UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D

. C. 20460

May 31, 2011 OFFICE OF CHEMICAL SAfETY
AND POLLUTION PREVENT I ON

MEMORANDUM

SUBJECT:

PC Code s : 00010 1

Decision No

. : 440822

P

et ition No s

. : NA Summary of Human Health Effects Data for the Glycolic A cid Registration Review Decision Document.

OP Barcode s lNo s: 0383022

R

e gistration No ( s).: 5813·80, 5813

· 86, 5 813 -87

, 5813·93, 5813-101 71654-1,71654-2, and 7 165 4·5

Re ulato Action: Human Health Re istration Review

Risk Assess Type: Single Chemical Case No(s .: 4045

TXRNo.:NA

MRIO No s.: NA

FROM:

TO:

THRU: C ASN s: 79

- 14

- 1

40 CFR : None

Nathan Mott l

, Biologist

# I./~**~** s-/3/ /11

Risk Assessment and Sc i ence Support Branch (RASSB)

Antimicrobials Di v ision (751 OP)

Seiichi Murasaki, Chemical Review Manager Regulatory Management Branch II

Antimicrobials Divis i on (75 1 OP)

Lance Wonnell, Team Leader Regulatory Management Branch II

An t imicrobials Divis i on (751 OP)

Nader Elkassabany, Branch Chief

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials D i vision (751 OP)

Page 1 of 14Page 2 of 14

EXECUTIVE SUMMARY

The Antimicrobial s Division (AD) Registration Review Team has evaluat ed the status

of the human health assessments for glycolic acid ( P.C. Code 000101, R egistration

Review case 4 0 45 ). Glycolic acid is a n antimicrobial pesticide used as an end

- use disinfectant and cleaner primarily used for toilet bowls, showers, baths, and sinks in

household bathrooms and restrooms. Additionally, end

- use products are also used in

kitchens as a disinfectant and cleaner on countertops, floors, and to launder clothes, fabrics and upholstery. AD looked at the hazard and exposure databases for gl ycolic acid to determine whether changes in science policy or deficiencies in the databases materially affected the overall risk picture. Glycolic acid was first registered as a pesticide in 2001 and a Registration Eligibility Decision (RED) document has not yet been initiated. A RED is not required for chemicals registered after November 1, 1984

.

According to Agency data in OPPIN, there are currently 8 registered glycolic acid products. The concentration can range from 1.5 to 68% active ingredient. Ho wever, the

68% a

. i

. product is a Manufacturing Use Product (MUP) used to formulate other antimicrobial products. Typically end use product concentration s are less than 10 % ai.

M any of the applications for glycolic acid typically involve the use of a child proof squeeze bottle to disinfect and deodorize toilet bowls and urinals . These squeeze bottles minimize aerosol generation and typically last for onl y 12 seconds. However, there are

also some registered disinfectant produc ts which a re used for spray , mop and wipe application s of countertops and floors in bathrooms and kitchens

. In addition, a registered disinfectant product is also used for laundry. The Agency typically assumes that a trigger pump sprayer or aerosolized can is used for the spray and wipe applications . The Agency will need product use information to understand whether this product is likely to have the potential to aerosolize.

There are no existing tolerances, exemptions from the requirement of tolerances, or tolerance petitions f

or this a ntimicrobial pesticide

. Glycolic acid is commonly used as a

cosmetic ; is ubiquitous in nature and is present in the human body, sugar cane, sugar beets, and several fruits

. G lycolic acid is also app roved by F DA as an indirect food

additive for use in food packaging adhesives (175.105) . In addition, t her e are some public

health claims for this pesticide when used as a disinfectant . T he label states it is effective against disease causing organisms such as S taphylococcus aureus, S almonella

cholerasesuis , and P seudomonas aeruginosa

.

Although the product is designed primarily as a disinfectant for bathroom and restroom premises, this disinfectant has some claims that it can be used on hard, non

porous , non

- food contact surfaces in kitchens such as countertops , sinks and stovetops, for a contact time of 30 seconds at full strength

. If used on a food preparation surface, the

label maintains that all food must be removed prior to application and after application surfaces must be rinsed with potable water. Altho ugh dietary exposure from indirect food

contact surfaces are expected to be minimized based on the application and label

statements, EPA will still need to perform dietary and aggregate risk assessments to determine if tolerances or exemptions from toleran ces will be needed to support the existing registered uses

.Page 3 of 14

No new sub

- chronic toxicity data for glycolic acid have been submitted to the Agency

since registration

. The purpose of this screen is to determine whether sufficient data are available to supp ort registration review , whether new human health assessments are needed to support registration review, and to report why the Agency feels it may be appropriate to conduct new risk assessments under the registration review process

.

Based on this review of the data, occupational and residential risk assessments would be needed to examine potential exposure scenarios including:

Dermal and inhalation application exposure to trigger pump spray and wipe,

Dermal and inhalation application exposure to aerosol spray can and wipe,

Dermal and inhalation application exposure by mopping, and

Dermal and inhalation appl ication exposure by open pour.

EPA als o expects that dermal and incidental oral postapplication exposures may occur

. The potential scenarios includ e children crawling on previousl y mopped floors, wearing

laundered clothes, mouthing treated fabrics or hand

- to

- mouth exposure from counter tops wiped with disinfectant

.

EPA expects that some of the exposures will also likely be minimized based upon speci fic label use directions, personal protective equipment (PPE) and specific application equipment which are designed to minimize aerosols. Therefore, product use data will be

essential to further characterize the need for these risk as sessment s

. In addition , the Agency will also require additional the following exposure data:

Inhalation Exposure Indoor (GLN 875.1 4 00); Dermal Exposure Indoor (GLN 875.1 20 0); Application Exposure Monitoring Data Reporting (GLN 875.1600) ; Product Use Data (GLN 875.1700 and 8 75.2800 ) ; Indoor Surface Residue Dissipation (GLN 875.2300)

Non

- dietary Ingestion (875.3000)

As a result o f the inhalation concerns, the Agency anticipates that a 90

- day inhalation study will be needed to identify an inhalation to xic ity endpoint for risk assessment. Typically the Agency also requires a 90

- day dermal study GLN (870.3250). However, during registration, the EPA waived this requirement and granted a data waiver for a

dermal sub

- chronic toxicity study based upon the pH of the test material and possible precautions based on the corrosivity of glycolic acid to animal skin. In lieu of a 90

- day dermal toxicity study, the Agency accepted an oral toxicity study (GLN 870.3150; D239541).

Section 1. Chemical Identity

Glycolic acid is an alpha

- hydroxy l acid in which there is a hydroxyl (

- OH) group attached at the two alpha positions of the carbon chain. Glycolic acid is a light amber liquid , which is highly miscible in water. It has a boiling point of 112 o C and a vapor pressure similar to water . At a 3 0% concentration in water , it has a pH ≥ 3.5

. It has a density of 10.6 lb/gal and dissociation constant of 1.5E

- 4. Glycolic acid is registered as anPage 4 of 14

active ingredient in six end

- use products for residential and public access premises to
clean toilet bowls . The registered products con tain 1.5

- 9.5 % active ingredient (ai.). Table 1 presents the chemical identity of glycolic acid.

Table 1

. Chemical Identity

Common

Name Glycolic acid

Synonyms Hydroxy Acetic Acid, Hydroacetic Acid,

and Hydro xy E thanoic A cid

PC Code 000101 CAS registr y number 79

- 14

- 1

Registration

Review Case

No. 4045

Empirical

Formula

Vapor

Pressure 11.2 mm Hg for 70% technical at 100C.

Section 2. Toxicology

The Agency has reviewed all toxicity studies submitted for glycolic acid and the

ex isting toxicity database and has determined that an additional 90

- day inhalation toxicity study may be needed

. The toxicological database for glycolic acid is currently comprised of published and unpublished studies either submitted to the Agency or obtain ed directly from published literature during the registration process.

Several studies for the acute toxicity 6

- pack were waived due to the low pH of glycolic acid (0.5). The acute dermal, dermal irritation, and eye toxicity studies w ere all waived

dur ing registration based on a low pH (<2) and the expected corrosivity of the product. The toxicity categor ies would default to toxicity category I based on the waiver.

For the other submitted tests , an acute oral toxicity of glycolic acid ranged from LD 5 0 of 1938 mg/kg in the MUP to 2968 mg/kg for the cosmetic formulation. In mice, the LD 50 was 2000 mg/kg, using a 70% concentration of glycolic acid. A n oral toxicity category of

III w as assigned to the product. The acute inhalation toxicity study reported an LC 50 of 3.6 to > 5.2 mg/L. The LC 50 would be expected to result in a toxicity category IV rating. A

modified draize test was conducted with glycolic acid. Following dermal application glycolic acid was determined not to be a dermal sensitizer.

Based on the registered uses, only one sub

- chronic study, one developmental study

and a battery of mutagenicity tests were determined to be needed for glycolic acid registration

. T he registrant submitted a 90

- day sub

- chronic oral toxicity test (MRID

449753

- 04) in lieu of a 90

- day dermal toxicity study. The rationale for not conducting a dermal test was based on the pH of the test material and possible precautions based on thePage 5 of 14

corrosivity of glycolic acid to animal skin. The Agency accepted this rationale and t h e oral study was considered the only study needed to satisfy th e sub

- chronic data requirement (GDLN 870.3100) during registration

. MRID 449753

- 04 was considered to
be an acceptable guideline study

.

In th e 90

- day sub

- chronic oral toxicity study, rats we re administered oral doses by gavage at 0, 150, 300 and 600 mg/kg/day for 90 days. The systemic toxicity of glycolic acid was evident at 300 mg/kg/day. At these dose levels decreases in body weight, body weight gain, food consumption, and food intake was reported. Male rats had kidney pathology which consisted of hyperplasia of renal pelvis dilation, unilateral hydronephrosis, and oxalate crystal formation. These results were not reported in the female. The systemic LOAEL of 300 mg/kg/day is based upon de creased body weight and body weight gain as a result of decreased food consumption and food efficiency in

both males and females. The NOAEL for systemic toxicity is 150 mg/kg/day in male and

female rats. For other parameters measured, a LOAEL was not es tablished for immunotoxicity, neurotoxicity or reproductive toxicity effects.

In a n acceptable guideline (GDLN 870.3700) developmental toxicity study (MRID 44589501) glycolic acid was administered to at 0, 75, 150, 300 and 600 mg/kg/day on gestation day s (GD) 7 through 21. The maternal toxicity LOAEL of 300 mg/kg/day was based on the effect of lung noise with a NOAEL of 150 mg/kg/day

. The developmental toxicity LOAEL of 300 mg/kg/day was based upon fused ribs and vertebrae and a developmental NOAEL was established at 150 mg/kg/day.

Three muta genicity studies were submitted to EPA. The studies include a reverse gene mutation study on S almonella t yphenium and Escherichia c oli (MRID 449753

- 0 5 )

, a n in

vitro forward gene mutation assay in mice lymphoma cel ls (MRID 449753

- 06), and a mouse erythrocyte micronucleus assay in mice (MRID 449753

- 07). The three mutagenicity studies submitted were reviewed in 2001 by EPA (D264011, D264012, and D264014). MRID 449753

- 05 did not induce gene mutation s with or without ac tivation in

bacteria and was classified guideline acceptable as per GDLN 870.5100. MRID 449753

- 06 also did not induce gene mutations in mice lymphoma cells and was found guideline acceptable as per GDLN 870.5300. MRID 449753

- 07 did not induce chromosome aberrations of erythrocytes and was found guideline acceptable as per GDLN 870.5395.

Since inhalation exposure is considered as a primary route of exposure , the Agency anticipates that a 90

- day inhalation study will be needed to identify an inh alation toxicological endpoint for risk assessment. No sub

- chronic inhalation toxicity studies for glycolic acid were identified in the existing literature.

Section 3. Dietary Assessment

G lycolic acid is ubiquitous in nature and is present in the huma n body, sugar cane, sugar beets, several fruits (pineapple, cantaloupe, unripe grapes) and vegetables (parsley, celery, and beans), as well as in a wide variety of common foods including coffee (D383020). However, there could be indirect food contact from countertops in residential

homes. Formulations on countertops are typically diluted and t he label recommends that food found on countertops must be removed prior to application, and c ountertop surfacesPage 6 of 14

must be rinsed with potable water. Although, r esidu es of glycolic acid on countertops after potable water rinses are not expected to concentrate on food products and exposure

will be minimal

, EPA will still need to conduct a dietary (food) assessment for this use.

According to the environmental fate and ecotoxicity registration review document (D383020), glycolic is expected to be readily biodegradable in the environment

. Glycolic

acid is also expected to be diluted when it is flushed down the drain. Resulting

concentrations drinking water are not expect ed to be above background levels found in the

environment and a drinking water assessment is not necessary

.

Section 4 . Occupational /Residential Exposure

There is potential short

- term application exposure to occupational workers and

homeowners while s pray ing disinfectant s to indoor surfaces

. The scenario s which the Agency will consider for assessment would include application of aerosol spray, trigger pump spray, and wiping. The Agency will need to conduct screening level risk

assessments for th e hard surface disinfection use; therefore, the Agency will anticipate needing exposure studies in the Anticipated Data Needs (S ection 7 )

. The potential exposure scenarios would include occupational and residential exposure assessments

which would include :

Derm al and inhalation application exposure to trigger pump spray and wipe

, Dermal and inhalation application exposure to aerosol spray can and wipe, Dermal and inhalation application exposure to open pouring, and Dermal and inhalation application exposure to m opping.

EPA expects that some of the exposures will also likely be minimized based upon specific label use directions

, and specific application equipment which are designed to

minimize aerosols

. In addition

, product use data will be essential to further characterize exposures to glycolic acid and whether a risk assessment will be needed on certain application equipment

. For example, glycolic acid can be used to disinfect, sanitize, and

deodorize toilet bowls and urinals and the products are applied in a child proof squeeze bottle. The inhalation concern for the squeeze bottle is expected to be minim ized by the design of the bottle which minimizes any inhalation aerosol s upon application

.

In addition, EPA expects that dermal and incidental oral posta pplication exposures may occur from children crawling on treated floors, wearing treated clothes, mouthing of

treated fabrics or hand

- to

- mouth exposure from counter tops and floors.

There are acute toxicity concerns for dermal and eye irritation for the technical active ingredient for occupational exposure

. How ever, the acute toxicity concerns for the diluted end use products are considerably less when considering labeling precautions that typically include eye protection and rubber or chemical resistant gloves

.

Section 5 . Aggregate and Cumulative ExposurePage 7 of 14

In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to glycolic acid residues in food and drinking water,

and non

- occupational pesti cide exposures. Residential application risks such as spraying, mopping, wiping exposures are expected to be aggregated as well as post

- application

hand

- to

- mouth exposure from treated counter tops and mouthing treated fabrics. The Agency will also need to conduct a dietary risk assessment for glycolic acid based on indirect food contact exposure on countertops

.

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider "available infor mation” concerning the cumulative effects of a particular pesticide's residues and "other substances that have a common mechanism of toxicity.” EPA does not have, at this time, available data to determine whether glycolic acid has a common mechanism of tox icity with other substances or how to include this pesticide chemical in a cumulative risk assessment.

Section 6. Incidents

No human i ncidents have been reported specifically for glycolic acid in the OPP

Incident Database.

Section 7 . Anticipated Data Ne eds

The Antimicrobial Division (AD) anticipate s requiring further exposure studies for glycolic acid for registration review

.

Toxicity Studies

90

- day inhalation toxicity study (GLN 870.3465).

Exposure Studies

Table 2

– Exposure Studies Needed for Gly colic Acid Registration Review

Study Needed Guideline Rationale Indoor Exposure ( Trigger Spray ) 875.1 2 00 (Dermal)

875.1 4 00 (Inhalation) 875.1600 (Data Reporting) Exposure may occur while spraying with a trigger pump cleaning spray in a bathroom, kitche n or other areas of the

home or office

. Indoor Exposure ( Aerosol Spray ) 875.1 2 00 (Dermal)

875.1 4 00 (Inhalation) 875.1600 (Data Reporting) Exposure may occur while spraying with a aerosol can in a bathroom, kitchen or other areas of the home or office

.

In door Exposure (Sp onge and Wipes ) 875.1 2 00 (Dermal)

875.1 4 00 (Inhalation) 875.1600 (Data Reporting) Exposure may occur while sponging or wiping disinfectant

on a hard surface area.

Product Use 875.1700 (Handler) 875.2800 (Postapplication) Product use dat a will be needed to characterize any uncertainties with regard to the application equipment.

Indoor Surface Residue Dissipation Data 875.2300 Residue data for countertops, floors, and clothing would be needed to assess dermal and incidental oral exposure. Nondietary Ingestion 875.3000 The design of the non dietary ingestion exposure study can be combined with the Indoor Surface Residue Dissipation study (875.2300) to determine the available residue leaching from hand

- to

- mouth behavior on countertops,Page 8 of 14 floo rs and mouthing treated fabric.

Section 8 . Tolerances

There are no tolerances or exemptions from tolerances for glycolic acid and no regi stered food uses. As mentioned, glycolic acid is used as a sanitizer on countertops and

is also use d by the FDA as an indirect food additive in food packaging adhesives. Therefore, EPA will be reassessing the need for a tolerance or exemption from tolerance.

It is noted that exemptions and regulations for food additives under Section 409 of the Federal Food, Drug, and Cosmetic Act (FFDCA) do not relieve the registrant of meeting the standard under Section 408 as amended by the Food Quality Protection Act (FQPA), when the active ingredient is subject to regulation as a food

- use pesticide under the Federal Insecticide, F ungicide, and Rodenticide Act (FIFRA). Under Section 408, a determination of safety for residues of a pesticide that may be in food is required, and as defined in Section 408(b)(2)(ii), “that there is a reasonable certainty that no harm will result from ag gregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information.” As a result, EPA will be performing risk assessments to determine if tolerances or exemptions from tolerances will be needed to support the existing registered uses of glycolic acid.

Section 9 . Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collec tively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocr ine influence

, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acu te tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its registration decision

, EPA reviewed these data and selected the most sensitive endpoints

for relevant risk assessment sce narios from the existing hazard database. However, as required by FFDCA section 408(p), glycolic acid is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

E PA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar 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 approach 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 estrogen, androgen, or thyroid (E, A, or T) hormonal systems . Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adversePage 9 of 14

endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must scree n all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Glycolic acid is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review,

EPA will issue future EDSP orders/data call

- ins, requiring the submission of EDSP screening assays for glycolic acid

. For furt her information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Section 1 0

. Reference s

D239543. DuPont’s Specialty Chemical Plan to Register Glycolic Acid for Certain Antimicrobial Uses. Memorandum from Norm Cook, Branch Chief, AD/ RASSB, U.S. EPA to Robert Brennis, Product Manager PM 32, U.S. EPA. June 29, 1998.

Memorandum: Glycolic Acid, New Chemical. Memorandum from Frank Sanders, Division Director, AD, U.S. EPA to Marcia Mulkey, Director, Office of Pesticide Programs, U.S. EPA. March 31, 2001.Page 10 of 14 APPENDIX A: TOXICITY

Guideline Numbers: 87 0

. 3465 Study Titles: 90

- day Inhalation Toxicity Study Rationale for Requiring the Data The Agency does not have a full picture of the potential effects which glycolic acid could occur as a result of exposure via the inhalation route. The needed study would provide insight into concerns regarding toxicity via the inhalation route. It may also provide a toxicity endpoint applicable to risk assessment. It is possible that a n inhalation toxicological endpoint may be established and the Agency may determine a level of safety b ased on the results of this study, which has not been determined

. The study could also eliminate any potential inhalation exposure concerns the Agency has if it is determined the dose response does not trigger the need to establish a n inhalation toxicolog ical endpoint.

Practical Utility of the Data

1. How will the data be used?

The inhalation toxicity data will be used to assess toxicity via the inhalation route. The needed study would provide insight into concerns regarding toxicity via the inhalati on route. It may also provide a toxicity endpoint applicable to risk assessment.

2. How could the data impact the Agency’s future decision

- making?

The study may result in a change in how risks are quantified. It is possible that an inhalation

toxicolo gical endpoint may be established and the Agency may determine a level of safety based on the results of this study, which has not been determined

. The study could also eliminate any potential inhalation exposure concerns the Agency has if it is determine d the dose response does not trigger the need to establish a n inhalation toxicological endpoint.

The difficulty of predicting real world human inhalation exposure with limited data and no inhalation data or other alternative information, such as SAR (str ucture

- activity

relationship), surrogate data, and/or weight

- of

- evidence to the Agency triggered the need

for a 90

- day (guideline) Inhalation toxicity study, in order to adequately evaluate real world human exposure to glycolic acid particles based on how it is used (The OPPTS Guidelines require an MMAD of 1

- 3 m in inhalation toxicity studies of aerosols so that a portion of the test article will reach the lungs). The potential inhalation exposure concerns from application equipment from aerosols from trig ger pump sprayer s are triggering this inhalation toxicity endpoint. The Agency believes there exists the potential for lung

irritation effects based on the corrosivity of this chemical

.Page 11 of 14 APPENDIX B : HUMAN EXPOSURE

Guideline Numbers: 875.1 2 00

St udy Titles: Dermal Exposure (Indoor) Rationale for Requiring the Data Note: Dermal exposure data are needed for both residential and occupational uses. The selection of an outdoor versus an indoor site is based on the high end exposure scenario. In a lmost all cases, repeating an exposure study for the same scenario outdoors and indoors is not necessary.

The potential for dermal exposure is very likely for exposure scenarios involving wiping and spraying hard surface disinfectants . The existing CMA d ata base and PHED for these scenarios are limited in scope for QA/QC and number of monitoring units. EPA presented the need for additional handler exposure data to the January 2007 Science Advisory Panel (SAP) as well as to the April 2007 Human Studies Re view Board (HSRB) and both groups agreed that additional data

are warranted.

The criteria for the dermal exposure data are based on the potential for dermal exposure from the labeled uses (e.g., occupational and residential exposures from spraying and wi ping ) and evidence of toxicity. If the toxicological endpoints from glycolic acid are used to assess the risks, there is an endpoint selected for the dermal route

.

Practical Utility of the Data

1. How will the data be used?

The dermal exposure data w ill be used to assess dermal exposures from wiping and spraying

disinfectants . For occupational uses, the dermal exposure data will be used to assess the short

- , and

intermediate

- term exposures. The dermal exposure data will be used to determine the accu racy of the dermal risks to both residence and occupational workers.

2. How could the data impact the Agency’s future decision

- making?

If risks warrant mitigation, the dermal exposure data will provide the types of mitigation necessary

such as chemical resistant gloves or closed systems for commercial uses, or potential removal of

uses from the label.

Guideline Numbers: 875.1 4 00 Study Titles: Inhalation Exposure (Indoor) Rationale for Requiring the Data Note: Inhalation exposure data are needed fo r both residential and occupational uses. The selection of an outdoor versus an indoor site is based on the high end exposure scenario (for inhalation the selection is typically indoors). In almost all cases, repeating an exposure study for

the same scen ario outdoors and indoors is not necessary.

The inhalation exposure route is very important for exposure scenarios such application of paints or metalworking fluids where aerosols would be generated. In addition, inhalation exposures from application are evident in exposure studies in the Pesticide Handlers Exposure Database (PHED). The significance of these exposures is directly affected by the severity of the inhalation toxicological endpoint of concern. At this point in time, no toxicological data ar e available to assess the inhalation risk. The existing Chemical Manufacturer Association (CMA) data base and PHED for these scenarios are limited in scope for QA/QC and number of monitoring units. EPA presented the need for additional handler exposure da ta to the January 2007 Science Advisory Panel (SAP) as well as to the April 2007 Human Studies Review Board (HSRB) and both groupsPage 12 of 14

agreed that additional data are warranted.

The criteria for the inhalation exposure data are based on the potential for res piratory exposure from the labeled uses (e.g., exposure to disinfectants ) and evidence of toxicity. If no toxicological endpoints of concern were identified, then the inhalation exposure data would not be needed.

Practical Utility of the Data

1. How w ill the data be used?

The inhalation exposure data would be used to assess the residential and occupational short

- term
duration of spraying disinfectants

.

2. How could the data impact the Agency’s future decision

- making?

If risks warrant mitigation, the inhalation exposure data will provide the types of mitigation necessary such as dust mist respirators, full face respirators or closed systems for commercial uses, or potential removal of uses from the label.

Guideline Numbers: 875.1600 Study Title : Data Reporting and Calculations Rationale for Requiring the Data For all exposure studies this data need is needed to facilitate the review of the data. The study report and all raw data/calculations would be reviewed for the adequacy of the

data.

P ractical Utility of the Data

1. How will the data be used?

The data are needed to interpret the dermal and inhalation exposure data collected.

2. How could the data impact the Agency’s future decision

- making?

This data need is triggered if an exposur e study is conducted. It would aid the Agency to make accurate interpretations of the studies to develop an accurate and refined risk assessment and refined mitigation.

Guideline Numbers: 875.1700 and 875.2800 Study Title: Product Use Information

Rati onale for Requiring the Data Product use information is a description of how the product is actually applied; it is not a field study. A description of how this product is used would provide for a comprehensive realistic assessment of its potential appli cations. The description of the application techniques would be used to define the exposure scenarios to be assessed in the risk

assessment. Product use will be required for handler as well as postappliction exposures Practical Utility of the DataPage 13 of 14

1. H ow will the data be used?

A complete description of product use would ensure that the risk assessment is inclusive of the types of exposures occurring during residential and occupational use.

2. How could the data impact the Agency’s future decision

- mak ing?

The need for a risk assessment as needed under Registration Review would require that the risk assessor understands how the product is applied.

Guideline Numbers: 875.2300 Study Title: Indoor Surface Residue Dissipation

Rationale for Requiring th e Data

Based on the use of glycolic acid as a hard surface disinfectant for countertops, human contact to treated countertops may occur. There are no data available to estimate exposure to adults and children from exposure to treated countertops , floors , carpets and clothing with glycolic acid Practical Utility of the Data

1. How will the data be used? Without data, the Agency will conduct a screening level assessment using a conservative surface residue value of 1 mg/cm 2 . Currently, there are no da ta that can be used to estimate exposure to adults or to children exposed to treated wood. These data will be used to refine the Agency’s risk

assessment and to confirm or refute the Agency’s screening level assessment.

2. How could the data impact the A gency’s future decision

- making? Depending on the results of the dislodgeable residue study, the Agency may pursue risk mitigation measures regarding the use of formulated products containing glycolic acid as the active ingredient in occupational and reside ntial scenarios.

Guideline Number: 875.3000 Data Requirement: Non

- Dietary Ingestion Rationale for Requiring the Data The design of the non dietary ingestion exposure study can be combined with the Indoor Surface Residue Dissipation study (875.2300) to determine the available residue leaching

from hand

- to

- mouth behavior on counter tops treated with glycolic acid disinfectant.

Practical Utility of the Data

1. How will the data be used? This product is used as a disinfectant on counter tops. The ava ilable residues from hard surfaces will be used to determine the magnitude of children’s incidental exposure from

these uses.

2. How could the data impact the Agency’s future decision

- making?

The data are needed to refine the risk estimates if risks of concern are identified assumingPage 14 of 14

100% residue transfer from contact from hard surfaces (e.g., counter tops). If risks of concern are not identified when 100% residue transfer is assumed, the data are not needed.