops (IT) 0.042 200 NA 0.0052 NA 29,000 NA

Wettable Powder/ Groundboom/ Turf (ST) 0.07 NA 0.0017 NA 87,000 NA

Wettable Powder/ Groundboom/ Turf (IT) 0.042 40 NA 0.00103 NA 150,000 NA

Wettable powder/ Low Pressure Handwand/ Turf (ST) 0.504 NA 0.0016 NA 97,000 NA

Wettable powder/ Low Pressure Handwand/ Turf (IT) 0.504 5 3.7 43

NA 0.0016 NA 97,000 NA 

### Applicator Scenarios

Liquid/ Aerial Application/ High Acreage Crops (ST) 9 0.35 NA 0.0004 NA 370,000 NA

Liquid/ Aerial Application/ High Acreage Crops (IT) 9 0.049 1200 Eng control only: 0.0055 Eng control only: 0.068 NA 0.0001 NA 2,600,000 NA

Airblast/ Nut Tree (ST) 0.49 NA 0.0013 NA 120,000 NA

Airblast/ Nut Tree (IT) 0.21 40 0.36 4.5 NA 0.00054 NA 280,000 NA

Groundboom/ High Acreage Crops (ST) 0.35 NA 0.00074 NA 200,000 NA

Groundboom/ High Acreage Crops (IT) 0.049 200 NA 0.0001 NA 1,400,000 NA

Groundboom/ Turf (ST) 0.35 NA 0.00015 NA 1,000,000 NA

Groundboom/ Turf (IT) 0.049 40 0.014 0.74

NA 0.00002 NA 7,200,000 NA 

### Mixer/Loader/Applicator Scenarios

Low Pressure Handwand/ Turf (ORETF data) (ST) 10 0.504 NA 0.00024 NA 630,000 NA

Low Pressure Handwand/ 0.504 5 No Data 6.6 NA 0.00024 NA 630,000 NA

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 45 of 85 Table 8.1.3. Exposure and Risks for Occupational Handlers of APE in Fungicide Products (All Exposure Durations) at Baseline Dermal PPE

Exposure Scenario

(Formulation/ Application/ Crop) Application
Rate 1 (lb inert/ A) Area Treated Daily 2 (acres) Dermal Unit Exposure

(mg/lb inert) 3 Inhalation Unit Exposure

(ug/ lb inert) 3 Baseline
Dermal

Dose (mg/kg /day) 4 Baseline Inhalation

Dose (mg/kg/

day) 5 Baseline
Dermal MOE 6 Baseline Inhalation

MOE 7 Total MOE 8

Turf (ORETF data) (IT) 10
Wettable Powder/ Low Pressure Handwand/ Ornamentals (ST) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (IT) 10 0.504 NA 0.0396 NA 3,800 NA

Wettable Powder/ Low Pressure Handwand/ Ornamentals (LT) 10 0.504 5 No Data 1100

NA 0.0396 NA 3,800 NA

Liquid/ Low Pressure Handwand/ Ornamentals (ST) 0.504 NA 0.001 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (IT) 0.504 NA 0.001 NA 140,000 NA

Liquid/ Low Pressure Handwand/ Ornamentals (LT) 0.504 5 100 30

NA 0.001 NA 140,000 NA 

### Flagger Scenarios

Liquid/ Flagger/ High Acreage Crops (ST) 0.35 NA 0.0021 NA 71,000 NA

Liquid/ Flagger/ High Acreage Crops (IT) 0.049 1200 0.011 0.35 NA 0.00029 NA 510,000 NA

1 Application rates are based on maximum application rates of produc ts containing inerts in APE multiplied by 7% to convert to application rate of just inert in a product (Pesticide products assumed to contain a maximum of 7% in ert APE). Application rat es for Short-term (ST) exposure risk estimates are based on maximu m application rates. Application rates for Intermediate-term (IT) and long-term (LT) exposures are based on average applicati on rates. Baseline Dermal PPE is single layer clothing, no gloves.

2 Area treated daily values are from the EP A HED estimates of acreage tr eated in a single day for each exposure scenario of

concern. 3 Unit Exposure values are reported in PHED Surrogate Exposure Guide dated August 1998 or fro m ORETF data. All exposure scenarios assess baseline dermal PPE plus baseline inhalation exposure except for aerial applicator scenarios, which assess inhalation and dermal exposures with engineering controls.

4 Daily Dermal Dose = NA

5 Daily Inhalation Dose = (Inhalation Unit Exposure (μg inert / lb inert) * Conversion Factor (1 mg /1000 μg) * Application Rate (lb inert /A) * Area Treated (A /day)) / Body Weight (70 kg)

6 Dermal MOE = NA

7 ST Inhalation MOE = PoD (NOAEL of 150 mg/kg/ day) / Daily inhala tion dose (mg/kg/day)

8 Total Combined MOE = NA; no quant itative dermal exposure assessment

9 Aerial applicators do not have baseline exposure: only engineerin g control exposure can be assessed.

10 These scenarios have baseline inhalation unit exposures , but not baseline dermal unit expos ures. The M/L/A scenario assessed has a higher unit exposure at baseline dermal exposure than either of the two scenarios shown at baseline PPE plus gloves derma l

exposure.



### 8.2 Occupational Postapplication Risk

HED uses the term postapplication to describe ex posures that occur when individuals are present in an occupational enviro nment that has been previously treate d with a pesticide (also referred to as re-entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including ac tivities related to crop producti on, such as scouting for pests or harvesting. Postapplication e xposure levels vary over time and depend on such things as the type of activity, the nature of the crop or target that was trea ted, the type of pesticide application,

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 46 of 85 and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for postapplication exposure.

Inhalation exposures are not typically calculated for postapplication scenarios because inhalation exposures generally account for a negligible percentage of the overa ll body burden for most pesticide chemicals. This is particularly true fo r chemicals with a low vapor pressure such as the APEs (1.79E-011 to 5.55E-43 mmHg at 25°C). The exposures typically considered for occupational post-application workers result from dermal contact with treated plants which occurs as workers engage in various job task s such as harvesting. Occupational postapplication exposures were not assessed for the APEs because no dermal hazard was identified.

9.0 Environmental Justice

Potential areas of environmental ju stice concerns, to the extent possi ble, were considered in this human health risk assessment, in accordance w ith U.S. Executive Order 12898, "Federal Actions to Address Environmental Just ice in Minority Populations an d Low-Income Populations," http://www.eh.doe.gov/oepa/ guidance/justice/eo12898.pdf ).

As a part of every pesticide risk assessment , OPP considers a large variety of consumer subgroups according to well-esta blished procedures. In line with OPP policy, HED estimates risks to population subgroups fr om pesticide exposures that ar e based on patterns of that subgroup’s food and water consumption, and activ ities in and around the home that involve pesticide use in a residential se tting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered fo od uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess di etary exposure to smaller, specialized subgroups and exposure assessments are performed when c onditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of pesticide products and associated risks for adult applicators and for t oddlers, youths, and adults enteri ng or playing on treated areas postapplication are evaluated. Further considerat ions are currently in development as OPP has committed resources and expertise to the developm ent of specialized software and models that consider exposure to bystanders and farm worker s as well as lifestyle and traditional dietary patterns among specific subgroups.

10.0 Human Studies

This assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide. These stud ies, listed below, have received the appropriate ethical review for use in risk assessment.

The PHED Task Force, 1998. The Pestic ide Handler Exposure Database (PHED), Version 1.1. Task Force members: Health Canada, U.S. Environmental Protection

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 47 of 85 Agency, the California Department of Pe sticide regulation, and the American Crop Protection Association; released August 1998.

ORETF Handler Studies (MRID 44972201): Ou tdoor Residential Exposure Task

Chemical Manufacturers Association (CMA ) antimicrobial exposure study (USEPA, 1999: DP Barcode D247642)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 48 of 85 APPENDIX A. Toxicity Data

Table A.1. Acute Toxicity Profile of Alkylphenol Ethoxylates (APE)

Guideline No. Study Type MRIDs # Results Toxicity Category



### 81-1 Acute Oral –

rat JITF Cluster Support Team 5, 10/31/08 CAS 9002-93-1
LD50 = 500 mg/kg (males) II

81-1 Acute Oral –

rat JITF Cluster Support Team 5, 10/31/08 CAS 9036-19-5
LD50 = 16000 mg/kg IV

81-2 Acute Dermal JITF Cluster Support Team 5, 10/31/08 CAS 9002-93-1
LD50 = 8000 mg/kg
LD50 = 12,300 mg/kg IV

81-2 Acute Dermal JITF Cluster Support Team 5, 10/31/08 CAS 9036-19-5
LD50 = 4490 mg/kg III

81-5 Dermal Irritation JITF Cluster Support Team 5, 10/31/08 Mild to moderate skin irritation III

Table A.2 Acute Toxicity Profil e of Octyl Phenol (OP)

Guideline
No. Study Type MRIDs # Results Toxicity Category



### 81-1
(OECD

401) Acute Oral

rat JITF Cluster Support Team 5,

April 15, 2009 CAS 140-66-9
LD50 >2000 mg/kg III

81-1 Acute Dermal rabbit JITF Cluster Support Team 5,

April 15, 2009 CAS 140-66-9
LD50 = 1880 mg/kg II

81-3 Acute Inhalation rat JITF Cluster Support Team 5,

April 15, 2009 CAS 140-66-9
LC100 (24 hrs) ≤ 116 mg/L IV

81-4 Eye Irritation JITF Cluster Support Team 5,

April 15, 2009 Severe eye irritation I

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 49 of 85 Table A.2 Acute Toxicity Profil e of Octyl Phenol (OP)

Guideline No. Study Type MRIDs # Results Toxicity Category



### 81-5 Dermal Irritation JITF Cluster Support Team 5,

April 15, 2009 Mild skin irritation IV

Table A.3. Toxicology Profile of th e Alkylphenol Ethoxylates (APE)

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

OECD 422 ReproductionDevelopmental Screen in rats (MRID 47585801)
Octylphenoxy poly(ethyleneoxy)ethanol, branched

CAS 9002-93-1 MRID 47585801 (2008)
0, 50, 150, 300 mg/kg/day
(Purity 99.5%)

Acceptable/guideline Parental NOAEL= 150 mg/kg/day Parental LOAEL = 300 mg/kg/da y, based on clinical signs (pushing head through bedding after dosing), decreased body-weight gain in both sexes during the premating period, decreased thymus weight in females, increased liver weight in males, and increased incidence of centrilobular hepatocyte hypertrophy in males

Developmental toxicity NOAEL = 150 mg/kg/day Developmental toxicity LOAE L = 300 mg/kg/day based on decreased pup weight in both sexes.

Reproductive toxicity NOAEL = 300 mg/kg/day Rat Developmental Study (GD 6-17)
Octylphenoxy poly(ethyleneoxy)ethanol,
branched

CAS 9002-93-1 Hazelden, KP and Wilson, JA (1986).

0.06 or 0.3% in diet
(70 and 340 mg/kg/day) NOAEL= 70 mg/kg/day LOAEL- 340 mg/kg/day, based on skeletal abnormalities in pups (supernumerary ribs and enhanced ossification)



### Table A.4. Toxicology Profil e for the Octylphenol (OP)

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 50 of 85 Table A.4. Toxicology Profil e for the Octylphenol (OP)

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results 870.3800 2-generation reproduction study –
rat

Octylphenol

CAS 140-66-9 Tyl, et al. (1999) Regul. Toxicol. Pharmacol. 30, 81- 95. Purity: 90.2% 0, 0.2, 20, 200, or 2000 ppm

ranges: OP intake, depending on age and sex 0.2 ppm = 0.011-0.034 mg/kg/day 20 ppm = 1.05-3.3 mg/kg/day 200 ppm = 10.9-32.6 mg/kg/day 2000 ppm = 111-369 mg/kg/day Systemic/postnatal toxicity NOAEL = 10 mg/kg/day Systemic/postnatal toxicity LOAEL = 111 mg/kg/day, based on decreased body weights in adults and during the latter portion of lactation in offspring and minor delays in acquisition of vaginal opening and preputial separation.

Reproductive toxicity NOAEL = 111 mg/kg/day

No effects on reproductive parameters, testes, prostate, or ovary weights or morphology, on sperm counts, motility, morphology, production, or on estrous cyclicity; Non-guideline

4-tert-octylphenol

maintenance of pregnancy rats. Harazono, A and Ema, M (2001). Toxicology Letters 119: 79-84. Dams dosed on GD 0-8 (sacrificed on GD 20)

0, 15.6, 31.3, 62.5, 125 mg/kg/day gavage (olive oil) NOAEL = 15.6 mg/kg/day LOAEL = 31.3 mg/kg/day, based on increased incidence of post-implantation loss, decreased BWG and FC pregnancy rate not affected

Non-guideline

p-octylphenol Nagao, T; Yishimura, S; Saito, Y; et al. (2001). Reproductive Toxicology 15: 683-692.

(96%) 12.5, 25, 50, 100 mg/kg/day PND 1-5 gavage (corn oil) NOAEL = 25 mg/kg/day, based on LOAEL = 50 mg/kg/day, based on slight delays in acquisition of puberty in males and females, slight ↓ BW; ↓ viability; deaths during PND 1-6: 2 ♀ 50 mg/kg/day; 5 ♀ /6 ♂ 100 mg/kg/day; no deaths in control , 12.5 and 25 mg/kg/day no dysfunction of reproductive performance (mating, fertility) in male or female; no disruption of development or reproductive tract @ 100 mg/kg/day Non-guideline

4-tert-octylphenol

female prepubertal rats dosed on days 21- 35 and monitored daily for vaginal opening, evaluation of estrous cyclicity

3-day uterotrophic

assay Laws, et al. (2000). Toxicological Sciences 54, 154-167.

(97%)

0, 50, 100, 200 mg/kg/day gavage (corn oil)

0, 50, 100, 200, 400 mg/kg/day once/day for 3 days (oral gavage or sc) ↑ uterine wt @ 100-400 mg/kg/day (both groups) vaginal opening accelerated by about 3.2 days @ 200 mg/kg/day decreased # of 4- and 5-day cycles @ 200 mg/kg/day increased # days in diestrus @ 200 mg/kg/day

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 51 of 85 Table A.5. Octylphenol Mutagenicity Studies Study Type Citation/Year/Doses Results Ames test/Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538/ no data (±S9) Directive 84/449/EEC (GLP) Huels Report # AM-91/11, 1991 0-5000 μg/plate p-octylphenol (95%) DMSO Genotoxic effect : negative

Ames test/Salmonella typhimurium TA98, TA100, TA1535, TA1537,
±S9 Ames, et al. Mutat Research 31: 347-364, 1982 (not GLP) Bayer report # 11209, 1982 EPA/OPTS Public File 878213505; microfiche # 0205841 0-12500 μg/plate 95% isooctylphenol,(containing 93.1% poctylphenol) ethanol Genotoxic effect : negative

Bacterial gene mutation study/Salmonella typhimurium TA98, TA100, TA1535, TA1537 and E.coli WP2 uvrA
±S9 Guidelines for Screening Mutagenicity Testing of Chemicals (Japan, 1994) (GLP) Chemical Investigation Promoting Committee Toxicity Testing Reports of Environmental Chemicals, Volume 1, 1994. S. typhimurium 0, 1.56, 3.13, 6.25, 12.5, 25, 100, 200 μg/plate E. coli 0, 125, 250, 500, 1000, 2000 μg/plate p-tert-octylphenol (>97%) vehicle: no data Cytotoxicity : +S9: 200 μg/plate; -S9: 25 μg/plate Genotoxic effects : E. coli and S. typhimurium: negative ±S9

Chromosomal Aberration/ Chinese
hamster CHL cells
±S9 Guidelines for Screening Mutagenicity Testing of Chemicals (Japan, 1994) (GLP) -S9: 0, 0.004, 0.008, 0.016 mg/mL +S9: 0, 0.010, 0.020, 0.040 mg/mL p-tert-octylphenol (>97%) vehicle: no data Cytotoxicity : +S9: >0.04 mg/mL; -S9: >0.16 mg/mL Genotoxic effects : negative ±S9

His+ revertant assay with use of Salmonella thyphimurim TA98 and TA100 Standard plate incorporation: Maron & Ames, 1983 Boyacioglu, M. et al., 2007. EU L. Fisheries & Aquatic Sciences 24, 299-302 10, 20, 40, 80, 160 μg/L octylphenol

DMSO Mutagenicity observed at 40 μg/L in TA 98 strains; 20 μg/L with TA 100 strain without metabolic activation

in vivo genotoxic effects (rat) using single-cell gel electrophoresis (comet assay) Ulutas, et al., 2009 abstract – Toxicology Letters 1895: 557- S273 125, 250 mg/kg/ day (30 days) 4-tert-octylphenol Tail length and tail moment foun d significantly different at 250 mg/kg/day; not at 125 mg/kg/day

study for genotoxicity in CHO-K1 cells using sister-chromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays Tayama, S. et al., 2008.
Mutation Research 649: 114-

125 OP : 0, 0.025, 0.05, 0.075, 0.1, 0.125, 0.15 mM 4-octylphenol (>97%) DMSO Octylphenol caused DNA migration in comet a ssay and induced high incidence of SCE; results suggest octylphenol causes repairable DNA damage, including SCEs; does not re sult in chromosome aberration (CA).

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 52 of 85 Table A.5. Octylphenol Mutagenicity Studies Study Type Citation/Year/Doses Results Chinese hamster lung (CHL/IU) cells OECD HPV testing program ±S9 5 mg/mL or 10 mM p-tert-octylphenol (CAS 140-66-9) DMSO Structural chromosomal aberration and polyploidy cells were not induced at doses manifesting 50% or less than 50% cytotoxicity (or at 5 mg/mL or 10 mM)

Ethoxylated Octylphenol Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 GLP Lawlor,TE, Haworth, L (1989). Mutagenicity Test on C-1358 in the Ames Salmonella/Microsome Reverse Mutation Assay. Hazleton Laboratories America, Inc. Study No. 10882-0-4-1. (EPA/OTS Doc# 86960000404S) 0, 5, 10, 25, 50, 100, 150 μL/plate C-1358 (mixture of 3 components, A, B, C) (deionized water) CAS 9036-19-5 Caused reproducible positive increas es in mean number of TA1535 revertants per plate in both presen ce (3.7 and 4.4-fold) and absence (5.0 and 2.9-fold) of S-9

I n Vitro Cytogenicity Assay Measuring Chromosome Aberration Frequencies in Chinese Hamster Ovary (CHO) Cells. ±S9 GLP Galloway, SM and Brusick, DJ. (1981). Mutagenicity Evaluation of C-213 in an I n Vitro Cytogenicity Assay Measuring Chromosome Aberration Frequencies in Chinese Hamster Ovary (CHO) Cells. Litton Bionetics, Inc. Project No. 20990. (EPA/OTS Doc# 86960000410S) -S9: 0, 0.456, 0.683, 0.911, 1.139, 1.367 μL/mL

+S9: 0, 0.24, 0.49, 0.98, 1.46*, 1.95* μL/mL (*cytotoxic) repeat +S: 0.91, 1.14, 1.37, 1.60, 1.82 μL/mL C-213 CAS 9036-19-5 Caused significant increase in chromosome aberrations both with and without metabolic activation; considered clearly positive

Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 GLP DeGraff WG and Brusick, DJ (1983). Mutagenicity Evaluation of C-445 (Ingredients A, G, J, K, L) in the Ames Salmonella/ Microsome Plate Test. Litton Bionetics, Inc. Project No. 20988. ( EPA/OTS Doc# 86960000419S) 0, 1, 5, 10, 25, 50, 100, 150 μL/plate

C-445 (ingredients A, G, J. K. And L); CAS 9036-19-5 Exhibited genetic activity in st rains TA-1535 and TA-100 with and without S9 and was considered mutagenic

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 53 of 85 Table A.5. Octylphenol Mutagenicity Studies Study Type Citation/Year/Doses Results Mouse lymphoma forward mutation assay (L5178Y TK+/-) ±S9
GLP Cifone, MA and Myhr, BC. (1983). Mutagenicity Evaluation of C-445 in the Mouse Lymphoma Forward Mutation Assay. Litton Bionetics, Inc. Project No. 20989. (EPA/OTS Doc# 86960000422S) -S9: 0, 3.91, 7.81, 15.6, 31.3, 62.5 nL/mL +S9: 0, 15.6, 31.3, 62.5, 125, 250, 600 nL/mL C-445; CAS 9036-19-5 Induced significant increases in the mutant frequency at the TK locus in L5178Y mouse lymphoma cells; considered active in the mouse lymphoma forward mutation assay with and without metabolic activation

Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 GLP Lawlor,TE, Valentine, DC. (1989). Mutagenicity Test on C-1358 in the Ames Salmonella/Microsome Reverse Mutation Assay. Hazleton Laboratories America, Inc. Study No. 10985-0-401. (EPA/OTS Doc# 86960000420S)

0, 1, 5, 10, 25, 50, 100, 150 μL/plate C-1008; CAS 9036-19-5 Did not cause a positive increase in the number of histidine revertants per plate of any of the te ster strains with or without S9

Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 GLP Jagannath, DR and Myhr, BC (1986). Mutagenicity Evaluation of C-1008 Batch No. 26050 in the Ames Salmonella/Microsome Reverse Mutation Assay. Hazleton Laboratories America, Inc. Project No. 20988. (EPA/OTS Doc# 86960000415S) 0, 1, 5, 10, 25, 50, 100, 150 μL/plate C-233; CAS 9036-19-5 Did not exhibit mutagenic activ ity in these assays (±S9)

Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 Jagannath, DR and Brusick, DJ (1981). Mutagenicity Evaluation of C-233 in the Ames Salmonella/ Microsome Reverse Mutation Assay. Litton Bionetics, Inc. Project No. 20988. (EPA/OTS Doc# 86960000414S) 0, 1, 5, 10, 25, 50, 100, 150 μL/plate C-233; CAS 9036-19-5 Did not exhibit mutagenic activ ity in these assays (±S9)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 54 of 85 Table A.5. Octylphenol Mutagenicity Studies Study Type Citation/Year/Doses Results Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 DeGraff WG and Brusick, DJ (1983). Mutagenicity Evaluation of C-449 in the Ames Salmonella/ Microsome Spot Test. Litton Bionetics, Inc. Project No. 20988. ( EPA/OTS Doc# 86960000421S) One 5 cm strand of test material /plate C-449 (glossy white fibers) CAS 9036-19-5 Did not exhibit mutagenic activ ity in these assays (±S9)

in vitro HeLa cell assay MSDS/JITF CST 5 21mg/L CAS 9002-93-1 Positive in an in vitro HeLa cell assay at 20 mg/L;

Table A.6 Acute Toxicity Profile of Nonylphenol Etho xylate (NPE) Phosphate and Sulfate Derivatives - CST 9

Guideline No. Study Type MRIDs # Results Toxicity Category

81-1 Acute Oral – rat No MRID NPE phosphates CAS 68 412-53-3 (ester, branched) LD50 = 4450 mg/kg CAS 68954-84-7 (Na salt, branched) LD50 = 5.7 mL/kg (5700 mg/kg) CAS 68584-47-4 (K salt, branched) LD50 > 4000 mg/kg CAS 51811-79-1 (linear NPE phosphate ) LD50 >500-5000 mg/kg III

IV

III

III

81-1 Acute Oral – rat No MRID NPE sulfates CAS 9014-90-8 (linear Na salt)
LD 50 = 10000 mg/kg CAS 68649-55-8 (branched ammonium salt) LD50 = 29328 mg/kg IV

IV

81-2 Acute Dermal -rabbit No MRID CAS 68649-55-8 (branched ammonium salt) LD50 = 4400 mg/kg III

81-3 Acute Inhalation - rat No data

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 55 of 85 Table A.6 Acute Toxicity Profile of Nonylphenol Etho xylate (NPE) Phosphate and Sulfate Derivatives - CST 9

Guideline No. Study Type MRIDs # Results Toxicity Category

81-4 Primary Eye Irritation

Rabbit No MRID CAS 68412-53-3 (ester, branched) Severely irritating CAS 68954-84-7 (Na salt, branched) Severely irritating CAS 68584-47-4 (K salt, branched) Severe eye irritant CAS 51811-79-1 (linear NPE phosphate ) Severely irritating CAS 68649-55-8 (branched ammonium salt) Severely irritating I

I

I

I

I

81-5 Primary Skin Irritation – rabbit No MRID CAS 68412-53-3 (ester, branched) corrosive CAS 68954-84-7 (Na salt, branched) Severely irritating CAS 68584-47-4 (K salt, branched) Skin irritant CAS 68649-55-8 (branched ammonium salt) Severely irritating I

I

I

I

81-6 Dermal Sensitization No data

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 56 of 85 Table A.7: Toxicology Profile of Nonylphenol Ethoxylate (NPE) Phosphate and Sulfate Derivatives - CST 9

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

OECD 422 (870.3650) Combined repeated dose toxicity study w/ a reproduction/developmental toxicity screening test - rats [HanRcc:WIST (SPF)] MRID 47603701 (2008)

0, 100, 300 or 1000 mg/kg bw/day (actual doses: 0, 132, 396 and 1321 mg/kg/day due to the misapplication of a correction factor of 1.39) (gavage)
95% inert males dosed for 28 days (14 days premating/14 days post mating); females dosed for 14 days prior to mating, through gestation until offspring reached PND 4

CAS 68412-53-3 ( polyoxyethylene nonylphenyl ether, branched, phosphate Acceptable/guideline Parental systemic NOAEL = 100 mg/kg/day. Parental systemic LOAEL = 300 mg/kg/day, based on clinical signs [pushing head through bedding (both sexes; throughout study), soft feces (females; mating and gestation periods)], decreased food consumption and decreased body weight gain in males and females during the pre-mating period.

Developmental toxicity NOAEL = 300 mg/kg bw/day in males and females. Developmental toxicity LOAEL = 1000 mg/kg bw/day, based on decreased body weight and body-weight gain in the offspring (both sexes).

At 1000 mg/kg/day, the viability index was decreased (93% of control) slightly, but the number of litters affected at 1000 mg/kg/day was not significantly increased compared to the control (2 vs 1).

Reproductive toxicity NOAEL = 1000 mg/kg/day

OECD 422 (870.3650) Combined repeated dose toxicity study w/ a reproduction/developmental toxicity screening test - rats [HanRcc:WIST (SPF)] MRID 47693702 (2008) 0, 100, 300, or 1000 mg/kg/day (gavage)

males dosed for 28 days (14 days premating/14 days post mating); females dosed for 14 days prior to mating, through gestation until offspring reached PND 4

CAS 9014-90-8

(sodium nonylphenol
etho xylate sulfate

(30.76% purity) acceptable/nonguideline Parental systemic NOAEL = 300 mg/kg/day.
Parental s y stemic LOAEL = 1000 m g /k g /da y , based on mortality, clinical si g ns (soft feces, si g ns of discomfort),
decreased bod y wei g ht g ain, liver toxicit y , and lesions in the

non g landular stomach in both sexes and decreased bod y temperature and locomotor activit y , hematolo g ic effects, and kidney lesions in females.

Developmental toxicity NOAEL = 300 mg/kg/day. Developmental toxicity LOAEL = 1000 mg/kg/day, based on a reduction in the birth index, increased post-implantation loss, decreased number of live pups/litter at birth, increased number of dead pups and litters with dead pups, decreased viability index, and decreased pup body weight and bodyweight gain.

Reproductive toxicity NOAEL = 1000 mg/kg/day Reproductive toxicity LOAEL = not attained.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 57 of 85 Table A.7: Toxicology Profile of Nonylphenol Ethoxylate (NPE) Phosphate and Sulfate Derivatives - CST 9

Guideline No./ Study Type MRID No. (year)/ Classification /Doses Results

870.5100

Bacterial reverse mutation

test 870.5100 No MRID strains TA1535, TA1537, TA98 and TA100 of Salmonella typhimurium 0, 40, 200, 1000, 5000, or 25000

μ g/plate with and without S9 activation Negative without S9 all strains; negative with S9 in TA1535, TA 1537, and TA 100; TA98, 30% revertants @ two highest doses with marked toxicity at highest dose

cited in JITF Cluster 9 Support Team petition

Table A.8: Toxicology Profile of Nonylphenol (CAS 25154-52-3 and 84852-15-3)

Study Type Citation (year)/Doses Results
870.3800 2-generation reproduction study – rat
branched 4-nonylphenol

CAS# 84852-15-3 Chapin, et al. (1999). Toxicological Sciences 52, 80- 91. 200, 650, 2000 ppm in diet (NIH-07 feed)

F0 pairs consumed NP for 6 weeks prior to mating calculated doses: 9-35; 30- 100; 100-350 mg/kg/day NOAEL (offspring/developmental) = 9 mg/kg/day LOAEL (offsprin g /developmental) = 30 m g /k g /da y , based on early onset of puberty in female offspring

NOAEL (reproductive toxicity) = 100 mg/kg/day (HDT)

NOAEL (systemic) = not attained LOAEL (systemic) = 9 mg/kg/day, based on increased incidence of kidney lesions (tubular mineralization and dilatation, medullary cysts, hydronephrosis) in male rats.

870.3800 2-generation reproduction study – rat
nonylphenol

CAS 25154-52-3 Nagao, et al. (2001). Reproductive Toxicology 15, 293-315. 99% pure 0, 2, 10, or 50 mg/kg/day gavage; corn oil
F0 males dosed for 12 weeks/F0 females dosed for 2 weeks prior to mating Parental systemic NOAEL = 10 mg/kg/day.
Parental s y stemic LOAEL = 50 m g /k g /da y , based on increased liver, kidney, and pituitar y wei g hts in males, decreased thymus weight ( ↓ 24%) in males, decreased ovar y weight ( ↓ 18%) in females, increase in TSH levels (males), centrilobular hepatocyte hy pertrophy in both sexes

Developmental toxicity NOAEL = 10 mg/kg/day. Developmental toxicity LOAEL = 50 mg/kg/day, based on significant decreases in the # implantation sites in F1 females and live F2 pups/litter, vaginal opening was accelerated (F1). No effect on the timin g of preputial separation. No adverse changes in behavior or learning in offspring @ 250 mg/kg/day, ↓ testosterone, ↑ FSH, TSH, T3 (males) Reproductive toxicity NOAEL = 50 mg/kg/day (HDT)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 58 of 85 Table A.8: Toxicology Profile of Nonylphenol (CAS 25154-52-3 and 84852-15-3)

Study Type Citation (year)/Doses Results

870.3800 2-generation reproduction study – rat
para-nonylphenyl

CAS 84852-15-3 Tyl, et al. (2006). Toxicological Sciences 92(1), 295-310

94.25% purity 0, 20 200, 650, or 2000 ppm in Purina 5002 diet

0 or 650 ppm in NIH-07 diet

≈ 0, 1.5, 15, 50, 150, mg/kg/day Developmental toxicity NOAEL = 650 ppm (50 mg/kg/day). Developmental toxicity LOAEL = 2000 ppm (150 mg/kg/day), based on decreased pup body weight on PND 21 ( ↓ 16, 11, 8% in F1, F2, F3, respectively) and d ecreased absolute and relative ovary weight (all generations). Offspring: pup survival not affected (PND 4 and weaning); # live pups, sex ratio, pup BW PND 4 comparable among groups; PND 21 BW (litter basis) @ 2000 ppm ↓ 16%, 11%, 8% (F1, F2, F3); male pup BW @ sacrifice on PND 21 18%, 12%, 9% (F1, F2, F3)

(acquisition of VO and PPS not assessed; AGD and estrous cyclicity not assessed)

Parental systemic NOAEL = 200 ppm (15 mg/kg/day). Parental systemic LOAEL = 650 ppm (50 mg/kg/day), based on increased kidney weights and kidney histopathology (medullary cysts, mineralization of corticomedullary junction, and tubular nephropathy) in males. At 2000 ppm (150 mg/kg/day), decreased ovarian weight (absolute and relative).

Reproductive toxicity NOAEL = 150 mg/kg/day

Enhanced OECD Test Guideline 407 (rat)
p-nonylphenol (branched)

CAS 84852-15-3 Woo, et al. (2007).
Arch. Toxicol 81: 77-88.

oral (gavage) 10, 50, 250 mg/kg/day for 28 days (olive oil) NOAEL = 10 mg/kg/day LOAEL = 50 mg/kg/day, based on increased thyroid weight (males), ↑ LH in females
At 250 mg/kg/day; there was an increase in days in estrus and irregular estrous cycling in 8/ 10 females; increased thyroid weight (females), ↑ TSH (females; atrophy of spleen and thymus (females) Non-guideline

4-nonylphenol (mixture of branched side chains containing 85% p-isomers)

female prepubertal rats dosed on days 21-35 and monitored daily for vaginal opening, evaluation of estrous cyclicity

3-day uterotrophic assay Laws, et al. (2000). Toxicological Sciences 54, 154-167.

0, 25, 50, 100 mg/kg/day (PND 21-35) gavage (corn oil)

0, 25, 50, 100, 200 mg/kg/day once/day for 3 days (oral gavage or sc) Accelerated timing of vaginal openi ng opening [1.5 days at 25 mg/kg/day; 5.3 days at 50 mg/kg/day; 6.8 days at 100 mg/kg/day]; decrease in # 4-5 day cycles; increased uterine weight at ≥ 50 mg/kg/day

Non-guideline
male pubertal assay (rat) Tan, et al. (2003). Toxicology Letters 143: 261-270.

PND 23-52/53 corn oil gavage

100 mg/kg/day body weight not affected but preputial separation age was delayed; 33% reached preputia l separation before PND 53 compared to 100% of controls ; seminal vesicle + coagulation gland weight and testicular tubul e diameter were significantly decreased; all control rats showed normal pattern of spermatogenic cycle, but 5 of 12 NP rats did not show any form of spermatogenic cycle; there were presence of multinucleated giant cells and sloughing of seminiferous epithelium and spermatogenic cells into the lumen of seminiferous tubule

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 59 of 85 Table A.8: Toxicology Profile of Nonylphenol (CAS 25154-52-3 and 84852-15-3)

Study Type Citation (year)/Doses Results

Non-guideline
3-day uterotrophic assay female pubertal onset assay
p-nonyl- phenol, (mixture of branched side-chains containing a minimum of 92% p-isomers)

CAS# 104-40-5 Kim, et al. (2002). Reproductive Toxicology 16: 259-268. uterotrophic assay (sc) 3 consecutive days (PND 20, 21, 22) 10, 25, 50, 100, 200 mg/kg/day Pubertal onset assay gavage 10, 50, 100 mg/kg/day from PND 21 for 20 days
ethanol/corn oil 3-day uterotrophic assay: ↑ uterine weight @ 100 and 200 mg/kg/day (dose-related); @ 200 mg/kg/day, 3.19-fold ↑ in uterine weight; 1.77-fold ↑ vaginal weight; ↓ ovarian weight @ 100 mg/kg/day (30%) and 200 mg/kg/day (33%)
female pubertal onset assay: ↓ ovarian and uterine weights at 100 mg/kg/day (no effect on BW); thyroid weight ns ↑ ; VO significantly accelerated @ 50 (1.5 days) and 100 (6.7 days) mg/kg/day (mean BW at age of VO significantly decreased @ 100 mg/kg/day); decreased serum T4 levels @ 100 mg/kg/day ( ↓ 19%), serum TSH increased (>30%); estrous cycle significantly affected @ 100 mg/kg/day (# days in diestrus was ↑ from VO to day 32, which was ≈ the mean VO day of control animals) Non-guideline

4-tert-octylphenol

maintenance of pregnancy
rats. Harazono, A and Ema, M (2001). Toxicology Letters 119: 79- 84. Dams dosed on GD 0-8 (sacrificed on GD 20)

0, 15.6, 31.3, 62.5, 125 mg/kg/day gavage (olive oil) NOAEL = 15.6 mg/kg/day LOAEL = 31.3 mg/kg/day, based on increased incidence of post-implantation loss, decreased BWG and FC pregnancy rate not affected

870.5900
I n Vitro Cytogenicity Assay for Sister Chromatid Exchange in Chinese Hamster Ovary (CHO) Cells.
±S9 Murli, H. and Ivett, JL. (1986). Mutagenic Evaluation of C-818 Lot #92748 in an I n Vitro Cytogenic Assay Measuring Sister Chromatid Exchange in Chinese Hamster Ovary (CHO) Cells. Hazleton Biotechnologies. HB Project No. 20990. (EPA/OTS Doc# 889200002872)

0, 1, 3.33, 10, 33.3, 100 μg/mL Repeat ; 0, 20, 30, 40, 50, 75 μg/mL C-818 (CAS 25154-52-3) vehicle acetone Positive for inducing sister chromatid exchange in CHO cells without S9; negative with S9

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 60 of 85 Table A.8: Toxicology Profile of Nonylphenol (CAS 25154-52-3 and 84852-15-3)

Study Type Citation (year)/Doses Results

870.5300 Mouse lymphoma forward mutation assay (L5178Y TK+/-) ±S9 Cifone, MA and Myhr, BC. (1985). Mutagenicity of C-818 in a Mouse Lymphoma Mutation Assay. Litton Bionetics, Inc. Project No.
20989. ( EPA/OTS Doc# 889200002872)

+S9: 0, 12.9, 25.8, 38.6, 51.5, 77.3, 103, 129 μg/mL -S9: 0, 10.3, 20.6, 41.2, 51.5, 61.8, 82.4 μg /mL

C-818 (CAS 25154-52-3) Acetone Mutagenic with activation (2.2-fold to 4-fold); Non-mutagenic without S9.

study for genotoxicity inCHO-K1 cells using sisterchromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays Tayama, S. et al., 2008. Mutation Research 649: 114- 125 NP : 0, 0.025, 0.05, 0.075, 0.1
mM 4-nonylphenol (>97%) DMSO Nonylphenol caused DNA migration in comet assay and induced SCE; results suggest nonylphenol causes repairable DNA damage, including SCEs; does not result in chromosome aberration (CA).

870.5100 Ames Salmonella Microsome Reverse Mutation Assay Tester strains TA98, TA100, TA1535, TA1537, TA1538 ±S9 (Aroclor-induced rat liver) Ames, et al., 1975 ±S9 Jagannath, DR and Myhr, BC (1985). Mutagenicity Evaluation of C-818 Batch No. 92748 in the Ames Salmonella/Microsome Plate Test. Litton Bionetics, Inc. Project No. 20989. (EPA/OTS Doc# 86960000408S) 0, 1, 10, 100, 500, 1000, 2500, 5000 μg/plate C-818 (CAS 25154-52-3) Did not exhibit mutagenic activity in these assays (±S9)

870.
In vitro transformation of BALB/C-3T3 cells assay Matthews, EJ and Myhr, BC (1985). Evaluation of C-818 in the In Vitro Transformation of BALB/C-3T3 Cells Assay. Litton Bionetics, Inc. Project No. 20992 (EPA/OTS Doc# 86960000409S) 0, 3.67, 14.7, 29.3, 44, 55 μg /mL C-818 (CAS 25154-52-3) Did not induce a significant in crease in the frequency of transformed foci

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 61 of 85 Table A.9. Other Nonylphenol Studies Study Type Citation/Year/Doses Results Two-stage transformation of BALB/C-3T3 cells (a model of two-stage carcinogenesis Sakai, A. (2001). PNonylphenol Acts as a Promoter in the BALB/3T3 Cell Transformation

5, 10, 20, 40 μM
NP CAS 25154-52-3 Treatment at 5-40 μM NP in promotion phase markedly enhanced transformation of cells pretreat ed with sub-threshold dose of carcinogen (MCA) but not of cell s not pretreated with MCA. Treatment at 5-40 μM NP in initiation phase did not induce cell transformation with and without pos t-treatment by TPA (potent tumor promoter) Results indicate that NP acts as a pure promoter and may causeenhancement of carcinogenesis in vivo. Enhancement by NP of MCAinitiated transformation was suggeste d not to be mediated by estrogen receptors in BALB/3T3 cells Multi-organ carcinogenesis model
in male F344 rats Seike, N.; Wanibuchi, H; Morimura, K; et al. (2003). Enhancement of Lung Carcinogenesis by Nonylphenol and Genistein in a F344 Rat Multiorgan Carcinogenesis Model. Cancer Letters 192: 25-36.

25 or 250 ppm nonylphenol

(NP) in diet for 28 weeks

250 ppm NP after DHPN initiation Total incidence of adenomas and carcinomas in lungs significantly higher

Formation of 8-hydroxy-2’-deoxyquanosine, a marker of oxygen radical-mediated DNA damage, was signifi cantly increased

Prostate carcinogenesis assessment Yoshino, H Nabae, K, Doi, Y, et al. (2005). Lack of effects of Gestational and Lactational Exposure to 4-Nonylphenol on PhIP-Induced Rat Prostate Carcinogenesis. J. Toxicol Pathol 18: 183-188.

Gavage 0, 0.1, 10, 100 mg/kg/day 4-nonylphenol during pregnancy and lactation period

♂ F344 rats PhIP 1/week from 5 weeks of age for 19 weeks Prolonged gestation @ 100 mg/kg/day NP does not modify susceptibility of ♂ offspring to food-derived prostate carcinogen PhIP

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 62 of 85 APPENDIX B. Structure-Activity Relationship (SAR) Discussion

HED used DEREK for Windows (V. 11) to assess the potential toxicity of compounds in the inerts mixture as well as potential degradates. Two compounds were scr eened, the smallest APE compound in this cluster as well as the t-octylp henol degradate. The st ructures are shown in Figure 1 below.

Figure B-1. Structures of Compounds Subjected to Structure-Activity Analysis

O O O

O



### Derek for Windows (LHASA Ltd.) is an expert syst em for the prediction of toxicity. It relies on a knowledge base of structural al erts and rules developed by scie ntists. When a test compound is inputted into the program, Derek for Windows s cans the test compound fo r structural alerts contained within its database that are associated with specific t oxicological endpoints and applies a series of reasoning rules to determine the likelihood of toxicity for the test compound. Information is provided on the rules used to ma ke the prediction, along with descriptions of structural alerts identified, comments, available example com pounds linked to the alerts and literature references.

There were no structural alerts of significance fo r the parent APE. There were alerts for the degradate, including the estrogeni c effects noted in the literatur e, as well as concern for chromosome damage. T-octyl phenol is in the data set for the DEREK alerts for chromosome damage 6



### .

6 Title: Relevance of chemical structure and cytotoxicity to the induction of chro mosome aberrations based on the testing results of 98 high production volume industria l chemicals. Author: Kusakabe H, Yamakage K, Wakuri S, Sasaki K, Nakagawa Y, Watanabe M, Hayashi M, Sofuni T, Ono H and Tanaka
N. Source: Mutation Research, 2002, 517, 187-198, availabl e at "http://dx.doi.org/10.1016/S1383-5718(02)00062-1".

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 63 of 85 APPENDIX C. Drinking Water Surrogate Analysis

Summary of Drinking Water Estimates of Four Surrogate Inert Chemicals

Notes:

1. Used a North Carolina cotton scenario with appli cation date on July 1. This scenario should be a good representative of the numbers that you can expect from EFED. Also tried manipulation of application date s and weather files to ensure that there are no aberrations; these values look good in that regard.

2. PCA factors were not applied, bu t the impact of applying such factors (i.e., 0.5 to 0.9) would be insignificant in comparison to the va st uncertainties surrounding generation of concentrations from surrogate chemicals as we ll as uncertainties regarding the actual timing of applications.

3. All simulations were made at approximately 1 lb/A. Concentrations resulting from other application rates will be directly pr oportional to the application rate.

4. Table 1 gives the normalized concentration esti mates for the case where all mass is applied on a single day. This should be the most conservative case.

5. Table 2 gives the normalized concentration esti mates for the case where mass is distributed evenly over a 100-day period (April to June).

6. A range of degradation rates were used because degradation information was not available. 3 simulations were made 1) chemically stable in water and soil, 2) a 100 day half life in water and soil, and 3) a 10-day half life in water and soil. This should cover degradation.

7. Table 3 gives the chemical inputs used in the simulations.

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 64 of 85 Table 1. DW concentration for application lumped on a single day. (This maximizes the acute concentrations.) All concentrations are normalized to a yearly application of 1 kg/hA (1.12 lb/acre).

Chemical
1 Chemical
2 Chemical 3 Chemical
4 Estimates based on Stable Assumption Acute (ppb) 1.1 41 33 0.005 Chronic 0.69 15 19 0.003
Cancer 0.47 12 15 0.002

Estimates based on assumption of a 100- day half life in soil and water Acute (ppb) 0.74 36 22 0.003 Chronic 0.33 8.8 7.7 0.002
Cancer 0.25 6.4 6.4 0.001

Estimates based on assumption of a 10-day half life in soil and water Acute (ppb) 0.48 25 15 0.002 Chronic 0.04 1.1 0.96 0.0002
Cancer 0.03 0.65 0.60 0.0002

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 65 of 85 Table 2. DW concentration for applications spread out over a 100-day period. This simulates a more even distribution of pesticide over the growing season. All concentrations are normalized to a yearly application of 1 kg/hA (1.12 lb/acre). Chemical
1 Chemical
2 Chemical 3 Chemical
4 Spread Out Values

Estimates based on Stable Assumption Acute (ppb) 0.98 29 28 0.004 Chronic 0.70 13 18 0.003
Cancer 0.48 10 15 0.002

Estimates based on assumption of a 100-day half life in soil and water
0.57 21 17 0.003
0.36 6.9 7.2 0.002
0.27 5.3 6.4 0.001

Estimates based on assumption of a 10-day half life in soil and water
0.16 7.8 4.3 0.001
0.04 0.79 0.77 0.0002
0.03 0.61 0.63 0.0002

Table 3 Chemical Inputs us ed in Simulations. Chemical 1 Chemical 2 Chemical 3 Chemical 4
Chemical Inputs: MW 928 274 302 1185 Solubility (mg/L) 382 299 19.5 6.69e-8 V.P. (mmHg) 5.8e-27 1.76e-8 3.86e-8 3.77e-33 Koc (ml/g) 9.44e6 152 1345 2.57e9

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 66 of 85 APPENDIX D. Detailed Dietary Exposure and Risk Information

D.1. Input File for Acute and Ch ronic Dietary Exposure Assessment Filename: C:\Documents and Settings\colinger\My Documents\Inerts\Cst5\Inerts_57active_Cluster5_100ppbH2Orev_7PCTform.R98 Chemical: Octylphenols (Cluster 5) RfD(Chronic): .1 mg/kg bw/day NOEL(Chronic): 10 mg/kg bw/day RfD(Acute): .156 mg/kg bw/day NOEL(Acute): 15.6 mg/kg bw/day Date created/last modified: 12-03-2009/13:18:38/8 Program ver. 2.03 Comment: Inert 57 active ingredients + drinking water (100ppb); 100x safety factor

-------------------------------------------------------------------------------- EPA Crop Def Res Adj.Factors Comment Code Grp Commodity Name (ppm) #1 #2

-------- ---- ------------------------------- ---------- ------ ------ ------- 95000010 O Acerola 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 18000020 18 Alfalfa, seed 0.500000 1.000 0.140 glypho Full comment: glyphosate 14000030 14 Almond 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 14000031 14 Almond-babyfood 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 14000040 14 Almond, oil 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 14000041 14 Almond, oil-babyfood 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 04010050 4A Amaranth, leafy 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 95000060 O Amaranth, grain 5.000000 1.000 0.140 glypho Full comment: glyphosate [wheat] 11000070 11 Apple, fruit with peel 25.000000 1.000 0.140 captan 11000080 11 Apple, peeled fruit 25.000000 1.000 0.140 captan 11000081 11 Apple, peeled fruit-babyfood 25.000000 1.000 0.140 captan 11000090 11 Apple, dried 25.000000 8.000 0.140 captan 11000091 11 Apple, dried-babyfood 25.000000 8.000 0.140 captan 11000100 11 Apple, juice 25.000000 1.000 0.140 captan 11000101 11 Apple, juice-babyfood 25.000000 1.000 0.140 captan 11000110 11 Apple, sauce 25.000000 1.000 0.140 captan 11000111 11 Apple, sauce-babyfood 25.000000 1.000 0.140 captan 12000120 12 Apricot 15.000000 1.000 0.140 TM 12000121 12 Apricot-babyfood 15.000000 1.000 0.140 TM 12000130 12 Apricot, dried 15.000000 6.000 0.140 TM 12000140 12 Apricot, juice 15.000000 1.000 0.140 TM 12000141 12 Apricot, juice-babyfood 15.000000 1.000 0.140 TM 01030150 1CD Arrowroot, flour 1.000000 1.000 0.140 diuron Full comment: diuron (potato transl] 01030151 1CD Arrowroot, flour-babyfood 1.000000 1.000 0.140 diuron Full comment: diuron (potato transl] 95000160 O Artichoke, globe 5.000000 1.000 0.140 permet Full comment: permethrin 01030170 1CD Artichoke, Jerusalem 1.000000 1.000 0.140 diuron Full comment: diuron (potato transl] 04010180 4A Arugula 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 95000190 O Asparagus 10.000000 1.000 0.140 carbar Full comment: carbaryl 95000200 O Avocado 25.000000 1.000 0.140 fosety Full comment: fosetyl-al 09020210 9B Balsam pear 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 95000220 O Bamboo, shoots 0.200000 1.000 0.140 glypho Full comment: glyphosate

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 67 of 85 95000230 O Banana 10.000000 1.000 0.140 carbar Full comment: carbaryl 95000231 O Banana-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 95000240 O Banana, dried 10.000000 3.900 0.140 carbar Full comment: carbaryl 95000241 O Banana, dried-babyfood 10.000000 3.900 0.140 carbar Full comment: carbaryl 15000250 15 Barley, pearled barley 20.000000 1.000 0.140 glypho Full comment: glyphosate 15000251 15 Barley, pearled barley-babyfood 20.000000 1.000 0.140 glypho Full comment: glyphosate 15000260 15 Barley, flour 20.000000 1.000 0.140 glypho Full comment: glyphosate 15000261 15 Barley, flour-babyfood 20.000000 1.000 0.140 glypho Full comment: glyphosate 15000270 15 Barley, bran 30.000000 1.000 0.140 glypho Full comment: glyphosate for bran 19010280 19A Basil, fresh leaves 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19010281 19A Basil, fresh leaves-babyfood 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19010290 19A Basil, dried leaves 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19010291 19A Basil, dried leaves-babyfood 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 06030300 6C Bean, black, seed 7.000000 1.000 0.140 maneb 06020310 6B Bean, broad, succulent 10.000000 1.000 0.140 maneb; Full comment: maneb;carbaryl (CG 6) 06030320 6C Bean, broad, seed 7.000000 1.000 0.140 maneb 06020330 6B Bean, cowpea, succulent 10.000000 1.000 0.140 maneb; Full comment: maneb;carbaryl (CG 6) 06030340 6C Bean, cowpea, seed 5.000000 1.000 0.140 carbar Full comment: carbaryl 06030350 6C Bean, great northern, seed 7.000000 1.000 0.140 maneb 06030360 6C Bean, kidney, seed 7.000000 1.000 0.140 maneb 06020370 6B Bean, lima, succulent 10.000000 1.000 0.140 maneb; Full comment: maneb;carbaryl (CG 6) 06030380 6C Bean, lima, seed 7.000000 1.000 0.140 maneb 06030390 6C Bean, mung, seed 2.000000 1.000 0.140 triflu Full comment: trifluralin 06030400 6C Bean, navy, seed 7.000000 1.000 0.140 maneb 06030410 6C Bean, pink, seed 7.000000 1.000 0.140 maneb 06030420 6C Bean, pinto, seed 7.000000 1.000 0.140 maneb 06010430 6A Bean, snap, succulent 5.000000 1.000 0.140 chloro Full comment: chlorothalonil 06010431 6A Bean, snap, succulent-babyfood 5.000000 1.000 0.140 chloro Full comment: chlorothalonil 21000440 M Beef, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfuran 21000441 M Beef, meat-babyfood 2.000000 1.000 0.140 endosu
Full comment: endosulfuran 21000450 M Beef, meat, dried 2.000000 1.920 0.140 endosu
Full comment: endosulfuran 21000460 M Beef, meat byproducts 1.000000 1.000 0.140 diuron 21000461 M Beef, meat byproducts-babyfood 1.000000 1.000 0.140 diuron 21000470 M Beef, fat 13.000000 1.000 0.140 endosu
Full comment: endosufuran 21000471 M Beef,fat-babyfood 13.000000 1.000 0.140 endosu
Full comment: endosufuran 21000480 M Beef, kidney 4.000000 1.000 0.140 glypho Full comment: glyphosate; 2,4-D 21000490 M Beef, liver 5.000000 1.000 0.140 endosu

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 68 of 85 Full comment: endosulfuran 21000491 M Beef, liver-babyfood 5.000000 1.000 0.140 endosu
Full comment: endosulfuran 01010500 1AB Beet, garden, roots 5.000000 1.000 0.140 carbar Full comment: carbaryl 01010501 1AB Beet, garden, roots-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 02000510 2 Beet, garden, tops 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 01010520 1A Beet, sugar 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos 01010521 1A Beet, sugar-babyfood 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos 01010530 1A Beet, sugar, molasses 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos 01010531 1A Beet, sugar, molasses-babyfood 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos 95000540 O Belgium endive 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 13010550 13A Blackberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13010560 13A Blackberry, juice 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13010561 13A Blackberry, juice-babyfood 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13020570 13B Blueberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13020571 13B Blueberry-babyfood 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13010580 13A Boysenberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 14000590 14 Brazil nut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 95000600 O Breadfruit 0.200000 1.000 0.140 glypho Full comment: glyphosate 05010610 5A Broccoli 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05010611 5A Broccoli-babyfood 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05010620 5A Broccoli, Chinese 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05020630 5B Broccoli raab 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05010640 5A Brussels sprouts 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5)
15000650 15 Buckwheat 0.100000 1.000 0.140 metola
Full comment: metolachlor 15000660 15 Buckwheat, flour 0.100000 1.000 0.140 metola
Full comment: metolachlor
01010670 1AB Burdock 10.000000 1.000 0.140 carbar Full comment: carbaryl (carrot) 14000680 14 Butternut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 05010690 5A Cabbage 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05020700 5B Cabbage, Chinese, bok choy 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05010710 5A Cabbage, Chinese, napa 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 05010720 5A Cabbage, Chinese, mustard 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 95000730 O Cactus 0.500000 1.000 0.140 glypho Full comment: glyphosate

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 69 of 85 95000740 O Canistel 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 09010750 9A Cantaloupe 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 04020760 4B Cardoon 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4)
95000770 O Carob 0.050000 1.000 0.140 chloro Full comment: chlorothanil
01010780 1AB Carrot 10.000000 1.000 0.140 carbar Full comment: carbaryl 01010781 1AB Carrot-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 01010790 1AB Carrot, juice 10.000000 1.000 0.140 carbar Full comment: carbaryl 09010800 9A Casaba 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 14000810 14 Cashew 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 01030820 1CD Cassava 1.000000 1.000 0.140 diuron Full comment: diuron [potato transl] 01030821 1CD Cassava-babyfood 1.000000 1.000 0.140 diuron Full comment: diuron [potato transl] 05010830 5A Cauliflower 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 01010840 1AB Celeriac 10.000000 1.000 0.140 carbar Full comment: carbaryl (carrot) 04020850 4B Celery 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04020851 4B Celery-babyfood 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04020860 4B Celery, juice 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04020870 4B Celtuce 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 09020880 9B Chayote, fruit 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 95000890 O Cherimoya 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 12000900 12 Cherry 50.000000 1.000 0.140 captan 12000901 12 Cherry-babyfood 50.000000 1.000 0.140 captan 12000910 12 Cherry, juice 50.000000 1.000 0.140 captan 12000911 12 Cherry, juice-babyfood 50.000000 1.000 0.140 captan 14000920 14 Chestnut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 40000930 P Chicken, meat 5.000000 1.000 0.140 carbar Full comment: carbaryl 40000931 P Chicken, meat-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 40000940 P Chicken, liver 5.000000 1.000 0.140 iprodi Full comment: iprodione 40000950 P Chicken, meat byproducts 1.000000 1.000 0.140 glypho Full comment: glyphosate 40000951 P Chicken, meat byproducts-babyfoo 1.000000 1.000 0.140 glypho Full comment: glyphosate 40000960 P Chicken, fat 5.000000 1.000 0.140 carbar Full comment: carbaryl 40000961 P Chicken, fat-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 40000970 P Chicken, skin 5.000000 1.000 0.140 carbar Full comment: carbaryl 40000971 P Chicken, skin-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 06030980 6C Chickpea, seed 7.000000 1.000 0.140 maneb

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 70 of 85 06030981 6C Chickpea, seed-babyfood 7.000000 1.000 0.140 maneb 06030990 6C Chickpea, flour 7.000000 1.000 0.140 maneb 01011000 1AB Chicory, roots 10.000000 1.000 0.140 carbar Full comment: carbaryl [carrot] 02001010 2 Chicory, tops 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 09021020 9B Chinese waxgourd 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 19011030 19A Chive 110-Uncooked; Fresh or N/S; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 210-Cooked; Fresh or N/S; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 211-Cooked; Fresh or N/S; Baked 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 212-Cooked; Fresh or N/S; Boiled 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 213-Cooked; Fresh or N/S; Fried 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 221-Cooked; Frozen; Baked 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 240-Cooked; Canned; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 242-Cooked; Canned; Boiled 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herbs] 04011040 4A Chrysanthemum, garland 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 19021050 19B Cinnamon 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 19021051 19B Cinnamon-babyfood 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 10001060 10 Citrus citron 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10001070 10 Citrus hybrids 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10001080 10 Citrus, oil 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 95001090 O Cocoa bean, chocolate 0.050000 1.000 0.140 chloro Full comment: chlorothalonil 95001100 O Cocoa bean, powder 0.050000 1.000 0.140 chloro Full comment: chlorothalonil 95001110 O Coconut, meat 0.100000 1.000 0.140 glypho Full comment: glyphosate 95001111 O Coconut- meat-babyfood 0.100000 1.000 0.140 glypho Full comment: glyphosate 95001120 O Coconut, dried 0.100000 2.100 0.140 glypho Full comment: glyphosate 95001130 O Coconut, milk 0.100000 1.000 0.140 glypho Full comment: glyphosate 95001140 O Coconut, oil 0.100000 1.000 0.140 glypho Full comment: glyphosate 95001141 O Coconut, oil-babyfood 0.100000 1.000 0.140 glypho Full comment: glyphosate 95001150 O Coffee, roasted bean 1.000000 1.000 0.140 glypho Full comment: glyphosate 95001160 O Coffee, instant 1.000000 1.000 0.140 glypho Full comment: glyphosate

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 71 of 85 05021170 5B Collards 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 19011180 19A Coriander, leaves 30.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19011181 19A Coriander, leaves-babyfood 30.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19021190 19B Coriander, seed 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 19021191 19B Coriander, seed-babyfood 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 15001200 15 Corn, field, flour 0.150000 1.000 0.140 lambda Full comment: lambda-cyhalothrin 15001201 15 Corn, field, flour-babyfood 0.150000 1.000 0.140 lambda Full comment: lambda-cyhalothrin 15001210 15 Corn, field, meal 1.000000 1.000 0.140 glypho Full comment: glyphosate 15001211 15 Corn, field, meal-babyfood 1.000000 1.000 0.140 glypho Full comment: glyphosate 15001220 15 Corn, field, bran 1.000000 1.000 0.140 glypho Full comment: glyphosate 15001230 15 Corn, field, starch 1.000000 1.000 0.140 glypho Full comment: glyphosate 15001231 15 Corn, field, starch-babyfood 1.000000 1.000 0.140 glypho Full comment: glyphosate 15001240 15 Corn, field, syrup 1.000000 1.500 0.140 glypho Full comment: glyphosate 15001241 15 Corn, field, syrup-babyfood 1.000000 1.500 0.140 glypho Full comment: glyphosate 15001250 15 Corn, field, oil 3.000000 1.000 0.140 chloro Full comment: chloropyrifos 15001251 15 Corn, field, oil-babyfood 3.000000 1.000 0.140 chloro Full comment: chloropyrifos 15001260 15 Corn, pop 0.500000 1.000 0.140 mancoz
Full comment: mancozeb 15001270 15 Corn, sweet 5.000000 1.000 0.140 maneb; Full comment: maneb;carbaryl 15001271 15 Corn, sweet-babyfood 5.000000 1.000 0.140 maneb; Full comment: maneb;carbaryl 95001280 O Cottonseed, oil 35.000000 1.000 0.140 glypho Full comment: glyphosate 95001281 O Cottonseed, oil-babyfood 35.000000 1.000 0.140 glypho Full comment: glyphosate 11001290 11 Crabapple 20.000000 1.000 0.140 phosme Full comment: phosmet 95001300 O Cranberry 10.000000 1.000 0.140 carbar Full comment: carbaryl 95001301 O Cranberry-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 95001310 O Cranberry, dried 10.000000 1.000 0.140 carbar Full comment: carbaryl 95001320 O Cranberry, juice 10.000000 1.000 0.140 carbar Full comment: carbaryl 95001321 O Cranberry, juice-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 04011330 4A Cress, garden 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04011340 4A Cress, upland 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 09021350 9B Cucumber 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 13021360 13B Currant 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13021370 13B Currant, dried 40.000000 1.000 0.140 fosety

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 72 of 85 Full comment: fosetyl-al (berries) 04011380 4A Dandelion, leaves 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 01031390 1CD Dasheen, corm 1.000000 1.000 0.140 diuron Full comment: diuron [potato transl] 02001400 2 Dasheen, leaves 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 95001410 O Date 0.200000 1.000 0.140 glypho Full comment: glyphosate 13011420 13A Dewberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 19021430 19B Dill, seed 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 19011440 19A Dillweed 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herb] 70001450 P Egg, whole 1.500000 1.000 0.140 iprodi Full comment: iprodione 70001451 P Egg, whole-babyfood 1.500000 1.000 0.140 iprodi Full comment: iprodione 70001460 P Egg, white 1.500000 1.000 0.140 iprodi Full comment: iprodione 70001461 P Egg, white (solids)-babyfood 1.500000 1.000 0.140 iprodi Full comment: iprodione 70001470 P Egg, yolk 1.500000 1.000 0.140 iprodi Full comment: iprodione 70001471 P Egg, yolk-babyfood 1.500000 1.000 0.140 iprodi Full comment: iprodione 08001480 8 Eggplant 10.000000 1.000 0.140 carbar Full comment: carbaryl 13021490 13B Elderberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 04011500 4A Endive 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 95001510 O Feijoa 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 04021520 4B Fennel, Florence 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 95001530 O Fig 7.000000 1.000 0.140 maneb 95001540 O Fig, dried 7.000000 1.000 0.140 maneb 14001550 14 Filbert 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 14001560 14 Filbert, oil 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 80001570 F Fish-freshwater finfish 2.000000 1.000 0.140 diuron Full comment: diuron [catfish] 80001580 F Fish-freshwater finfish, farm ra 2.000000 1.000 0.140 diuron 80001590 F Fish-saltwater finfish, tuna 2.000000 1.000 0.140 diuron Full comment: diuron [catfish] 80001600 F Fish-saltwater finfish, other 2.000000 1.000 0.140 diuron Full comment: diuron [catfish] 80001610 F Fish-shellfish, crustacean 3.000000 1.000 0.140 glypho Full comment: glyphosate [shellfish] 80001620 F Fish-shellfish, mollusc 3.000000 1.000 0.140 glypho Full comment: glyphosate [shellfish] 20001630 20 Flaxseed, oil 5.000000 1.000 0.140 carbar Full comment: carbaryl 03001640 3 Garlic 0.200000 1.000 0.140 glypho Full comment: glyphosate (CG 3) 03001650 3 Garlic, dried 0.200000 1.000 0.140 glypho Full comment: glyphosate (CG 3) 03001651 3 Garlic, dried-babyfood 0.200000 1.000 0.140 glypho Full comment: glyphosate (CG 3) 01031660 1CD Ginger 0.200000 1.000 0.140 glypho

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 73 of 85 Full comment: glyphosate 01031661 1CD Ginger-babyfood 0.200000 1.000 0.140 glypho Full comment: glyphosate 01031670 1CD Ginger, dried 0.200000 1.000 0.140 glypho Full comment: glyphosate 01011680 1AB Ginseng, dried 4.000000 1.000 0.140 iprodi Full comment: iprodione 23001690 M Goat, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfan 23001700 M Goat, meat byproducts 1.000000 1.000 0.140 diuron Full comment: diuron; propanil 23001710 M Goat, fat 13.000000 1.000 0.140 endosu
Full comment: endosulfan 23001720 M Goat, kidney 4.000000 1.000 0.140 endosu Full comment: endosulfan; 2,4-D 23001730 M Goat, liver 5.000000 1.000 0.140 endosu
Full comment: endosulfan 13021740 13B Gooseberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 95001750 O Grape 25.000000 1.000 0.140 captan 95001760 O Grape, juice 25.000000 1.000 0.140 captan 95001761 O Grape, juice-babyfood 25.000000 1.000 0.140 captan 95001770 O Grape, leaves 25.000000 1.000 0.140 captan 95001780 O Grape, raisin 25.000000 1.000 0.140 captan 95001790 O Grape, wine and sherry 25.000000 1.000 0.140 captan 10001800 10 Grapefruit 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10001810 10 Grapefruit, juice 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 06031820 6C Guar, seed 7.000000 1.000 0.140 maneb 06031821 6C Guar, seed-babyfood 7.000000 1.000 0.140 maneb 95001830 O Guava 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95001831 O Guava-babyfood 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19011840 19A Herbs, other 110-Uncooked; Fresh or N/S; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 150-Uncooked; Cured etc; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 210-Cooked; Fresh or N/S; Cook Meth N/S 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 211-Cooked; Fresh or N/S; Baked 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 212-Cooked; Fresh or N/S; Boiled 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 213-Cooked; Fresh or N/S; Fried 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 215-Cooked; Fresh or N/S; Boiled/baked 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 221-Cooked; Frozen; Baked 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 230-Cooked; Dried; Cook Meth N/S 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 232-Cooked; Dried; Boiled 260.000000 1.000 0.140 azoxys

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 74 of 85 Full comment: azoxystrobin 233-Cooked; Dried; Fried 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 240-Cooked; Canned; Cook Meth N/S 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 242-Cooked; Canned; Boiled 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 250-Cooked; Cured etc; Cook Meth N/S 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 252-Cooked; Cured etc; Boiled 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 253-Cooked; Cured etc; Fried 260.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19011841 19A Herbs, other-babyfood 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin 14001850 14 Hickory nut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 95001860 O Honey 30.000000 1.000 0.140 glypho Full comment: glyphosate[sugarcane mol trans] 95001861 O Honey-babyfood 30.000000 1.000 0.140 glypho Full comment: glyphosate[sugarcane mol trans] 09011870 9A Honeydew melon 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 95001880 O Hop 1.000000 1.000 0.140 methyl Full comment: methyl parathion 24001890 M Horse, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfuran 01011900 1AB Horseradish 5.000000 1.000 0.140 carbar Full comment: carbaryl 13021910 13B Huckleberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 95001920 O Jaboticaba 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95001930 O Jackfruit 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 05021940 5B Kale 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 95001950 O Kiwifruit 25.000000 1.000 0.140 phosme Full comment: phosmet 05011960 5A Kohlrabi 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 10001970 10 Kumquat 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG)
03001980 3 Leek 3.000000 1.000 0.140 methom Full comment: methomyl 10001990 10 Lemon 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002000 10 Lemon, juice 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002001 10 Lemon, juice-babyfood 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002010 10 Lemon, peel 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 19012020 19A Lemongrass 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herb] 06032030 6C Lentil, seed 10.000000 1.000 0.140 carbar Full comment: carbaryl 04012040 4A Lettuce, head 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04012050 4A Lettuce, leaf 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4)

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 75 of 85 10002060 10 Lime 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002070 10 Lime, juice 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002071 10 Lime, juice-babyfood 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 13012080 13A Loganberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 95002090 O Longan 3.000000 1.000 0.140 imidac Full comment: imidacloprid 11002100 11 Loquat 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002110 O Lychee 3.000000 1.000 0.140 imidac Full comment: imidacloprid 95002120 O Lychee, dried 3.000000 1.850 0.140 imidac Full comment: imidacloprid 14002130 14 Macadamia nut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 95002140 O Mamey apple 0.200000 1.000 0.140 glypho Full comment: glyphosate 95002150 O Mango 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002151 O Mango-babyfood 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002160 O Mango, dried 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002170 O Mango, juice 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002171 O Mango, juice-babyfood 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95002180 O Maple, sugar 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos [sugarbeet] 95002190 O Maple syrup 15.000000 1.000 0.140 chlorp Full comment: chlorpyrifos [sugarbeet] 19012200 19A Marjoram 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herb] 19012201 19A Marjoram-babyfood 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin [herb] 28002210 M Meat, game 2.000000 1.000 0.140 endosu
Full comment: endosulfan 27002220 D Milk, fat 2.000000 1.000 0.140 endosu
Full comment: endosulfan 27002221 D Milk, fat - baby food/infant for 2.000000 1.000 0.140 endosu
Full comment: endosulfan 27012230 D Milk, nonfat solids 0.500000 1.000 0.140 iprodi Full comment: iprodione 27012231 D Milk, nonfat solids-baby food/in 0.500000 1.000 0.140 iprodi Full comment: iprodione 27022240 D Milk, water 0.500000 1.000 0.140 iprodi Full comment: iprodione 27022241 D Milk, water-babyfood/infant form 0.500000 1.000 0.140 iprodi Full comment: iprodione 27032251 D Milk, sugar (lactose)-baby food/ 0.500000 1.000 0.140 iprodi Full comment: iprodione 15002260 15 Millet, grain 2.000000 1.000 0.140 carbar Full comment: carbaryl 95002270 O Mulberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al [blueberry] 95002280 O Mushroom 5.000000 1.000 0.140 permet Full comment: permethrin 05022290 5B Mustard greens 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 12002300 12 Nectarine 25.000000 1.000 0.140 captan

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 76 of 85 15002310 15 Oat, bran 20.000000 1.000 0.140 mancoz
Full comment: mancozeb 15002320 15 Oat, flour 20.000000 1.000 0.140 glypho Full comment: glyphosate 15002321 15 Oat, flour-babyfood 20.000000 1.000 0.140 glypho Full comment: glyphosate 15002330 15 Oat, groats/rolled oats 20.000000 1.000 0.140 glypho Full comment: glyphosate 15002331 15 Oat, groats/rolled oats-babyfood 20.000000 1.000 0.140 glypho Full comment: glyphosate
08002340 8 Okra 10.000000 1.000 0.140 carbar Full comment: carbaryl 95002350 O Olive 10.000000 1.000 0.140 carbar Full comment: carbaryl 95002360 O Olive, oil 10.000000 1.000 0.140 carbar Full comment: carbaryl 03002370 3 Onion, dry bulb 7.000000 1.000 0.140 maneb; Full comment: maneb; ziram 03002371 3 Onion, dry bulb-babyfood 7.000000 1.000 0.140 maneb; Full comment: maneb; ziram 03002380 3 Onion, dry bulb, dried 7.000000 9.000 0.140 maneb; Full comment: maneb; ziram 03002381 3 Onion, dry bulb, dried-babyfood 7.000000 9.000 0.140 maneb; Full comment: maneb; ziram 03002390 3 Onion, green 10.000000 1.000 0.140 fosety Full comment: fosetyl-al 10002400 10 Orange 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002410 10 Orange, juice 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002411 10 Orange, juice-babyfood 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 10002420 10 Orange, peel 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 95002430 O Palm heart, leaves 0.200000 1.000 0.140 glypho Full comment: glyphosate 95002440 O Palm, oil 0.100000 1.000 0.140 glypho Full comment: glyphosate 95002441 O Palm, oil-babyfood 0.100000 1.000 0.140 glypho Full comment: glyphosate 95002450 O Papaya 15.000000 1.000 0.140 chloro Full comment: chlorothanil 95002451 O Papaya-babyfood 15.000000 1.000 0.140 chloro Full comment: chlorothanil 95002460 O Papaya, dried 15.000000 1.800 0.140 chloro Full comment: chlorothanil 95002470 O Papaya, juice 15.000000 1.000 0.140 chloro Full comment: chlorothanil 04012480 4A Parsley, leaves 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 19012490 19A Parsley, dried leaves 12.000000 1.000 0.140 carbar Full comment: carbaryl 19012491 19A Parsley, dried leaves-babyfood 12.000000 1.000 0.140 carbar Full comment: carbaryl 01012500 1AB Parsley, turnip rooted 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 01012510 1AB Parsnip 5.000000 1.000 0.140 carbar Full comment: carbaryl 01012511 1AB Parsnip-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 95002520 O Passionfruit 3.000000 1.000 0.140 chloro Full comment: chlorothanil 95002521 O Passionfruit-babyfood 3.000000 1.000 0.140 chloro

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 77 of 85 Full comment: chlorothanil 95002530 O Passionfruit, juice 3.000000 1.000 0.140 chloro Full comment: chlorothanil 95002531 O Passionfruit, juice-babyfood 3.000000 1.000 0.140 chloro Full comment: chlorothanil 95002540 O Pawpaw 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 06022550 6B Pea, succulent 10.000000 1.000 0.140 carbar Full comment: carbaryl 06022551 6B Pea, succulent-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 06032560 6C Pea, dry 8.000000 1.000 0.140 glypho Full comment: glyphosate 06032561 6C Pea, dry-babyfood 8.000000 1.000 0.140 glypho Full comment: glyphosate 06012570 6A Pea, edible podded, succulent 3.000000 1.000 0.140 bentaz
Full comment: bentazon 06032580 6C Pea, pigeon, seed 8.000000 1.000 0.140 glypho Full comment: glyphosate 06022590 6B Pea, pigeon, succulent 10.000000 1.000 0.140 carbar Full comment: carbaryl 12002600 12 Peach 15.000000 1.000 0.140 captan 12002601 12 Peach-babyfood 15.000000 1.000 0.140 captan 12002610 12 Peach, dried 15.000000 7.000 0.140 captan 12002611 12 Peach, dried-babyfood 15.000000 7.000 0.140 captan 12002620 12 Peach, juice 15.000000 1.000 0.140 captan 12002621 12 Peach, juice-babyfood 15.000000 1.000 0.140 captan
95002630 O Peanut 5.000000 1.000 0.140 carbar Full comment: carbaryl 95002640 O Peanut, butter 5.000000 1.890 0.140 carbar Full comment: carbaryl 95002650 O Peanut, oil 0.600000 1.000 0.140 azoxys Full comment: azoxystrobin 11002660 11 Pear 25.000000 1.000 0.140 captan 11002661 11 Pear-babyfood 25.000000 1.000 0.140 captan 11002670 11 Pear, dried 25.000000 6.250 0.140 captan 11002680 11 Pear, juice 25.000000 1.000 0.140 captan 11002681 11 Pear, juice-babyfood 25.000000 1.000 0.140 captan 14002690 14 Pecan 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 08002700 8 Pepper, bell 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002701 8 Pepper, bell-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002710 8 Pepper, bell, dried 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002711 8 Pepper, bell, dried-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002720 8 Pepper, nonbell 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002721 8 Pepper, nonbell-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 08002730 8 Pepper, nonbell, dried 10.000000 1.000 0.140 carbar Full comment: carbaryl 19022740 19B Pepper, black and white 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 19022741 19B Pepper, black and white-babyfood 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 95002750 O Peppermint 200.000000 1.000 0.140 glypho Full comment: glyphosate 95002760 O Peppermint, oil 200.000000 1.000 0.140 glypho Full comment: glyphosate 95002770 O Persimmon 3.000000 1.000 0.140 imidac

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 78 of 85 Full comment: imidacloprid 95002780 O Pine nut 1.000000 1.000 0.140 glypho Full comment: glyphosate 95002790 O Pineapple 2.000000 1.000 0.140 carbar Full comment: carbaryl 95002791 O Pineapple-babyfood 2.000000 1.000 0.140 carbar Full comment: carbaryl 95002800 O Pineapple, dried 2.000000 5.000 0.140 carbar Full comment: carbaryl 95002810 O Pineapple, juice 2.000000 1.000 0.140 carbar Full comment: carbaryl 95002811 O Pineapple, juice-babyfood 2.000000 1.000 0.140 carbar Full comment: carbaryl 14002820 14 Pistachio 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 95002830 O Plantain 10.000000 1.000 0.140 carbar Full comment: carbaryl [banana] 95002840 O Plantain, dried 10.000000 3.900 0.140 carbar Full comment: carbaryl [banana] 12002850 12 Plum 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002851 12 Plum-babyfood 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002860 12 Plum, prune, fresh 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002861 12 Plum, prune, fresh-babyfood 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002870 12 Plum, prune, dried 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002871 12 Plum, prune, dried-babyfood 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002880 12 Plum, prune, juice 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 12002881 12 Plum, prune, juice-babyfood 10.000000 1.000 0.140 captan Full comment: captan;carbaryl 95002890 O Pomegranate 0.900000 1.000 0.140 imidac Full comment: imidacloprid 25002900 M Pork, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfan 25002901 M Pork, meat-babyfood 2.000000 1.000 0.140 endosu
Full comment: endosulfan 25002910 M Pork, skin 13.000000 1.000 0.140 endosu
Full comment: endosulfan 25002920 M Pork, meat byproducts 1.000000 1.000 0.140 diuron 25002921 M Pork, meat byproducts-babyfood 1.000000 1.000 0.140 diuron 25002930 M Pork, fat 13.000000 1.000 0.140 endosu
Full comment: endosulfan 25002931 M Pork, fat-babyfood 13.000000 1.000 0.140 endosu
Full comment: endosulfan 25002940 M Pork, kidney 4.000000 1.000 0.140 glypho Full comment: glyphosate 25002950 M Pork, liver 5.000000 1.000 0.140 endosu
Full comment: endosulfan 01032960 1C Potato, chips 1.000000 1.000 0.140 imidac Full comment: imidacloprid 01032970 1C Potato, dry (granules/ flakes) 1.000000 6.500 0.140 diuron 01032971 1C Potato, dry (granules/ flakes)-b 1.000000 6.500 0.140 diuron 01032980 1C Potato, flour 1.000000 1.000 0.140 diuron 01032981 1C Potato, flour-babyfood 1.000000 1.000 0.140 diuron 01032990 1C Potato, tuber, w/peel 1.000000 1.000 0.140 diuron 01032991 1C Potato, tuber, w/peel-babyfood 1.000000 1.000 0.140 diuron 01033000 1C Potato, tuber, w/o peel 1.000000 1.000 0.140 diuron 01033001 1C Potato, tuber, w/o peel-babyfood 1.000000 1.000 0.140 diuron

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 79 of 85 60003010 P Poultry, other, meat 5.000000 1.000 0.140 carbar Full comment: carbaryl 60003020 P Poultry, other, liver 5.000000 1.000 0.140 iprodi Full comment: iprodione 60003030 P Poultry, other, meat byproducts 1.000000 1.000 0.140 glypho Full comment: glyphosate 60003040 P Poultry, other, fat 5.000000 1.000 0.140 carbar Full comment: carbaryl 60003050 P Poultry, other, skin 5.000000 1.000 0.140 carbar Full comment: carbaryl 95003060 O Psyllium, seed 10.000000 1.000 0.140 propan Full comment: propanil [rice] 10003070 10 Pummelo 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 09023080 9B Pumpkin 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 09023090 9B Pumpkin, seed 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 11003100 11 Quince 10.000000 1.000 0.140 mancoz
Full comment: mancozeb 95003110 O Quinoa, grain 5.000000 1.000 0.140 glypho Full comment: glyphosate 29003120 M Rabbit, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfan 04013130 4A Radicchio 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 01013140 1AB Radish, roots 5.000000 1.000 0.140 carbar Full comment: carbaryl 02003150 2 Radish, tops 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 01013160 1AB Radish, Oriental, roots 5.000000 1.000 0.140 carbar Full comment: carbaryl 02003170 2 Radish, Oriental, tops 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 05023180 5B Rape greens 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 20003190 20 Rapeseed, oil 10.000000 1.000 0.140 glypho Full comment: glyphosate 20003191 20 Rapeseed, oil-babyfood 10.000000 1.000 0.140 glypho Full comment: glyphosate 13013200 13A Raspberry 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13013201 13A Raspberry-babyfood 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13013210 13A Raspberry, juice 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 13013211 13A Raspberry, juice-babyfood 40.000000 1.000 0.140 fosety Full comment: fosetyl-al (berries) 04023220 4B Rhubarb 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 15003230 15 Rice, white 10.000000 1.000 0.140 propan Full comment: propanil 15003231 15 Rice, white-babyfood 10.000000 1.000 0.140 propan Full comment: propanil 15003240 15 Rice, brown 10.000000 1.000 0.140 propan Full comment: propanil 15003241 15 Rice, brown-babyfood 10.000000 1.000 0.140 propan Full comment: propanil 15003250 15 Rice, flour 10.000000 1.000 0.140 propan Full comment: propanil 15003251 15 Rice, flour-babyfood 10.000000 1.000 0.140 propan Full comment: propanil 15003260 15 Rice, bran 40.000000 1.000 0.140 propan

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 80 of 85 Full comment: propanil 15003261 15 Rice, bran-babyfood 40.000000 1.000 0.140 propan Full comment: propanil 01013270 1AB Rutabaga 5.000000 1.000 0.140 carbar Full comment: carbaryl 15003280 15 Rye, grain 5.000000 1.000 0.140 mancoz
Full comment: mancozeb 15003290 15 Rye, flour 5.000000 1.000 0.140 mancoz
Full comment: mancozeb 20003300 20 Safflower, oil 85.000000 1.000 0.140 glypho Full comment: glyphosate 20003301 20 Safflower, oil-babyfood 85.000000 1.000 0.140 glypho Full comment: glyphosate 01013310 1AB Salsify, roots 5.000000 1.000 0.140 carbar Full comment: carbaryl 02003320 2 Salsify, tops 50.000000 1.000 0.140 azoxys Full comment: azoxystrobin (CG 2) 95003330 O Sapote, Mamey 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 19013340 19A Savory 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 95003350 O Seaweed 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 95003351 O Seaweed-babyfood 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 95003360 O Sesame, seed 0.100000 1.000 0.140 glypho Full comment: glyphosate 95003361 O Sesame, seed-babyfood 0.100000 1.000 0.140 glypho Full comment: glyphosate 95003370 O Sesame, oil 0.100000 1.000 0.140 glypho Full comment: glyphosate 95003371 O Sesame, oil-babyfood 0.100000 1.000 0.140 glypho Full comment: glyphosate 03003380 3 Shallot 0.200000 1.000 0.140 pendim Full comment: pendimethalin 26003390 M Sheep, meat 2.000000 1.000 0.140 endosu
Full comment: endosulfan 26003391 M Sheep, meat-babyfood 2.000000 1.000 0.140 endosu
Full comment: endosulfan 26003400 M Sheep, meat byproducts 5.000000 1.000 0.140 endosu
Full comment: endosulfan 26003410 M Sheep, fat 13.000000 1.000 0.140 endosu
Full comment: endosulfan 26003411 M Sheep, fat-babyfood 13.000000 1.000 0.140 endosu
Full comment: endosulfan 26003420 M Sheep, kidney 4.000000 1.000 0.140 glypho Full comment: glyphosate 26003430 M Sheep, liver 5.000000 1.000 0.140 glypho Full comment: glyphosate 15003440 15 Sorghum, grain 15.000000 1.000 0.140 glypho Full comment: glyphosate 15003450 15 Sorghum, syrup 15.000000 1.000 0.140 glypho Full comment: glyphosate 95003460 O Soursop 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 06003470 6 Soybean, seed 20.000000 1.000 0.140 glypho Full comment: glyphosate 06003480 6 Soybean, flour 5.000000 1.000 0.140 carbar Full comment: carbaryl 06003481 6 Soybean, flour-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 06003490 6 Soybean, soy milk 5.000000 1.000 0.140 carbar Full comment: carbaryl

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 81 of 85 06003491 6 Soybean, soy milk-babyfood or in 5.000000 1.000 0.140 carbar Full comment: carbaryl 06003500 6 Soybean, oil 0.300000 1.000 0.140 bifent Full comment: bifenthrin 06003501 6 Soybean, oil-babyfood 0.300000 1.000 0.140 bifent Full comment: bifenthrin 95003510 O Spanish lime 3.000000 1.000 0.140 imidac Full comment: imidacloprid 95003520 O Spearmint 200.000000 1.000 0.140 glypho Full comment: glyphosate 95003530 O Spearmint, oil 200.000000 1.000 0.140 glypho Full comment: glyphosate 19023540 19B Spices, other 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 19023541 19B Spices, other-babyfood 38.000000 1.000 0.140 azoxys Full comment: azoxystrobin [spice] 04013550 4A Spinach 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 04013551 4A Spinach-babyfood 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 09023560 9B Squash, summer 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 09023561 9B Squash, summer-babyfood 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 09023570 9B Squash, winter 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 09023571 9B Squash, winter-babyfood 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 95003580 O Starfruit 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95003590 O Strawberry 75.000000 1.000 0.140 fosety Full comment: fosetyl-al 95003591 O Strawberry-babyfood 75.000000 1.000 0.140 fosety Full comment: fosetyl-al 95003600 O Strawberry, juice 75.000000 1.000 0.140 fosety Full comment: fosetyl-al 95003601 O Strawberry, juice-babyfood 75.000000 1.000 0.140 fosety Full comment: fosetyl-al 95003610 O Sugar apple 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 95003620 O Sugarcane, sugar 2.000000 1.000 0.140 glypho Full comment: glyphosate;2,4-D 95003621 O Sugarcane, sugar-babyfood 2.000000 1.000 0.140 glypho Full comment: glyphosate;2,4-D 95003630 O Sugarcane, molasses 30.000000 1.000 0.140 glypho Full comment: glyphosate 95003631 O Sugarcane, molasses-babyfood 30.000000 1.000 0.140 glypho Full comment: glyphosate 20003640 20 Sunflower, seed 2.500000 1.000 0.140 alachl
Full comment: alachlor 20003650 20 Sunflower, oil 0.300000 1.000 0.140 lambda Full comment: lambda-cyhalothrin 20003651 20 Sunflower, oil-babyfood 0.300000 1.000 0.140 lambda Full comment: lambda-cyhalothrin 01033660 1CD Sweet potato 10.000000 1.000 0.140 phosme Full comment: phosmet 01033661 1CD Sweet potato-babyfood 10.000000 1.000 0.140 phosme Full comment: phosmet 04023670 4B Swiss chard 100.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 4) 95003680 O Tamarind 2.000000 1.000 0.140 azoxys Full comment: azoxystrobin 10003690 10 Tangerine 10.000000 1.000 0.140 azoxys

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 82 of 85 Full comment: azoxystrobin ( citrus CG) 10003700 10 Tangerine, juice 10.000000 1.000 0.140 azoxys Full comment: azoxystrobin ( citrus CG) 01033710 1CD Tanier, corm 1.000000 1.000 0.140 diuron Full comment: diuron [potato transl] 95003720 O Tea, dried 10.000000 1.000 0.140 propar Full comment: propargite 95003730 O Tea, instant 7.000000 1.000 0.140 glypho Full comment: glyphosate 08003740 8 Tomatillo 10.000000 1.000 0.140 carbar Full comment: carbaryl
08003750 8 Tomato 10.000000 1.000 0.140 carbar Full comment: carbaryl 08003751 8 Tomato-babyfood 10.000000 1.000 0.140 carbar Full comment: carbaryl 08003760 8 Tomato, paste 6.000000 1.000 0.140 imidac Full comment: imidacloprid 08003761 8 Tomato, paste-babyfood 6.000000 1.000 0.140 imidac Full comment: imidacloprid 08003770 8 Tomato, puree 3.000000 1.000 0.140 imidac Full comment: imidacloprid 08003771 8 Tomato, puree-babyfood 3.000000 1.000 0.140 imidac Full comment: imidacloprid 08003780 8 Tomato, dried 10.000000 14.300 0.140 carbar Full comment: carbaryl 08003781 8 Tomato, dried-babyfood 10.000000 14.300 0.140 carbar Full comment: carbaryl 08003790 8 Tomato, juice 10.000000 1.000 0.140 carbar Full comment: carbaryl 95003800 O Tomato, Tree 10.000000 1.000 0.140 carbar Full comment: carbaryl [tomato] 15003810 15 Triticale, flour 5.000000 1.000 0.140 glypho Full comment: glyphosate [wheat transl] 15003811 15 Triticale, flour-babyfood 5.000000 1.000 0.140 glypho Full comment: glyphosate [wheat transl] 50003820 P Turkey, meat 5.000000 1.000 0.140 carbar Full comment: carbaryl 50003821 P Turkey, meat-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 50003830 P Turkey, liver 5.000000 1.000 0.140 iprodi Full comment: iprodione 50003831 P Turkey, liver-babyfood 5.000000 1.000 0.140 iprodi Full comment: iprodione 50003840 P Turkey, meat byproducts 1.000000 1.000 0.140 glypho Full comment: glyphosate 50003841 P Turkey, meat byproducts-babyfood 1.000000 1.000 0.140 glypho Full comment: glyphosate 50003850 P Turkey, fat 5.000000 1.000 0.140 carbar Full comment: carbaryl 50003851 P Turkey, fat-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 50003860 P Turkey, skin 5.000000 1.000 0.140 carbar Full comment: carbaryl 50003861 P Turkey, skin-babyfood 5.000000 1.000 0.140 carbar Full comment: carbaryl 01033870 1CD Turmeric 1.000000 1.000 0.140 diuron Full comment: diuron [potato transl] 05023890 5B Turnip, greens 60.000000 1.000 0.140 fosety Full comment: fosetyl-Al (CG 5) 01013880 1AB Turnip, roots 15.000000 1.000 0.140 fosety Full comment: fosetyl-al 95003900 O Vinegar 25.000000 1.000 0.140 captan Full comment: captan [apple]

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 83 of 85 14003910 14 Walnut 1.000000 1.000 0.140 glypho Full comment: glyphosate (tree nut) 86010000 O Water, direct, all sources 0.100000 1.000 1.000 defaul Full comment: default 100 ppb 86020000 O Water, indirect, all sources 0.100000 1.000 1.000 defaul Full comment: default 100 ppb
95003970 O Water chestnut 1.000000 1.000 0.140 carbar Full comment: carbaryl [pecan]
95003980 O Watercress 6.000000 1.000 0.140 methom Full comment: methomyl 09013990 9A Watermelon 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 09014000 9A Watermelon, juice 15.000000 1.000 0.140 fosety Full comment: fosetyl-Al (curcurbits) 15004010 15 Wheat, grain 5.000000 1.000 0.140 glypho Full comment: glyphosate 15004011 15 Wheat, grain-babyfood 5.000000 1.000 0.140 glypho Full comment: glyphosate 15004020 15 Wheat, flour 5.000000 1.000 0.140 glypho Full comment: glyphosate 15004021 15 Wheat, flour-babyfood 5.000000 1.000 0.140 glypho Full comment: glyphosate 15004030 15 Wheat, germ 5.000000 1.000 0.140 glypho Full comment: glyphosate 15004040 15 Wheat, bran 20.000000 1.000 0.140 glypho Full comment: glyphosate 15004050 15 Wild rice 5.000000 1.000 0.140 azoxys Full comment: azoxystrobin 01034060 1CD Yam, true 10.000000 1.000 0.140 phosme Full comment: phosmet 01034070 1CD Yam bean 10.000000 1.000 0.140 phosme Full comment: phosmet

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 84 of 85 D.2. Results File for Acute Dietary Assessment

U.S. Environmental Protection Agency Ver. 2.02 DEEM-FCID ACUTE Analysis for OCTYLPHENOLS (CLUSTER 5) (1994-98 data) Residue file: Inerts_57active_Cluster5_100ppbH2Orev_7PCTform.R98 Adjustment factor #2 used. Analysis Date: 12-03-2009/13:20:11 Residue file dated: 12-03-2009/13:18:38/8 NOEL (Acute) = 15.600000 mg/kg body-wt/day Daily totals for food and foodform consumption used. Run Comment: "Inert 57 active ingredients + drinking water (100ppb); 100x safe ty factor"

===============================================================================

Summary calculations (per capita):

95th Percentile 99th Percentile 99.9th Percentile Exposure % aRfD MOE Exposure % aRfD MOE Exposure % aRfD MOE

---------- ------- -------- ---------- ------- -------- ---------- ------- -------- Females 13-49 yrs:
0.057907 37.12 269 0.088782 56.91 175 0.133126 85.34 117

### Alkylphenol Ethoxylates Human Health Risk Assessment

Page 85 of 85 D.3. Results File for Ch ronic Dietary Assessment

U.S. Environmental Protection Agency Ver. 2.00 DEEM-FCID Chronic analysis for OCTYLPHENOLS (CLUSTER 5) (1994-98 data) Residue file name: C:\Documents and Settings\colinger\My Documents\Inerts\Cst5\Inerts_57active_Cluster5_100ppbH2Orev_7PCTform.R98 Adjustment factor #2 used. Analysis Date 12-03-2009/13:23:24 Residue file dated: 12-03-2009/13:18:38/8 Reference dose (RfD, Chronic) = .1 mg/kg bw/day COMMENT 1: Inert 57 active ingredients + drinking water (100ppb); 100x safety factor

=============================================================================== Total exposure by population subgroup

-------------------------------------------------------------------------------

Total Exposure

----------------------------------- Population mg/kg Percent of Subgroup body wt/day Rfd

-------------------------------------- ------------- --------------- U.S. Population (total) 0.028624 28.6%

U.S. Population (spring season) 0.029168 29.2% U.S. Population (summer season) 0.029070 29.1% U.S. Population (autumn season) 0.028092 28.1% U.S. Population (winter season) 0.028176 28.2%

Northeast region 0.030808 30.8% Midwest region 0.028497 28.5% Southern region 0.025730 25.7% Western region 0.031395 31.4%

Hispanics 0.030295 30.3% Non-hispanic whites 0.028050 28.0% Non-hispanic blacks 0.027661 27.7% Non-hisp/non-white/non-black 0.036798 36.8%

All infants (< 1 year) 0.061534 61.5% Nursing infants 0.031984 32.0% Non-nursing infants 0.072752 72.8% Children 1-6 yrs 0.071949 71.9% Children 7-12 yrs 0.035224 35.2%

Females 13-19 (not preg or nursing) 0.020727 20.7% Females 20+ (not preg or nursing) 0.022710 22.7% Females 13-50 yrs 0.023387 23.4% Females 13+ (preg/not nursing) 0.024700 24.7% Females 13+ (nursing) 0.029474 29.5%

Males 13-19 yrs 0.022081 22.1% Males 20+ yrs 0.021804 21.8% Seniors 55+ 0.023120 23.1%

Children 1-2 yrs 0.090052 90.1% Children 3-5 yrs 0.067194 67.2% Children 6-12 yrs 0.037482 37.5% Youth 13-19 yrs 0.021487 21.5% Adults 20-49 yrs 0.021909 21.9% Adults 50+ yrs 0.023071 23.1% Females 13-49 yrs 0.022040 22.0%

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