UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460

MEMORANDUM

SUBJECT:

PC Code(s): 011105

Decision No.: 455964

Petition No(s).: NA OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

February 2, 2012

Perboric Acid, Sodium Salt Monohydrate (PBSM) Human Health

Risk Assessment Scoping Document in Support of Registration

Review.

DP Barcode(s)/No(s): D394846 Registration Number 

### (s): 3573-56 and 3573-58 Regulatory Action: Registration Review

Risk Assess Type: Single Chemical Case No(s): 5007

TXRNo.:NA

MRID No(s).: NA

FROM:



### 1'0:

THRU: CAS No(s): 10332-33-9

40 CFR: None

Nathan Mottl, Biologist 

# 1/'**~~** William Hazel, Chemist

Jonathan Chen, Toxicologist

Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (7510P)

Seiichi Murasaki, Chemical Review Manager Regulatory Management Branch II



### Antimicrobials Division (751OP) 

# 4.

Nader Elkassabany, Branch Chief 

# Itc

Timothy Leighton, Senior Scientist

## ~....--­ Risk Assessment and Science Support Branch (RASSB)

Antimicrobials Division (751 OP)

12 EXECUTIVE SUMMARY

The Antimicrobial Division ( AD ) Regist ration Review Team has evaluated the status
of the human health assessments for perboric acid

, sodium salt, monohydrate (PBSM)

. The PBSM registration review case includes one active ing redient PBSM (PC Code 011105). PBSM is the active ingredient in two registered pesticide products Tide with Bleach II (EPA Reg 3573

- 56) and Gain with Bleach II ( EPA Reg 3573

- 58). PBSM is used in combination with sodium nonanoyloxyben zenesulfate (NOBS ) in laundry detergents as a sanitizer to kill odor causing germs and bacteria on clothes

. NOBS was

assessed in a recent registration review decision

. EPA Docket: EPA

- HQ

- OPP

- 2010

- 0424

The PBSM active ingredient is formulated as a dry flowable product in laundry detergents at concentrations of approximatel y 5% active ingredient ( a.i. ). Initially The Agency reviewed hazard and exposure databases for PBS M and have attempted to determine whether changes in science policy , use patterns, or available data have materially affected the overall risk picture. PBSM was first registered in 1998

. A

R eregistration E ligibility D ecision (RED) document was not require d since PBSM was registered after November 1, 1984.

The purpose of this screen is to determine whether sufficient data are available to support registration review

, report on whether past risk assessments are still applicable

, and to determine whether new human health assessments are needed to support the registration review process

.

The original registrations for the products that included the active ingredients NOBS

and PBSM were assessed together in conditional registrations. PBSM and NOBs were

q ualitatively assessed together in 1998 for the purpose of registration (D240707, D240713, D242289, D242290, and D246258). Toxicity data was required for NOBS, but was not required for PBSM. The reason for waiving the requirements was that the Agency determ ined that PBSM was a ‘peroxy compound

. ’ T he Agency had waived all

the non

- acute toxicity data in the 1993 Hydrogen Peroxide RED (D250491)

. Quantitative occupational and residential and dietary risk assessments were not developed during registration because no toxicological endpoints were developed. Human health data requirements were required for NOBS, but not for PBSM.

PBSM rapidly hydrolyzes in water to boric acid and hydrogen peroxide. The degradate, hydrogen peroxide

, then perhydrolyzes NOBS to form pernonanoic acid in

situ . PBSM acts as both laundry bleaching agent and as sanitizer in combination with

NOBS . The PBSM residues are expected to be very reactive and are also expected to rapidly biodegrade for the laundry use . The Agency does not expect t hat PBSM will

contaminate water or remain on washed clothes as directed by the present product label

.

For registration review, the Agency identified potential inhalation exposure concerns for pouring PBSM dry flowable concentrates into a laundry machine. As a result, the Ag ency anticipates th at dermal and inhalation tox ic ological endpoint s will be needed t o develop occupational and residential risk assessment s

. The Agency does not expect to
conduct risk assessments for d ietary

, aggregate and cumulative ex posures

. The Agency3 no longer believes that the toxicity data requirements should be waived since 1) the PBSM active ingredient is not included in the Peroxy Compounds RED case and 2)

PBSM contains borate which is a known male reproductive toxicant and was already assessed in a recent registration review decision (EPA Docket: EPA

- HQ

- OPP

- 2007

- 0675 ).

Section 1. Chemical Identity

PBSM is a highly water soluble and non

- vol atile white dry flowable that hydrolyzes rapidly in water at higher pH levels and hydrolyzes and more slowly at lower pH levels (MRID 45236201)

. Table 1 presents the chemical identity of PBSM

. In aqueous solutions at room temperature, equilibrium between PBSM and hydrogen peroxide and sodium borate instantly established (See equation I ). H ydrogen peroxide is also expected to further degrade to (active) oxygen and water (Equation II).

(Equation I)

H

2 O 2 

## → H 2 O + [ O ] (Equation II)

Table 1 Chemical Identity

Common

Name Perboric acid , sodium salt, monohydrate and

s odium per borate, monohydrate

CAS name Perboric acid , sodium salt, monohydrate

PC Code 011105 CAS registry

number 10332

- 33

- 9

Registration

Review Case

No. 5007

Structure4 Section 2. Toxicology

Acute Toxicity

In acute toxicity studies, PBSM has been shown to have low toxicity by the oral route (Toxicity C ategory III) and dermal route (Toxicity Category III) and PBSM is a mild skin irritant (Toxicity Category IV) . PBSM shows a strong response as an eye irritant (Toxicity Category I). There is no available acute inhalation study for PBSM. Therefore, an ac ute inhalation study for technical PBSM is considered a data gap. Acute toxicity for PBSM is presented below in Table 2.

Table 2 . Acute Toxicity Data for PBSM Technical Grade Active Ingredient (97.9

- 100%)

Guideline Number Study Type MRID

Number Resul ts Toxicity Category

870.1100 Acute oral toxicity 41716201 LD 50 ( males ) = 1300 mg/kg

LD 50 ( females ) = 890 mg/kg

LD 50 (combined) = 1120 mg/kg (M+F) III

870.1200 Acute dermal toxicity 41716202 LD 50 > 2000 mg/kg (M and F) III

870.1300 Acute inhalatio n toxicity

- Data gap

-

870.2400 Acute eye irritation 41716203 Corrosive (corneal opacity persist up to 21

- days post

- application) I

870.2500 Acute dermal irritation 4176204 S light irritation (moderate irritation at 72 hours post

- application) III

870. 2600 Skin sensitization 43375211 Non

- sensitizer

M = males; F = females ; NA = not applicable

Subchronic Toxicity

There is no acceptable subchronic study in the PBSM toxicology database and EPA anticipates the need for an inhalation toxicity study

. The A gency expects that there could

be i nhalation exposure to the dry flowable detergent containing PBSM

. PBSM breaks

down to boric acid and H 2 O 2 under physiological conditions . Both the parent compound and the degradation product H 2 O 2 are strong oxidant s . T he data from a wide variety of experiments have suggested that reactive oxygen metabolites may play an important role in the pathophysiology of lung inflammation and injury, and evidence has shown

formation of short

- lived reactive oxygen species within the lung tissue may result in lung injury.

No studies are available which address potential subchronic toxicity of PBSM via the

oral and dermal route. Since sodium perborate is rapidly hydrolyzed in water to boric acid and hydrogen peroxide

, oral and derm al exposure of the parent compound would be limited once the parent compound is in water.

Prenatal Developmental Toxicity5 There is no developmental study in the PBSM database. There is one developmental study on sodium perborate tetrahydrate been cited i n the draft HERA Risk Assessment of

Sodium Perborate mono

- and tetrahydrate indicating sodium perborate may cause developmental concern including decrease fetal body weight, skeletal and visceral

variants (HERA, 2002). A developmental toxicity is conside red as a data gap.

Reproduction and Fertility Effects Toxicity

There is no reproductive study in the PBSM database. Since sodium perborate is rapidly hydrolyzed in water to boric acid and hydrogen peroxide. Borate is a known male reproductive toxicant and was already assessed in a recent registration review decision (EPA Docket : EPA

- HQ

- OPP

- 2007

- 0675 ). The Agency will use the decision made in the borate registration rev iew to address the reproductive concern for PMBS.

Chronic Toxicity

Chronic toxicity data are not required at this time since there are no chronic exposures based on the current labeled use patterns for PBSM.

Carcinogenicity

There is no carcinogenic ity study in the PBSM database and not needed

.

Mutagenicity

There is no mutagenicity study in the PBSM database. Both in vitro and in vivo mutagenicity are cited in the draft HERA Risk Assessment of Sodium Perborate mono

and tetrahydrate (HERA, 20 02). The reports suggest perborate may cause:

**•** Positive responses in Ames Assay with strains TA 100 and TA 102 in the absence

of metabolic activation;

**•** A positive response was obtained in a DNA repair assay was conducted using E
coli repair deficient and r epair proficient strains suggesting the perborate was
capable of inducing preferential DNA repair; and

**•** A positive response in Chinese hamster ovary mammalian cells (CHO

- K1) on

chromosomal aberrations was obtained in the absence of S9

.

All the positive res ponses were reduced or abolished with S9 and/or catalase treatment, indicating the repose is caused by the degradation product H 2 O 2 . Hydrogen peroxide is produced under physiological conditions

.

Dermal Absorption Factor

There is no dermal absorption s tudy in the PBSM database. PBSM is an inorganic

water

- soluble solid of relatively low molecular weight. Dermal absorption of PBSM is assumed to be low due to the hydrophilic character and ionic structure of the substance.6 Toxicity Endpoint Selection for Human Health Assessments.

A t oxicity e ndpoint selection has not been selected for PBSM.

.

Section 3. Dietary and Drinking Water Assessment

Given that the only EPA

- registered use of PBSM is as part of an antimicrobial system in laundry dete rgents, there is no opportunity for residues of this active ingredient to result in human dietary exposure via contaminated food.

As PBSM is an active ingredient in laundry detergents, discharges of washing machine waste water into municipal waste wa ter treatment plants are expected from homes and from commercial and institutional facilities. However, sodium perborate is rapidly hydrolyzed in water to boric acid and hydrogen peroxide. The hydrogen peroxide perhydrolyzes the NOBS to form pernonanoic ac id in situ which acts as both laundry bleaching agent and as sanitizer. These residues are either very reactive or are rapidly biodegraded. Therefore none of these residues are expected to survive long enough to contaminate drinking water. Thus, human diet ary exposure via contaminated drinking water is not likely to occur.

Section 4 . Occupational /Residential Exposure

An occupational and/or residential exposure assessment is required for an active ingredient if (1) certain toxicological criteria are tri ggered and (2) there is potential exposure to handlers (mixers, loaders, applicators, etc.) during use or to persons entering treated sites after application is complete. For PBSM , the Agency needs to select and identify toxicological endpoints before a r isk assessment can be conducted. The Agency may need to conduct handler dermal and inhalation risk assessments once the toxicity data has been submitted, reviewed, and accepted by the Agency.

The Agency did not conduct a quantitative occupational and re sidential risk

assessment for NOBS/ PBSM in registration since there were no NOBs/PBSM toxicological endpoints

. Based on the available use information, AD concludes that there is potential exposure to handlers when pouring the dry flowable detergent (i.e.,

commercial and homeowner laundry ). Although potential exposure could occur via

exposure to laundered clothes , the Agency believes this dermal and incidental oral exposure is negligible because of the rapid degradation of perborate after the laundry is

was h ed and dr ied . The Agency expects that minimal residues will remain on the

laundered clothes

.

Hander Exposure

The Agency has identified potential inhalation occupational and homeowner handler exposures for PBSM

. Since dermal absorption of PBSM is assu med to be low due to the hydrophilic character and ionic structure of the substance, the Agency will not develop dermal handler exposures. For inhalation, the Agency is aware that the fraction of respirable particles in PBSM dry flowable product is low and much of the particulate would not be respirable . According to HERA , 90 to 100% of the PBSM particles have a7 diameter above 0.15 mm (HERA, 2002) . However, the Agency is concerned that in the aqueous media of the lung, the large r PBSM particles would imme diately dissociate to hydrogen peroxide

and boric acid . The Agency is concerned since the parent compound and the degradation product H 2 O 2 are strong oxidant s

. As a result the Agency expects to need toxicological inhalation endpoints for PBSM and also anti cipate the need to develop inhalation risk

assessments. The inhalation exposure scenarios include:

**•** Occupational applicators/loading d ry flowable concentrate for laundry machines at commercial laundromats; and,

**•** Residential applicators loading dry flowa ble concentrate for laundry machines and hand washing clothes.

R isk assessments may be needed depending on whether toxicity studies triggers the development of hazard endpoints. The hazard database is inadequate at this t ime to permit select ion of inhala tion toxicological endpoints.

Product use information was provided to the Agency in 2001 (MRID 45436203), which will aid the Agency in developing use and usage inputs in order to estimate occupational and residential handler exposures. The risk assessmen t will be conducted if

and when appropriate toxicological endpoints are selected by the Agency. Based on the data submitted by the registrant, the Agency will assess the product s as a dry flowable

and will use the product use data to develop exposure assum ptions.

Postapplication Exposure

T he Agency believes that dermal , inhalation and incidental ingestion exposure are expected to be negligible based on dilution, solubility of PBSM in water and rapid degradation in the resulting alkaline wash water solut ions ( MRID 45236201 ) . The Agency came to this conclusion after review of the description of human activity data and hydrolysis data submitted by the registrant (MRID 45436203/MRID 45236201). As a

result no additional data are anticipated as being needed fo r post

- application exposure.

Section 5 . Aggregate and Cumulative Exposure

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

non

- o ccupational pesticide exposures

. Dietary (food and drinking water) exposures of concern are not anticipated for PBSM because concentrations are significantly diluted, does not contact food, and residues are either very reactive or are rapidly biodegraded

. The Agency does expect that it will need to conduct a residential assessment. A n aggregate assessment is not anticipated.

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not ma de a common mechanism of toxicity finding as to PBSM and any other substances and PBSM does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that PBSM has a common mechan ism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals8 have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects

from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/c umulative/.

Section 6. Incidents

There have been no human incidents reported in any of the OPP databases associated with exposure to PBSM

.

Section 7 . Anticipated Data Needs

The Antimicrobial Division (AD) anticipates the need for the following st udies to complete risk assessments for the registration review process for PBSM and to develop toxicological endpoints

. Complete justifications for these studies are presented in Appendix A.

Toxicological Data Needs

**•** Acute Inhalation (GLN 870.1300)

**•** 90

- day Inhalation (GLN 870.3465)

**•** Rat Developmental (GLN 870.3700)

Occupational and Residential Applicator Exposure Data Needs

Table 3: Human Health Data Needs Based on End Use Labels

Study Needed * Guideline Rationale (also see Appendix B) Indoor Exposure from

L oading dry F lowable

Concentrate 875.1 4 00 (Inhalation) 875.1600 (Data Reporting) An inhalation e xposure stud y is needed for individuals loading detergent dry flowable concentrate into washing

machines.

* Note: Product use and human activity informat ion for NOBS/PBSM were submitted during registration (MRID 45436203) and are not anticipated as needed for registration

review

.

Section 8 . Tolerances

There are no tolerances or exemptions from tolerances for PBSM and no registered

food uses. Since th e only registered uses are for non

- food uses and no dietary assessment is needed, no tolerances or exemptions from tolerances will be needed to support the existing registered uses of PBSM

.9 Section 9 . Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, 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 endocrine 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 acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part

of its reregistration decis ion

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), PBSM is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA 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 est rogen, 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 chemic al 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 t he 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 adverse 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 screen 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 p esticide active ingredients and 9 inert ingredients. PBSM 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 cal l

- ins, requiring the submission of EDSP screening assays for PBSM

. For further 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 o ur website: http://www.epa.gov/endo/

.

Section 1 0 . Reference

**•** U.S. EPA, 1998. RASSB Review For NOBS, Sodium Nonanoyloxybenzene Sulfonate and Sodium Perborate (Sodium Peroxyborate); Product Chemistry, Toxicology, Hum an Exposure, Environmental Fate, and Ecological Effects. July 8, 1998. D240707; D240713; D242289; D242290; D246258.

**•** U.S. EPA, 1999. Sodium nonanoyloxybenzenesulfonate (NOBS); review of toxicology data in support of registration of the active ingredient. No vember 24,10 1999. Memorandum from T. McMahon, phD , RASSB to D. Edwards, Branch Chief, RMB1. D250491.

**•** MRID 45436203.Human exposure data to support the use of nonanoyloxybenzene (NOBS) as an active ingredient in sanitizing laundry detergents. Karen D. Smith, ph.D., Proctor and Gamble Company. June 14, 2001.

**•** MRID 4523601. The determination of hydrolysis of E3411.01 as a function of pH. MacDonald, I.A., Howes, D.A. and G. J. Davies. September 21, 1988.

**•** HERA (200 2 ). Draft Human and Environmental Risk Assessment on ingredients of European cleaning products

– Perboric acid, sodium salt, mono and tetrahydrate.11 Appendix A Toxicity and Exposure Study Justifications12 Guideline Number: 87 0

. 3 4 65 Data Requirement: 90

- day Inhalation Toxicity Study Rationale for Requiring the Data The Agency does not have a full picture of the potential effects which PBSM 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.

P ractical Utility of the Data

1. How would the data be used? The study may result in a change in how risks are quantified. The data would allow the Agency to conclude more definitively wheth er or not there would be any concerns for inhalation toxicity in the rat. This would provide a more complete hazard characterization of biobor in regards to the potential risks to the U.S. general population.

2. How could the data affect the risk assess ment? The study may result in a change in how risks are quantified. It is possible that the database uncertainty factor be reduced or removed, resulting in different magnitude of the value of the endpoint used for regulation.

3. What is triggering the n eed for this data?
The difficulty of predicting real world human inhalation exposure with limited data and no inhalation data or other alternative information, such as SAR (structure

- 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 PBSM particles based on how it is used (The OPPTS Guidelines require an MMAD of 1

- 3 **μ** m in inhalation toxicity studies of aerosols so that a portion of the test article will reach the lungs). The exposure to dusts during mixing/loading are triggering the need for toxicological data in order to conduct a risk assessment.13 Guideline Number: 87 0

. 1300 Data Requirement: Acute Inhalation Toxicity Study Rationale for Requiring the Data Waiver criteria have been updated based on advances in inhalation toxicology. The newer criteria state that a registrant requesting a waiver on the basis of particle size must demonstrate that t heir product contains large, non

- inhalable particles which are resistant to attrition and that a particle is essentially non

- inhalable if > 99% of the particles by mass are >100 μm in diameter. The Agency’s information indicates a large proportion of the particles of the technical powder have diameters less than 100 microns. On this basis, the

waive r for an acute inhalation toxicity study can no longer be supported for the dry flowable material. Practical Utility of the Data

1. How would the data be used? Determination of acute oral, dermal and inhalation toxicity are one of the initial steps i n the assessment and evaluation of the toxic characteristics of a pesticide.

2. How could the data affect the risk assessment? Data from acute studies serve as a basis for classification and precautionary labeling. For example, acute toxicity data are u sed to develop precautionary label statements pertaining to protective clothing requirements for applicators.

3. What is triggering the need for this data? There is no available acute inhalation study for PBSM. Therefore, an acute inhalation study for

t echnical PBSM is considered a data gap.

Guideline Number: 87 0

. 3700 Data Requirement: Rat Developmental Toxicity Study Rationale for Requiring the Data The needed study would provide insight into concerns regarding pre

- and/or postnatal toxicity as requi red by FQPA. It may also provide a toxicity endpoint applicable to risk assessment.

Practical Utility of the Data

1. How would the data be used? The study may result in a change in how risks are quantified. The data would allow the Agency to

conclude more definitively whether or not there are any concerns for pre

- and/or postnatal toxicity in the rabbit. This would provide a more complete hazard characterization of PBSM in regards to the potential risk of developmental toxicity.

2. How could the da ta affect the risk assessment? The study may result in a change in how risks are quantified. It is possible that the database uncertainty factor may be reduced or removed, resulting in different magnitude of the value of the endpoint used for regulation.

3. What is triggering the need for this data?
The difficulty of predicting real world human exposure via oral route with limited data and no developmental toxicity data in rabbit or other alternative information, such as SAR (structure

- activity

relations hip), surrogate data, and/or weight

- of

- evidence to the Agency triggered the need for a developmental (guideline) toxicity study in the rabbit, in order to adequately evaluate real world human exposure to PBSM, particularly women in the 15

- 49 years of age a nd infants and children, based on how it

used.14 Guideline Number: 875.1400 Data Requirement: Inhalation Exposure

- Indoor Rationale for Requiring the Data The inhalation exposure route is very important for exposure scenarios such mixing/loading expos ure for liquid detergent dry flowable concentrate . In addition, inhalation exposures from dry flowable concentrate are evident in exposure studies in the Pesticide Handlers Exposure Database (PHED). The significance of these exposures is directly affecte d by the severity of the inhalation toxicological endpoint of concern. At this point in time, no toxicological data are available to assess the inhalation risk. The existing Chemical Manufacturer Association (CMA) data base and PHED for these scenarios ar e 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 Review Board (HSRB) and both groups agreed that additional data are warranted. Practical Utility of the Data

1. How would the data be used? The inhalation exposure data would be used to assess the occupational exposure from mixing/loading exposure for detergent dry flowable concentrates

. 2. H ow could the data affect the risk assessment? The inhalation exposure data would be used to determine the accuracy of the inhalation risks to both residence and occupational workers. If risks warrant mitigation, the inhalation exposure data would provide the types of mitigation necessary such as respiratory protection from respirators or closed systems for commercial uses to potential removal of uses from the label. 3. What is triggering the need for this data?
The criteria for the inhalation exposure dat a are based on the potential for respiratory exposure from the labeled uses (e.g., exposure to PB S M dry flowable concentrate ) and evidence of toxicity. If no toxicological endpoints of concern were identified, then the inhalation exposure data would not b e needed.

Guideline Number: 875.1600 Data Requirement: Applicator Exposure Monitoring Data Reporting Rationale for Requiring the Data For all exposure studies this data need is needed to facilitate the review of the data. Practical Utility of the Data

1. How would the data be used? The study report and all raw data/calculations would be reviewed for the adequacy of the data.

2. How could the data affect the risk assessment? The data are needed to interpret the inhalation exposure data collected. 3. What is triggering the need for this data?
This data need is triggered if an exposure study is conducted.