August 16, 2013 

U.S. Environmental Protection Agency 

Office of Pollution Prevention and Toxics 

Confidential Business Information Center (CBIC) – TS7407M 

Attention: Audrey Binder 

EPA East Building, Room 6428 

1201 Constitution Avenue, NW 

Washington, DC 20004-3302 

Dear Ms. Binder: 

Reference: PMN P-12-0425 

 Submission Report Number – 

Update of Attachment 1 (Toxicity Testing Summary) 

Please also find attached an updated version of Attachment 1 (confidential copy and public copy). 

A new study has been added for the PMN substance. 

The study will be conducted in compliance with the Good Laboratory Practice Standards. An 

OECD Guideline OECD, Section 4 (Part 412): Subacute Inhalation Toxicity: 28-Day Study, 

Guideline for the Testing of Chemicals (2009) has been scheduled for the test substance. The 

objective of this study is to evaluate the potential cumulative toxicity of the test substance when 

administered 6 hours per day, 5 days per week by inhalation to male and female rats for a period 

of approximately 28 days. 

Male and female rats will be exposed to the test substance via inhalation to the test substance 6 

hours per day, 5 days per week for 28 days, and then sacrificed. Additional satellite recovery 

groups will be sacrificed after an approximate 28-day recovery period. The following parameters 

will be used to assess the potential toxicity: body weight, food consumption, 

mortality/moribundity, clinical observations, ophthalmological evaluations, neurobehavioral 

evaluations, and anatomic and clinical pathology evaluations. 

Dose levels will be selected based on previous repeated dose oral toxicity studies (up to 90 days in 

duration) and an acute inhalation study where the rat whole-body 4-hour LC50 was greater than 

15,000 ppm (the highest achievable vapor concentration). In this study, anesthetic effects were 

observed at concentrations greater than or equal to 9700 ppm and the no-observed-adverseeffect-level (NOAEL) for CNS effects during exposure was 5000 ppm. There were no other 

abnormal clinical signs of toxicity observed in any rats when they were removed from the 

exposure chamber or throughout the 14-day recovery period. The NOAEL for histopathological 

changes of the respiratory tract, liver and kidneys was 15,000 ppm. 
Please contact me if you have any questions about this submission or need further clarification. 

Via eTSCA Client (attachments) 

cc: Rebecca von dem Hagen (EPA, Office of Air and Radiation, Stratospheric Protection 

Division) 
EPA Support Form 

Support Form Report Number Mark (X) if anything is CBI

I. ORIGINAL NOTICE SUBMISSION IDENTIFICATION 

Report Number TS 

Number 

Case 

Number 

Original Submission Date 

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II. ORIGINAL NOTICE SUBMITTER IDENTIFICATION CBI 

Authorized Official 

Name 

Company Name

Mailing Address 

(Number & Street) 

City State Postal Code 

e-mail Telephone 

(include area code) 

III. CURRENT SUPPORT DOCUMENT IDENTIFICATION INFORMATION CBI 

Mailing Address 

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e-mail Telephone 

(include area code) 

IV. TYPE OF SUPPORT (Check One) 

Letter of Support (Mark the certification statement checkbox below)

Withdrawal Request 

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TEST DATA (Health/Eco/Fate) 

Amendment (Changes made to PMN pages 1-13, MSDS or Physical/Chemical 

properties) 

Check if requested by EPA/ contractor 

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All information provided in this Letter of Support is complete and truthful

as of the date of the submission.

Form Approved. O.M.B. No. 2070-0173.

EPAX130816959911761 X

PPXP120622354273551 D1493P P120425

Jun 22, 2012

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SANITIZED SUBMISSION

SUP2013P1
V. TEXT / DESCRIPTION OF CHANGES CBI 

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SANITIZED SUBMISSION

SUP2013P2
LIST OF ATTACHMENTS

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 Mark (X) this box if the data continues on the next page.

Attachment Name Attachment Filename 

001 EPA Letter (P-12-0425) (New Study - 26-Day

Inhalation) (8-16-2013) (public)

EPA Letter (P-12-0425) (New

Study - 26-Day Inhalation) (8-16-

2

002 P-12-0425 Toxicity Testing Summaries (Updated

8-16-2013 (public)

P-12-0425 Toxicity Testing

Summaries (Updated 8-16-2013)

4

SANITIZED SUBMISSION

SUP2013P3
ATTACHMENT HEADER SHEET

Attachment Number 001

Attachment Name

EPA Letter (P-12-0425) (New Study - 26-Day Inhalation) (8-16-2013) (public)

Associated PMN Section Number

N/A

Does not contain CBI

Report Number

EPAX130816959911761

SANITIZED SUBMISSION
ATTACHMENT HEADER SHEET

Attachment Number 002

Attachment Name

P-12-0425 Toxicity Testing Summaries (Updated 8-16-2013 (public)

Associated PMN Section Number

N/A

Does not contain CBI

Report Number

EPAX130816959911761

SANITIZED SUBMISSION
15-Jun-2012; UPDATED 12-Nov-2012, 7-May-2013; 16-August-2013

Test Type Report # Test System Comments Results

Acute Oral (LD50) Rat GLP; Guideline The female rat oral LD50 was greater than 5000 mg/kg (limit 

deaths during the exposure recovery period. 

Acute Inhalation (4-hr LC50) Rat, whole- body GLP; Not Guideline

The male and female rat, whole-body inhalation 4-hr LC50 wppm (the highest achievable vapor concentration). There were no deathor recovery period. Anesthetic effects were observed at concentrations to 9700 ppm and the no-observed-adverse-effect-level (NOAEL) for CNexposure was 5000 ppm. There were no abnormal clinical signs of toxirats when they were removed from the exposure chamber or throughouperiods. The NOAEL for histopathological changes of the respiratory tris also 15,000 ppm.

Acute Inhalation (4-hr LC50) Rat, nose-only GLP; Guideline

The test substance was an azeotrope blend containing 

.

The azeotrope blend male and female rat, nose-only inhalation 4-hr LC(140 mg/L).

Acute Dermal (LD50) Rat GLP; Guideline The male and female rat dermal LD50 was greater than 5000 

There were no deaths during the exposure recovery period. 

Dermal Irritation Rabbit GLP; Guideline was not a dermal irritant when tested in rabbits. No clinical s

observed in the study.

Dermal Sensitization Mouse GLP; Guideline was not a dermal sensitizer when tested in mice. No clinical 

observed in the study.

Eye Irritation Rabbit GLP; Guideline was not an eye irritant when tested in rabbits. No clinical sig

observed in the study.

Bacterial Reverse Mutation Assay(Ames) Bacteria GLP; Guideline was not mutagenic in the Bacterial Reverse Mutation Assay (

Salmonella strains TA98, TA100, TA1535, and TA1537 and E. coli st

in the presence or absence of an S9-activated test system.

In Vitro Chomosome Aberration

Chinese 

hamster ovary 

(CHO) cells

GLP; 

Guideline

 did not produce structural or numerical chromosome aberrati

mammalian chromosome aberration test using Chinese hamster ovary (the presence or absence of an S9-activated test system.

In Vivo Micronucleus Rat GLP; Guideline

Male and female rats were exposed to a single oral dose of 0, 500, 1000

. No clinical signs of toxicity or mortality was observed in the stud

induce biologically relevant increases in micronucleated reticulocytes icells.

28-Day Oral Rat GLP; Guideline

Male and female rats were exposed to 0, 250, 500 or 1000 mg/kg for 28 days. No test substance-related adverse effects were observed in pathology assessments. The no-observed-adverse-effect level (NOAELmg/kg/day.

Completed Studies (PMN Substance)

Page 1 of 4
28-Day Oral with FOB (a) P100578 Rat GLP; Guideline

Male and female rats were exposed to 0, 100, 250, or 1000 mg/kg for 28 days. No test substance-related adverse effects were observed in neurobehavioral, or anatomical pathology assessments. The no-observe(NOAEL) was 1000 mg/kg/day.

90-Day Oral with FOB DuPont 18157-1026 Rat GLP; Guideline

Male and female rats were exposed to 0, 250, 500 or 1000 mg/kg for 90 days. No test substance-related adverse effects were observed in neurobehavioral, or anatomical pathology assessments in females. A slseverity, but not incidence, of chronic progressive nephropathy (CPN) apathology changes was observed in males at all dose levels. The no-oblevel (NOAEL) for female rats was 1000 mg/kg/day. The NOAEL was male rats.

Pre-natal Oral Developmental DuPont 18157-841 Rat GLP; Guideline

Female rats were exposed to 0, 250, 500, or 1000 mg/kg per dduring gestation day (GD) 6-20. No test substance-related maternal or 

was observed at any dose level. The no-observed-adverse-effect level (Nand fetal effects was 1000 mg/kg.

Intravenous Tolerability Study DuPont 18157-1231 Rat

Not GLP; 

Not 

Guideline

Male and female rats were exposed to to a single intravenous injection 

. No deaths, clinical signs, or body weight losses occurred in 

days of observation. 

Toxicokinetics Test (Absorption) (e)

DuPont 18157-1389

(China report number 

ZWY2012HD006)

Rat

Not GLP; 

Not 

Guideline

Male rats were administered 10 mg/kg by a single intravenou30,000 mg/kg by a single oral gavage, or 1500 mg/kg by oral consecutive days. Blood was withdrawn at various timepoints by directhe concentration of in the blood was measured by GC-MS. limited cumulative effects in rats after repeated exposure.

Bioconcentration Study (b) A100071 Fish GLP; Guideline

Medaka were exposed to 0.005 or 0.05 mg/L in a continuous system for 60 days followed by a 14-day depuration period. The steadyranged from 1100 to 2210 for the 0.05 mg/L level and from 1560 to 285level. The concentration of in the fish decreased with time duperiod. The biological half-lives ranged from 3.1 to 6.6 days for the 0.0from 2.5 to 4.7 days for the 0.005 mg/L level. Average BCF for 12 data

Algae Growth Inhibition Test (b) A100360 Green algae GLP; Guideline

The green algae 72-hr ErC50 was greater than 0.000477 mg/L concentration tested). The no observed effect concentration (NOECr) a0.000477 mg/L (the highest dose tested). The concentration was the timthe limit of solubility (0.16 mg/L) after 72-hours. During the course of determined that the test substance was volatilized from the test solutionHenry's law constant of 4.75E6 m3/mol.

Algae Growth Inhibition Test DuPont 18157-315 RV1 Green algae Not GLP; Not Guideline The green algae 72-hr ErC50 was greater than 120 mg/L (the 

tested).

Fish Acute Toxicity Test (b) A100362 Medaka GLP; Guideline The Medaka 96-hr LC50 was greater than 0.0.960 mg/L (the 

tested). The concentration was the time-weighted mean of the limit of after 96-hours. The test solution was renewed every 24 hours.

Fish Acute Toxicity Test DuPont 18157-295 RV1 Fathead Minnow Not GLP; Not Guideline The fathead minnow 96-hr LC50 was greater than 120 mg/L 

concentration tested).

Page 2 of 

4
Daphnia Acute Immobilization Test 

(b)

Daphnia 

magna

GLP; 

Guideline

The Daphnia magna 48-hr EC50 was greater than 0.157 mg/L concentration tested). The concentration was the time-weighted mean osolubility (0.17 mg/L) after 48-hours. The test solution was renewed af

Daphnia Acute Immobilization Test Daphnia magna Not GLP; Not Guideline The Daphnia magna 48-hr EC50 was greater than 120 mg/L (

concentration tested).

Daphnia Reproduction Test (c) Daphnia magna Guideline The 21-day NOAEL (reproduction and body length) = 100 mg/L (meas

was 0.107 mg/L based on solubility) - highest concentration tested; LO

Zebrafish 14-day Growth Study (c) Zebrafish Guideline The 14-day NOAEC (lethality) = 100 mg/L (measured concentration w

based on solubility) - highest concentration tested; LOAEC > 100 mg/L

Earthworm Acute Toxicity Test (c) Eisenia foetida GLP; Guideline The Eisenia foetida 14-day LC50 was greater than 1011 mg/k

and only concentration tested).

Activated Sludge Respiration Inhibition Test Microbial GLP; Guideline The microbial respiration inhibition EC50 was greater than 1

dose tested). No inhibition was noted at any concentration.

Adsorption Coefficient (Log Koc) NA GLP; Guideline

The study was conducted using the HPLC Method for determining a sucoefficient (soil organic carbon/water) on soil and sewage sludge. The (log Koc) value of the test substance was calculated to be 4.50 on soil asludge.

LogKow (modelled) NA

Not GLP; 

Not 

Guideline

KOWWIN v1.68 was used to estimate LogKow. componentraining set's structural domain requirements completely, however, otherelated analogues and water solubility information provide corroboratinestimates made by the model are reasonable. LogKow prediction rangefor . A weighted average based on the typical component perestimated LogKow values was calculated to be approximately 4.97.

LogKow (measured) (b) NA Guideline The average log Kow ranged from 4.5 to 4.9 among 5 components. 

Ready Biodegradability (b) NA GLP; Guideline is not readily biodegradable. No transformation product was 

conditions of the test.

Inherent Biodegradability Test (d) NA GLP; Guideline is inherently biodegradable. Biodegradation was 44.3% after 

conditions of the test.

Page 3 of 

4
28-Day Inhalation Rat GLP; Guideline Male and female rats will be exposed to via inhalation 6 hour

week for approximately 28 days. The objective of this study is to evalucumulative toxicity of the test substance.

On-going Studies (PMN Substance)

Page 4 of 

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