Page 2 of 16 EXECUTIVE SUMMARY

The Antimicrobial s Division (AD) Registratio n Review Team has evaluated the status
of the human health assessments for the 1H

- Pyrazole

- 1

- methanol, 3,5

- dimethyl ( DMHMP ) case ( registration review case 5 0 3 5 ). O ne active ingredient (PC Code 129074) and one registered product exist s in the DMHMP case

. DMHMP is sold for use as a n in

can preservative that contains 93 % active ingredient . The registered label indicates that

DMHMP is formulated as a solid granular product intended as a preservative for emulsion paints, latex emulsions, polishes and waxes, papermaking chemicals and coatings, detergents, inks, textiles, and construction materials.

EPA examined the hazard and exposure databases for the DMHMP case to determine whether changes in science policy or deficiencies in the databases materially affected the overall risk picture. DMHMP was first regis tered as a pesticide in August 19, 1996

. A

R eregistration E ligibility D ecision (RED) document h as not been issued for DMHMP since this chemical was registered after November 1, 1984. The primary source of information for this assessment was registration re cords for the only registered product (EPA Reg. 1448

- 351 ) and applicable Agency risk assessment memoranda pertaining to this registration. The Agency did an open literature search and no relevant toxicological or exposure studies for DMHMP w ere available.

T he Agency did not select any dermal, inhalation or oral toxicological endpoints for

short

- term, intermediate

- term occupational

, residential and dietary exposures as indic ated

in the 1995 Toxicology Selection Endpoint Document (U.S. EPA, 199 5b )

. How ever, for registration review , the Agency believes that additional studies will be needed and new toxicological endpoints w ill be needed

. If relevant toxicological endpoints are available for dermal and inhalation, EPA will anticipate the need that new occ upational and

residential risk assessments will be needed (see section 5 )

.

According to the label, DMHMP “ may NOT be used for the preservation of materials which may contact food” in papermaking and adhesives. T herefore, AD will not need to

do an indir ect dietary assessment for these use s. No FDA clearances are available for this compound.

Section 1. Chemical Identity

DMHMP is a white solid, granular (93% active ingredient) end

- use product ( E P). Busan 1104 is registered for non

- food, indoor uses as a material preservative primarily for liquid emulsions subject to microbial degradation. D MHMP is a solid at room temperature

and has a melting point of 77 oC

. No boiling point is available since the product chemistry chapter indicates that it sublimes o r transitions from the solid phase to the gas phase without passing through an intermediate liquid phase

. D MHMP has a log Kow of 0.93 and

is very soluble in water as well as organic chemicals (MRID 41832503)

. The vapor pressure is listed as 3.4 x 10 - 3 hPa or 2.55 x 10 - 3 mm Hg (0.00255 mm Hg) at 20°C. The only registered product contain s 93 % active ingredient (a

. i.). Table 2 presents the chemical identity of DMHMP

.Page 3 of 16 Table 1

. Chemical Identity

Common

Name 1H

- Pyrazole

- 1

- methanol, 3,5

- dimethyl

Synonyms DMHM P

PC Code 129074 CAS registry

number 85264

- 33

- 1

Registration

Review Case

No. 5035

Structure

Vapor

Pres sure 2.55 x 10 - 3 mm Hg at 20°C

Section 2. Toxicology

The Agency has reviewed toxicity studies submitted for the one DMHMP active ingredient (PC Code 129074 ) in the DMHMP case ( Case # 5035)

. The toxicological

database for DMHMP i s currently comprised o f registrant submitted studies submitted to the Agency during registration

. The Agency did an open literature search and no

additional relevant toxicological information for DMHMP was available.

Acute Toxicity

Table 2 summarizes the acute toxicity of DMHMP

.

Table 2 : Acute Toxicity Studies

STUDY GLN RESULTS TOXICITY

CATEGORY
Acute Oral GLN 81

- 1/

MRID 418321

- 01 LD 50 = combined: 2.6 g m /kg III

Acute Dermal GLN 81

- 2/

MRID 418321

- 01 LD 50 > 2.0 g m /kg II I

Acute Inhalation GLN 81

- 3/ Waiver granted N APage 4 of 16 Primary Eye

Irritation GLN 81

- 4/

MRID 418321

- 03 Corrosive I

Primary Dermal

Irritation GLN 81

- 5/

MRID 418321

- 04 Irritation I

Dermal

Sensitization GLN 81

- 6 /

MRID 418321

- 05 Not a skin s ensitizer NA

Mutagenicity

An Ames test was conducted on a serie s of nonactivated and S9 activated Salmonella typhimurium assays were dosed up to 1000 μ g/plate (MRID 41832401). DMHMP was not mutagenic in strains TA1535, TA1538, and TA98, but histidine revertants were found for strain TA100. According to the EPA review, the initial findings were equivocal and the study was unacceptable according to 84

- 2a guidelines. However, on August 26, 1993 the study was later upgraded to acceptable.

DMHMP was tested for its potential to induce gene mutation in cultured Chinese hamster ovary cells (CHO/HGPRT) ( MRID 4182403) and reviewed in accordance with

Series 870.5100 . Acc ording to the review (U.S. EPA 1992) the study was suggestive of a mutagenic effect. However, the study was unacceptable based on the following reasons: 1)

f

ailure to reproduce dose related mutagenic responses; 2) i m proper dose selection; and 3) marked increase in mutation at cytotoxic levels. A follow up study (MRID 43639101) was

conducted and positive mutagenicity was confirmed and the study was regarded as acceptable.

A micronucleus assay was administered in mice ( MRID 41832402; Guideline 84

- 2b). A single oral gavage administration of 100, 200, 400 mg/kg was administered to male

mice and doses of 250, 500, and 1,000 mg/kg was administered to female mice

. In the study there was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow cells harvested 24, 48, or 72 hours post

- treatment. DMHMP was found to be nonclastogenic.

A n in vivo/in vitro unscheduled DNA synthesis (UDS) primary rat hepatocyte assay (MRID 43636601) was submitted in 3 groups of rats dosed at 300, 600, and 900 mg/kg Busan 1104 by oral gavage. Clinical signs of toxicity in the rats included prostration and hypoactivity. Cytotoxicity was ev ident in both the cell wall and increased vacuoles in the hepatocytes. There was however no evidence of increased genotoxicity at any dose. This study was classified as acceptable as per 84

- 4 guidelines. Based on the review of the submitted studies, no a dditional mutagenicity studies are anticipated as needed (D215585) . DMHMP was confirmed to have genotoxicity in vitro , but not in vivo.

Subchronic Toxicity

A 91

- day dermal study with groups of 10 rats/sex/dose were administered the

DMHMP at concentrati ons of 50, 250, and 500 mg/kg/day for 5 days/week for 91 days. Severe dermal irritation, ulceration and eschar formation occurred at all treatment

levels. Necrosis extended through the dermis and into the subcutaneous tissue. A number of parameters were affected either by the test material or by stress (increased platelets, polychromatophilia, hematopoietic activity of the spleen and bone marrow). ThePage 5 of 16 Agency stated that direct systemic effects of this chemical were difficult to determine

since the chemi cal is corrosive. T he Agency believed the effects were stress related based

on the severe dermal irritation . The systemic NOEL wa s 50 mg/kg and the systemic NOEL was 250 mg/kg. The Agency considered the dermal sub

- chronic study to be acceptable (GDLN 82

- 2 )

T he Agency anticipates the need for another dermal study since the previous study

identified dermal irritation at all the doses tested. AD commonly considers dermal irritation as a toxicity endpoint for material preservatives used in consumer goods (e. g., treated paints and textiles)

. Assumptions involved in this calculation include body weight of the rat and area of skin exposed. If it is decided during the registration review risk assessment process that the Agency will use irritation as the endpoint for short

- term dermal exposure (e.g. treated paints and textiles) , the Agency will likely need to convert the NOAEL to a dermal endpoint in the units of μg/cm 2 to do the risk assessment.

Developmental

DMHMP was orally dosed to pregnant rats at dose lev els of 0, 25, 75, and 150 mg/kg/day (20 rats/group) during gestation days 6

- 15 (MRID 41833001) . Maternal toxicity was evidenced by decreased body weight and food consumption in the 150 mg/kg dose group. The mean numbers of implants and corpora lutea in the test groups were comparable to controls. No treatment related effects were noted in the number of viable fetuses/dam, or the mean fetal body weights in the test group were either lower than or comparable to the control group. At a dose of 150 mg/kg, DMHMP appeared to have effects on developmental toxicity by increased litter incidence of rudimentary ribs at a dose response relationship, reduced ossification of the 13 th rib, and 14 th full rib and the

27 th presacral vertebrae. The developmental NOEL wa s 75 mg/kg and the maternal NOEL is 75 mg/kg. The study was guideline (84

- 2) acceptable.

DMHMP was orally dosed to pregnant rabbits at dose levels of 0, 10, 30, and 60 mg/kg/day (20 rats/group) during gestation days 6

- 18 (MRID 41833002) . Possible

mater nal toxicity was evidenced by statistically decreased body weight gain and food consumption in the 30 and 60 mg/kg dose groups. The mean number of implantations and corpora lutea in the test groups were comparable to controls. No treatment related effect s were noted in the number of viable fetuses/dam, the mean fetal body weights, or fetal sex ratios in any of the test groups. No evidence of developmental toxicity was noted in the highest dose tested (60 mg/kg), developmental NOEL= 60 mg/kg and maternal N OEL= 75 mg/kg. The study was guideline (84

- 2) acceptable.

Section 3. Dietary Assessment

Dietary

According to the label (EPA Reg 1448

- 351) , DMHMP or Busan 1104 “may NOT be used for the preservation of materials which may contact food” for adhesives and papermaking uses. Therefore, EPA anticipates that a n indirect dietary assessment will not

be needed

. Currently, n o FDA clearances are available for this compound.Page 6 of 16 Drinking Water

Although likely to be infrequent, dietary exposures via drinking water ma y occur in

the event of a down

- the

- drain discharge. The contaminated water could pass through wastewater treatment facilities into the drinking water or may be discharged directly to surface water which is later treated. However, at this time there are no environmental fate

data to determine whether DMHMP can pass through wastewater treatment facilities into drinking water or migrate into residential groundwater wells as a result of its current use patterns. Since the product is used as an industrial preser vative in slurries , the Agency anticipates that the effluent wastewater could discharge directly to surface water and exposures could occur.

Section 4 . Occupational /Residential Exposure

The Agency did an open literature search and did not identify any relevant exposure studies in the existing literature that could be used to supplement the existing Agency exposure database. There are potential short

- and intermediate

- term exposures for occupational and residential uses. There are potential dermal and inhalation occupational handler exposure scenarios identified by the Agency after review of the labels. The potential occupational handler scenarios (both short

- term (1

- 30 days) and intermediate

term (>30 days) include:

**•** Mixing/loading solid granulars for paints;

**•** Mixing/loading solid granulars for slurries (e.g., adhesives, polishes/waxes, construction materials, detergents, inks, papermaking chemicals/coatings, textile emulsions);

**•** Applying detergents (trigger sprays, mopping and wiping); and,

**•** Applying paints (airless sprayer, paint brush, and aerosol can)

The potential postapplication scenarios (both short

- term (1

- 30 days) and intermediate

- term (>30 days) include:

**•** Inhalation exposure to paints (e.g. bystander exposure indoors); and

**•** Dermal postappl ication exposures to treated clothing made from impregnated

textiles with DMHMP.

S ection 5 . Aggregate and Cumulative Exposure

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

occupational pesticide exposures

. EPA expects that the residential r isks and drinking

water risks will be the only exposures to be aggregated

.

Unlike other pesticides for which EPA has followed a cumulative risk ap proach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to DMHMP and any other substances and DMHMP does not appear to produce a toxic metabolite produced by other substances. For the purposes of thisPage 7 of 16 tole rance action, therefore, EPA has not assumed that DMHMP has a common mechanism of toxicity with other substances. For the purposes of this action, therefore, EPA has not assumed that DMHMP has a common mechanism of toxicity with other substances. For

infor mation regarding EPA’s efforts to determine which chemicals 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 d eterminations and procedures for cumulating effects from substances found

to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Section 6. Incidents

There hav e been no human incidents reported in any of the OPP databases (e.g. OPP Incident Data System (IDS)) associated with exposure to DMHMP

.

Section 7 . Anticipated Data Needs

The Antimicrobial Division (AD) anticipates requiring further toxicity and exposure

studies for DMHMP for registration review . The studies and a brief rationale are listed

below in Table 3

. Further clarification of the rationale for these studies are provided in Appendix A and B.

Table 3 : Human Health Data Needs Based on End Use Labe ls

Study Needed Guideline Rationale ( also see Appendix B)

90

- day Inhalation Toxicity 870.3465 As a result of inhalation exposures to aerosol sprays and the volatility of the chemical ; the Agency anticipates

that a 90

- day inhalation study will be needed to develop

short

- and intermediate

- toxicity inhalation endpoints.

90

- day Dermal Toxicity 870.3250 EPA is concerned about the cor r osivity of DMHMP and may need an additional dermal subchronic toxicity study to select dermal toxicity endpoints since dermal

irritation was found in all dose levels in the rat dermal

91

- day study. The Agency needs to identify the dermal risks to activities which involve prolonged de rmal exposure (particularly to dermal postapplication to treated clothing from preserved te xtiles).

Indoor Exposure (applicators) 875.1 2 00 (Dermal)

875.1 4 00 (Inhalation) 875.1600 (Data Reporting) Exposure studies are needed for painting (brush/roller, airless sprayer, and for using disinfectants (mopping and wiping). Indoor Exposure (mixer/ loaders) 875.1 2 00 (Dermal)

875.1 4 00 (Inhalation) 875.1600 (Data Reporting) Exposure may occur while mixing/loading granular preservative s in a manufacturing setting for slurries (paint, disinfectants) Indoor Exposure 875. 2 4 00 (Dermal)

875. 2500 (Inhalatio n)

875. 2 9 00 (Data Reporting) Bystander inhalation exposure may occur after painting. Dermal exposure to treated textiles that are used for clothing.

Product Use 875.1700 (Handler)

875.2 7 00 (Postapplication) Product use data will be needed to characteriz e any uncertainties with regard to the use or application of this

chemical (e.g., detergent use)

.

Section 8 . TolerancesPage 8 of 16 There are no pesticide tolerances or exemptions from the requirement of tolerance for

DMHMP.

Section 9 . Endocrine Disruption

As re quired 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,

d evelopmental, 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, f ertility, 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

re registration decision

, 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), DMHMP is subject to the endocrine sc reening 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 ident ify 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 p roceed 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 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 ch emicals, which contains 58 pesticide active ingredients and 9 inert ingredients. DMHMP 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 iss ue future EDSP orders/data call

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

. 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 sc reening battery, please visit our website: http://www.epa.gov/endo/

.Page 9 of 16 Section 1 0

. Reference s

United States Environmental Protection Agency (U.S. EPA 1995 a ) . Memorandum from George Z. Ghali, PhD., Toxicologist , HED to Joanne Miller, RD. RfD/Peer Review Report of Busan 1104 [3,5

- Dimethyl

- 1

- hydroxymethylpyrazole]. January 10, 1995

United States Environmental Protection Agency (U.S. EPA 1995 b ). Toxicology Endpoint Selection Document. Busan 1104. J. Rowe, HED. Fil e R073459. June 14, 1995.Page 10 of 16 APPENDIX A: TOXICITY

Guideline Numbers: 870. 3465 Study Titles: 90

- day I nhalation T oxicity S tudy Rationale for Requiring the Data The Agency does not have a full picture of the potential effects which DMHMP could

occur as a result of exposure via the inhalation route. The needed study which was not previously available would provide insight into concerns regarding toxicity via the inhalation route. It may also provide a toxicity endpoint applicable to an inhalation ris k assessment. The Agency previously used an oral toxicological endpoint from a maternal toxicity endpoint from a developmental study and assumed 100% absorption. Inhalation exposure is high for workers who apply paint through airless sprayers and brushes. These applicators would likely to be exposed to aerosols from paint applications. In addition, a n inhalation study is required to address uncertainties around the inhalation toxicity to refine the Agency’s risk assessment. Currently for inhalation expos ures an extra 10 X uncertainty factor is added for a lack of an inhalation toxicity endpoint. The study may result in a change in how risks are quantified and removal of a 10X uncertainty. The data would allow the Agency to conclude more definitively whet her or not there would be any concerns for inhalation toxicity in the rat. This would provide a more complete hazard characterization of DMHMP in regards to the potential risks to the U.S. general population.

Practical Utility of the Data

How will data be used? An inhalation study may result in changes to the endpoints and how the risks are quantified.

How could the data impact the Agency’s future decision

- making? The study would form the foundation for hazard characterization and toxicity endpoints selection for risk assessment through all exposure routes (oral, inhalation, and dermal). The data would allow the Agency to conclude more definitively whether or not there would be any concerns for inhalation toxicity in rodent species. It is possible t hat the database uncertainty factor be reduced or removed, resulting in different magnitude of the value of the endpoint used for regulation. . In many cases, toxicity observed via the inhalation route is higher than toxicity observed via oral exposure, w hich means that the

route

- to

- route extrapolation used in the RED risk assessment could have resulted in an underestimation of risks from inhalation. It is particularly important to properly assess

inhalation risks for DMHMP because there is high inhalation exposure for workers applying paints.Page 11 of 16 Guideline Numbers: 870. 3465 Study Titles: 90

- day Dermal T oxicity S tudy Rationale for Requiring the Data The Agency does not have a full picture of the potential effects which DMHMP could

occur as a result of exposure via the dermal route. The needed study which was not previously available would provide insight into concerns regarding toxicity via the

dermal route. It may also provide a toxicity endpoint applicable to a dermal risk assessment. The Agency previously did not develop a dermal toxicological endpoint.

EPA is concerned about the corrosivity of DMHMP and may need an additional dermal subchronic toxicity study to select dermal toxicity endpoints since dermal irritation was

found in all dose le vels in the rat dermal 91

- day study. The Agency needs to identify the dermal risks to activities which involve prolonged dermal exposure (particularly to dermal postapplication to treated clothing from preserved textiles).

The data would allow the Agency to conclude more definitively whether or not there would be any concerns for dermal toxicity in the rat. This would provide a more complete hazard characterization of DMHMP in regards to the potential risks to the U.S. general population.

Practical Util ity of the Data

How will data be used?

A dermal study may result in changes to the endpoints and how the risks are quantified.

How could the data impact the Agency’s future decision

- making? The study would form the foundation for hazard characterizatio n and toxicity endpoints selection for risk assessment through all exposure routes (oral, inhalation, and dermal). The data would allow the Agency to conclude more definitively whether or not there would be any concerns for dermal toxicity in rodent speci es. 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. . In many cases, toxicity observed via the

dermal route is higher than toxic ity observed via oral exposure. EPA is concerned about the corrosivity of DMHMP and may need an additional dermal subchronic toxicity study to select dermal toxicity endpoints since dermal irritation was found in all dose levels in

the rat dermal 91

- day study. The Agency needs to identify the dermal risks to activities which involve prolonged dermal exposure (particularly to dermal postapplication to treated clothing from preserved textiles).Page 12 of 16 APPENDIX B: EXPOSUREPage 13 of 16 Guideline Number: 875.1200 Study Titles: Derm al 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 almost 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 painting . The existing CMA data base and PHED for these scenarios are limited in sc ope 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 additiona l 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 painting ) and evidence of toxicity. If the toxicological endpoints fr om DMHMP 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 will be used to assess dermal exposures from painting . For occupational

us es, 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 accuracy of the dermal risks to both

residen tial and occupational workers.

2. How could the data impa ct 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 lab el.

Guideline Number : 875.1400 Study Titles: Inhalation Exposure (Indoor) Rationale for Requiring the Data
Note: Inhalation exposure data are needed for both residential and occupational uses. The selection of an outdoor versus an indoor site is ba sed on the high end exposure scenario (for inhalation the selection is typically indoors). In almost all cases, repeating an exposure study for the same scenario outdoors and indoors is not necessary.

The inhalation exposure route is very important for e xposure 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 are available to assess the inhalation risk. The existing Chemical Manufacturer Association (CMA) da ta 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 Rev iew Board (HSRB) and both groups agreed that additional data are warranted.

The criteria for the inhalation exposure data are based on the potential for respiratory exposure from the labeled uses (e.g., exposure to paints ) and evidence of toxicity. If n o toxicological endpoints of concern were identified, then the inhalation exposure data would not be needed.

Practical Utility of the Data

1. How will the data be used?Page 14 of 16 The inhalation exposure data would be used to assess the residential short

- term du ration of painting with a paint brush/roller and an airless sprayer. For occupational uses, the inhalation exposure data

would be used to assess the short

- and intermediate

- term exposure

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 full face respirators or closed systems for commercial uses, or potential removal

of uses from the label.

Guideline Number : 875.1600

Stud y 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

da ta.

Practical 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 exposure 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.Page 15 of 16 Guideline Number : 875.1700 and 870.2700 Study Title: Product Use Inf ormation Rationale for Requiring the Data Product use information is a description of how the product is actually applied; it is not afield study. A description of how this product is used would provide for a comprehensive realistic assessment of its po tential applications. The description of the application techniques would be used to define the exposure scenarios to be assessed in

the risk assessment. Practical Utility of the Data

1. How 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

- making?

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

Guideline Number: 875.2500 Study Title: Inhalation Exposure Rationale for Requiring the Data The post application inhalation exposure may be required if it is determin ed that the use of these products have the potential to release DMHMP during the product use conditions (e.g., painting ).

Practical Utility of the Data

1. How will the data be used? The post application inhalation exposure data will be used to assess t he residential and/or occupational inhalation risks to estimate reentry exposure to painting

. This data is needed to
conduct an inhalation postapplication assessment

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

- making? The inhalation expos ure data will be used to determine the accuracy of the post application inhalation risks to occupational bystanders. If risks warrant mitigation, the inhalation exposure data will provide the types of mitigation necessary such as respiratory protection fr om respirators or closed systems for commercial uses to potential removal of

uses from the label.Page 16 of 16 Guideline Number: 875. 29 00 Data Requirement: Data Reporting and Calculations
Rationale for Requiring the Data For all exposure studies, these data are needed occupationally and in the residential setting to

facilitate the review of the data.
Practical Utility of the Data

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

2

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

- making? The data are needed to define and interpret the inhalation and dermal exposure data collected. This data need is triggered any time an exposure 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.