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Subject #2 of 3 EHPV High Boiling EGEs

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Date: Fri, 3 Jul 2009 16:27:17 -0400

Subject: Substance: tetraethylene glycol ethyl ether / 3,6,9,12-tetraoxatetradecan-1-ol / 

3,6,9,12-tetraoxatetradecan-1-ol / 5650-20-4 / PCA Services, Inc. / Durham / United States of 

America

Content-Type: multipart/related;

boundary="_005_6875707670716565696866736977697675767965696578807274687_";

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Thread-Topic: Substance: tetraethylene glycol ethyl ether / 3,6,9,12-tetraoxatetradecan-1-ol / 

3,6,9,12-tetraoxatetradecan-1-ol / 5650-20-4 / PCA Services, Inc. / Durham / United States of 

America

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Printing Date 2009-07-03 16:26:34 EDT 

Restriction of specific regulatory purposes 

 

Confidentiality 

 

Name tetraethylene glycol ethyl ether 
Legal entity owner PCA Services, Inc. / Durham / United States of America 

Substance: tetraethylene glycol ethyl ether 

UUID IUC5-178944e7-91bd-422a-a252-50f5b47ca82b 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 10:47:38 EDT 

Remarks 

0 Related Information 

0.1 Templates 

0.2 Categories 

0.3 Mixtures 

1 General Information 

1.1 Identification 

Substance identification 

Chemical name tetraethylene glycol ethyl ether 

Legal entity PCA Services, Inc. / Durham / United States of America

Reference substance 

Reference substance 3,6,9,12-tetraoxatetradecan-1-ol / 3,6,9,12-tetraoxatetradecan-1-ol /

5650-20-4

 EC number EC name 

227-090-6 3,6,9,12-tetraoxatetradecan-1-ol 

CAS number CAS name 

5650-20-4 

IUPAC name 

3,6,9,12-tetraoxatetradecan-1-ol 

Type of substance 

Composition mono constituent substance 

Origin organic 

1.2 Composition 

1.3 Identifiers 

1.4 Analytical information 

1.5 Joint submission 

1.6 Sponsors 

1.7 Suppliers 

1.8 Recipients 

1.9 Product and process oriented research and development 

2 Classification and Labelling 

2.1 GHS 

2.2 DSD - DPD 

3 Manufacture, use and exposure 

3.1 Technological process 

3.2 Estimated quantities 

3.3 Sites 
3.4 Form in the supply chain 

3.5 Identified uses and exposure scenarios 

3.6 Uses advised against 

3.7 Waste from production and use 

3.8 Exposure estimates 

3.9 Biocidal information 

3.10 Application for authorisation of uses 

4 Physical and chemical properties 

4.1 Appearance/physical state/colour 

Appearance/physical state/colour.002 

UUID IUC5-f24606b9-1f08-408d-b54d-19222488b810 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 10:56:06 EDT 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence ( ) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type other: visual appearance and specification 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

No study reviewed. Manufacturer's data 

Data source 

Reference 

Reference type company data 

Author Year 

Title Pennzoil product data sheet for Pennzoil brake fluid 

Bibliographic 

source 

Available online at 

http://www.pennzoil.com/documents/Super%20HD%20Dot%203and4%20Bra

ke%20Fluid.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity DOT 4 Brake fluid 
Details on test material 

Data come from DOT 3 and DOT 4 specifications for brake fluid. Substance is available 

commercially only as a component in brake fluids. 

Results and discussion 

Physical state at 20oC and 1013 hPa 

liquid 

Colour 

clear amber 

Odour 

other: faint ether like 

Substance type 

organic 

4.2 Melting point/freezing point 

Melting point/freezing point.001 

UUID IUC5-42e97e77-427a-4bba-b872-7d19c69b97b0 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:47:35 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

read-across from supporting substance (structural analogue or 

surrogate) 

 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Melting point data come from DOT 3 and DOT 4 specifications for brake fluid. 

Substance is available commercially only as a component in brake fluids. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Pennzoil brake fluid DOT 4 data sheet 

Bibliographic 

source 

Available online at 

http://www.pennzoil.com/documents/Super%20HD%20Dot%203and4%20Bra

ke%20Fluid.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

GLP compliance 
no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Pennzoil brake fluid DOT 4 

Details on test material 

Data are for DOT 3 or 4 specification automotive brake fluid, of which tetraethylene glycol 

ethyl ether is a component. Tetraethylene glycol ethyl ether is not available commercially as a 

neat material. 

Results and discussions 

Melting / freezing point 

Melt./Freez. pt. ca. -40 °C 

Atm. pressure 

Decomposition no 

Decomp. temp. 

Sublimation no 

Subl. temp. 

Remarks 

4.3 Boiling point 

Boiling point.001 

UUID IUC5-aa6cfb2b-e461-4173-b317-45f19ce938cd 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:32:34 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

no data 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained from brake fluid Manufacturer's technical data sheet. 

Tetraethylene glycol ethyl ether is available commercially only as a brake fluid 

component. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 

Title Pennzoil Technical Data Sheet for Pennzoil (trademark) Brake Fluid (Dot 4) 

Bibliograp Available online at 
hic source http://www.pennzoil.com.au/downloads/tds/Pennzoil_Brake_Fluid_Dot_4.pdf 

Testing 

laboratory 

 Rep

ort 

no. 

 

Owner 

company 

 

Company 

study no. 

 Rep

ort 

date 

 

Reference type company data 

Author Year 

Title Pennzoil product data sheet for Pennzoil brake fluid 

Bibliographic 

source 

available online at 

http://www.pennzoil.com/documents/Super%20HD%20Dot%203and4%20Bra

ke%20Fluid.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Pennzoil (trademark) Brake Fluid (DOT 4) 

Results and discussions 

Boiling point 

Boiling pt. >= 272 °C 

Atm. pressure 1013 hPa 

Decomposition no 

Decomp. temp. 

Remarks Equilibrium Reflux Boiling Point 

4.6 Vapour pressure 

Vapour pressure.001 

UUID IUC5-6c922304-3983-471a-9134-5f423bc369a6 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:52:42 EDT 

Remarks 
 

Administrative Data 

Purpose 

flag 

key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study 

result type 

no data 

Reliablility 2 (reliable with restrictions) 

Rationale 

for 

reliability 

Data are from brake fluid manufacturer's safety data sheet for DOT 3 and DOT 4 

specification brake fluid. Tetraethylene glycol ethyl ether is one of the major 

components in automotive brake fluids. Therefore the data are reliable for 

commercial product, but the vapor pressure determination study is not available. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Shell Brake and Clutch Fluid DOT 4 Super Safety Data Sheet 

Bibliographic 

source 

Available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20c

lutch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Materials and methods 

Type of method 

other: method not known 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS 

No. 106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS 

No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 
CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3. 

Results and discussions 

Vapour pressure 

<= 0.005 hPa at ca. 20 °C 

Remarks 

4.7 Partition coefficient 

Partition coefficient.001 

UUID IUC5-dc534c7d-a0a2-4f36-ae98-837be71ceea4 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 16:18:02 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized Computer model program 

Data source 

Reference 

Reference type other: Computer model program output 

Author Year 2009 

Title EPIWIN KOWWIN (v1.67) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-09 

Materials and methods 

Partition coefficient type 

octanol-water 

Type of method 

other: 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 5650-20-4 
Identifier EC number 

Identity 227-090-6 

Identifier IUPAC name 

Identity 3,6,9,12-tetraoxatetradecan-1-ol 

Details on methods 

Input to Kowwin model was CAS No. 005650-20-4. 

Results and discussions 

Partition coefficient 

Type Pow 

Partition coefficient ca. -1.24 

Temp. 

pH 

4.8 Water solubility 

Water solubility.001 

UUID IUC5-8a849970-4f07-4aa4-96ad-65b4612fbe33 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:56:13 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

no data 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained from the brake fluid manufacturer's Safety Data Sheet. 

tetraethylene glycol ethyl ether is available commercially only as a component in 

automotive brake fluid. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company Report date 
study no. 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS No. 

106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene glycol 

monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS No. 

143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 

CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3. 

Results and discussions 

Water solubility 

ca. 1000000 mg/L 

Temp. 20 °C 

pH 

Remarks on results including tables and figures 

Test material is miscible in water. 

4.11 Flash point 

Flash point.001 

UUID IUC5-23e5e813-1084-4c7e-b16d-2f1c01587ae0 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:56:46 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

no data 

Reliablility 2 (reliable with restrictions) 

Rationale 

for 

reliability 

Data were obtained from the safety data sheet of the brake fluid manufacturer. The 

study for flash point determination is not available. Tetraethylene glycol ethyl 

ether is available commercially only as a component in automotive brake fluide. 
Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Results and discussions 

Flash point 

ca. 155 °C 

at 

5 Environmental fate and pathways 

5.1 Stability 

5.1.1 Phototransformation in air 

Phototransformation in air.001 

UUID IUC5-da1ebb09-9496-43fc-8ee0-511156436d13 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 12:01:25 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 
Rationale for 

reliability 

Data were estimated using a recognized computer program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 

Title EPIWIN AOP (v1.92) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-08 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 5650-20-4 

Identifier EC number 

Identity 227-090-6 

Identifier IUPAC name 

Identity 3,6,9,12-tetraoxatetradecan-1-ol 

Study design 

Estimation method (if used) 

PHOTOCHEMICAL REACTION WITH OH RADICALS

- Concentration of OH radicals: 1.5E6 OH/cm3

- Degradation rate constant 59.3889 E-12 cm3/molecule-sec: 

- Computer programme: EPIWIN AOP (v1.92)

- 12-hour day

- half-life: 0.180 day or 2.161 hours 

Light source 

sunlight 

5.2 Biodegradation 

5.2.1 Biodegradation in water: screening tests 

Biodegradation in water: screening tests Waggy TGME 1987.001 

UUID IUC5-3a55abfe-7469-4ed6-ab01-8680f352f421 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:30 EDT 
Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

7 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Test material purity was not specified. No data on GLP. Some deviations on 

test design. Otherwise a reliable study. 

Data source 

Reference 

Reference 

type 

study report 

Author Waggy GT Year 1987 

Title Glycol ethers: Summary of available ecological fate and effects data. 

Bibliographi

c source 

 

Testing 

laboratory 

 Report 

no. 

File Number 

35931 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1987-11-19 

Materials and methods 

Test type 

other: 

Test guideline 

Qual

ifier 

according to 

Guid

eline 

other guideline: A modified version of the biochemical oxygen demand (BOD) method 

published in "Standard Methods for the Examination of Water and Wastewater", 16th 

edition, Am. Public Health Association, 1985 was used. 

Devi

ation

s 

yes See test condition section for details. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 
Identifier Common name 

Identity triethylene glycol monomethyl ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Details on test material 

no data 

Study design 

Oxygen conditions 

aerobic 

Inoculum or test system 

activated sludge, domestic, non-adapted 

Duration of test (contact time) 

20 d 

Parameter followed for biodegradation estimation 

O2 consumption 

Details on study design 

Nonacclimated domestic sewage organisms were used as seed in the test. The test period was 

extended to 20 days. Reaeration (if needed) was accomplished by dividing the BOD bottle 

contents between 2BOD bottles, sealing, shaking twenty times, returning contents to the 

original BOD bottle, recording the oxygen level, resealing, and returning the BOD bottle to the 

incubator. A discussion of these modifications appears in Price et al., "Brine shrimp bioassay 

and seawater BOD of petrochemicals", J. Water Poll. Control Fed., Jan. 1974. 

Results and discussions 

Test performance 

The calculated theoretical oxygen demand was 1.75 mg/mg. After 5, 10 and 20 days of 

incubation, the percent biooxidation was 29, 33, and 71%. 

% Degradation of test substance 

%Degr. 71 

St. dev. 

Parameter O2 consumption 

Sampling time 20 d 

Remarks 

BOD5 / COD results 

Overall remarks 

Biological oxygen demand (BOD) of triethylene glycol monoethyl ether (TGEE, CAS No. 112-50-5) and 

triethylene glycol monobutyl ether (TGBE, CAS No. 143-22-6) were also tested in this study. The BOD 

of TGME was similar to that of TGEE, and greater than that of TGBE. The concentrations of test 

material and bacteria used in the test were not listed in the report.

Applicant's summary and conclusion 

Interpretation of results 

readily biodegradable 
5.3 Bioaccumulation 

5.3.1 Bioaccumulation: aquatic / sediment 

Bioaccumulation: aquatic / sediment.001 

UUID IUC5-049fe4d0-c961-479f-ab2c-2525c990cdab 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:28:25 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were estimated using a recognized, approved model. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN BCFBAF Program (v3.00) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-13 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 5650-20-4 

Identifier EC number 

Identity 227-090-6 

Identifier IUPAC name 

Identity 3,6,9,12-tetraoxatetradecan-1-ol 

Study design 

Water media type 
freshwater 

Test conditions 

Details on estimation of bioconcentration 

BASIS INFORMATION

- Measured/calculated logPow: -1.24

BASIS FOR CALCULATION OF BCF

- Estimation software: EPIWIN BCFBAF (v3.00)

- Result based on calculated log Pow of: -1.24 

Results and discussions 

Bioaccumulation factor 

Conc. in environment / dose 

Type other: log BCF 

Value ca. 0.5 

Basis 

Time of plateau 

Calculation basis 

Remarks 

5.4 Transport and distribution 

5.4.2 Henry's Law constant 

Henry's Law constant.001 

UUID IUC5-f5985d27-dfd8-4bf6-922c-357e73c9d20d 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 16:20:51 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized computer model program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN HENRY (v3.20) 

Bibliographic 

source 

 

Testing Report no. 
laboratory 

Owner company 

Company study 

no. 

 Report date 2009-06-08 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 5650-20-4 

Identifier EC number 

Identity 227-090-6 

Identifier IUPAC name 

Identity 3,6,9,12-tetraoxatetradecan-1-ol 

Details on methods 

CAS No. 5650-20-4 was the input to EPIWIN HENRY program 

Results and discussions 

Henry's Law constant H 

H ca. 0 atm m3/mol 

Temp. (°C) 

Atm. press. 

5.4.3 Distribution modelling 

Distribution modelling.001 

UUID IUC5-ec1f2658-f61a-4d0b-95fd-bbda6f6db3e3 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 16:24:21 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized, approved computer program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 
Title EPIWIN Fugacity Level III model program 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-08 

Materials and methods 

Model 

Calculation according to Mackay, Level III 

Calculation programme 

EPIWIN Fugacity Level III model 

Release year 

2009 

Media 

air - biota - sediment(s) - soil - water 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 5650-20-4 

Identifier EC number 

Identity 227-090-6 

Identifier IUPAC name 

Identity 3,6,9,12-tetraoxatetradecan-1-ol 

Test substance input data 

- Molar mass: 222.28

- Data temperature:25 deg C

- Water solubility: 1,000,000 mg/L

- Vapour pressure: 0.000881 mm Hg 

- log Pow: -1.24

- Melting point: - 40 deg C

- Boiling point 270 deg C 

- Reaction half-life estimates for

- Air: 4/322 hours

- Water: 360 hours

- Soil: 720 hours

- Sediment:3240 hours

Results and discussions 

Percent distribution in media 

Air (%) 

0 
Water (%) 

30.6 

Soil (%) 

69.4 

Sediment (%) 

0.07 

6 Ecotoxicological Information 

6.1 Aquatic toxicity 

6.1.1 Short-term toxicity to fish 

Short-term toxicity to fish DOW MPEG.006 

UUID IUC5-cf740418-a178-416a-b52c-8a6b72b1618d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:16:56 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original data from which MSDS was written were not available. 

Data source 

Reference 

Reference 

type 

 

Author Year 

Title 

Bibliograp

hic source 

Dow MSDS for CARBOWAX methoxypolyethylene glycol 350 (CAS No. 

9004-74-4), Number 870, Dated 7/5/2000. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Number 870 Report 

date 

2000-07-

05 

Materials and methods 

Test guideline 

Qualifier 

Guideline other guideline: no data on guideline 

Deviations 

GLP compliance 
no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier IUPAC name 

Identity Carbowax MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Analytical monitoring 

no data 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no data 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

other: fathead minnow 

Details on test organisms 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

96 h Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 
pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no datano data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect no data 

Remarks (e.g. 95% CL) 

6.1.3 Short-term toxicity to aquatic invertebrates 

Short-term toxicity to aquatic invertebrates DOW MPEG 2000.002 

UUID IUC5-b7684406-ad5e-4472-be22-7de5571acfbe 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:16:59 EDT 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Study data were available only from a secondary source 

Data source 

Reference 

Reference 

type 

company data 

Author Year 2000 

Title Dow MSDS for CARBOWAX methoxypolyethylene glycol 350 (CAS No. 

9004-74-4), 
Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Number 870 Report 

date 

2000-07-05 

Materials and methods 

Principles of method if other than guideline 

No data on guideline followed. Study probably conducted by typical method. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowas MGEP-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Analytical monitoring 

no data 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Daphnia magna 

Details on test organisms 

no data 

Study design 

Test type 
no data 

Water media type 

no data 

Total exposure duration 

48 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Any other information on materials and methods incl. tables 

no data 

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured no data 

Conc. based on no data Basis for effect 

Remarks (e.g. 95% CL) 

6.1.4 Long-term toxicity to aquatic invertebrates 

Long-term toxicity to aquatic invertebrates Waggy TGME 1987.001 

UUID IUC5-e4adc107-2c59-4dbc-bda7-e2647dcc1310 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:30 EDT 
Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

well conducted study, but purity of test material was not given. 

Data source 

Reference 

Reference 

type 

study report 

Author Waggy GT Year 1987 

Title Glycol ethers: Summary of available ecological fate and effects data. Union Carbide 

File Number 35931, November 19, 1987. 

Bibliogra

phic 

source 

 

Testing 

laboratory 

 Repor

t no. 

File 

Number

35931 

Owner 

company 

Union Carbide Corporation 

Company 

study no. 

 Repor

t date 

1987-11-19 

Materials and methods 

Principles of method if other than guideline 

Test practices followed those recommended by EPA and ASTM 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Details on test material 
no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Test organisms 

Test organisms (species) 

Daphnia magna 

Details on test organisms 

Daphnia magna stocks were originally obtained from the EPA laboratory at Duluth, MN. They 

were maintained at 20-22 degrees C in a series of 600 ml beakers filled with Kanawha River 

water obtained from the South Side Boat Ramp (Charleston, SC). Daphnia were fed three times 

a week with a laboratory -prepared food consisting of trout food, yeast and alfalfa powder. 

Daphnia used in the test were offspring of 20-50 gravid females isolated for 24 hours. 

Study design 

Test type 

static 

Water media type 

freshwater 

Limit test 

no 

Total exposure duration 

48 h Remarks 

Post exposure observation period 

No. 

Test conditions 

Hardness 

Total hardness = 55 mg/l as CaCO3, 36 mg/l as CaCO3, 6.7, and 250 micromhos/cm 

(respectively). 

Test temperature 

Alkalinity was 36 mg/l as CaCO3 

pH 

6.7 

Dissolved oxygen 

measured initially and at 48 hours. 

Nominal and measured concentrations 

A series of from 5-10 equidistant concentrations based on results of fish studies (plus control) 

were tested. 

Details on test conditions 

Tests were conducted in 250 ml beakers containing 100 ml of test solution (in Kanawha River 

water) and 5 Daphnia (less than 24 hours old). Tests were run in duplicate. Dissolved oxygen 
and pH were determined initially and at 48 hours for all test solutions. Mortalities were 

recorded at 24 and 48 hours. 

Any other information on materials and methods incl. tables 

Water conductivity = 250 micromhos/cm. 

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint 

Effect conc. > 10 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Details on results 

The LC50 value was higher than the highest concentration used (10000 mg/l). 

Remarks on results including tables and figures 

Toxicity of triethylene glycol monoethyl ether (TGEE, CAS No. 112-50-5) and of triethylene 

glycol monobutyl ether (TGBE, CAS No. 143-22-6) were also tested in this study. The LC50 

values for TGEE and TGBE were >10000 and 2210 mg/l, respectively.

6.1.5 Toxicity to aquatic algae and cyanobacteria 

Toxicity to aquatic algae and cyanobacteria BASF TGME 1989.001 

UUID IUC5-68513ab3-7121-4c6a-a2af-d2367f3ccaac 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:12 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1989 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau 

Data source 

Reference 

Reference type company data 
Author Year 1989 

Title Algentest for Methyltriglykol 

Bibliographic 

source 

 

Testing laboratory Report no. 2/1017/88/t72 

Owner company BASF AG 

Company study no. Report date 1990-03-09 

Materials and methods 

Principles of method if other than guideline 

Typical acute aquatic toxicity procedure for algae. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on analytical methods 

no data 

Vehicle 

no data 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Scenedesmus subspicatus (new name: Desmodesmus subspicatus) 

Details on test organisms 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 
72 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no datano data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 72 h 

Endpoint EC20 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC50 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC90 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

7 Toxicological information 

7.1 Toxicokinetics, metabolism and distribution 
7.1.2 Dermal absorption 

Dermal absorption Ward and Scott TGME 1986.001 

UUID IUC5-b63ce3c6-e7de-436e-be91-b6efaf9ae279 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:31 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

86 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study with test material composition provided. 

Data source 

Reference 

Reference 

type 

study report 

Author Ward RJ, Scott RC Year 1986 

Title Triethylene glycol ethers: Absorption through human epidermis in vitro. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

CTL/P/160

0 

Owner 

company 

Imperial Chemical Industries 

Company 

study no. 

 Report 

date 

1986-10-31 

Materials and methods 

Type of method 

in vitro 

Principles of method if other than guideline 

standard in vitro skin absorption rate study. 

GLP compliance 

no data 

Test materials 

Radiolabelling 

no data 

Test material equivalent to submission substance identity 

no 

Test material identity 
Identifier Common name 

Identity triethylene glycol monomethyl ether 

Identifier other: trade name 

Identity POLYSOLV-TM 

Identifier EC number 

Identity 203-962-1 

Identifier CAS number 

Identity 112-35-6 

Details on test material 

Purity of test material (POLYSOLV-TM, triethylene glycol monomethyl ether (TGME)) was 

99.98%. 

Test animals 

Species 

human 

Strain 

no data 

Sex 

no data 

Administration / exposure 

Vehicle 

unchanged (no vehicle) 

Duration of exposure 

12 hours 

Control animals 

no 

Details on in vitro test system (if applicable) 

Human abdominal whole skin (2.54 cmE2) was mounted in a glass diffusion apparatus (at 30 

+/- 1 degree C) and the diffusion of triethylene glycol monomethyl ether was monitored during 

a 12-hr period using gas chromatography (n = 6). The integrity of the epidermal membranes was 

first assessed by measuring permeability of membranes to tritiated water. Epidermal membranes 

displaying permeability constants greater than 1.5 x 10E-3 cm/hr were deemed to have been 

damaged during preparation and were rejected. 

Results and discussions 

Remarks on results including tables and figures 

The mean steady rate of absorption for triethylene glycol monomethyl ether was 34.0 micrograms/cm2hr 

(SD +/- 7.73), which was close to 100-fold less than EGME. Test material caused a small change in 

permeability of the membrane (average damage ratio of 3.36).

Overall remarks, attachments 

Overall remarks 

Absorption of ethylene glycol monomethyl ether (EGME), triethylene glycol monoethyl ether (TGEE), 

and triethylene glycol monobutyl ether (TGBE) also were tested in this study. The rate of absorption of 

EGME was 220 micrograms/cm2/hr. The rate of absorption of TGEE was 24.1 micrograms/cm2/hr and 
the mean damage ratio was 1.37 (no increase in permeability). The rate of absorption of TGBE was 

22.2 micrograms/cm2/hr and the mean damage ratio was 1.26 (no increase in permeability).

7.2 Acute Toxicity 

7.2.1 Acute toxicity: oral 

Acute toxicity: oral Moreno Rat TGEE 1977 for Olin.001 

UUID IUC5-d8f0fbad-d5cf-4f3b-a2f7-ef22460e45be 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 15:26:37 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1977 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Older study with somewhat limited detail, including purity not specified for 

test material. Otherwise well conducted standard test. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1977 

Title Report on oral LD50 in rats 

Bibliographic 

source 

EPA/OTS File 0206799. 

Testing laboratory MB Research Laboratories, Inc. Report no. MB 77-1818 

Owner company Olin Corporation 

Company study no. Report date 1977-08-10 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to typical standard procedure. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 
Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

male 

Details on test animals and environmental conditions 

Rats (200-300 g) were fasted for approximately 18 hours prior to test material administration. 

Administration / exposure 

Route of administration 

other: intubation 

Vehicle 

unchanged (no vehicle) 

Doses 

5.0, 7.12, 10.14, and 14.43 g/kg 

No. of animals per sex per dose 

10 males per dose. Forty rats total. 

Control animals 

no data 

Details on study design 

Test material was given by intubation at 5.0, 7.12, 10.14, and 14.43 g/kg to groups of 10 

animals. Food and water were freely available after treatment. Rats were observed for toxicity 

and death for 14 days. 

Statistics 

The LD50 value and 95% confidence limits were determined by the method of Horn 

(Biometrics 12:311, 1956). 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 8500 mg/kg bw 

95% CL 

Remarks 

Mortality 

One rat given 7.12 g/kg died on day 10. Nine out of 10 rats given 10.14 g/kg died by day 3, and 
all rats given 14.43 g/kg died within 24 hours. 

Clinical signs 

Signs of toxicity were lethargy, ataxia, blood in the urogenital area and piloerection. 

Body weight 

no data 

Acute toxicity: oral Smyth Rat TGEE 1945.002 

UUID IUC5-1a9bdaea-f483-4951-9e2d-a2439f223e0d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 09:01:12 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

4

5 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Older study predating GLP and guidelines. Purity of TS not given. Otherwise, 

generally a reliable study. 

Data source 

Reference 

Reference 

type 

study report 

Author Smyth HF, Jr. Year 1945 

Title Special report on single dose and thirty-day dose toxicity of ethoxy triglycol. 

Bibliographi

c source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research, University of 

Pittsburgh 

Report 

no. 

8-63 

Owner 

company 

Carbide and Carbon Chemicals Corporation 

Company 

study no. 

 Report 

date 

1945-06-2

6 

Reference 

type 

publication 

Author Smyth HF and Carpenter CP. Year 1948 

Title Further experience with the range-finding test in the industrial toxicology 

laboratory. 

Bibliographi J Ind Hyg 30:63-68. 
c source 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS. Year 1951 

Title Range-finding toxicity data: List IV 

Bibliographic 

source 

Arch Ind Hyg Occup Med 4:119-122. 

Testing laboratory Report no. 

Owner company 

Company study 

no. 

 Report date 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

Study predates guideline, but was conducted according to typical accepted procedure. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

other: albino 
Sex 

male 

Details on test animals and environmental conditions 

Groups of 10 male rats (87-124 g). Forty animals total. 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

other: 1% Tergito 

Doses 

Dispersion in 1% Tergitol 7 at doses of 7.95, 8.9, 10.0, and 12.6 g/kg (1.4 to 3.0 ml of 

dispersion containing 0.5 g/ml). 

No. of animals per sex per dose 

Groups of 10 male rats 

Control animals 

no data 

Details on study design 

Groups of 10 male rats (87-124 g) were given test material by gavage as a dispersion in 1% 

Tergitol 7 at doses of 7.95, 8.9, 10.0, and 12.6 g/kg (1.4 to 3.0 ml of dispersion containing 0.5 

g/ml). Mortality was recorded over 14 days. Body weights were determined at study termination 

(for survivors). 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 10610 mg/kg bw 

95% CL 

Remarks 

Mortality 

All rats given 7.95 g/kg lived to day 14. The incidence of mortality in the other groups was 1/10 

for the 8.9 g/kg group, 6/10 for the 10.0 g/kg group, and 10.10 for the 12.6 g/kg group. All 

deaths occurred within 5 days. The LD50 value was calculated as 10.61 g/kg, with a range of 

9.98 to 11.28 g/kg. 

Clinical signs 

no data 

Body weight 

All survivors gained weight. 

Gross pathology 

All survivors appeared normal histologically. 

Acute toxicity: oral Carpenter Rat TGME 1958.007 

UUID IUC5-156d1b9a-884e-447c-a59e-3addc6ac070d 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:13 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

58 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Older preguideline and pre GLP study. Purity of test material was not noted. 

Data source 

Reference 

Reference type study report 

Author Carpenter CP. Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

Standard acute oral toxicity study procedure. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 
Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

other: Carworth Farms-Nelson 

Sex 

male 

Details on test animals and environmental conditions 

5-6 weeks old, 90-120 g 

Administration / exposure 

Route of administration 

other: stomach intubation 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

stomach intubation 

Doses 

4, 8, or 16 ml/kg 

No. of animals per sex per dose 

5 males per dose 

Control animals 

no data 

Details on study design 

Male rats (5-6 weeks old, 90-120 g) were dosed with 4, 8, or 16 ml/kg test material by stomach 

intubation. Rats were observed for 14 days. Surviving rats were weighed on day 14. Autopsies 

were performed on those that died. 

Statistics 

The method of moving average was used to calculate the LD50 value. 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 11300 mg/kg bw 

95% CL 

Remarks 

Mortality 

All rats dosed with 16 ml/kg died within 1 day. None of the other animals died. 

Clinical signs 

no data 

Body weight 

All animals except 1 dosed with 4 ml/kg gained weight. 
Gross pathology 

Autopsies on rats that died revealed congested lungs, mottled livers and kidneys, GI 

tractirritation, and congested adrenals. 

Acute toxicity: oral MB Res rat TGME 1977 Olin Corp.001 

UUID IUC5-c49e3814-a93f-403b-a2a9-4f769ed55c19 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:14 EDT 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence ( ) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

77 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Too little detail in study to assign a reliability rating 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1977 

Title MB Research Laboratories, Inc. 1977. Unpublished report toOlin Corp. 

Bibliographic 

source 

 

Testing 

laboratory 

MB Research Laboratories, Inc Report 

no. 

 

Owner 

company 

Olin Corp. 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

The LD50 and 95% confidence limits were calcuated by themethod of Litchfield and Wilcoxon 

(J Pharm Exp Ther 96:99,1949). 

GLP compliance 

no data 
Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

no data 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

other: no data 

Vehicle 

no data 

Details on oral exposure 

no data 

Doses 

no data 

No. of animals per sex per dose 

no data 

Control animals 

no data 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LD50 

Effect level 12600 mg/kg bw 

95% CL 
Remarks 

Mortality 

The LD50 ranged from 10.4 to 15.3 g/kg, and the average was 12.6 g/kg 

Acute toxicity: oral Gardner Rat Brake Fluid 1992.008 

UUID IUC5-0ae2ba4e-0639-4e36-84cb-3d5bf224dfe4 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-06 16:52:33 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

2 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Test substance composition was well characterized, and study followed GLP. 

Few study details provided however. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

 

Owner 

company 

Shell 

Company 

study no. 

DocumentNumber SBGR.92.011 Report 

date 

1992-06-3

0 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard acute oral toxicity procedure. 

GLP compliance 

yes 

Test materials 
Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethyleneglycol monomethyl ether borate ester 

(CAS No. 106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 

Test animals 

Species 

rat 

Strain 

Fischer 344 

Sex 

male/female 

Details on test animals and environmental conditions 

no details 

Administration / exposure 

Route of administration 

oral: unspecified 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no data 

Doses 

5000 mg/kg bw 

No. of animals per sex per dose 

10 

Control animals 

no 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 5000 mg/kg bw 
95% CL 

Remarks 

Acute toxicity: oral Reid Rat MPEG.003 

UUID IUC5-67b8fbe2-1714-4726-8c41-af0a49a6e5da 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:00 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

88 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted, robust study following recognized procedure. 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Project Report 51-41 Report 

no. 

Project Report 

51-41 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1988-05-23 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

No guideline mentioned. Study was conducted using typical standard protocol for acute oral 

test. 

GLP compliance 

no data 

Test materials 
Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Rats were fasted overnight before dosing. Male and female rats weighed approximately 250 and 

200 g at study initiation. 

Administration / exposure 

Route of administration 

other: stomach intubation 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Rats (5/sex/dose) received 8.0 or 16.0 ml/kg test material by stomach intubation. Two male rats 

were also dosed with 4.0 ml/kg. A total of 22 animals were used in the study. 

Doses 

8.0 or 16.0 ml/kg 

No. of animals per sex per dose 

5/sex/dose 

Control animals 

no data 

Details on study design 

Rats (5/sex/dose) received 8.0 or 16.0 ml/kg test material by stomach intubation. Two male rats 

were also dosed with 4.0 ml/kg. Doses were varied by adjusting the volume of test material or 

its dilution. Rats were fasted overnight before dosing. Male and female rats weighed 

approximately 250 and 200 g at study initiation. Animals were weighed before dosing and at 

days 7 and 14 after dosing. At death or sacrifice, each animal was subjected to gross pathologic 

evaluation. 
Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 16 mg/kg bw 

95% CL 

Remarks 

Mortality 

None of the animals treated with any dose of test material died. 

Clinical signs 

no data 

Body weight 

Animals were weighed before dosing and at days 7 and 14 after dosing. None of the animals 

treated with any dose of test material died. 

Gross pathology 

At death or sacrifice, each animal was subjected to gross pathologic evaluation. 

Acute toxicity: oral Carpenter Rat MPEG 1947.004 

UUID IUC5-f008b67b-4968-4421-9745-3ec11622bd61 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:01 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

47 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Old study, conducted preguidelines and pre GLP 

Data source 

Reference 

Reference 

type 

study report 

Author Carpenter CP Year 1947 

Title Range finding tests on methoxy polyethylene glycols of approximate molecular 

weights 350, 550 and 750. 

Bibliograp

hic source 

Melon Institute of Industrial Research, University of Pittsburgh. 
Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1947-05-

13 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

Standard acute method conducted pre-guideline. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity MPEG-350 

Details on test material 

Methoxy polyethylene glycol of approximately 350 molecular weight. 

Test animals 

Species 

rat 

Strain 

other: common albino 

Sex 

male 

Administration / exposure 

Route of administration 

other: stomach tube 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no details 

Doses 

10 ml/kg and 50 ml/kg 

No. of animals per sex per dose 

Six male animals per dose. Twelve animals were used in the study. 

Control animals 

no data 
Details on study design 

Groups of 6 rats (91-106 g) were dosed with 10 ml/kg (approximately 1 ml) or 50 ml/kg 

(approximately 4.7-5.3 ml) undiluted test material by stomach tube. Body weight gain and 

deaths were observed over a period of 14 days. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 22 mL/kg bw 

95% CL 

Remarks Method of estimation not given. 

Mortality 

All animals dosed with 50 ml/kg died within 1 day. None of the rats dosed with 10 ml/kg died. 

The LD50 was estimated to be 22 ml/kg (method of extrapolation not given). 

Clinical signs 

no data 

Body weight 

Animals dosed with 10 ml/kg gained from 23 to 68 grams over 14 days. 

Gross pathology 

no data 

7.2.2 Acute toxicity: inhalation 

Acute toxicity: inhalation Moreno Rat TGEE 1977 for Olin.001 

UUID IUC5-ca8bbd02-91ef-4259-a6fa-90fe7d2f6461 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 16:54:07 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

7

7 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Older study, GLP or guideline not specified. TS purity not given. In general a 

good study run by typical procedure. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1977 
Title Report on inhalation toxicity in rats 

Bibliographic 

source 

EPA/OTS File 0206799. 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. MB 77-1818 

Owner company Olin Corporation 

Company study 

no. 

 Report date 1977-08-01 

Materials and methods 

Test type 

fixed concentration procedure 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

no data 

Details on test animals and environmental conditions 

200-250 g, sex not stated 

Administration / exposure 

Type of inhalation exposure 

no data 

Vehicle 

unchanged (no vehicle) 

Details on inhalation exposure 

probably whole body, since no statement to the contrary. 

Analytical verification of test atmosphere concentrations 

no data 

Duration of exposure 
1 h Remarks 

Concentrations 

A nominal concentration of 200 mg/liter 

No. of animals per sex per dose 

10 animals, one dose, sex not noted 

Control animals 

no 

Details on study design 

Ten rats (200-250 g, sex not stated) were placed in a 50 liter chamber and exposed to a nominal 

concentration of 200 mg/liter of test material for one hour. The rats were observed daily over 14 

days for signs of toxicity. Bodyweights were recorded prior to and 14 days after treatment. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LC0 

Effect level > 200 mg/L air 

95% CL 

Exp. duration 

Remarks 

Mortality 

All animals survived the exposure. 

Clinical signs 

There were no signs of toxicity. 

Body weight 

Rats gained weight over the 14 day period. 

Gross pathology 

no data 

Acute toxicity: inhalation Smyth TGME Rat 1962.002 

UUID IUC5-4361a360-20fe-4360-a5c5-a2b0fdab8536 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:15 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

62 

Reliablility 2 (reliable with restrictions) 
Rationale for 

reliability 

Purity of test material was not noted. Also older study predating guidelines 

or GLP. 

Data source 

Reference 

Reference type study report 

Author Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA 

Year 1962 

Title Range-finding toxicity data: List VI 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard prodecure of the time for acute inhalation toxicology 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 
Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

other: Carworth-Wistar 

Sex 

female 

Administration / exposure 

Route of administration 

inhalation: vapour 

Type of inhalation exposure 

no data 

Vehicle 

unchanged (no vehicle) 

Details on inhalation exposure 

Six female rats were exposed to a flowing stream of vapor-ladened air generated by passing 2.5 

l/min of dried air at room temperature through a fritted disc immersed to a depth of at least once 

inch in approximately 50 ml of test material contained in a gas-washing bottle. Rats were 

exposed from time periods ranging from 15 minutes to 8 hours (until the inhalation period 

killing about one half of the rats within 14 days was defined). The result is the longest 

inhalation period which permitted all rats to survive the14-day observation period. 

Analytical verification of test atmosphere concentrations 

no data 

Duration of exposure 

8 h Remarks 

Concentrations 

not measured but probably saturated 

No. of animals per sex per dose 

six females 

Control animals 

no data 

Results and discussions 

Mortality 

All animals survived an 8-hr exposure period to concentrated vapor and had normal weight 

gains. 

Clinical signs 

no data 

Body weight 

All animals had normal weight gains. 

Gross pathology 

no data 

Other findings 

no data 
7.2.3 Acute toxicity: dermal 

Acute toxicity: dermal Smyth et al. Rabbit TGEE 1951.001 

UUID IUC5-f45a9e98-de1a-42de-8738-bcbedf3d5db2 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 16:37:17 EST 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence ( ) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

51 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Details on how value was obtained were not given. No data on test material 

purity. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS. Year 1951 

Title Range-finding toxicity data: List IV. 

Bibliographic 

source 

Arch Ind Hyg Occup Med 4:119-122. 

Testing laboratory Report no. 

Owner company 

Company study 

no. 

 Report date 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

Predates guidelines or GLP. Standard acute method of the period 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 
Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Sex 

no data 

Administration / exposure 

Type of coverage 

no data 

Vehicle 

no data 

Details on dermal exposure 

no data 

Duration of exposure 

no data 

Doses 

no data 

No. of animals per sex per dose 

no data 

Control animals 

no data 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LD50 

Effect level 8200 mg/kg bw 

95% CL 

Remarks 

Acute toxicity: dermal Moreno Rabbit TGEE 1976.002 

UUID IUC5-faac3656-f262-409a-ae24-573babd140e9 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 17:10:49 EST 

Remarks 
 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Test substance purity not given. Guideline or GLP not specified. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1976 

Title Report on acute dermal toxicity in rabbits. 

Bibliographic 

source 

EPA/OTS Document File 0206799. 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. Project Number MB 

77-1818 

Owner 

company 

Olin Corporation. 

Company 

study no. 

 Report 

date 

1977-08-02 

Materials and methods 

Test type 

standard acute method 

Limit test 

yes 

Principles of method if other than guideline 

standard acute method, no guideline specified 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 
Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

no data 

Details on test animals and environmental conditions 

1.9 to 3.2 kg 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

The rabbits were clipped free of abdominal hair. Epidermal abrasions were made longitudinally 

every 2 to 3 cm over the clipped area of 5 rabbits. The abrasions were deep enough to penetrate 

the stratum corneum, but not deep enough to produce bleeding. A single dose of 2.0 g/kg was 

applied to the exposed area. The area was covered with gauze and the trunk wrapped with 

impervious material for 24 hours. 

Duration of exposure 

24 hours 

Doses 

2.0 g/kg 

No. of animals per sex per dose 

ten rabbits, sex not specified, one dose level. Epidermal abrasions were made longitudinally 

every 2 to 3 cm over the clipped area of 5 of the rabbits. 

Control animals 

no 

Details on study design 

Ten rabbits (1.9 to 3.2 kg) were clipped free of abdominal hair. Epidermal abrasions were made 

longitudinally every 2 to 3 cm over the clipped area of 5 rabbits. The abrasions were deep 

enough to penetrate the stratum corneum, but not deep enough to produce bleeding. A single 

dose of 2.0 g/kg was applied to the exposed area. The area was covered with gauze and the 

trunk wrapped with impervious material for 24 hours. The dressing was removed, rabbits were 

cleaned, and animals were evaluated over 14 days. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LD0 

Effect level 2000 mg/kg bw 
95% CL 

Remarks 

Mortality 

There were no deaths. 

Clinical signs 

No signs of systemic toxicity. 

Body weight 

no data 

Gross pathology 

no data 

Acute toxicity: dermal Rabbit TGME Mellon 1958.001 

UUID IUC5-4428421a-0f92-4dfe-8314-99c1aef4d436 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:32 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

1

9

5

8 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Adequate older study, but guideine and GLP not specified and test material 

purity not specified. 

Data source 

Reference 

Reference type study report 

Author Year 1958 

Title Range finding tests on methoxytriglycol 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research. Report no. 21-44, 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 
standard acute method 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male 

Details on test animals and environmental conditions 

Male rabbits (3-5 months old, avg. weight 2.5 kg). Eight animals total. 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

Male rabbits (3-5 months old, avg. weight 2.5 kg) weretreated dermally on clipped trunk skin 

with 2.5 ml/kg (N=2),5 ml/kg (N=4), or 10 ml/kg (N=2) test material. VINYLITE sheeting used 

to keep the material in contact with the skin. Rabbits were immobilized for 24 hours. After 24 

hours, the sheeting was removed. The rabbits were observed for a totalof 14 days. The moving 

average method was used to calculatethe LD50 value. 

Duration of exposure 

24 hours 

Doses 

2.5 ml/kg (N=2),5 ml/kg (N=4), or 10 ml/kg (N=2), where N=number of animals per dose. 

No. of animals per sex per dose 

See "doses" above for information. 

Control animals 

no data 

Details on study design 

no further details 

Results and discussions 
Effect levels 

Sex male 

Endpoint LD50 

Effect level 7.13 mL/kg bw 

95% CL 

Remarks 

Mortality 

The two rabbits treated with 10 ml/kg died within 4 days. 

Clinical signs 

Marked erythema of skin was noted after removal of thedressing (doses and number affected 

not noted). One of the rabbits reated with 10 ml/kg had internal hemorrhage asevidence by 

bloody exudate in the peritoneal cavity atautopsy. All other rabbits survived and appeared 

normal. 

Body weight 

no data 

Gross pathology 

no data 

Acute toxicity: dermal Gardner BF DOT 4 1992.004 

UUID IUC5-e2d25c04-5a3a-4961-aea4-136f0b27eca6 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:52 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

92 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

few study details given 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit 

Bibliographi

c source 

 

Testing Shell Research Limited, Sittingbourne Research Centre Report 
laboratory no. 

Owner 

company 

Shell 

Company 

study no. 

DocumentNumber SBGR.92.011 Report 

date 

1992-06-3

0 

Materials and methods 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 

Test animals 

Species 

rat 

Strain 

Fischer 344 

Sex 

male/female 

Administration / exposure 

Type of coverage 

no data 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

no data 

Duration of exposure 

no data 

Doses 

2000 mg/kg bw 

No. of animals per sex per dose 

5 per sex per dose 

Control animals 

no data 
Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 2000 mg/kg bw 

95% CL 

Remarks 

Acute toxicity: dermal Reid MPEG Rabbit 1988.003 

UUID IUC5-babe08a6-9fc1-478e-8fb1-fa7c0b961d11 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:02 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

8 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted study with good documentation. Test material is well 

characterized as to composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

51-41 

Owner 

company 

 

Company 

study no. 

Union Carbide Report 

date 

1988-05-23 

Materials and methods 
Test type 

standard acute method 

Principles of method if other than guideline 

standard acute inhalation test method 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350)(CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Ten animals total were used in the study. Five rabbits of each sex (weighing between 2 and 3 

kg). 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

Five rabbits of each sex (weighing between 2 and 3 kg) were subjected to 24 hours of contact 

with the test material (16 ml/kg) , which was retained under impervious sheeting on the clipped, 

intact skin of the trunk. If necessary, gauze was wrapped around the trunk over the sample to 

prevent leakage. Bandaging tape was wrapped over the impervious sheeting. Excess fluid was 

removed after the contact period to diminish ingestion. 

Duration of exposure 

24 hours of skin contact. 

Doses 
16 ml/kg, single dose level 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

no 

Details on study design 

Body weights were determined before and 7 and 14 days following test material application. 

Deaths were monitored for 14 days. 

Statistics 

no data 

Results and discussions 

Preliminary study (if fixed dose study) 

no preliminary study 

Effect levels 

Sex male/female 

Endpoint LDLo 

Effect level > 16 mL/kg bw 

95% CL 

Remarks 

Mortality 

No animals died during the course of the study. 

Clinical signs 

No signs of systemic toxicity or irritation were noted. 

Body weight 

no data 

Gross pathology 

no data 

7.2.4 Acute toxicity: other routes 

Acute toxicity: other routes NAMSA MPEG 1997.001 

UUID IUC5-2a6353e6-f244-4575-9bf5-d18c1cb8d2c7 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:11 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

97 

Reliablility 1 (reliable without restriction) 

Rationale for well conducted, thorough study following GLP. Test substance was well 
reliability defined. 

Data source 

Reference 

Reference 

type 

study report 

Author Pohl DR, et al Year 1997 

Title Acute systemic toxicity screen in the rat. Carbowax Sentry MPEG 350, NF grade 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

NAMSA Study 

Number 97U1635 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1997-08-20 

Materials and methods 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity CAS No. 9004-74-4 

Identifier Common name 

Identity CARBOWAX Sentry MPEG 350 

Details on test material 

Test material was CARBOWAX Sentry MPEG 350 (CAS No. 9004-74-4), NF grade. This a 

mixture of several methylated glycol ethers of differing molecular weight (ranging from 

diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303%triethylene 

glycol monomethyl ether (CAS No. 112-35-6), and 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 
other: i.v. 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Two rats/group were injected daily with 0.5, 1.1 and 2.2 g/kg/day for 5 days. 

Doses 

0.5, 1.1 and 2.2 g/kg/day for five days 

No. of animals per sex per dose 

Two male rats/group 

Control animals 

no data 

Details on study design 

Necropsies were performed on Day 6. 

Results and discussions 

Effect levels 

Sex no data 

Endpoint other: toxic dose 

Effect level > 1100 — <= 2200 mg/kg bw 

95% CL 

Remarks 

Mortality 

There were no overt signs of toxicity (either clinical or gross upon necropsy) in rats (191 to 222 

g) injected with 0.5g/kg/day or 1.1 g/kg/day for 5 days. Both animals injected with 2.2 g/kg/day 

for 5 days had labored breathing, ataxia and hypoactivity following each daily dose. No animals 

died. 

Clinical signs 

There were no overt signs of toxicity (either clinical or gross upon necropsy) 

Body weight 

no data 

Gross pathology 

No signs of toxicity upon necropsy. 

Other findings 

Both animals injected with 2.2 g/kg/day for 5 days had labored breathing, ataxia and 

hypoactivity following each daily dose. 

7.3 Irritation / corrosion 

7.3.1 Skin irritation / corrosion 

Skin irritation / corrosion Moreno Rabbit TGEE 1977.001 

UUID IUC5-5b6e3058-fa4a-4977-b835-f80d3b45df4d 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 17:09:17 EST 

Remarks 

 

Administrative Data 
Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

77 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of TS not provided. 

Data source 

Reference 

Reference 

type 

 

Author Moreno OM. Year 1977 

Title Report on primary dermal irritation in rabbits. 

Bibliographic 

source 

EPA/OTS File 0206799. 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. Project number MB 

77-1818 

Owner 

company 

Olin Corporation 

Company 

study no. 

 Report 

date 

1977-08-08 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No guideline specified, but test was carried out per typical recgonized procedure. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 
Strain 

no data 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

abraded 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.5 ml 

Duration of treatment / exposure 

24 hours 

Observation period 

24 and 72 hours in accordance with the Consumer Product Safety Act, Title 16 CFR 1500.41. 

Number of animals 

Six rabbits 

Control animals 

no 

Details on study design 

Six rabbits were clipped over the back and sides with an electric clipper. A site to the left of the 

spinal column was abraded. Abrasions were minor incisions through the stratum corneum that 

did not disturb the derma or produce bleeding. Test material (0.5 ml) was applied to a surgical 

gauze (1" square, 2 layers thick). The patches were placed on test sites and secured with 

adhesive tape. The trunk was wrapped with impervious material. Patches were removed after 24 

hours. Dermal reactions were evaluated at 24 and 72 hours in accordance with the Consumer 

Product Safety Act, Title 16 CFR 1500.41. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter primary dermal irritation index (PDII) 

Basis mean 

Time point 24 and 72 hours 

Score 0.17 

Max. score 1 

Reversibility 

Remarks 

Irritant/corrosive response data 

An erythema score of 1 (barely perceptible) was observed in 2 rabbits at 24 hours (intact and 

abraded skin). All others received erythema scores of 0. The mean erythema score was 0.33. No 

edema was observed at 24 or 72 hours. The mean primary irritation score was 0.17. 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Skin irritation / corrosion Smyth TGME 1962.007 

UUID IUC5-c4be5879-bee8-41ba-ab31-eaaf8f96b405 
Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:15 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

6

2 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Some study details of test method animals and TS purity are lacking, but 

otherwise the study was well conducted. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title . Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Reference type study report 

Author Carpenter CP Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 
Type of method 

in vivo 

Principles of method if other than guideline 

No test guideline specified, but study was conducted according to procedure commonly used. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

open 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

undiluted substance 

Duration of treatment / exposure 

24 hours 

Observation period 

24 hours 

Number of animals 

5 rabbits 

Control animals 

no data 

Details on study design 

Undiluted test solution (0.01 ml) was applied to the clipped belly skin of 5 rabbits. Irritation that 
occurred within 24 hours was scored in a graded fashion (from 1 to 10), with Grade 1 = no 

irritation, Grade 2 = the least visible capillary injection, Grade 6 = necrosis when undiluted. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis 

Time point 24 hours 

Score 2 

Max. score 

Reversibility 

Remarks 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Conclusions 

An irritation Grade of 2 was obtained with undiluted test material, indicating minimal irritation. 

Skin irritation / corrosion Palazzolo TGME 1969.001 

UUID IUC5-336e80e1-75f9-4814-8e1a-a96cc7302b09 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:16 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

69 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Good study but predating current guidelines and GLP and not providing test 

substance purity. 

Data source 

Reference 

Reference 

type 

study report 

Author Palazzolo RJ. Year 1969 

Title Comparative human skin irritation study on five test materials. Industrial 

Bibliographi

c source 

 

Testing 

laboratory 

Bio-Test Laboratories Report 

no. 

IBT F7445 

Owner Olin Research Center 
company 

Company 

study no. 

 Report 

date 

1969-06-25 

Materials and methods 

Type of method 

in vivo 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Details on test material 

no data 

Test animals 

Species 

other: human volunteers 

Strain 

other: Caucasian 

Details on test animals and environmental conditions 

10/sex, 20-56 years old, 90% Caucasian 

Test system 

Type of coverage 

semiocclusive 

Preparation of test site 

other: no special preparation 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.03 ml 

Duration of treatment / exposure 

3 days 

Observation period 

daily one hour after exposure 

Number of animals 

10 per sex 

Control animals 

no 

Details on study design 

Twenty human subjects (10/sex, 20-56 years old, 90% Caucasian) were employed in the study. 
Band-aids (3/8 " x 1-1/2 ") with gauze centers were coated with 0.03 ml of test material just 

prior to application. Patches were placed on skin for 24 hours, and then removed. The skin site 

was examined approximately 1 hour after patch removal. After grading, a second patch was 

applied to the same site. The procedure was repeated for 3 consecutive days. Erythema and 

Eschar formation were scored on a basis of 0-4, with 1= barely perceptible erythema, 2= 

well-defined erythema. 3 = moderate to severe erythema, and 4 = severe erythema to slight 

eschar formation. Edema was scored on a basis of 0-4, with 1= barely perceptible, 2 = 

slight(definite raising), 3 = moderate (area raised 1 mm), 4 = severe (raised more than 1 mm and 

extends beyond area of exposure). The total possible primary irritation score is the sum of the 

highest erythema and edema scores (8). 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis mean 

Time point 72 hours 

Score 1.65 

Max. score 

Reversibility 

Remarks 

Irritant/corrosive response data 

By 24 hours, erythema scores of 1 or 2 were present in 10/20, and 3/20 subjects, respectively. 

At 48 hours, erythema scores of 1 or 2 were present in 11/20 and 9/20 subjects, respectively. At 

72 hours, more subjects had scores of 2 (13/20), than 1 (7/20). Edema scores were 0 throughout 

the test. The average total irritation score by 72 hours was 1.65.

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Skin irritation / corrosion MB Res TGME 1977.002 

UUID IUC5-bd4beac8-a6ab-4e13-8798-ec437b656154 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:17 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1977 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Adequate study, but no guideline or GLP specified, test substance purity not 

noted, rabbit strain not noted. Irration scores not given. 

Data source 
Reference 

Reference type study report 

Author Year 1977 

Title MB Research Laboratories, Inc. 1977. 

Bibliographic 

source 

 

Testing laboratory MB Research Laboratories, Inc. Report no. 

Owner company 

Company study 

no. 

Olin Corp. Report date 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Standard type of dermal absorption study in vivo 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Test animals 

Species 

rabbit 

Strain 

no data 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

abraded 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Test material (2.0 g/kg) was applied to intact and abraded skin and covered for 24 hours. 

Duration of treatment / exposure 

24 hours 
Observation period 

not stated 

Number of animals 

five 

Control animals 

no 

Details on study design 

Dermal reactions were evaluated by the Draize technique 

Results and discussions 

Irritant/corrosive response data 

Erythema was obsered in 4/5 rabbits with intact skin and 1/5 rabbits with abraded skin. Edema 

was observed in 1/5 rabbits with abraded skin and none of the rabbits with intact skin. 

Skin irritation / corrosion UC MSDS TGME 2000.003 

UUID IUC5-097dc352-b1a6-44e9-a2f9-918661d0a948 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:18 EDT 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence ( ) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

not 

provid

ed 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Secondary source (company MSDS) 

Data source 

Reference 

Reference type company data 

Author Year 2000 

Title Material Safety Data Sheet for Methoxytriglycol 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. MSDS #1286. 

Owner 

company 

Union Carbide Corporation 

Company study 

no. 

 Report date 

Materials and methods 

Type of method 
in vivo 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier EC number 

Identity 203-962-1 

Identifier CAS number 

Identity 112-35-6 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether (TGME) 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

open 

Preparation of test site 

no data 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

no data 

Duration of treatment / exposure 

24 hours 

Observation period 

no data 

Number of animals 

five 

Control animals 

no 

Results and discussions 

Irritant/corrosive response data 

Minimal erythema in 2/5 rabbits and no irritation in 3/5. 

Skin irritation / corrosion Gardner BF DOT 4 1992.006 

UUID IUC5-b12ca6b1-af6a-4130-94fe-44178f4aecdd 
Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:52 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1992 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Study well conducted following GLP and providing good data on test material 

purity. Details provided in the study were somewhat limited as to methodology. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

011 

Owner 

company 

Shell 

Company 

study no. 

 Report 

date 

1992-06-3

0 

Materials and methods 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to normally followed procedures for 

this type of study. 

GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 
Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CASNo. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

semiocclusive 

Preparation of test site 

no data 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

applied undiluted 

Duration of treatment / exposure 

4 hours 

Observation period 

no data 

Number of animals 

six 

Control animals 

no data 

Details on study design 

no data 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Conclusions 

not irritating 

Skin irritation / corrosion Reid MPEG 1988.004 

UUID IUC5-f34f885b-8184-4d8d-996a-e22151307e57 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:03 EDT 
Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

88 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study with strong detail documentation 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

51-41 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1988-05-23 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Standard Draize procedure. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350, CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 
glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Test material (0.5 ml) was applied to the clipped, intact skin of six rabbits (3 of each sex). The 

material was loosely covered with a gauze patch an impervious sheeting. Rabbits were 

restrained for a 4-hour contact period. Excess material was removed after contact. 

Duration of treatment / exposure 

4-hour contact period 

Number of animals 

three of each sex 

Control animals 

no 

Details on study design 

The skin reaction was scored by the method of Draize at one hour, and 1, 2, 3, and 7 days 

following dosing. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis mean 

Time point 1 hr, and 1, 2, 3 and 7 days 

Score ca. 0 

Max. score 0 

Reversibility 

Remarks 

Irritant/corrosive response data 

Scores of 0 were obtained for both erythema (and eschar formation) and edema. The material 

was therefore non-irritating. 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

7.3.2 Eye irritation 
Eye irritation Moreno Rabbit TGEE 1976.001 

UUID IUC5-9cc80ff2-db99-4739-9719-88de07d19db4 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-18 23:57:05 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted older study. GLP and guideline not specified. TS purity not 

specified. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1976 

Title Report on rabbit eye irritation. 

Bibliographic 

source 

EPA/OTS File 0206799. 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. Project number MB 77-1818 

Owner company Olin Corporation 

Company study 

no. 

 Report date 1977-08-12 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Standard eye irritation study. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 
Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Test material (0.1 ml) in neat form 

Duration of treatment / exposure 

72 hours after instillation of test material 

Observation period 

1, 2, and 3 days after instillation of the test material 

Number of animals 

Six 

Control animals 

other: The contralateral (untreated) eye of each animal served as a control. 

Details on study design 

Six New Zealand white rabbits were used in the study. Test material (0.1 ml) was instilled into 

the conjunctival sac of one eye of each rabbit on Day 0. The contralateral eye served as a 

control. Ocular reactions were graded in accordance with the Consumer Product Safety Act, 

Title 16 CFR 1500.42 at 1, 2, and 3 days after instillation of the test material. 

Results and discussions 

Overall irritation / corrosion results 

Irritation parameter cornea score 

Basis other: all animals 

Time point all time points 

0 — 8 

Max. score 110 

Reversibility not fully reversible within: 72 hours 

Remarks 

Irritant/corrosive response data 

Conjunctival redness, chemosis and/or discharge scores of 1 or 2 were noted at 24 hours in all 

rabbits. These findings completely resolved in 2 rabbits by 72 hours. Slight redness and 

discharge was observed in 4 and 2 rats (respectively) at 72 hours. Iris and corneal opacity scores 

of 0 were observed in all animals at each time point. The total conjunctival score [(redness + 

chemosis + discharge) x 2] at 24 hours ranged from 2-8 out of a possible 20. The highest overall 

score was 8 out of a possible 110. 

Applicant's summary and conclusion 
Interpretation of results 

irritating 

Eye irritation Smyth TGME 1962.006 

UUID IUC5-9da90c34-0bb6-42d6-8a27-8fc06b81df81 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:18 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1958 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Rabbit strain not given. Details of number of animals exposed to each dose not 

given. GLP not specified. Purity of test substance not noted. Otherwise thie was 

a credible study. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP. Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 
Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to typical procedure for eye 

irritation. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no details. 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

.5 ml 

Duration of treatment / exposure 

no data 

Observation period 

no data 

Number of animals 

not specified 

Control animals 

no data 

Details on study design 

Various volumes and concentrations of test material were applied to rabbit eyes (number of 

rabbits and time of exposure was not indicated). Eye injury was scored on a 10 point scale 

according to the degree of corneal necrosis that resulted from instillation of the various 
concentrations. Grade 1 = very small area of necrosis from 0.5 ml undiluted material, Grade 5 = 

severe burn from 0.005 ml undiluted material, Grade 10 = severe burn from 0.5 ml of a 1% 

solution in water or propylene glycol. 

Results and discussions 

Overall irritation / corrosion results 

Irritation parameter overall irritation score 

Basis 

Time point 

 

Max. score 1 

Reversibility 

Remarks 

Irritant/corrosive response data 

Five rabbit eyes were not injured by 0.5 ml undiluted test material (grade 1). 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Eye irritation Gardner BF DOT 1992.005 

UUID IUC5-04899188-a49c-496e-b723-da44c6bc006f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:53 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study following GLP, with the composition of the test 

material well characterized. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit 

Bibliograph

ic source 

 
Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

011 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1992-06-3

0 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to standard procedure for eye 

irritation. 

GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, (20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CASNo. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

.1 ml 

Duration of treatment / exposure 

72 hours 

Observation period 

72 hours 
Number of animals 

six 

Control animals 

no data 

Details on study design 

no data 

Results and discussions 

Irritant/corrosive response data 

sllightly irritating 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Eye irritation Reid MPEG 1988.003 

UUID IUC5-35d9d086-c13f-4db2-af80-6a9c2dad0f6a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:04 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

8 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Study was well conducted with detailed information. Test material was well 

characterized with regard to composition. 

Data source 

Reference 

Reference 

type 

 

Author Reid ME. 1988 Year 1988 

Title MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographic 

source 

 

Testing 

laboratory 

Bushy Run Research Center Report no. 51-41 

Owner 

company 

Union Carbide 

Company Report 1988-05-23 
study no. date 

Materials and methods 

Principles of method if other than guideline 

No guideline specified. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350, CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.1 ml 

Duration of treatment / exposure 

Not specified whether eye was rinsed at some point after instillation of test material. 

Observation period 

1 and 4 hours, and 1, 2, 3, and 7 days after dosing 

Number of animals 

Six 

Control animals 

yes, concurrent no treatment 

Details on study design 

Six male New Zealand white rabbits were dosed with 0.1 ml of test material. The test material 

was instilled into the lower conjunctival sac or placed directly on one eye per animal. The other 

eye served as a control. The eyes were scored at 1 and 4 hours, and 1, 2, 3, and 7 days after 
dosing. Florescein (2%) was added to the eyes before dosing and after 1 day of exposure to 

assess corneal injury. 

Results and discussions 

Irritant/corrosive response data 

Instillation of test material resulted in no corneal injury or iritis. Minor conjunctival irritation 

developed in all 6 rabbits. Moderate discharge was seen in several of the eyes. These effects 

resolved by 24 hours. 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

7.5 Repeated dose toxicity 

7.5.1 Repeated dose toxicity: oral 

Repeated dose toxicity Smyth Rat TGEE 1945: oral.001 

UUID IUC5-98f184d2-309e-48e5-870a-f882f46018dd 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 09:14:27 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1945 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Study predates guidelines or GLP. Purity of test substance not given. 

Otherwise, a very well-conducted study for the time period. 

Data source 

Reference 

Reference 

type 

study report 

Author Smyth HF, Jr. Year 1945 

Title Special report on single dose and thirty-day dose toxicity of ethoxy triglycol. 

Bibliographi

c source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research, University of 

Pittsburgh 

Report 

no. 

8-63 

Owner 

company 

Carbide and Carbon Chemicals Corporation 

Company 

study no. 

 Report 

date 

1945-06-26 

Materials and methods 

Test type 
subacute 

Limit test 

no 

Principles of method if other than guideline 

Study predates guidelines, but procedure was typical for oral subacute studies using drinking 

water 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-50-5 

Identifier EC number 

Identity 203-978-9 

Identifier Common name 

Identity triethylene glycol monoethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

no data 

Sex 

male 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

water 

Details on oral exposure 

Groups of 10 rats (90-120 g) were given doses of test material in the drinking water at 

concentrations of 0 (control), 0.12, 0.5, 2 and 8% for 30 days. The actual doses received were 0, 

180, 750, 3300 and 13290 mg/kg/d. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

30 days 
Frequency of treatment 

daily 

Doses/concentrations 

0, 180, 750, 3300 and 13290 mg/kg/d 

Basis nominal in water 

No. of animals per sex per dose 

10 male rats per dose 

Control animals 

yes, concurrent vehicle 

Examinations 

Observations and examinations performed and frequency 

Water consumption and deaths were monitored daily. 

Sacrifice and pathology 

no data 

Other examinations 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoin

t 

NOEL 

Effect 

level 

750 mg/kg bw/day (nominal) 

Sex male 

Basis 

for 

effect 

level / 

Remarks 

Rats exposed to 3300 mg/kg/d exhibited decreased weight gain, high blood urea 

concentrations (4/10), kidney damage (1/10), liver abnormalities (6/10). Animals 

exposed to 750 or 180 mg/kg/day appeared normal. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

no data 

Food consumption and compound intake (if feeding study) 

no data 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

yes 

Ophthalmoscopic examination 

no data 

Urinalysis 
no data

Neurobehaviour 

no data 

Organ weights 

no data 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

Rats receiving the highest dose consumed only 25% of the amount of water as controls. All of 

them died within 6 to 24 days of exposure (average 13). Necropsy of these animals revealed 

congestion and cloudy swelling of the liver and cloudy swelling and degeneration of epithelium 

of the convoluted tubules of the kidneys. None of the other rats died. Rats exposed to 3300 

mg/kg/d exhibited decreased weight gain, high blood urea concentrations (4/10), kidney damage 

(1/10), liver abnormalities (6/10). Animals exposed to 750 or 180 mg/kg/day appeared normal. 

Repeated dose toxicity: oral Gill and Negley TGME 1990.001 

UUID IUC5-8f04c5e5-4cf0-46e4-9582-8ffb211e8bbc 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:20 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study performed following GLP 

Data source 

Reference 

Reference 

type 

study report 

Author Gill MW and Negley JE. Year 1990 

Title Triethylene glycol monomethyl ether. Ninety day subchronic drinking water 

inclusion neurotoxicity study in rats. 

Bibliogra

phic 

source 

 
Testing 

laboratory 

Bushy Run Research Center Repor

t no. 

Project Report 

52-607, 

Owner 

company 

Union Carbide 

Company 

study no. 

 Repor

t date 

1990-09-21 

Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 1998 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats. 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

This study is also summarized as a fertility study in Toxicity to reproduction.003 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Test guideline 

Qualifier equivalent or similar to 

Guideline EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents) 

Deviations 

Principles of method if other than guideline 

EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 
Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The purity of the material was at least 98.7%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 weeks old 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Male and female rats (8 weeks old, 15/sex/group) were treated with triethylene glycol 

monomethyl ether (TGME) for 91 days via drinking water at target doses of 0, 400, 1200 and 

4000 mg/kg/day. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

It is assumed that test material of 98.7% purity was diluted into the drinking water, such that the 

animals drinking an historically expected amount of water daily would ingest the target dose. 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily 

Doses/concentrations 

0, 400, 1200 and 4000 mg/kg/day. 

Basis nominal in water 

No. of animals per sex per dose 

15/sex/group 

Control animals 

yes, concurrent no treatment 

Positive control 

no data 

Examinations 

Observations and examinations performed and frequency 

Rats were observed daily for clinical signs and weekly for body weight and water and food 

consumption. Ten rats/sex/group were observed periodically for behavior (functional 

observational battery) and motor activity. 
Sacrifice and pathology 

After 91 days of treatment, tissues of 10 animals/sex/group were fixed in situ, and brains were 

removed. These animals received complete necropsies, and tissues from 6 animals/sex/group 

were processed for evaluation of the nervous system by light microscopy. The 5 

animals/sex/group not sacrificed and perfused in situ were killed by severing the brachial 

vessels to permitexsanguination. These animals received complete necropsies, and the liver, 

kidneys, brain, lungs, adrenals, and testes (males) were weighed. Liver and testes were 

examined by light microscopy. 

Statistics 

Data for continuous variables were analyzed with Levene's test for homogeneity of variance, 

analysis of variance (ANOVA), and by pooled variance t-tests. If Levene's test indicated 

heterogeneous variances, groups were analyzed with an ANOVA for unequal variances, 

followed by separate variance t-tests. Fisher's exact 2 x 2 groups comparisonswere used to 

analyze functional observational battery data. Motor activity counts were log transformed prior 

to analysis. Motor activity dose-effects, dose-sex interactions, and time-dose interactions were 

determined using repeated measures ANOVAs with dose and sex as grouping factors and time 

as a within-subject factor. Comparisons between treated and control groups were made for total 

test session activity (the sum of the counts across the 90-min test session) using ANOVA. To 

reduce the increased false positives associated with repeated significance testing, the correction 

procedure described by Mantel (Biometrics 36:381-399, 1980) was used when testing for 

overall significance. The frequency data for anatomic pathology were analyzed as described by 

Sokal and Rohlf (Biometry, WHFreeman, 1981). 

Any other information on materials and methods incl. tables 

No post obs. period was conducted.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 400 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Liver weight effects. 

Endpoint LOAEL 

Effect level 1200 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Liver weight effects. 

Endpoint NOAEL 

Effect level 1200 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Testicular effects. 

Endpoint LOAEL 

Effect level 4000 mg/kg bw/day (nominal) 

Sex male 
Basis for effect level / Remarks Testicular effects. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

yes 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

no data 

Urinalysis 

no data 

Neurobehaviour 

yes 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

The actual doses attained in the study (time weighted average) were 0, 420, 1240 and 4300 

mg/kg/day for males and 0, 420, 1290 and 4100 mg/kg/day for females.

One female in the high dose treatment group (approximately 4000 mg/kg/day) died on Day 37. 

Males and females treated with the highest dose consumed less food and had lower body 

weights and body weight gains than control animals. Water consumption decreased in high-dose 

females (by an average of 17%). 

Treatment with triethylene glycol monomethyl ether did not result in any clinical signs of 

toxicity, alterations in the functional observational battery, or gross microscopic lesions in the 

nervous system. Significant, small decreases in total test session motor activity were observed 

in the high-dose treatment group at the Day 60 (males only) and Day 90 (females) evaluation 

periods. Study personnel stated that “the decreases in motor activity were not considered to be 

neurotoxicologically significant based on the small magnitude of the changes, the parallel 

changes in body weights at the evaluation periods, and the lack of corroborative behavioral 
effects from the functional observational battery evaluations or histological changes in central 

or peripheral nervous system tissues.”

Increased relative liver weight was observed in males treated with 4000 mg/kg/day (5.229 ± 

0.3984) and 1200 mg/kg/day (3.951 ± 0.4191) versus control (3.214 ± 0.1519). Absolute liver 

weights of males treated with 4000 mg/kg/day were significantly greater than controls (25.926 ± 

3.1591 versus 18.978 ± 1.4925). Microscopic changes (hepatocellular cytoplasmic 

vacuolization and/or hypertrophy) were noted in livers of high-dose males (14/15). The severity 

of these liver lesions was minimal or mild (with the exception of moderate or marked 

vacuolization for 4 high dose males). Mild cholangiofibrosis was observed around a small 

number of bile ducts in high-dose males (7/15). This was not considered by study personnel to 

be physiologically significant due to the limited number of bile ducts affected and the mild 

nature of the effect (Gill et al., Int J Toxicol. 17:1-22, 1998). Minimal or mild hepatocellular 

hypertrophy was seen in 10/15 high dose females. Three males treated with 400 mg/kg/day and 

4 treated with 1200 mg/kg/day also exhibited minimal-mild hepatocellular cytoplasmic 

vacuolization and/or cellular hypertrophy (not statistically different from the controls). One 

control male had mild hepatocellular cytoplasmic vacuolization. None of the females treated 

with 400 or 1200 mg/kg/day exhibited these changes. Hepatocellular hypertrophy was 

considered by study personnel to be a possible adaptive change to accommodate increased 

demand to metabolize the test substance. 

The testes of males in the high dose group exhibited degeneration (12/15) and/or atrophy (5/5) 

of the seminiferous tubules (spermatocytes or developing spermatids). These effects were 

concluded to be related to treatment. The severity of the lesions was primarily mild to moderate 

for degeneration (11/12) and minimal to moderate for atrophy (5/5), indicating that not all 

tubules were affected and that a limited number of cells was affected within the affected 

tubules. One male treated with 1200 mg/kg had severe seminiferous tubule atrophy, a complete 

loss of cell types in the tubules (except for Sertoli cells) and moderate Leydig cell hypertrophy 

(not significant from control). This was not considered to be related to treatment because of the 

lack of a plausible explanation for the unusual dose-response relationship (the effect at this dose 

was more severe than that of a higher dose) and the low incidence of animals affected at this 

dose level (Gill et al., Int J Toxicol 17:1-22, 1998). No testicular changes were noted in males 

treated with 400 mg/kg/day TGME. 

Remarks on results including tables and figures 

Overall remarks, attachments 

Overall remarks 

The route of administration and maximum dose level was specified in a testing consent order (EPA. 

1989. 40 CFR 799, Fed Reg 54:13470-13477). The highest dose level was initially set at 5000 

mg/kg/day, but was decreased to 4000 mg/kg/day based on results of a 14-day dose range-finding 

drinking water study that demonstrated signs of debilitationat levels greater than 4000 mg/kg/day (Gill 

and Hurley, 1990). 
The authors state that a possible contributing factor in the development of testicular lesions at the high 

dose was low-level contamination of the test substance with the known testicular toxicant 

2-methoxyethanol (EGME). EGME was present in the test substance at a concentration of 0.02  0.04 

%, resulting in a EGME dose up to 1.7 mg/kg/day for animals in the high dose group. Given the length of 

the study, it is possible that EGME contributed to the testicular lesions. A comparison between the doses 

of EGME and TGME required to produce testicular toxicity indicated that TGME is 350 times less potent 

than EGME in producing testicular lesions in the rat.The dose of TGME that caused testicular toxicity 

(4200 mg/kg/day) is 4 times greater than the 1000 mg/kg/day limit dose generally recommended for 

subchronic studies. 

Based on the results of the study, the summary preparer assigned a NOAEL for effects on the liver of 

400 mg/kg/day, and a LOAEL of 1200 mg/kg/day (based on increased relative liver weight of males at 

this dose). The summary preparer-assigned NOAEL and LOAEL for testicular effects are 1200 and 4000 

mg/kg/day, respectively. The EPA has determined the NOAEL for testicular effects is between 400 and 

1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers RM1 

screening document (draft), Feb. 24, 1995). 

Repeated dose toxicity: oral Rat TGME DW Gill and Hurley 14 day 1990.001 

UUID IUC5-8d0a00b9-e400-4e19-a21a-aba4486f3a7b 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:20 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1990 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted guideline study following GLP and providing test substance 

purity. However, since only a 2 week study, it cannot be a key study. 

Data source 

Reference 

Reference 

type 

study report 

Author Gill MW, Hurley JM Year 1990 

Title Triethylene glycol monomethylether: Fourteen-day drinking water inclusion dose 

rangefinding study in rats 

Bibliograp

hic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

52-606 

Owner 
company 

Company 

study no. 

 Report 

date 

1990-03-06 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: OECD Guideline 401 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether (TGME) 

Identifier EC number 

Identity 203-962-1 

Details on test material 

Purity of test material was 99.23%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male 

Details on test animals and environmental conditions 

8 weeks old 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Groups of 10 male rats (8 weeks old) were treated with testmaterial in drinking water for 14 

days. Target doses were0, 0.5, 1.0, 2.5 and 5.0 g/kg/day; actual doses were 0,0.75, 1.6, 3.9 and 

8.0 g/kg/day. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no details 
Duration of treatment / exposure 

14 days 

Frequency of treatment 

daily 

Doses/concentrations 

750, 1600, 3900, 8000 mg/kg/day 

Basis nominal in water 

No. of animals per sex per dose 

10 male rats per dose 

Control animals 

yes, concurrent no treatment 

Details on study design 

Positive control 

none 

Examinations 

Observations and examinations performed and frequency 

Evaluations of toxicity included daily clinical signs, periodic water consumption (approximately 

every two to three days), weekly food consumption and body weights and a functional 

observational battery and necropsy at study termination. 

Statistics 

Homogeneous data were analyzed using Levene's test, analysis of variance, and pooled variance 

t-tests. If Levene's test indicated heterogeneous variances, groups were compared by anaysis of 

variance for unequal variance, follwed (if necessary) by separate variance t-tests. Intergroup 

comparisons for functional observational battery frequency data were performed using Fisher's 

exact probability testand linear trends across dose levels were evaluated with achi-square test. 

The fiducial limit of 0.05 was used as the critical level of significance for all tests. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1600 mg/kg bw/day (nominal) 

Sex 

Basis for effect level / Remarks 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

yes 

Ophthalmoscopic examination 
no data 

Haematology 

not examined 

Urinalysis 

not examined 

Neurobehaviour 

yes 

Organ weights 

no data 

Gross pathology 

yes 

Histopathology: non-neoplastic 

not examined 

Histopathology: neoplastic 

not examined 

Details on results 

All animals survived treatment. Treatment with 8 g/kg/dayresulted in decreases in mean water 

consumption, decreases in food consumption (56 to 64% lower than control), and decreased 

body weight. Clinical signs and functiona lobservational battery findings in animals treated with 

8g/kg/day included cachexia, piloerection, gait alterations, decreases in mean hind-limb grip 

strength and mean rearing events (vertical acitivty) compared to controls. There was also a 

tendency for labored or slow respiration and/or decreased mean rectal temperature. Seven out of 

10 rats treated with the high dose had focal and multifocal discoloration in the lungs (compared 

to 1 or 2 animals inthe other groups). Mean food consumption and body weightgain were also 

decreased for the 3.9 g/kg/day group. The No effect level was 1.6 g/kg/day. 

Repeated dose toxicity: oral Cosse and Atkin (DOW) TGME Rat 2-Week 1989.002 

UUID IUC5-08a3f55d-a5d4-417c-9d34-d72e0a81206c 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:21 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

9 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Two week study with guideine not specified. Test material purity not provided. 

Otherwise good study following GLP. 
Data source 

Reference 

Reference 

type 

study report 

Author Cosse PF, Atkin L. Year 1989 

Title Triethylene glycol monomethylether: Two-week dietary and drinking water 

palatabilitystudy in Sprague-Dawley rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Laboratory Project Study ID K-005610-003. Report 

date 

 

Materials and methods 

Test type 

subacute 

Principles of method if other than guideline 

typical two week drinking water study procedure. Palatability study 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier EC number 

Identity 203-962-1 

Identifier CAS number 

Identity 112-35-6 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

no data 

Administration / exposure 
Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no data 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

Two weeks 

Frequency of treatment 

daily 

Doses/concentrations 

5000 mg/kg bw/day 

Basis other: nominal in drinking water and diet 

No. of animals per sex per dose 

no data 

Control animals 

yes 

Details on study design 

Male and remale rats were fed diets or drinking water formulated to provide 0 (control) or 5000 

mg test material/kg/day for two weeks. Paramters measured included in-life clinical 

observations, body weight, and feed and/or water consumption. 

Positive control 

none 

Examinations 

Observations and examinations performed and frequency 

Paramters measured included in-life clinical observations, body weight, and feed and/or water 

consumption. 

Sacrifice and pathology 

no data 

Other examinations 

no data 

Statistics 

no data 

Results and discussions 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 
Water consumption and compound intake (if drinking water study) 

yes 

Ophthalmoscopic examination 

no data 

Haematology 

not examined 

Clinical chemistry 

not examined 

Urinalysis 

not examined 

Neurobehaviour 

not examined 

Organ weights 

not examined 

Gross pathology 

not examined 

Histopathology: non-neoplastic 

not examined 

Histopathology: neoplastic 

not examined 

Details on results 

No effects were noted in the dietary palatability study. Inthe drinking water study, decreased 

body weights in males(17.2% versus control) decreased food consumption in males (up to 

34.2% versus control) and females (up to 20.8% versus control) and increased water 

consumption (up to 48.0% versus control) were noted in treated animals versus controls. 

Repeated dose toxicity: oral Taupin BF DOT 1993.002 

UUID IUC5-781f189d-6f30-4e92-8b0d-36f76336bc68 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:57 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1993 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted study run according to GLP and with good characterization of 

test material composition. Number of animals per dose not completely 

specified. 

Data source 

Reference 
Reference 

type 

study report 

Author Taupin PJY Year 1993 

Title Brake fluid DOT 4: A 28 day oral (gavage) toxicity study in the rat. 

Bibliographic 

source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

 

Owner 

company 

Shell 

Company 

study no. 

SBGR.92.180 Report 

date 

1993-10-07 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

Guideline was not specified, but study was conducted according to typical procedures for 28 

day oral repeated dose testing. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 
no data 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no data 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

28 days 

Frequency of treatment 

daily 

Doses/concentrations 

25, 150, 1000 mg/kg/day 

Basis 

No. of animals per sex per dose 

not detailed 

Control animals 

yes 

Details on study design 

no data 

Positive control 

no data 

Examinations 

Sacrifice and pathology 

Gross pathology examinations were performed 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOEL 

Effect level 150 mg/kg bw/day (nominal) 

Sex male/female 

Basis for effect 

level / Remarks 

No treatment related effects seen at 150 mg/kg bw per day. Effects were seen 

at the next higher dose 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 
Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

no data 

Histopathology: neoplastic 

not examined 

Details on results 

Food intake of males dosed with 1000 mg/kg/day was slightly reduced for first 2 weeks of 

treatment. Livers of all 5 males and some females dosed with 1000 mg/kg/day showed slight 

centrilobular hypertrophy (which was considered by the investigators to be adaptive). None of

the controls exhibited this effect. There was no significant effect of treatment on liver weight. 

No effects on other organs (including ovaries and testes) were noted. A NOEL of 150 

mg/kg/day was assigned by the investigator. 

7.5.2 Repeated dose toxicity: dermal 

Repeated dose toxicity: dermal Corley TGME 1990.001 

UUID IUC5-b027845b-b085-4e1c-adee-4a5b7d285d64 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:22 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 19
period 90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted guideline study per GLP, with purity of test substance 

provided. 

Data source 

Reference 

Reference 

type 

 

Author Corley RA, Ciesslak, Breslin WJ, Lomax LG. 13-Week 

dermal toxicity study in Sprague-Dawley rats 

Year 1990 

Title 13-Week dermal toxicity study in Sprague-Dawley rats 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

Study ID 

K-005610-004 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

 Report 

date 

1990-09-26 

Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats. 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a fertility study in Sprague-Dawley rats. 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: as specified in a testing consent order (EPA. 1989. 40 CFR 799, 

Fed Reg 54:13470-13477). 

Deviations 
GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The test substance was triethylene glycol monomethyl ether (CAS 112-35-6). Purity (as 

determined by gas chromatography) was 99.23 % at the onset of the study and 99.24% at 

completion of the in-life phase. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 week-old rats 

Administration / exposure 

Type of coverage 

semiocclusive 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 4000 mg/kg/day for 13 weeks. Test 

material was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

Purity (as determined by gas chromatography) was 99.23 % at the onset of the study and 

99.24% at completion of the in-life phase. 

Duration of treatment / exposure 

Six hours daily, 5 days/week for 13 weeks, 91 days. There was no post exposure observation 
period. 

Frequency of treatment 

5 days/week for 13 weeks 

Doses/concentrations 

0 (sham control), 400, 1200 or 4000 mg/kg/day 

Basis analytical per unit body weight 

No. of animals per sex per dose 

10/sex/dose level 

Control animals 

yes, sham-exposed 

Details on study design 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 4000 mg/kg/day for 13 weeks. Test 

material was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. Parameters evaluated throughout the study included 

clinical and ophthalmic observations, dermal irritation, body weight, food consumption, clinical 

pathology, estrous cyclicity (daily vaginal smears during study weeks 12 and 13), hematology 

(just prior to sacrifice), clinical chemistry (just prior to sacrifice), and urinalysis (just prior to 

dosing and during final week of dosing). Organ weight (standard set), gross pathology and 

histopathology (control and high dose group) were evaluated upon necropsy. The oocytes, 

corpora lutea, and follicles from each ovary were evaluated with regard to their normal 

development. Bone marrow smears were prepared from each animal from the shaft of the femur. 

The testes and epididymes also were examined microscopically for males in the intermediateand low-dose groups. 

Examinations 

Observations and examinations performed and frequency 

Parameters evaluated throughout the study included clinical and ophthalmic observations, 

dermal irritation, body weight, food consumption, clinical pathology, estrous cyclicity (daily 

vaginal smears during study weeks 12 and 13), hematology (just prior to sacrifice), clinical 

chemistry (just prior to sacrifice), and urinalysis (just prior to dosing and during final week of 

dosing). 

Sacrifice and pathology 

Organ weight (standard set), gross pathology and histopathology (control and high dose group) 

were evaluated upon necropsy. The oocytes, corpora lutea, and follicles from each ovary were 

evaluated with regard to their normal development. Bone marrow smears were prepared from 

each animal from the shaft of the femur. The testes and epididymes also were examined 

microscopically for males in the intermediate- and low-dose groups. 

Other examinations 

Additional satellite groups of 5 rats/sex/dose level were administered TGME for 30 days for 

interim hematological (48 hr and 30 days), clinical chemistry (48 hr and 30 days), body weight 

determinations, clinical observations, and dermal irritation. 

Statistics 

For the main study group, the data for continuous variables were evaluated by Bartlett's test for 

equality of variances. Depending on the outcome of the test, data were analyzed using a 
parametric or nonparametric analysis of variance (ANOVA), followed by a Dunnett's test 

(parametric data) or Wilcoxon rank-sum test (nonparametric data) with a Bonferroni correction 

for multiple comparisons when appropriate. Statistical outliers were identified by a sequential 

test, but were not excluded from analyses.

For the satellite group, all data (except those for differential leukocyte count and red blood cell 

parameters) were first tested for equality of variance using Bartlett’s test. Hematologic and 

clinical chemistry parameters were evaluated during a two-way analysis of variance with the 

factors of sex and dose. Examinations were first made for a significant sex-dose interaction. If 

this existed, a one-way ANOVA was preformed separately for each sex. If no sex-dose 

interaction was identified and a dose effect was identified, or if in the subsequent ANOVA 

separated by sex a dose-effect was identified, then separate ANOVAs were used for each 

treatment group with the control. A Bonferroni correction was used to control for multiple 

comparisons.

Any other information on materials and methods incl. tables 

The route of administration and maximum dose level was specified in a testing consent order (EPA. 

1989. 40 CFR 799, Fed Reg 54:13470-13477). The highest dose level (4000 mg/kg/day) represented 

the maximum amount of test substance that could be retained on the back and sides of the rat as 

determined in a preliminary 2-week study (Yano et al. 1987. Dow Chemical Company Study ID: 

K-005610-001, Dated Nov. 25, 1987).The EPA has determined that based on severe testicular toxicity in 

1/10 rats given 4000 mg/kg/day and minimal decreases in developing germ cells (1-5% of seminiferous 

tubules affected) in 1/10 rats given 1,200 mg/kg/day, the NOAEL for systemic toxicity is between 400 

and 1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers 

RM1 screening document (draft), Feb. 24, 1995). This value was reached even though it was recognized 

that the testicular changes in the 1,200 mg/kg/day rat were within historical control limits for 

Sprague-Dawley rats (0-17%).

Results and discussions 

Effect levels 

Endpoin

t 

NOAEL 

Effect 

level 

4000 mg/kg bw/day (actual dose received) 

Sex male/female 

Basis for 

effect 

level / 

Remarks 

NOAEL = 4000 mg/kg bw (summary preparer); > 400 and < 1200 mg/kg bw (EPA). 

A significant decrease (15%) in platelet counts was noted in females dosed with 4000 

mg/kg for 13 weeks when compared to control. 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 
yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

yes 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

Mean body weight and food consumption were comparable to controls throughout the study. 

There were no treatment-related hematological changes in the interim groups or in males 

administered test material for 13 weeks. A significant decrease (15%) in platelet counts was 

noted in females dosed with 4000 mg/kg for 13 weeks when compared to control (1217 +/- 280 

x 103/cu mm); however, the value (1034 +/- 92 x 103/cu mm) was only slightly below the 

historical control range (1050 to 1262 +/- 93 to 294 x 103/cu m) Therefore, it was not 

considered to be toxicologically significant (Gill et al., Int J Toxicol 17:1-22, 1998). There were 

no other changes in any hematological parameters (hematocrit, hemoglobin, erythrocyte count, 

total leukocyte count, and red blood cell indices). There were no changes in clinical chemistries, 

urinalyses, organ weights, or estrous cyclicity measurements. 

Bilaterally decreased spermatogenesis in seminiferous tubules and decreased spermatozoa in the 

epididymes (both were graded as severe) were noted in the testes of one high dose male rat. 

This animal had a complete lack of mature spermatids in greater than 41% of tubules in each 

testicle, few spermatids beyond stage 12 of development in the seminiferous epithelium, and 

decreased spermatic elements in the head and tail of greater than 41% of the tubules and ducts 

in the epididymides. The testes of one male treated with 1200 mg/kg exhibited different 

testicular changes [bilateral multifocal degeneration of spermatocytes and spermatids from 

germinal epithelium (graded as very slight), and multinucleated spermatids]. In this rat, all 

stages of the cycle of the seminiferous epithelium were observed in morphologically normal 

tubules. The epididymides of this rat had decreased spermatic elements in the head and tail of 

1-5% of ducts. Some of the ducts also contained immature spermatids. 
Remarks on results including tables and figures 

Study personnel concluded that the bilateral microscopic testicular changes observed in one high-dose 

and one mid-dose male rat were unrelated to treatment. Reasons given were that the dissimilarity of the 

lesions for the two animals suggested that they occurred spontaneously, and the incidence of animals 

with lesions (1/10 in each group) was well within that of historical controls (0-17%). Study personnel also 

stated that the degenerative changes in the testes of one mid-dose and one high-dose rat were not 

consistent with the types of lesions that have been attributed to 2-methoxyethanol (2-ME). The cell types 

that are most vulnerable to 2-ME are the pachytene spermatocytes and round spermatids (Chapin et al., 

Fund Appl. Toxicol 5:182-189, 1985). As the dose of 2-ME is increased, the number and types of cells 

affected increase up to the point that the germinal epithelium is significantly degenerated and all stages 

of spermatogenesis are affected (Chapin et al., Fund Appl. Toxicol 5:182-189, 1985; Miller et al., Fund 

Appl Toxicol 3:49-54, 1983.). In contrast, the testicular effects seen with the high dose animal treated 

with TGME consisted of a virtually complete lack of mature spermatids beyond stage 12. All other 

stages, including spermatogonia and spermatocytes, were present and appeared morphologically 

normal. In the mid-dose rat, the only effects noted consisted of very slight degeneration of 

spermatocytes and spermatids similar to those seen in historical control animals. 

Study personnel also stated that the lymphoid tissues and hematologic parameters, which have been 

reported to be affected at doses of 2-methoxyethanol that have been associated with testicular changes 

(Miller et al., Fund. Appl. Toxicol. 3:49-54, 1983) were unattected in this TGME study. Taking all factors 

into considereation, the testicular lesions observed in this dermal study could not be directly attributed to 

TGME exposure. 

Repeated dose toxicity: dermal Yano TGME 1987.006 

UUID IUC5-c813ffe0-38cc-4fc7-a413-59a7bced453d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:22 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted study, but of only 2 week duration. Purity of test substance 

not stated. 

Data source 

Reference 

Reference 

type 

study report 

Author Yano BL, Phillips JE, Battjes JE. Year 1987 
Title Triethylene glycol monomethyl ether: 2-week dermal toxicity study in male and 

female Sprague-Dawley rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Study ID:K-005610-001, Report 

date 

1987-11-

25 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

Standard procedure used at the time for a two week repeat dose dermal study. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6). 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity is unknown. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

200 to 350 g weight 

Administration / exposure 

Type of coverage 

semiocclusive 

Vehicle 
unchanged (no vehicle) 

Details on exposure 

Groups of five rats/sex (200 to 350 g)were dosed with 0, 1000, 2500, or 4000 mg/kg/day of test 

material on clipped back skin, 6 hours/day for a total of 9 applications during a 12 day period. 

Test material was held in place with a gauze patch and elastic bandage. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

two weeks, 9 dose applications 

Frequency of treatment 

daily 

Doses/concentrations 

0, 1000, 2500, 4000 mg/kg/day 

Basis nominal per unit body weight 

No. of animals per sex per dose 

five rats/sex 

Control animals 

yes, concurrent no treatment 

Examinations 

Observations and examinations performed and frequency 

Parameters evaluated included clinical observations (including skin evaluations), body weight, 

feed consumption, clinical chemistry, hematology, urinalysis, and fasted body weights.

Sacrifice and pathology 

Organ weight measurement, gross pathology, and histopathology were conducted. 

Other examinations 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 4000 mg/kg bw/day (nominal) 

Sex male/female 

Basis for 

effect level / 

Remarks 

No significant obverse effects were observed at this or lower doses that were 

considered treatment related. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 
Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

There were no treatment-related adverse systemic effects. A few males and females treated with 

either 1000 or 2500 mg/kg/day had a few small scabs or crusts at the test site. These alterations 

were slight in degree and did not adversely affect the rats.

A number of clinical chemistry, hematological and urinalysis variables were significantly 

different from control. The lower albumin concentration in females from the 1000 mg/kg/day 

group and higher urea nitrogen concentration in males from the 2500 mg/kg/day group were not 

considered by study personnel to be related to treatment because the effects were not noted at 

higher concentrations. The lower albumin concentration in males treated with 4000 mg/kg/day 

also was not attributed to treatment by study personnel because the value was within the range 

of individual animal values in the control group. A slightly higher alanine aminotransferase 

activity was also statistically identified in rats from the 4000 mg/kg/day group. As the value was 

only marginally different from control and was not associated with any histologic changes in the 

liver, study personnel did not consider this to be related to treatment. A slightly higher red 

blood cell count and hemoglobin concentration was observed in rats given 4000 mg/kg/day. 

Since these were only slightly higher than control values, study personnel did not consider them 

to be related to treatment. A few of therats given 2500 or 4000 mg/kg/day had watery cecal 

contents and/or hemolyzed blood in the stomach. These gross pathologic observations were not 

associated with any histologic abnormalities in these tissues or alterations in hematologic and 

clinical chemistry parameters. Therefore, they were not attributed by study personnel to be 

related to treatment. 

Repeated dose toxicity: dermal IRDC Rabbit 21-Day TGME 1986.002 

UUID IUC5-5ce59765-2907-4266-a845-3f34f42bb820 
Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:23 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

86 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

3 week study per GLP, but no guideline specified and test material purity not 

provided 

Data source 

Reference 

Referenc

e type 

study report 

Author Year 1986 

Title 21-Day dermal toxicity study in rabbits-limit test on triethylene glycol monobutyl 

ether, triethylene glycolmonoethyl ether and triethylene glycol monomethyl ether. 

Bibliogr

aphic 

source 

 

Testing 

laborator

y 

International Research and Development Corportation (IRDC). Rep

ort 

no. 

 

Owner 

company 

 

Compan

y study 

no. 

 Rep

ort 

date 

1986-0

7-22 

Referenc

e type 

publication 

Author Leber AP, Scott RC, Hodge MCE, Johnson D, Krasavage WJ. Year 1990 

Title Triethylene gylcol ethers. Evaluation of in vitroabsorption through human epidermis, 

21-day dermal toxicityin rabbits and a developmental toxicity screen in rats 

Bibliogra

phic 

J AmColl Toxicol 9:507-515 
source 

Testing 

laborator

y 

 Repo

rt no. 

 

Owner 

company 

 

Compan

y study 

no. 

 Repo

rt 

date 

 

Materials and methods 

Test type 

subacute 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Rabbits were observed over a 51-52 day pretest period for clinical abnormalities. Prior to 

randomization, rabbits were fasted (19-23 hours), and blood samples were taken from the 

central ear artery for control hematological and biochemical evaluations. Healthy rabbits (4- 4.5 

months of age) were randomly divided into groups of 5 per sex. 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 
Details on exposure 

Prior to study initiation, hair was removed from the back of each rabbit with an electric clipper. 

Rabbits were shaved as necessary during the course of the study to prevent the test material 

from becoming matted in the hair and to facilitate accurate observations. One group of rabbits 

was left untreated and the other was treated with 1000 mg/kg test material, five days per week 

for 3 weeks. Dose volumes were calculated based on the specific gravity of test material (as 

determined at the study site) and the body weight of animals (determinedweekly). Test material 

was placed on the back using a 5 cc plastic syringe. A glass rod was used to evenly distribute 

the dose over the test site. Following dosing, test sites (of all animals, including controls) were 

wrapped with gauze bandaging and Dermiform tape and plastic restraint collars were attached 

to the rabbits. Collars were removed after 6hours, and test sites (of all animals, including 

controls) were washed with tepid tap water and dried with paper towels. All animals were fasted 

for 19-23 hours before study termination. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

3 weeks 

Frequency of treatment 

6 hr/day, 5 days/week 

Doses/concentrations 

1000 mg/kg test material 

Basis nominal per unit body weight 

No. of animals per sex per dose 

5 per sex 

Control animals 

yes, concurrent no treatment 

Examinations 

Observations and examinations performed and frequency 

Animals were observed once daily for clinical signs and twice daily for mortality. Food 

consumption was estimated daily based on a visual assessment of remaining food. Body weights 

were recorded weekly. Rabbits were scored immediately prior to each dosing for dermal 

irritation in accordance with the Draize method. 

Sacrifice and pathology 

Blood samples taken fromthe central ear artery of animals at study termination were analyzed 

for standard hematological (total and differential leukocyte count, erythrocyte count, 

hemoglobin, hematocrit, platelet count, reticulocyte count, mean corpuscular volume, mean 

corpuscular hemoglobin and mean corpuscular hemoglobin concentration) and biochemical 

(sodium, potassium, chloride, calcium, phosphorus, total bilirubin, gamma 

glutamyltranspeptidase, aspartate aminotransferase, alanine aminotransferase, ornithine 

carbamoyltransferase, urea nitrogen, creatinine, total protein, albumin, globulin, cholesterol and 

glucose) parameters. All animals were examined grossly upon study termination. Weights of 

adrenals, brain, kidneys, liver, ovaries and testes were taken. A full complement of tissueswas 

examined microscopically. 

Statistics 

Body weights (weeks 1, 2, 3, and 4), clinical pathology parameters and organ weights (absolute 

and relative) were analyzed using Bartlett’s test for homogeneity of variance and analysis of 
variance (one-way). The treatment groups were compared to the controls using the appropriate 

t-statistic (for equal or unequal variance). Dunnett’s multiple comparison tables were used to 

judge the significance of the differences. Total bilirubin data was transformed to ranks and 

analyzed using a non-parametric test. All tests were two-tailed, with p < 0.05 and p < 0.01 as 

levels of significance. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1000 mg/kg bw/day (nominal) 

Sex male/female 

Basis for effect level / 

Remarks 

No adverse effects observed at only dose level tested. 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

Some hematological and biochemical values from treated animals were different from controls 
at termination. However, since the same changes were noted in blood samples taken from the 

animals prior to treatment, they were not considered by the investigators to be related to 

treatment. No macroscopic skin lesions were observed in treated animals. There were no organ 

weight variations that could be related to test material administration. Microscopic changes 

(trace acanthosis and trace to moderate dermatitis) were observed in skin of treated animals. 

Testicular degeneration (trace in severity) occurred in one rabbit. This lesion was characterized 

by the presence of spermatid giant cells, focal tubular hypospermatogenesis or cytoplasmic 

vacuolization. This was not considered to be related to test material by the study investigators 

since there is a high spontaneous incidence of similar changes in normal New Zealand White 

rabbits. Based on the results, the investigators concluded that in this study, there was no 

systemic toxicity induced by treatment with 1000 mg/kg/day test material. 

Repeated dose toxicity: dermal UC MPEG 1985.002 

UUID IUC5-fcd8f596-8f6c-4657-a83b-7944a9d0b03b 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:05 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result Study 

period 

198

5 

Reliablility 1 (reliable without restriction) 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1985 

Title Nine-day and ninety-day dermal toxicity studies of CARBOWAX MPEG-350 in 

rabbits 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1985-05-3

0 

Reference 

type 

 

Author Hermansky SJ, Leung HW. Year 1997 
Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a fertility study. This is toxicity to reproduction.002 

Materials and methods 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG 350 

Details on test material 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) was reported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. This material is a 

mixture of several methylated glycol ethers of differing molecular weight (ranging from 

diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Body weights of males and females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study 

initiation 

Administration / exposure 

Type of coverage 

open 
Vehicle 

other: methyl cellulose in distilled water 

Details on exposure 

Dosing: New Zealand white rabbits (10/sex/dose) were treated dermally on clipped dorsal skin 

with 1.0 ml of vehicle (0.1% (w/v) methyl cellulose in distilled water), 50% CARBOWAX 

MPEG-350 (w/v dilution in 0.1% methyl cellulose in water) or 100% CARBOWAX 

MPEG-350, for six hours/day, five days per week for 90 days. Body weights of males and 

females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study initiation. Rabbits were fitted with 

Elizabethan collars after dosing to prevent ingestion of test material. After each 6-hour exposure 

the application site was wiped with a paper towel dampened with water and then dried using a 

towel. Rabbitswere then uncollared until the next treatment. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) was reported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. 

Duration of treatment / exposure 

six hours/day, five days per week for 90 days. 

Frequency of treatment 

five days per week 

Doses/concentrations 

1 ml of 50% and 100% material (approximately 169 and 338 mg/kg/day) 

Basis analytical per unit body weight 

No. of animals per sex per dose 

10/sex/dose 

Control animals 

yes, concurrent vehicle 

Examinations 

Observations and examinations performed and frequency 

Observations: All rabbits were observed daily (weekdays) for death, clinical signs and dermal 

irritation. Any irritation was scored immediately prior to dosing using the Draize system. Body 

weights were recorded on the morning of the first day of dosing, weekly thereafter and prior 

tosacrifice. Food consumption was measured weekly. Urine was collected from 5 

animals/sex/group during the last two weeks of dosing and subjected to standard analyses. 

Standard hematology and clinical chemistry parameters were evaluated for all animals just prior 

to sacrifice. 

Sacrifice and pathology 

Necropsy: All animals were sacrificed and necropsied after 13 weeks of treatment. Weights 

were recorded for liver, kidneys, brain and adrenals of all animals and testes of males. 

Histopathologic examinations were performed on tissues from high-dose and control animals. 

Statistics 

Statistical Analyses: Body weight, food consumption, organ weight and clinical pathology data 

from the three groups were compared using Levene's test for homogeneity of variance. An 

analysis of variance was performed on the groups when data were homogeneous. If 

significantdifferences were found, group differences were delineated by grouped variance 

Student t-tests. When data were heterogeneous, Welch and Brown-Forsyth analyses were 
performed and significant differences among groups were determined using separate variance 

Student t-tests. Draize skin irritation scores were analyzed using the Kruskal-Wallis test, and 

significant differences in groups were determined using the Wilcoxon rank sum test (as 

modified by Mann-Whitney). Frequency data (i.e. histological) were compared using Fisher's 

exact tests. The p value of 0.05 (two-tailed) was used as the critical level of significance for all 

analyses. 

Any other information on materials and methods incl. tables 

A preliminary range-finding study in 15 rabbits dosed 6 hr/day for 9 days (Carpenter, Range finding tests 

on methoxy polyethylene glycols of approximate molecular weights 350, 550 and 750. Melon Institute of 

Industrial Research, University of Pittsburgh. Report dated 5-13-47.1947) showed that daily 

administration of 1 ml of 50% or 100% test material only caused mild skin irritation. Therefore, these 

doses were chosen for the 90-day study.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 338 mg/kg bw/day (actual dose received) 

Sex female 

Basis for effect level / 

Remarks 

Mild acanthosis (epidermal thickening) 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 
yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

Mild acanthosis (epidermal thickening) was found in 3 females dosed with 100% material. 

Transient, dose-related erythema (Grade 1) and desquamation of skin occurred. No systemic 

effects were observed in rabbits treated with either 50% or 100% test material. 

Remarks on results including tables and figures 

The NOAELs for local or systemic effects were not listed by the investigators. Based on the data, these 

values are 50% and 100%, respectively. Based on weights of animals determined at weekly intervals 

and the reported density of test material (1.09 g/ml) doses can be calculated on average mg/kg/day 

basis. These doses are 169 mg/kg/day (for 50%) and 338 mg/kg/day (for 100%).

Repeated dose toxicity: dermal Gray MPEG 1987.003 

UUID IUC5-a152eeff-b2c3-44ce-b497-3da04a5800af 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:06 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1987 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP with test substance well characterized as to 

composition. No guideline specified but study was conducted according to 

standard procedures. 

Data source 

Reference 

Reference 

type 

study report 

Author Gray TM. Year 1987 

Title A 28-day dermal toxicity study in rats on PEG-methyl ether (Medical Group 

Number #85-166). 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

Document 

Number 4257, 

Owner Armour-Dial, Inc. 
company 

Company 

study no. 

 Report 

date 

1987-05-15 

Reference 

type 

study report 

Author Hermansky SJ, Leung HW. Year 1997 

Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

No guideline specified but study was conducted according to standard procedures. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowax MPEG-350 ( 

Details on test material 

Test material was Carbowax MPEG-350 (CAS No. 9004-74-4) from Union Carbide. This 

material is a mixture of several methylated glycol ethers of differing molecular weight (ranging 

from diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3).

Test material also contained 1 ppm of 2-methoxyethanol. 

Test animals 
Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male 

Details on test animals and environmental conditions 

The animals were 52 days old. 

Administration / exposure 

Type of coverage 

open 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Male rats (52 days old) were divided into 4 groups of 15 animals (control, low-, mid-, and 

high-dose groups and were acclimated to Elizabethan collars for 7 days before treatment. One 

mid-dose and 3 high-dose animals were dropped before treatment because they appeared 

dehydrated. Each group was treated with 0 (sham control), 1.25, 2.5 or 5 g/kg/day test material 

on shaved backs. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

four weeks 

Frequency of treatment 

five days per week 

Doses/concentrations 

0 (sham control), 1.25, 2.5 or 5 g/kg/day 

Basis no data 

No. of animals per sex per dose 

15 male animals per dose 

Control animals 

yes, sham-exposed 

Details on study design 

Rats were sacrificed 3 days after the last treatment. 

Positive control 

no data 

Examinations 

Observations and examinations performed and frequency 

Signs of irritation, body weights of animals 

Sacrifice and pathology 

Organ weights, gross pathology 

Statistics 

no data 

Results and discussions 

Effect levels 
Endpoint NOAEL 

Effect level 1250 mg/kg bw/day 

Sex male 

Basis for effect 

level / Remarks 

This value is based on significant effects on body weight or weight gain at 

higher doses. 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

no effects 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

no data 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

no data 

Histopathology: neoplastic 

not examined 

Details on results 

Minor, transient irritation was noted at the application site of all treated animals. Body weights 

of animals given 5.0 g/kg/day and body weight gains of animals given 2.5 g/kg/day were 

depressed. Absolute weights of the thymus and testes of rats treated with 1.25 g/kg/day were 

83% and 93%, respectively of control weights (significantly different). Relative weights of 

these organs were not significantly different from control. There were no pathological 

abnormalities in either of these organs. 

Remarks on results including tables and figures 

One, 3, and 2 animals in the low-, mid- and high-dose groups slipped their collars and therefore may 
have ingested the material during grooming. Results in these animals were not significantly different 

from those animals that did not slip their collars. Therefore, possible ingestion of material in these 

animals did not appear to affect the results of the study. 

The investigators did not identify a NOAEL for the study. However, they stated that there were no 

indications of systemic toxicity secondary to repeated cutaneous exposure to MPEG-350 in this study. 

Based on the information given, the summary preparer assigned a NOAEL of 1250 mg/kg/day. This 

value is based on significant effects on body weight or weight gain at higher doses (although the authors 

stated that these effects may have been due to use of Elizabethan collars). Although the absolute 

weights of the thymus and testes of rats treated with 1.25 g/kg/day were significantly less than control, 

relative weights of these organs were not different from control, there were no histological changes in 

these organs, and these effects were not noted at higher doses. Therefore, they were considered by the 

summary preparer to be unrelated to treatment.

7.5.4 Repeated dose toxicity: other routes 

Repeated dose toxicity: other routes NAMSA MPEG 1997.001 

UUID IUC5-cdd9494a-be57-4406-a8ac-8dcbb9f859b0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:07 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

97 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted, thorough study following GLP. Test substance was well 

defined. 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1997 

Title Subchronic intravenous toxicity study in the rat. Carbowax Sentry M-PEG 350-NF 

and Carbowax Sentry PEG 400 NF and FCC. 

Bibliogra

phic 

source 

 

Testing 

laboratory 

North American Science Associates, Inc (NAMSA). Repor

t no. 

Report 

TS064-900/
S. 

Owner 

company 

 

Company 

study no. 

 Repor

t date 

 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Principles of method if other than guideline 

One i.v. dose plus concurrent control. Typical battery of observations for a two week study. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX Sentry MPEG-350 

Details on test material 

Test material was CARBOWAX Sentry MPEG-350 (CAS No. 9004-74-4), NF grade. This 

material is a mixture of several methylated glycol ethers of differing molecular weight (ranging 

from diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Groups of six rats/sex (6-8 weeks of age, 114 g to 189 g 

Administration / exposure 

Route of administration 

intraveneous 

Vehicle 

other: 

Details on exposure 
Groups of six rats/sex (6-8 weeks of age, 114 g to 189 g) were dosed intravenously for 14 

consecutive days with either vehicle (0.9% sodium chloride, USP), or 1 g/kg/day test material. 

Analytical verification of doses or concentrations 

yes 

Duration of treatment / exposure 

fourteen days 

Frequency of treatment 

daily for fourteen consecutive days 

Doses / concentrations 

either vehicle (0.9% sodium chloride, USP), or 1 g/kg/day test material. 

No. of animals per sex per dose 

six rats/sex 

Control animals 

yes, concurrent vehicle 

Examinations 

Observations and examinations performed and frequency 

Animals were observed daily for general health. Body weights were recorded on days 1, 8 and 

15 of treatment. 

Sacrifice and pathology 

All animals were euthanized on day 15. Blood was collected from the posterior vena cava and 

standard hematological and clinical chemistries were performed. The heart, liver, spleen, 

kidneys, adrenal glands and gonads were weighed, fixed, and processed for microscopic 

evaluation. The data were analyzed using a standard BMDP Statistical Software Package. 

Statistics 

The data were analyzed using a standard BMDP Statistical Software Package. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1000 mg/kg bw/day (actual dose received) 

Sex male/female 

Basis for effect level / 

Remarks 

No adverse effects were observed at the single dose tested. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption 

no data 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 
Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

There was no effect of treatment on body or organ weights or hematological values. Tissues 

(including testes) from treated animals were histologically similar to those of controls. There 

was a significant difference in aspartate aminotransferase activity in control (95 +/- 13 IU/L) 

and treated males (81 +/- 6 IU/L) that was not considered by the investigators to be related to 

treatment since the values for both groups were within the normal expected range. An increase 

in aspartate aminotransferase activity, rather than a decrease would be indicative of liver 

toxicity. 

7.6 Genetic toxicity 

7.6.1 Genetic toxicity in vitro 

Genetic toxicity in vitro Samson & Gallapudi TGME Ames 1990.002 

UUID IUC5-cd79d78d-780a-4457-a831-6f03cd84dcad 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:24 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Only four strains of bacteria were used in the test. 

Data source 
Reference 

Referenc

e type 

study report 

Author Samson YE and Gollapudi BB. Yea

r 

1990 

Title Evaluation of triethylene glycol monomethyl ether (TGME) in the Ames 

Salmonella/mammalian-microsome bacterial mutagenicity assay. 

Bibliogr

aphic 

source 

 

Testing 

laborator

y 

 Rep

ort 

no. 

Study ID 

TXT:K-00561

0-005, 

Owner 

compan

y 

Dow Chemical Company 

Compan

y study 

no. 

 Rep

ort 

date 

1990-03-07 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: Test Standard 40 CFR 798.5265 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Method 
Species/strain 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Details on mammalian cell 

lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation system not stated 

Test concentrations 

up to 5000 micrograms/plate 

Vehicle 

DMSO and water 

Controls 

Negative controls yes 

Solvent / vehicle 

controls 

 

True negative 

controls 

 

Positive controls yes 

Positive control 

substance 

other: 2-nitrofluorene, ICR-191, 2-anthramine and sodium azide 

Remarks 

Details on test system and conditions 

Test Concentrations: The test material was dissolved in distilled water at stock concentrations of 

50, 16.67, 5, 1.667, and 0.5 mg/ml. Concentrations were verified by HPLC to be: 51.4, 18.3, 

4.91, 1.75 and 0.523 mg/ml. All positive control solutions (1 mg/ml 2-nitrofluorene, 100 

micrograms/ml ICR-191, 30 micrograms/ml 2-anthramine) were prepared in DMSO (with the 

exception of 250 micrograms/ml sodium azide dissolved in water). 

Test: Bacteria (0.1 ml of 10E8 or 10E9 S. typhimurium TA 98, TA100, TA1535, or TA1537), 

test chemical (0.1 ml of test solution, positive control, or solvent) and either buffer or S-9 mix 

(0.5 ml) were pre-incubated in sterile 12 x 75 mm tightly-capped culture tubes in a gyratory 

incubator (300rpm) at 30 degrees C for 30 minutes. Supplemented top agar (2 ml) was then 

added, the overlay was poured onto plates, and plates were incubated at 37 degrees C for 2 days. 

All dose levels (including positive and negative controls) were assayed in triplicate. 

Revertant colonies were counted manually or with an automatic colony counter. The counter 

was calibrated periodically. A correction factor was used to compensate for the area not scanned 

by the counter (i.e. dish edge) and overlapping colonies. 

Evaluation criteria 

Evaluation Criteria: The test material was considered a mutagen if both the mean number of 

revertant colonies was at least 3 times higher than the mean of the negative (solvent) control and 

it induced a reproducible dose-response relationship over several concentrations. If the 

dose-response was not definitive, it was considered to be a presumptive mutagen. If the 

reversion rates were between 2 and 3 times that of negative controls, the results were considered 

equivocal or inconclusive. 
Statistics 

no data 

Results and discussions 

Test results 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid 

Positive controls valid yes 

Additional information on results 

Concentrations up to 5000 micrograms/plate did not cause toxicity or cause an increase in 

mutagenicity above that of negative controls. 

The study was valid, as the positive controls induced at least 3 times the number of revertants as 

the negative controls in each tested strain. 

Remarks on results including tables and figures 

Cytotoxic concentration = > 5000 micrograms/plate

Genetic toxicity in vitro Liscombe & Gollapudi TGME 1990.004 

UUID IUC5-84ed9121-fd34-4892-8608-896d6e34aa66 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:25 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP. Purity of test substance stated. 

Data source 

Reference 

Reference 

type 

study report 

Author Liscombe VA, Gollapudi BB. Year 1990 
Title Evaluation of triethylene glycol monomethyl ether in the Chinese hamster ovary 

cell/hypoxanthine-guanine-phosphoribosyl-transferase(CHO/HGPRT) forward 

mutation assay 

Bibliographi

c source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

ID TXT:K-005610-006 Report 

date 

1990-03-0

7 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

mammalian cell gene mutation assay 

Test guideline 

Qualifier according to 

Guideline other guideline: Test Standard 40 CFR 798.5300 

Deviations 

Principles of method if other than guideline 

HGPRT Assay using Chinese hamster ovary cell 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Method 

Target gene 

the gene locus for the enzyme (hypoxanthine-guanine phosphoribosyl transferase) 

Species/strain 

Species/strain Chinese hamster Ovary (CHO) 

Details on mammalian cell lines (if 

applicable) 

 

Additional strain characteristics 
Metabolic activation with and without 

Metabolic activation system S-9 

Test concentrations 

2000 to 5000 micrograms/plate 

Vehicle 

water and DMSO 

Controls 

Negative controls yes 

Solvent / vehicle controls yes 

True negative controls no data 

Positive controls yes 

Positive control substance other: EMS or 20-MC 

Remarks 

Details on test system and conditions 

Indicator cells: The CHO-K1-BH4 cell line was used in the study. Periodic examinations 

revealed no mycoplasma contamination. Cells were grown as a monolayer in Ham's F-12 

nutrient mix supplemented with 5% heat-inactivated, dialyzed fetal bovine serum, 25 mM 

HEPES, 0.25 micrograms/ml Fungizone, 100 units/ml penicillin G and 0.1 mg/ml streptomycin 

sulfate. The selection medium used for the detection of mutants was Ham's F-12 nutrient mix 

without hypoxanthine, and supplemented with 10 micromolar 6-thioguanine, 5% serum, 25 mM 

HEPES, 2 mM L-glutamine and the antibiotics mentioned above.

Test materials: Test material was dissolved in water and further diluted (1:100) in culture 

medium. The concentrations of test material in stock solutions (200, 300, 400, 500 mg/ml)were 

verified by analytical methods.20-methylchlolanthrene (20-MC) was initially dissolved in 

DMSO, and further diluted in culture medium. Ethyl methanesulfonate (EMS) was dissolved in 

culture medium.

Preliminary test : The cytotoxicity of the test material was assessed by determining the ability of 

the treated cells to form colonies. The cultures (3 per dose level) were treated with test material 

in the absence or presence of S-9, incubated for up to 7 days, fixed with methanol and stained 

with crystal violet. The number of colonies/dish was counted and the mean 

colonies/dish/treatment were expressed relative to the negative control value. The test material 

was not cytotoxic at up to 5000 micrograms/ml. Based on this result, this was the highest 

concentration used for the genemutation assay.

Mutation test: Cells in logarithmic growth phase were trypsinized and plated in medium 

containing 5% serum at a standard density (200 cells/100 mm dish for toxicity assay and 1 x 

10E6 cells/100 mm dish for gene mutation assay) prior to treatment. Approximately 24 hours 

after plating,the medium was replaced with Ham's medium without serum, S-9 mix prepared 

from liver homogenate of Aroclor-1254 treated (500 mg/kg) male, Sprague Dawley rats (when 

applicable) and test material (2000 to 5000 micrograms/ml), positive control (either 621 

micrograms/ml EMS or 4 micrograms/ml 20-MC) or water. The total volume of the treatment 

medium was 10 ml/100 mm dish. The number of dishes treated at each dose level was based on 

the expected degree of toxicity that would yield at least 1 x 10E6 surviving cells. Cells were 

treated for 4 hours at 37 degrees C. Exposure was terminated by washing the cells with 
phosphate-buffered saline. Cells were trypsinized 18-24 hours after termination of the treatment 

and replated at a density of 1 x 10E6 cells/100 mm dish. This step was repeated on the third and 

sixth days following treatment. On Day 8, cultures were trypsinized and plated at a density of 2 

x 10E5 cells/100 mm dish (5 dishes per treatment) in selection medium for the determination of 

HGPRT-mutants and 200 cells/60 mm dish (5 dishes/treatment) in Ham's medium without 

hypoxanthine for determination of cloning efficiency. Dishes were incubated for 7-9 days, fixed 

with methanol and stained with crystal violet. The mutation frequency per 10E6 clonable cells 

was calculated as the total number of mutant colonies/cloning efficiency(number of colonies per 

number of cells plated). 

Evaluation criteria 

The assay was considered valid, if the positive control chemicals induced significant increased 

in mutation frequencies in assays with and without S-9 (EMS: 142.0-153.6; 20-MCA: 

64.7-86.3). 

Statistics 

Statistical analysis: The frequencies of mutants per 10E6 clonable cells were statistically 

evaluated by pairwise tests (treatment vs. negative control) and by linear and quadratic trend 

analysis over the dose range. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid yes 

Positive controls valid yes 

Additional information on results 

The mutation frequencies observed in cultures treated with the test chemical in the absence (1.4 

to 7.1) and presence of S-9 (0 to 7.1) were not significantly different from the concurrent 

negative control values (1.4 to 9.6) and were within the laboratory historical negative control 

range. 

Cytotoxic concentration: > 5000 micrograms

The assay was valid, since the positive control chemicals induced significant increased in 

mutation frequencies in assays with and without S-9 (EMS: 142.0-153.6; 20-MCA: 64.7-86.3). 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Genetic toxicity in vitro Brooks & Wiggins AMES BF DOT 1992.005 

UUID IUC5-bca2ad09-6b79-4a3d-9a5b-04be1e640b35 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 
Date 2009-03-24 17:24:58 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted study run according to glp, with good characterization of test 

material composition. 

Data source 

Reference 

Reference type study report 

Author Brooks TM, Wiggins DE. Year 1992 

Title Brake fluid Dot 4: Bacterial mutagenicity studies 

Bibliographic 

source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research 

Centre 

Report no. SBGR.92.022 

Owner 

company 

Shell 

Company study 

no. 

 Report date 1992-04-09 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Principles of method if other than guideline 

Guideline not specified, but study was run according to standard Ames study procedure 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid Dot 4 

Details on test material 
Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Method 

Species/strain 

Species/strain other: TA98, TA100, TA1535, TA1537, TA1538 and E. coli 

WP2uvrA pKM101 

Details on mammalian 

cell lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation 

system 

 

Test concentrations 

up to 5000 micrograms per plate 

Vehicle 

no vehicle 

Controls 

Negative controls no data 

Solvent / vehicle controls no data 

True negative controls no data 

Positive controls no data 

Positive control substance no data 

Remarks 

Details on test system and conditions 

no data 

Evaluation criteria 

no data 

Statistics 

no data 

Any other information on materials and methods incl. tables 

Results and discussions 

Test results 

Species/strain other: TA98, TA100, TA1535, TA1537, TA1538 

Metabolic activation with and without 

Test system 

Genotoxicity negative 

Cytotoxicity no, but tested up to limit concentrations 

Vehicle controls valid no data 
Negative controls valid no data 

Positive controls valid no data 

Remarks on results including tables and figures 

Cytotoxic concentration = > 5000 micrograms per plate 

Genetic toxicity in vitro Brooks & Wiggins BF DOT CHO 1992.006 

UUID IUC5-b78d5368-f874-4f09-9c1d-e5e5dd901d8d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:59 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust well conducted study following GLP, with good characterization of the 

test substance composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Brooks TM, Wiggins DE Year 1992 

Title Brake fluid Dot 4: In vitro chromosome studies using cultured Chinese hamster 

ovary cells. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

090 

Owner 

company 

Shell 

Company 

study no. 

 Report 

date 

1992-07-2

3 

Materials and methods 

Type of genotoxicity 

chromosome aberration 

Type of study 

in vitro mammalian chromosome aberration test 
Principles of method if other than guideline 

Guideline was not specified, but study was carried out following standard procedures for this 

type of study. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid Dot 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Method 

Species/strain 

Species/strain Chinese hamster Ovary (CHO) 

Details on mammalian cell lines (if 

applicable) 

no details 

Additional strain characteristics 

Metabolic activation with and without 

Metabolic activation system S-9 

Test concentrations 

The concentrations of test material used (from 10 to 5000 micrograms/ml without S-9 and 100 

to 5000 micrograms/ml with S-9). 

Vehicle 

no vehicle 

Controls 

Negative controls yes 

Solvent / vehicle controls yes 

True negative controls 

Positive controls yes 

Positive control 

substance 

other: methyl methanesulphonate and benzo(a)pyrene 

Remarks 

Details on test system and conditions 

Cells (2 x 10E5) were incubated with medium containing the test compound or relevant controls 

[untreated control, solvent control and positive controls methyl methanesulphonate (20 
micrograms/ml without S-9) and benzo(a)pyrene (25 micrograms/ml with S-9)] for either 3 

hours in the presence of S9 mix (from Aroclor 1254-induced rat liver) or 24 hours in the 

absence of S9 mix. The concentrations of test material used (from 10 to 5000 micrograms/ml 

without S-9 and 100 to 5000 micrograms/ml with S-9) were chosen based on the results of 

preliminary miscibility and mitotic index studies. Duplicate cultures were prepared for each test 

condition. Two separate experiments were conducted using different concentrations. Metaphase 

cells were prepared on glass microscope slides for the analysis of chromosome aberrations 24 

hours following exposure for the cultures with or without S9 mix. All slides were coded. Where 

possible, 200 metaphases were scored for each dose group. Only those cells showing the modal 

chromosome number (20) +/- 2 were analyzed for chromosome damage. Chromosome 

aberrations were classified according to the scheme described by Savage (J Med Genetics 

12:103-122, 1976). 

Evaluation criteria 

Not specified. 

Statistics 

The mitotic index of each group was assessed by counting the number of metaphases in a total 

of 1000 cells. Data were assessed for heterogeneity using the Fisher’s exact test. The number of 

aberrations excluding gaps, aberrations including gaps, isogaps and/or chromatid gaps and 

polyploidy and/or endoreduplication of treated cells was compared to controls using the Fisher’s 

exact test. A Cochran-Armitage trend test was carried out on the dose/response. The test was 

performed twice, once excluding control data and the other including the solvent control. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity no, but tested up to limit concentrations 

Vehicle controls valid 

Negative controls valid 

Positive controls valid 

Additional information on results 

Cells exposed to test material at concentrations up to 5000 micrograms/ml showed no increase 

in chromosome damage or no linear trend compared to negative controls in either experiment. 

The positive control induced significantly more cells with aberrations compared to the negative 

controls (for untreated control and for solvent control). In the first experiment with S-9 (up to 

1875 micrograms/ml test material), there was no effect of treatment on the incidence of type of 

aberration observed. However, there was a significant difference in the number of cells with 

chromatid gaps and/or isogaps between the untreated control (7/200) and solvent control 

cultures (1/200). In the second experiment with S-9 (cells were treated with 1500, 3000 or 5000 

micrograms/ml test material), there was a significant difference in the number of cells with 

aberrations including gaps (11/200) and cells with chromatid gaps and/or isogaps (8/200) at the 

1500 micrograms/ml compared to the solvent control (2/199 and 0/199, respectively). There 

also was a significant increase in the number of cells with chromatid gaps and/or isogaps at the 

high concentration (5/200) compared to control, and between both controls (untreated control 

had 7/200). No linear trend was observed either by including or excluding the solvent control 
from the analysis. The positive control caused increases in aberrations with and without gaps 

compared to the solvent control in both studies. 

The cytotoxic concentration was > 5000 micrograms/ml. 

Remarks on results including tables and figures 

The small random increases in the number of chromatid gaps and/or isogaps in one experiment 

with S-9, which were not dose-dependent and not different from the untreated controls were not 

considered to be compound-related effects by study personnel. 

Overall remarks, attachments 

Overall remarks 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Conclusions 

Study personnel concluded that under the test conditions, the test material did not induce 

chromosomal aberrations either in the presence or absence of S9 mix. 

Genetic toxicity in vitro UC MPEG 1984.003 

UUID IUC5-69753a40-2c9e-4e54-8a36-02ad24a8bc1e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:08 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

84 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study per GLP and with test substance well characterized as 

to composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1984 

Title Carbowax methoxy polyethylene glycol 350 Salmonella/microsome (Ames) 

bacterial mutagenicity assay. 
Bibliograph

ic source 

 

Testing 

laboratory 

Bushy Run Research Center. Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1984-10-2

3 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Principles of method if other than guideline 

No guideline was referenced in the study, but the study method followed conventional 

procedure for Ames studies. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowax MPEG-350 

Details on test material 

The test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3).Purity 

of test material was 99.8%. Impurities included 0.1% water, 0.05% ethylene glycol, 0.05% 

diethylene glycol, and 50-150 ppm BHT. 

Method 

Species/strain 

Species/strain other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 

Details on 

mammalian cell 

lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic 

activation 

with and without 
Metabolic 

activation system 

0.5 ml of S9 mix containing 50 microliters of S9 liver homogenate from 

Aroclor 1254-induced, Sprague-Dawley male rats 

Test concentrations 

1, 3, 10, 30 and 110 mg/plate 

Vehicle 

water 

Controls 

Negative controls yes 

Solvent / vehicle 

controls 

yes 

True negative 

controls 

no 

Positive controls yes 

Positive control 

substance 

other: 4-nitro-o-phenylenediamine, sodium azide, 9-aminoacridine and 

2-aminoanthracene 

Remarks 

Details on test system and conditions 

Test material was dissolved in water to a concentration of 300 mg/ml for doses of 30 mg/plate 

and below. All subsequent dilutions were made in the same solvent. Dilutions of test substance 

were made fresh each day and were gravimetrically analyzed. The volume of test material used 

in each test was 100 microliters. If necessary, phosphate buffered saline was added to adjust the 

volume.

A preliminary toxicity test was performed in strain TA100 to determine concentrations to use on 

other strains (TA98, TA1535, TA1537, TA1538). None of the doses used (up to 100 mg/plate) 

were toxic. Test material was tested in the Ames assay in triplicate at five doses (1, 3, 10, 30 

and 110 mg/plate). Testing was performed with and without metabolic activation (0.5 ml of S9 

mix containing 50 microliters of S9 liver homogenate from Aroclor 1254-induced, 

Sprague-Dawley male rats). Concurrent water and positive controls 

(4-nitro-o-phenylenediamine for TA98 and TA 1538, sodium azide for TA100 and TA1535 and 

9-aminoacridine for TA1537 in the absence of S9 and 2-aminoanthracene for all stains in the 

presence of S9) were run with each test. 

Evaluation criteria 

The test was considered valid, if positive controls caused mutagenicity and negative controls 

exhibited spontaneous reversion rates that were within historical range. 

Statistics 

no data 

Results and discussions 

Test results 

Species/strain other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid 
Positive controls valid yes 

Additional information on results 

The test was valid, as positive controls caused mutagenicity and negative controls exhibited 

spontaneous reversion rates that were within historical range.

Cycotoxic concentration: > 110 mg/plate 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Conclusions 

Mutagenic activity was not observed with any concentration in any of the strains (with or 

without bacterial activation). 

7.6.2 Genetic toxicity in vivo 

Genetic toxicity in vivo McClintock & Gallapudi Mouse MN TGME 1990.001 

UUID IUC5-0fa2b92b-8f46-46bd-b785-b62cbe5a929b 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:25 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP with test substance purity noted. 

Data source 

Reference 

Reference 

type 

study report 

Author McClintock ML and Gollapudi B. Year 1990 

Title Evaluation of triethylene glycol monomethyl ether in the mouse bone marrow 

micronucleus test. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company Study ID TXT:K-005610-007 Report 1990-03-0
study no. date 7 

Materials and methods 

Type of study 

micronucleus assay 

Test guideline 

Qualifier according to 

Guideline EPA OPPTS 870.5200 (Mouse Visible Specific Locus Test) 

Deviations 

Principles of method if other than guideline 

Study reference for protocol used is: Test Standard 40 CFR 798.5395 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Test animals 

Species 

mouse 

Strain 

CD-1 

Sex 

male/female 

Details on test animals and environmental conditions 

Strain specifically denoted to be CD-1 (ICR)BR. The animals were approximately 8 weeks old. 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle(s) 

water 

Details on exposure 

Test material was dissolved in water and administered to mice (approximately 8 weeks old) by 

single oral gavage at dose levels of 0 (water), 500, 1667 and 5000 mg/kg body weight (10 

ml/kg). A previous study revealed that 5000 mg/kg did not affect survival. Concentrations of 

test material in dosing solutions were verified by HPLC. Groups of animals(5/sex/dose/sacrifice 

time) were sacrificed by cervical dislocation 24, 48 and 72 hours after treatment. Mice (5/sex) 
treated with 120 mg/kg cyclophosphamide and sacrificed after 24 hours of treatment served as 

positive controls. 

Duration of treatment / exposure 

Single dose 

Frequency of treatment 

Single dose 

Post exposure period 

up to 72 hours 

Doses / concentrations 

500, 1667, 5000 mg/kg bw 

Basis nominal in water 

No. of animals per sex per dose 

5 animals per sex per dose 

Control animals 

yes, concurrent vehicle 

Positive control(s) 

Mice (5/sex) treated with 120 mg/kg cyclophosphamide and sacrificed after 24 hours of 

treatment served as positive controls. 

Examinations 

Tissues and cell types examined 

Bone marrow samples were obtained from both femurs at sacrifice. Cell smears were prepared 

from cell suspensions. 

Details of tissue and slide preparation 

The slides were air dried, fixed in methanol and stained in 5% Giemsa. Slides were coded and 

scored blindly. One thousand polychromatic erythrocytes (PCE) were evaluated from each 

surviving animal and the frequencies of micronucleated polychromatic erythrocytes (MN-PCE) 

were recorded. Micronuclei were identified as darkly stained bodies with sharp contours and 

varying shapes such as round, almond, or ring. The ratio of PCE-NCE (normochromatic 

erythrocytes) in the bone marrow was determined by examining 100 erythrocytes. 

Evaluation criteria 

The test was valid if positive controls had significantly more MN-PCE than controls (62.2 in 

males and 34.6 in females). 

Statistics 

Statistical Analysis: The raw data on the counts of MN-PCE for each animal were transformed 

by adding 1 to each count and then taking the natural log of the adjusted number. The 

transformed MN-PCE data and the data on percent PCE were analyzed by a three-way analysis 

of variance looking only at main effects. Pairwise comparisons between treated vs. negative 

controls were done (if necessary) by a t-test usingBonferroni correction for multiple 

comparisons. 

Results and discussions 

Test results 

Sex male/female 

Genotoxicity negative 

Toxicity 

Vehicle controls valid yes 
Negative controls valid 

Positive controls valid yes 

Additional information on results 

One female dose with 1667 mg/kg test material died prior to scheduled sacrifice. The cause of 

death was not determined. There were no significant increases in the frequencies of 

micronucleated polychromatic erythrocytes (MN-PCE) in groups treated with test material 

(range from 0.2 to 1.6) versus negative controls (range 0.4 to 1.2). The ratios of polychromatic 

erythrocytes (PCE) to normochromatic erythrocytes (NCE) (% PCE) in test animals (67.3 to 

82.0) also were similar to those of negative controls (70.6 to 78.7). 

The test was valid as positive controls had significantly more MN-PCE than controls (62.2 in 

males and 34.6 in females). 

Applicant's summary and conclusion 

Interpretation of results 

negative 

7.8 Toxicity to reproduction 

7.8.1 Toxicity to reproduction 

Toxicity to reproduction Corley 13-Week TGME 1990.001 

UUID IUC5-bc1d6241-8df0-4e2d-a692-b5539b165837 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:26 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

0 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Effect on mating was not characterized. Otherwise study was robust per 

current protocol following GLP. 

Data source 

Reference 

Reference type study report 

Author Corley RA, Ciesslak, Breslin WJ, Lomax LG. Year 1990 

Title 13-Week dermal toxicity study in Sprague-Dawley rats. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 
Owner 

company 

Dow Chemical Company 

Company study 

no. 

Study ID K-005610-004 Report date 1990-09-26 

Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 1998 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a 91 day dermal repeat dose study in Sprague-Dawley rats. 

This is repeated dose toxicity dermal.001 

Materials and methods 

Test type 

fertility 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477). 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity (as determined by gas chromatography) was 99.23 % at the onset of the study and 
99.24% at completion of the in-life phase. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 week-old rats 

Administration / exposure 

Route of administration 

dermal 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 400 mg/kg/day for 13 weeks. Test material 

was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. 

Details on mating procedure 

No mating 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

Purity of test substance as administered (as determined by gas chromatography) was 99.23 % at 

the onset of the study and 99.24% at completion of the in-life phase. 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily, 6 hr/day, 5 days/week 

Doses / concentrations 

0 (sham control), 400, 1200 or 400 mg/kg/day 

Basis analytical conc. 

No. of animals per sex per dose 

10/sex/dose level 

Control animals 

yes, sham-exposed 

Examinations 

Parental animals: Observations and examinations 

Upon necropsy the test animals were examined. The oocytes, corpora lutea, and follicles from 

each ovary were evaluated with regard to their normal development. The testes and epididymes 

also were examined microscopically for males in the intermediate- and low-dose groups. 
Postmortem examinations (Parental animals) 

See Repeated dose dermal study.001 for details 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect level 4000 mg/kg bw/day (actual dose received) 

Basis for 

effect level / 

Remarks 

NOAEL for systemic effects on test animals. Conclusion of summary preparer; 

no adverse systemic effects seen at highest dose. 

Endpoint NOAEL 

Generati

on 

P 

Sex male/female 

Effect 

level 

>= 400 — < 1200 mg/kg bw/day (actual dose received) 

Basis for 

effect 

level / 

Remarks 

Interpretation of EPA, based on bilaterally decreased spermatogenesis observed in 

one male treated with the highest dose (4000 mg/kg bw) and testicular changes 

observed in one male treated with 1200 mg/kg. 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

yes 

Reproductive function: sperm measures (parental animals) 

yes 

Reproductive performance (parental animals) 

not examined 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

There were no indications of systemic toxicity at any dose. Mean body weight and food 

consumption were comparable to controls throughout the study. Bilaterally decreased 

spermatogenesis in seminiferous tubules and decreased spermatozoa in the epididymes (both 

were graded as severe) were noted in the testes of one high dose male rat. This animal had a 

complete lack of mature spermatids in greater than 41% of tubules in each testicle, few 

spermatids beyond stage 12 of development in the seminiferous epithelium, and decreased 
spermatic elements in the head and tail of greater than 41% of the tubules and ducts in the 

epididymides. The testes of one male treated with 1200 mg/kg exhibited different testicular 

changes [bilateral multifocal degeneration of spermatocytes and spermatids from germinal 

epithelium (graded as very slight), and multinucleated spermatids]. In this rat, all stages of the 

cycle of the seminiferous epithelium were observed in morphologically normal tubules. The 

epididymides of this rat had decreased spermatic elements in the head and tail of 1-5% of ducts. 

Some of the ducts also contained immature spermatids. There were no effects on estrous 

cyclicity or ovaries of females. 

Observations: offspring 

Remarks on results including tables and figures 

Study personnel concluded that the bilateral microscopic testicular changes observed in one high-dose 

and one mid-dose male rat were unrelated to treatment. Reasons given were that the dissimilarity of the 

lesions for the two animals suggested that they occurred spontaneously, and the incidence of animals 

with lesions (1/10 in each group) was well within that of historical controls (0-17%). Study personnel also 

stated that the degenerative changes in the testes of one mid-dose and one high-dose rat were not 

consistent with the types of lesions that have been attributed to 2-methoxyethanol (2-ME). The cell types 

that are most vulnerable to 2-ME are the pachytene spermatocytes and round spermatids (Chapin et al., 

Fund Appl. Toxicol 5:182-189, 1985). As the dose of 2-ME is increased, the number and types of cells 

affected increase up to the point that the germinal epithelium is significantly degenerated and all stages 

of spermatogenesis are affected (Chapin et al., Fund Appl. Toxicol 5:182-189, 1985; Miller et al., Fund 

Appl Toxicol 3:49-54, 1983.). In contrast, the testicular effects seen with the high dose animal treated 

with TGME consisted of a virtually complete lack of mature spermatids beyond stage 12. All other 

stages, including spermatogonia and spermatocytes, were present and appeared morphologically 

normal. In the mid-dose rat, the only effects noted consisted of very slight degeneration of 

spermatocytes and spermatids similar to those seen in historical control animals. 

Study personnel also stated that the lymphoid tissues and hematologic parameters, which have been 

reported to be affected at doses of 2-methoxyethanol that have been associated with testicular changes 

(Miller et al., Fund. Appl. Toxicol. 3:49-54, 1983) were unaffected in this TGME study. Taking all factors 

into consideration, the testicular lesions observed in this dermal study could not be directly attributed to 

TGME exposure. 

Overall remarks, attachments 

Overall remarks 

Additional details for this study can be found in the Repeated dose dermal study.001 summary. 

The EPA has determined that based on severe testicular toxicity in 1/10 rats given 4000 mg/kg/day and 

minimal decreases in developing germ cells (1-5% of semiferous tubules affected) in 1/10 rats given 

1,200 mg/kg/day, the NOAEL for testicular toxicity is between 400 and 1200 mg/kg/day (Anderson, L. 

Triethylene glycol monomethyl, monoethyl and monobutyl ethers RM1 screening document (draft), Feb. 

24, 1995). This value was reached even though it was recognized that the testicular changes in the 

1,200 mg/kg/day rat were within historical control limits for Sprague-Dawley rats (0 1 7 %).

Toxicity to reproduction Gill & Negley TGME 1990.003 

UUID IUC5-65051ae6-6747-493c-8e40-94db9826a616 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:26 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted, robust study, following GLP, but the effect on mating was 

not characterized. 

Data source 

Reference 

Reference 

type 

 

Author Gill MW and Negley JE. Year 1990 

Title Triethylene glycol monomethyl ether. Ninety day subchronic drinking water 

inclusion neurotoxicity study in rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

Project Report 52-607, Report 

date 

1990-09-

21 

Cross-reference to same study 

This study is also summarized as a repeated dose study in Repeated dose study oral.001 

Materials and methods 

Test type 

fertility 

Limit test 

no 

Principles of method if other than guideline 

The route of administration and maximum dose level was specified in a testing consent order 

(EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477). 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 
Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The purity was at least 98.7%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Rats were treated with triethylene glycol monomethyl ether (TGME) for 91 days via drinking 

water at target doses of 0, 400, 1200 and 4000 mg/kg/day. 

Details on mating procedure 

Study did not include mating. Study examined male reproductive organs. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily 

Doses / concentrations 

0, 400, 1200 and 4000 mg/kg/day. 

Basis nominal in water 

No. of animals per sex per dose 

15/sex/group 

Control animals 

other: concurrent water 

Positive control 

no data 

Examinations 
Parental animals: Observations and examinations 

Rats were observed daily for clinical signs and weekly for body weight and water and food 

consumption. Rats were also observed periodically for behavior (functional observational 

battery) and motor activity. 

Estrous cyclicity (Parental animals) 

no data 

Sperm parameters (Parental animals) 

Yes, see results section. 

Litter observations 

no 

Postmortem examinations (Parental animals) 

Gross lesions and organ weights were recorded at necropsy. Microscopic analyses of liver, 

testes and the nervous system also were performed. 

Postmortem examinations (Offspring) 

no 

Statistics 

no data 

Reproductive indices 

no data 

Offspring viability indices 

no data 

Any other information on materials and methods incl. tables 

The authors state that a possible contributing factor in the development of testicular lesions at the high 

dose was low-level contamination of the test substance with the known testicular toxicant 

2-methoxyethanol (EGME). EGME was present in the test substance at a concentration of 0.02  0.04 

%, resulting in a EGME dose up to 1.7 mg/kg/day for animals in the high dose group. Given the length of 

the study, it is possible that EGME contributed to the testicular lesions. A comparison between the doses 

of EGME and TGME required to produce testicular toxicity indicated that TGME is 350 times less potent 

than EGME in producing testicular lesions in the rat.The dose of TGME that caused testicular toxicity 

(4000 mg/kg/day) is 4 times greater than the 1000 mg/kg/day limit dose generally recommended for 

subchronic studies.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect level 1200 mg/kg bw/day (nominal) 

Basis for effect level / 

Remarks 

Interpretation by summary preparer for reproduction organ toxicity. 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect level > 400 — < 1200 mg/kg bw/day (nominal) 

Basis for effect Interpretation by the Environmental Protection Agency for testicular 
level / Remarks effects. 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Test substance intake (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

no data 

Reproductive function: sperm measures (parental animals) 

yes 

Reproductive performance (parental animals) 

no data 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

The testes of males in the high dose group exhibited degeneration (12/15) and/or atrophy (5/5) 

of the seminiferous tubules (spermatocytes or developing spermatids). The authors concluded 

that these effects were related to treatment. The severity of the lesions was primarily mild to 

moderate for degeneration (11/12) and minimal to moderate for atrophy (5/5), indicating that 

not all tubules were affected and that a limited number of cells was affected within the affected 

tubules. One male treated with 1200 mg/kg had severe seminiferous tubule atrophy, a complete 

loss of cell types in the tubules (except for Sertoli cells) and moderate Leydig cell hypertrophy 

(not significant from control). This was not considered to be related to treatment because of the 

lack of a plausible explanation for the unusual dose-response relationship (the effect at this dose 

was more severe than that of a higher dose) and the low incidence of animals affected at this 

dose level (Gill et al., Int J Toxicol 17:1-22, 1998) One male treated with 1200 mg/kg had 

severe seminiferous tubule atrophy and moderate Leydig cell hypertrophy (not significant from 

control). No testicular changes were noted in males treated with 400 mg/kg/day TGME. 

Observations: offspring 

Viability (offspring) 

not examined 

Clinical signs (offspring) 

not examined 

Body weight (offspring) 

not examined 

Sexual maturation (offspring) 

not examined 

Organ weights (offspring) 

not examined 
Gross pathology (offspring) 

not examined 

Histopathology (offspring) 

not examined 

Details on results (offspring) 

91 Day repeated dose study did not include mating, but examined male testes. 

Remarks on results including tables and figures 

The NOAEL listed is for reproductive organ toxicity. Other results are shown in section 5.4. The 

summary preparer-assigned NOAEL and LOAEL for testicular effects is 1200 and 4000 mg/kg/day, 

respectively. By contrast, the EPA has determined that the NOAEL for testicular effects is between 400 

and 1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers 

RM1 screening document (draft), Feb. 24, 1995).

Toxicity to reproduction UC MPEG 1985.002 

UUID IUC5-5d2c5dc1-58d6-41e5-9873-37382b3a4d95 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-25 13:17:09 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1985 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted, robust study with test substance well characterized as to 

composition. Study conducted following GLP. No guideline specified 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1985 

Title Nine-day and ninety-day dermal toxicity studies of CARBOWAX MPEG-350 in 

rabbits. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1985-05-3

0 
Reference 

type 

 

Author Hermansky SJ, Leung HW. Year 1997 

Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

This study is also summarized as a 90 day repeated dose dermal study. See repeated dose 

toxicity dermal.002 for further details. 

Materials and methods 

Test type 

fertility 

Limit test 

no 

Principles of method if other than guideline 

No guideline specified, but study was conducted following standard procedures and principles. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG 350 

Details on test material 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) wasreported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. This material is a 

mixture of several methylated glycol ethers of differing molecular weight (ranging from 

diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 
rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Body weights of males and females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study 

initiation. 

Administration / exposure 

Route of administration 

dermal 

Vehicle 

other: methyl cellulose in distilled water 

Details on exposure 

Dosing: New Zealand white rabbits (10/sex/dose) were treated dermally on clipped dorsal skin 

with 1.0 ml of vehicle (0.1% (w/v) methyl cellulose in distilled water), 50% CARBOWAX 

MPEG-350 (w/v dilution in 0.1% methyl cellulose in water) or 100% CARBOWAX 

MPEG-350, for six hours/day, five days per week for 90 days. Rabbits were fitted with 

Elizabethan collars after dosing to prevent ingestion of test material. After each 6-hour exposure 

the application site was wiped with a paper towel dampened with water and then dried using a 

towel. Rabbits were then uncollared until the next treatment.

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

90 days 

Frequency of treatment 

daily, six hours/day, five days per week 

Doses / concentrations 

1 ml of 50% and 100% material (approximately 169 and 338 mg/kg/day) 

Basis nominal conc. 

No. of animals per sex per dose 

10/sex/dose 

Control animals 

yes, concurrent vehicle 

Further details on study design 

A preliminary range-finding study in 15 rabbits dosed 6 hr/day for 9 days showed that daily 

administration of 1 ml of 50% or 100% test material only caused mild skin irritation. Therefore, 

these doses were chosen for the90-day study.

Based on weights of animals determined at weekly intervals and the reported density of test 

material (1.09 g/ml) doses can be calculated on average mg/kg/day basis. These doses are 169 

mg/kg/day (for 50%) and 338 mg/kg/day (for 100%). 

Examinations 

Parental animals: Observations and examinations 

Observations: All rabbits were observed daily (weekdays) for death, clinical signs and dermal 

irritation. Body weights were recorded on the morning of the first day of dosing, weekly 
thereafter and prior to sacrifice. Food consumption was measured weekly. Urine was collected 

from 5 animals/sex/group during the last two weeks of dosing and subjected to standard 

analyses. Standard hematology and clinical chemistry parameters were evaluated for all animals 

just prior to sacrifice. 

Estrous cyclicity (Parental animals) 

no data 

Sperm parameters (Parental animals) 

no data 

Postmortem examinations (Parental animals) 

Necropsy: All animals were sacrificed and necropsied after 13 weeks of treatment. Weights 

were recorded for liver, kidneys, brain and adrenals of all animals and testes of males. 

Histopathologic examinations were performed on tissues (including testes, epididymes, prostate, 

accessorysex glands, uterus, ovaries and mammary gland) from high-dose and control animals. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect 

level 

338 mg/kg bw/day (nominal) 

Basis for 

effect level 

/ Remarks 

The NOAEL listed is for reproductive organ toxicity. The NOAEL for systemic 

effects was not listed by the investigators. Based on the data, this value is 100% 

(338 mg/kg/day). 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Test substance intake (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

no data 

Reproductive function: sperm measures (parental animals) 

yes 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

No effects on any test animal sex organ were observed 

Observations: offspring 

Remarks on results including tables and figures 
The NOAEL listed is for reproductive organ toxicity. Further details of this study can be found in the 

summary for repeated dose toxicity dermal.002. The NOAEL for systemic effects was not listed by the 

investigators. Based on the data, this value is 100% (338 mg/kg/day).

7.8.2 Developmental toxicity / teratogenicity 

Developmental toxicity / teratogenicity Hoberman TGME Rats 1990.002 

UUID IUC5-b7c1466f-70d0-481e-817f-c4f81d91cf44 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:27 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP and standard protocol. 

Data source 

Reference 

Reference 

type 

study report 

Author Hoberman AM. Year 1990 

Title Triethylene glycol monomethyl ether (TGME): oral developmental toxicity study in 

Crl:CD(SD)BR pregnant rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Argus Research Laboratories, Inc. Report 

no. 

StudyNumber 

503-005. 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Limit test 

no 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 
yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol methyl ether 

Details on test material 

no details 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Details on test animals and environmental conditions 

203 to 256 g 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Groups of 25 mated female rats (203 to 256 g) were given daily dosages of 4.8 ml of deionized 

water (control), or 0.6, 1.2, 2.4, and 4.8 ml/kg/day of triethylene glycol monomethyl ether 

(TGME) by gavage. These doses corresponded to 0, 625, 1250, 2500 or 5000 mg/kg/day. All 

doses were adjusted daily according to body weights recorded immediately prior to intubation. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

Days 6 to 15 of gestation 

Frequency of treatment 

daily 

Duration of test 

15 days 

Doses / concentrations 

0, 625, 1250, 2500 or 5000 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

25 females per dose 

Control animals 

yes, concurrent vehicle 

yes, sham-exposed 
Examinations 

Maternal examinations 

Rats were observed at least twice daily during the dosage and postdosage periods for clinical 

signs, signs of resorption, premature deliveries and death. Body weight and feed consumption 

were recorded on Day 0 of presumed gestation and from days 6 through 20 of gestation. Dams 

that were found dead were necropsied on day of death and subjected to the same procedures 

described for scheduled sacrifice. 

Ovaries and uterine content 

Rats were sacrificed on Day 20 of presumed gestation, and the thoracic and abdominal viscera 

were examined for gross lesions. The uterus was excised from each rat and weighed. The 

number and placement of implantations were recorded and sites were categorized as early or 

late resorptions, or live or dead fetuses. Each ovary was examined for the number of corpora 

lutea. 

Fetal examinations 

Fetuses were weighed, sexed, and examined for external alterations. One-half were examined 

for soft tissue alterations, and the remaining half were examined for skeletal alterations. 

Statistics 

Maternal and fetal incidence data were analyzed suing the variance test for homogeneity of the 

binomial distribution. Maternal body weight and feed consumption data, organ weight data, and 

litter averages for percent male fetuses, percent dead or resorbed conceptuses per litter, fetal 

body weights, fetal ossification sites, and percent fetal alterations were analyzed using Bartlett's 

Test of homogeneity of variances and the analysis of variance (when data were homogeneous). 

If the analysis of variance was significant, Dunnett's Test was used to identify the statistical 

significance of individual groups. If data were not homogeneous, the Kruskal-Wallis test was 

used when less than or equal to 75% ties were present; when more than 75% ties were present 

the Fisher's Exact Test was used. In cases where the Kruskal-Wallis Test was statistically 

significant, Dunn's Method of Multiple Comparisons was used to identify the statistical 

significance of individual groups.

All other Caesarean-sectioning data were evaluated using the procedures previously described 

for the Kruskal-Wallis Test. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 1250 mg/kg bw/day (nominal) 

Basis for effect 

level / Remarks 

Reduced food consumption was observed at the next higher dose (2500 

mg/kg bw). 

Endpoint NOAEL 

Effect type teratogenicity 

Effect 

level 

625 mg/kg bw/day (nominal) 

Basis for 

effect level 

Groups given 1250 mg/kg/day and higher doses of TGME had significant increases 

in the litter and/or fetal incidences of reversible delays in fetal ossification. 
/ Remarks 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

One nonpregnant animal in the high dose group (5000 mg/kg/day) was found dead on day 13 of 

presumed gestation. This was considered by the authors to be treatment-related. Significant 

numbers of rats treated with the high dose exhibited decreased motor activity, excess salivation, 

ataxia, and impaired righting reflex. Food consumption of high dose animals were reduced over 

the entire dosage period. Average maternal body weight gains of rats in the high dose group 

were reduced on days 6-9, 6-12, 12-16, and 6-16 of gestation. Consequently, average body 

weights of these animals were reduced on days 9, 12, and 16. Average gravid uterine weights of 

high-dose animals were also reduced. 

Food consumption of rats receiving 2500 mg/kg/day was reduced during days 6-16, 6-18, and 

12-16. Food consumption and average maternal body weights and body weight gains in rats 

receiving 1250 mg/kg/day were not significantly different from controls. Therefore, 1250 

mg/kg/day was considered by study personnel to be the NOAEL for maternal toxicity.

There was no effect of TGME on the number of pregnant dams or number of copora lutea, 

implantations, live litter size or fetal sex ratios. 

Embryotoxic / teratogenic effects 

yes 

Details on embryotoxic / teratogenic effects 

Fetal: Significant increases in embryo-fetal lethality (litter averages for total resorptions (1.6 

versus 0.6 in control), late resorptions (0.3 versus 0 in controls), percentage of resorbed 

conceptuses (12.0 versus 4.4 incontrol) and dams with at least one resorption (81.8% versus 

47.8 in control) occurred in the 5000 mg/kg group. Fetuses from rats treated with 2500 or 5000 

mg/kg had lower body weights than controls (3.04 and 2.56 g (respectively) versus 3.32 in 

controls). 

There was no effect of TGME on the incidences or types of gross external or internal soft tissue 

malformations. Groups given 1250 mg/kg/day and higher doses of TGME had significant 

increases in the litter and/or fetal incidences of reversible delays in fetal ossification. Fetuses 

from rats given 2500 or 5000 mg/kg/day also had a significant increase in the incidence of 

cervical ribs. The NOAEL for developmental toxicity was considered by study personnel to be 

625 mg/kg/day. 

Remarks on results including tables and figures 

The authors remarked that the skeletal variations noted were common observations in fetuses with 

reduced body weights. Since only reversible delays in fetal ossification were observed in the 1250 

mg/kg/day group, the actual NOAEL may be close to this concentration. The NOAEL listed under 

teratogenicity is the NOAEL for developmental toxicity.

Developmental toxicity / teratogenicity Hoberman TGME Rabbits 1990.003 

UUID IUC5-d2c695b2-ef8c-491e-b413-e22684b2304f 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:28 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP and standard methodology 

Data source 

Reference 

Reference 

type 

study report 

Author Hoberman AM. Year 1990 

Title Triethylene glycol monomethyl ether (TGME): oral developmental toxicity study 

in New Zealand White rabbits. 

Bibliograp

hic source 

 

Testing 

laboratory 

Argus Research Laboratories, Inc. Report 

no. 

503-004

. 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Limit test 

no 

Principles of method if other than guideline 

Study followed standard methodology 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 
Identifier Common name 

Identity Triethylene glycol methyl ether (TGME) 

Details on test material 

no details 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: gavage 

Details on exposure 

Groups of 20 artificially inseminated female rabbits were given daily dosages of 0 (same 

volume of deionized water as the highest dose), 250, 500, 1000 or 1500 mg/kg/day of 

triethylene glycol monomethyl ether (TGME) by gavage. All doses were adjusted daily 

according to body weights recorded immediately prior to intubation. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

artificial insemination 

Duration of treatment / exposure 

days 6 to 18 of gestation 

Frequency of treatment 

daily 

Duration of test 

24 days 

Doses / concentrations 

0, 250, 500, 1000 or 1500 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

20 artificially inseminated female rabbits 

Control animals 

yes, concurrent vehicle 

Examinations 

Maternal examinations 

Rabbits were observed daily during the course of the study for clinical signs, abortions, 

premature deliveries and death. Body weights were recorded on Day 0, and Days 6 through 29 

of presumed gestation. Food consumption was recorded daily. 

Ovaries and uterine content 

Rabbits were sacrificed on Day 29 of presumed gestation, and the thoracic and abdominal 
viscera were examined for gross lesions. The uterus was excised from each animal and weighed. 

The number and placement of implantations were recorded and sites were categorized as early 

or late resorptions, or live or dead fetuses. Each ovary was examined for the number of corpora 

lutea. 

Fetal examinations 

Fetuses were weighed, sexed, and examined for external and soft tissue or skeletal alterations. 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 500 mg/kg bw/day (nominal) 

Basis for 

effect level / 

Remarks 

Mortallity and maternal toxicity was observed for dose groups above 500 mg/kg 

bw, but effects and mortality did not occur at 500 mg/kg bw. 

En

dp

oin

t 

NOAEL 

Eff

ect 

typ

e 

teratogenicity 

Eff

ect 

lev

el 

1000 mg/kg bw/day (nominal) 

Ba

sis 

for 

eff

ect 

lev

el / 

Re

ma

rks 

The authors concluded that the NOAEL for fetal toxicity was 1500 mg/kg/day because the 

skeletal abnormalities observed at this dose were not unique. However, in a similar study 

performed by the same laboratory in rats (see previous record), common skeletal 

abnormalities were considered to be adverse. On this basis, the NOAEL for developmental 

toxicity in rabbits should be the dose that did not produce an increase in any skeletal 

abnormalities (1000 mg/kg/day). The NOAEL listed under teratogenicity is the NOAEL for 

developmental toxicity. 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

Maternal: Eight rabbits treated with the 1500 mg/kg/day dose died, and three aborted. A 

significant number of rabbits treated with this dose exhibited decreased motor activity, labored 

breathing, a red substance in the cage pan, dehydration, no feces, ataxia, gastric 
ulceration,anogenital staining, mottled gallbladders, thin-walled stomach, reddened stomach, 

and fluid-filled or empty small intestines, and lower average gravid uterine weight. There was 

one death in the 1000 mg/kg/day group. This was considered to be possibly related to treatment. 

One rabbit in the low dose group aborted. Study personnel did not consider this to be related to 

test material because it was not dose-dependent. 

There was no effect of treatment on the number of pregnant rabbits, average number of corpora 

lutea, implantations, live fetuses, resorptions, or fetal sex ratios. 

Rabbits treated with all doses except 250 mg/kg/day gained more weight during the postdosage 

period than controls, reflecting increased food consumption during this period. Study personnel 

did not consider this weight gain to be an adverse effect, as it is commonly seen in 

developmental studies after dosing is terminated. 

Details on embryotoxic / teratogenic effects 

Fetal: There was no effect of treatment on fetal body weight, or incidences or types of gross 

external or internal soft tissue malformations. The fetal and/or litter incidences of angulated 

hyoid alae and reversible delays in ossification of the xiphoid were increased in the 1500 

mg/kg/day group. 

Developmental toxicity / teratogenicity Bates & deSerres TGME Rats 1992.004 

UUID IUC5-77fa4421-7d6d-4f7c-8c44-5c5a55ab7755 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:15:29 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following standard procedure and following GLP. Purity of test 

substance was provided. 

Data source 

Reference 

Referen

ce type 

 

Author Bates HK and de Serres FJ. Yea

r 

1992 

Title Developmental neurotoxicity evaluation of triethylene glycol monomethyl ether (CAS 

112-35-6) administered by gavage to time-mated CD rats on gestational day 6 through 
postnatal day 21. 

Bibliogr

aphic 

source 

CMA Reference Ge-43.0-DEV/NEU-RTI 

Testing 

laborato

ry 

 Rep

ort 

no. 

 

Owner 

compan

y 

 

Compan

y study 

no. 

 Rep

ort 

date 

1992-

03-03 

Materials and methods 

Limit test 

no 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol methyl ether 

Details on test material 

The analyzed chemical purity was 99.2%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Details on test animals and environmental conditions 

Timed pregnant CD" (Sprague-Dawley) rats, 64 sperm plug-positive females per group 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 
Timed pregnant CD" (Sprague-Dawley) rats, 64 sperm plug-positive females per group, were 

gavaged with the neat test material, triethylene glycol monomethyl ether (TGME), once daily, 

on gestational day (GD) 6 through postnatal day (PND) 21 at doses of 0, 300, 1650 or 3000 

mg/kg/day. The volume of TGME administered was adjusted based on each animal's most 

recent body weight. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

no details other than the females were plug-positive females per group 

Duration of treatment / exposure 

day 6 of gestation through postnatal Day 21 

Frequency of treatment 

daily 

Duration of test 

38 days 

Doses / concentrations 

300, 1650, 3000 

Basis nominal conc. 

No. of animals per sex per dose 

64 pregnant females per dose. 

Control animals 

yes, concurrent vehicle 

Examinations 

Maternal examinations 

Clinical observations were made at least twice daily during the dosing period and daily 

otherwise. Maternal body weights were measured on GD 0, 6, 9, 12, 15, 18, 20, and on PND 0, 

4, 7, 13, 17, and 21. Food consumption was measured for the intervals GD 0-6, 6-9, 9-12, 

12-15, 15-18, 18-20, and PND 0-3, 3-6, 6-9, and 9-12. Maternal animals were allowed to deliver 

and rear their young. 

On PND 22 the dams were evaluated for body weight, liver and kidney weight and the number 

of uterine implants (metrial glands).

Fetal examinations 

Pups were counted, examined externally, weighed, and sexed on PND 0 and PND 4. After 

examination on PND 4, litter size was standardized by random culling to either a 4:4 or 5:3 sex 

ratio. Litters with insufficient numbers of pups were removed from the study after culling. 

Litters with sufficient numbers of pups remained on study, and pups wereexamined and 

weighed on PNDs 7, 13, 17, 21,35, 49, and 68. Male pups were examined daily starting at PND 

17 for testicular descent, and females were examined daily starting on PND 30 for vaginal 

opening. One male and one female pup from each litter were assigned to each of three 

behavioral tests. Motor activity was assessed for one hour in a Figure-8 maze on PNDs 13, 17, 

21, 47, and 58. Auditory startle response was assessed on PNDs 22 and 60, and learning and 

memory were assessed with an active avoidance paradigm run on PNDs 60-64. Three 

euthanizations occurred during the course of this study. The first took place after culling and 
involved those dams that had failed to deliver as well as the dams and pups from litters of 

insufficient size or sex ratio. The second took place on PND 22 and the third on PND 68.

On PND 22 and PND 68 one male and one female pup from each litter were weighed and killed. 

A total of 24 of these pups were perfused in situ at each euthanization (PND 22 and PND 68 

i.e., 48 animals total) and were examined for histopathologic lesions of the central and 

peripheral nervous system. The brains of the remaining animals at each sacrifice were removed 

and separated into the telencephalon, diencephalon, medulla oblongata/pons, and the 

cerebellum. These sections were all weighed separately. 

Statistics 

Data were analyzed using the FREQ, GLM, NPAR1WAY and LIFETEST procedures in the 

SAS software package, in conjunction with a set of custom-designed analysis procedures. 

Results and discussions 

Effect levels 

En

dp

oin

t 

NOAEL 

Eff

ect 

typ

e 

maternal toxicity 

Eff

ect 

lev

el 

1650 mg/kg bw/day (nominal) 

Ba

sis 

for 

eff

ect 

lev

el / 

Re

ma

rks 

Conclusion of summary preparer, EPA. The authors stated that “TGME administered by 

gavage to pregnant and lactating CD" (Sprague- Dawley) rats resulted in no overt signs of 

maternal toxicity”. However, they also stated that the increased kidney weights in the high 

dose animals occurred as a result of exposure to TGME. Based on this comment, a 

maternal NOAEL of 1650 was assigned by the summary preparer. This is in agreement 

with the maternal NOAEL derived by the EPA (Anderson, L. Triethylene glycol 

monomethyl, monoethyl and monobutyl ethers RM1 screening document (draft), Feb. 24, 

1995). 

Endpo

int 

NOAEL 

Effect 

type 

teratogenicity 

Effect 

level 

300 mg/kg bw/day (nominal) 

Basis 

for 

Conclusion of summary preparer, EPA. The authors arrived at a no observable effect 

level (NOEL) of “equal to or greater than 300 mg/kg/day” based on decreased postnatal 
effect 

level / 

Remar

ks 

weight gains at 1650 and 3000 mg/kg/day. The reviewer does not believe that a 

NOAEL can be assigned from this study due to the unclear significance of minor 

reductions in body weight gains of animals at various time points and changes in startle 

response at 1650 and 3000 mg/kg. A NOAEL for teratogenicity of 300 mg/kg/day has 

been derived by the EPA (Anderson, L. Triethylene glycol monomethyl, monoethyl and 

monobutyl ethers RM1 screening document (draft), Feb. 24, 1995). The NOAEL listed 

under teratogenicity is the NO(A)EL for developmental toxicity. 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

Of the 256 mated animals assigned to this study 33, 27, 28, and 31 litters in the control to 

high-dose group, respectively, had sufficient pups of both sexes to be used for the behavioral 

evaluations. Evaluation of data from the maternal animals revealed no dose- related patterns of 

clinical signs of toxicity or lethality. Maternal body weights were equivalent across all groups 

and for all time points. No statistically significant effects on maternal weight gain or food 

consumption were noted. The length of gestation was significantly increased in the high-dose 

group animals compared to control although this finding was “of questionable biological 

significance since the difference between the groups was smaller than the 14-hour breeding 

time.” Necropsy of maternal animals in the high- dose group revealed significantly heavier 

kidneys than controls. Kidney weights increased in a dose-dependent manner.

Necropsy of maternal animals revealed that kidneys from the maternal animals exposed to 3000 

mg/kg/day of TGME were significantly heavier than controls 

Details on embryotoxic / teratogenic effects 

Analysis of pup in life data revealed no significant effects for PND 0/4 pup sex ratio or for pup 

survival during any period. Female pups from the mid- and high-dose groups (6.7 and 6.8 +/- 

0.1 g) and male pups from the high- dose group (7.0 and 7.1 +/- 0.1 g) were significantly 

heavier than their control cohorts on PND O (6.2 and 6.7 +/- 0.1 g for females and males, 

respectively). Pups from these same groups gained significantly less weight in the period from 

PND 4 to PND 21. Although born heavier, the male pups from the high-dose group were 

significantly lighter than the control pups at the end of the study on PND 68 (440.7 +/- 6.0 vs. 

462.4 +/- 4.8 g). Final body weights (PND 68) of mid and high dose females and mid-dose 

males were not significantly different from control.

Evaluation of pup development through the determination of vaginal opening revealed no 

differences between groups. Male pup development, as gauged by time of testes descent, was 

shown to be significantly advanced in the pups from the mid- and high-dose groups. Evaluation 

of the behavioral data generated during the course of this study indicated no dose-related effects 

on motor activity or active avoidance data. Significant effects on auditory startle response 

parameters were noted. In particular, the auditory startle amplitude (magnitude of the startle 

reflex) was increased in male and female pups in the high-dose group on PND 22. Auditory 

startle amplitude was also increased for male pups on PND 60 and a similar trend of smaller 

magnitude was observed in PND 60 females. When startle latency (time to maximum startle 

reflex) was examined, the pups showed no consistent effect on PND 22, but both male and 

female pups demonstrated a decrease in the startle latency on PND 68.
Necropsy of weanling and adolescent pups revealed no findings that could be related to 

treatment. Histopathological assessment of the peripheral and central nervous systems of the 

pups showed no treatment related lesions in any group. 

Applicant's summary and conclusion 

Conclusions 

“In conclusion, TGME administered by gavage to pregnant and lactating CD" (SpragueDawley) rats resulted in no overt signs of maternal toxicity. In addition, no discernible effects 

were noted in the offspring on motor activity, active avoidance, or neuropathology at exposures 

up to 3000 mg/kg/day. Exposure to TGME at 3000 mg/kg/day resulted inincreases in auditory 

startle amplitude and decreases in latency to maximum startle, but no changes in the habituation 

process evaluated in the auditory startle test. The significance of these auditory startle 

observations with regard to the condition of the test animals is notclear. Exposure to TGME at 

levels of 1650 and 3000 mg/kg/day produced developmental toxicity evidenced by decreased 

postnatal weight gains. Therefore, the no observable effect level" (NOEL) for this study is 

considered to be equal to or greater than 300 mg/kg/day.” 

Developmental toxicity / teratogenicity Taupin BF DOT 1993.005 

UUID IUC5-79004ca6-0383-4857-9e88-728137a942cf 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-03-24 17:24:59 EDT 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1993 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Pups were not examined for malformations. Statistical analyses were not 

performed. Otherwise the study was well conducted according to GLP and 

standard procedures. 

Data source 

Reference 

Reference 

type 

study report 

Author Taupin PJY Year 1993 

Title Brake Fluid DOT 4: Chernoff and Kavlock (CKA) developmental toxicity screen 

in the rat 

Bibliographi

c source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.2

33 

Owner Shell 
company 

Company 

study no. 

 Report 

date 

1993-02-0

2 

Materials and methods 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: Chernoff-Kavlok teratogenicity screening test 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake Fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Groups of 10 female rats were dosed by oral gavage with 25, 150 or 1000 mg/kg/day test 

material on days 7-17 of gestation. Additional groups of females were sham dosed (negative 

control) or dosed with 1000 mg/kg/day ethylene glycol diethyl ether (positive control). 

Analytical verification of doses or concentrations 

no data 
Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

no data 

Duration of treatment / exposure 

days 7-17 of gestation 

Frequency of treatment 

daily 

Duration of test 

From Day 7 of gestation to Day 5 of lactation. 

Doses / concentrations 

25, 150, 1000 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

10 female rats. 

Control animals 

other: sham dosed (negative control) or dosed with 1000 mg/kg/day ethylene glycol diethyl 

ether (positive control). 

Further details on study design 

Groups of 10 female rats were dosed by oral gavage with 25, 150 or 1000 mg/kg/day test 

material on days 7-17 of gestation. Additional groups of females were sham dosed (negative 

control) or dosed with 1000 mg/kg/day ethylene glycol diethyl ether (positive control). Animals 

were allowed to litter naturally, and any that did not deliver by day 25 of gestation were killed. 

Dams and surviving pups were killed on day 5 of lactation. 

Examinations 

Maternal examinations 

Body weights were recorded on days 1, 7 and 21 of gestation and on day 5 of lactation (or at 

termination for animals that did not reproduce). Food intake was recorded over days 1 to 7 and 

7 to 17 of gestation, day 17 of gestation to day 1 of lactation and days 1-5 of lactation. 

Ovaries and uterine content 

Uteri of all dams were examined for implantation sites. 

Fetal examinations 

The birth index [total number of pups born (live and dead) x 100/ number of implantation sites], 

live birth index (number of pups alive at day 1 of lactation/ total number of pups born x 100) 

and viability index (number of pups alive on day 5 of lactation/ number of pups alive on day 1 

of lactation x 100) were calculated for each litter and group. Litter weights were recorded on 

days 1 and 5 of lactation and the uteri of all dams were examined for implantation sites. Pups 

were not necropsied. 

Statistics 

Statistical analyses were not performed. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 1000 mg/kg bw/day 
Basis for effect 

level / Remarks 

1000 mg/kg bw was highest dose tested and showed no adverse effects. 

Endpoint NOAEL 

Effect type teratogenicity 

Effect level 1000 mg/kg bw/day 

Basis for effect level 

/ Remarks 

1000 mg/kg bw was highest dose tested and showed no adverse effects. 

Maternal toxic effects 

no effects 

Details on maternal toxic effects 

There was no effect of Brake Fluid DOT4 on maternal body weight of food intake. 

Embryotoxic / teratogenic effects 

no effects 

Details on embryotoxic / teratogenic effects 

Mean litter weights of low dose (25 mg/kg/day) animals were slightly lower than negative 

controls at birth (79 +/- 24 g vs. 90 +/- 23 g in sham control) and on day 5 of lactation (109 +/- 

29 g vs. 133 +/- 34 g in sham control). In contrast, mean litter weights of high dose animals 

were higher than negative controls at birth (97 +/- 10 g) and on day 5 of lactation (150 +/- 24 g). 

The authors stated that the reduction at 25 mg/kg/day could be related to slightly smaller litter 

sizes (the birth index was 85 +/- 15 vs. 95 +/- 7 in the sham control). Two rats in this group had 

a lower number of implant sites (8 and 6) than the others (ranged from 15-19), which led to a 

decrease in the number of pups delivered(5 in each of the animals vs. 13-18 in the others). 

Another low dose animal that had 16 implant sites only delivered 9 pups. The birth index of 

animals treated with 150 (94 +/- 6) or 1000 mg/kg/day test material (95 +/- 6) was similar to the 

sham control (95 +/- 7). There was no effect of treatment on the number of dead pups (4 in 

control vs. 1 in each treated group). There were no treatment-related necropsy findings. There 

was no effect of treatment with Brake Fluid DOT 4 of the duration of gestation, the number of 

females littering, the mean number of implant sites, or the live birth index or viability index. 

Based on these data, the authors concluded that 1000 mg/kg/day Brake Fluid DOT4 did not 

cause fetal growth retardation or embryolethality.

By contrast, the positive control animals lost weight from days 7 to 21 of gestation. All nine 

pregnant animals treated with ethylene glycol diethyl ether (EGDE) resorbed their litters. Most 

animals treated with EGDE had enlarged livers and/or spleens. 

Remarks on results including tables and figures 

It is not known whether the decreased mean litter weights or birth index at 25 mg/kg/day or the 

increased mean litter weights at 1000 mg/kg/day are significantly different from control, since statistical 

analyses were not performed. However, these findings do not appear to be related to treatment since 

they are not dose-dependent. Since the investigators concluded that 1000 mg/kg/day Brake Fluid DOT4 

did not cause fetal growth retardation or embryo or fetal lethality, the NOAEL for these effects is 1000 

mg/kg/day. The NOAEL listed under teratogenicity is the NOAEL for developmental toxicity. 

Overall remarks, attachments 

Overall remarks 
Reference substance: 3,6,9,12-tetraoxatetradecan-1-ol 

UUID ECB5-2734aded-8007-4016-8c23-63e6ef180819 

Dossier UUID 0 

Author European Commision/Joint Research Centre/European 

Chemicals Bureau 

Date 2007-05-10 05:00:00 EDT 

Remarks Created 

General information 

Reference substance name 3,6,9,12-tetraoxatetradecan-1-ol 

EC inventory 

EC number 227-090-6 CAS number 5650-20-4 

EC name 3,6,9,12-tetraoxatetradecan-1-ol 

Molecular formula C10H22O5 

Reference substance information 

CAS information 

CAS number 5650-20-4 

IUPAC name 

IUPAC name 3,6,9,12-tetraoxatetradecan-1-ol 

Synonyms 

Name 3,6,9,12-tetraoxatetradecan-1-ol 

Name 3,6,9,12-Tetraoxatetradecan-1-ol 

Name 3,6,9,12-Tetraoxatetradecan-1-ol 

 DSL Category: Organics

USEPA Category: Ethylene Glycol Ethers;Neutral Organics;Nonionic Surfactants 

Molecular and structural information 

Molecular formula C10H22O5 

Molecular weight range 222.2787 

SMILES notation CCOCCOCCOCCOCCO 

InChI InChI=1/C10H22O5/c1-2-12-5-6-14-9-10-15-8-7-13-4-3-11/h

11H,2-10H2,1H3 

Structural formula 
Legal entity: PCA Services, Inc. 

UUID IUC5-627340ec-79cf-4d47-86f0-902729c7a

dc2 

Dossier UUID 0 

Author rgerwe / (No legal entity) 

Date 2008-11-16 11:49:37 EST 

Remarks 

General information 

Legal entity name PCA Services, Inc. 

Identifiers 

Other IT system identifiers 

IT system LEO 

ID 8869 

Contact information 

Contact address 

Address 2704 Trail Wood Drive 

Postal code 27705 

Town Durham 

Region / State North Carolina 

Country United States of America 

Phone (919) 382-8787 

Fax (919) 382-8788 

E-mail r.gerwe2@verizon.net 

Web site www.pcaserve.com 
Contact persons 

Organisation PCA Services, Inc. 

Title President 

First name Roderick 

Last name Gerwe 

Phone (919) 382-8787 

Fax (919) 382-8788 

E-mail r.gerwe2@verizon.net 

Address 2704 Trail Wood Drive 

Postal code 27705 

Town Durham 

Region / State North Carolina 

Country United States of America 

From: Saved by Windows Internet Explorer 7 <Saved by Windows Internet Explorer 7>

Date: Fri, 3 Jul 2009 16:22:31 -0400

Subject: Substance: pentaethylene glycol butyl ether / 3,6,9,12,15,18-hexaoxaicosane / 

3,6,9,12,15,18-hexaoxaicosane / 23601-39-0 / PCA Services, Inc. / Durham / United States of 

America

Content-Type: multipart/related;

boundary="_005_7679806876737777756876717374697074697779796576797679686_";

type="multipart/alternative"

Thread-Topic: Substance: pentaethylene glycol butyl ether / 3,6,9,12,15,18-hexaoxaicosane / 

3,6,9,12,15,18-hexaoxaicosane / 23601-39-0 / PCA Services, Inc. / Durham / United States of 

America

Thread-Index: AcrBZmuh+PbFY/FoSxSSSWNxTSgrPw==

X-MS-Has-Attach: yes

X-MS-TNEF-Correlator:

MIME-Version: 1.0

Printing Date 2009-07-03 16:20:40 EDT 
Restriction of specific regulatory purposes 

 

Confidentiality 

 

Name pentaethylene glycol butyl ether 

Legal entity owner PCA Services, Inc. / Durham / United States of America 

Substance: pentaethylene glycol butyl ether 

UUID IUC5-8071b42b-3df0-48d4-a57e-7b8904e12227 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:23:45 EDT 

Remarks Created endpoint study record 4.11 Flash point 

0 Related Information 

0.1 Templates 

0.2 Categories 

0.3 Mixtures 

1 General Information 

1.1 Identification 

Substance identification 

Chemical name pentaethylene glycol butyl ether 

Legal entity PCA Services, Inc. / Durham / United States of America

Reference substance 

Reference substance 3,6,9,12,15,18-hexaoxaicosane / 3,6,9,12,15,18-hexaoxaicosane /

23601-39-0

 EC number EC name 

245-774-2 3,6,9,12,15,18-hexaoxaicosane 

CAS number CAS name 

23601-39-0 

IUPAC name 

3,6,9,12,15,18-hexaoxaicosane 

Type of substance 

Origin organic 

1.2 Composition 

1.3 Identifiers 

1.4 Analytical information 

1.5 Joint submission 

1.6 Sponsors 

1.7 Suppliers 

1.8 Recipients 

1.9 Product and process oriented research and development 

2 Classification and Labelling 

2.1 GHS 
2.2 DSD - DPD 

3 Manufacture, use and exposure 

3.1 Technological process 

3.2 Estimated quantities 

3.3 Sites 

3.4 Form in the supply chain 

3.5 Identified uses and exposure scenarios 

3.6 Uses advised against 

3.7 Waste from production and use 

3.8 Exposure estimates 

3.9 Biocidal information 

3.10 Application for authorisation of uses 

4 Physical and chemical properties 

4.1 Appearance/physical state/colour 

Appearance/physical state/colour.001 

UUID IUC5-9e513793-d036-459f-92e7-fb61e065feac 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:01:37 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

other: visual observation and specification 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's material safety data sheet. Pentaethylene glycol 

butyl ether is available commercially only as a component in automotive brake 

and clutch fluid formulations. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

Available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 
Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS No. 

106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene glycol 

monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS No. 

143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 

CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3.. 

Results and discussion 

Physical state at 20oC and 1013 hPa 

liquid 

Colour 

clear amber 

Odour 

other: ether like 

4.2 Melting point/freezing point 

Melting point/freezing point.001 

UUID IUC5-29924571-7d67-412a-a861-ec607567bb82 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:10:05 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's data sheet. Pentaethylene glycol butyl ether is 

available commercially only as a component in automotive brake and clutch 

fluid formulations. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 
Title Pennzoil product data sheet for Pennzoil brake fluid 

Bibliograp

hic source 

available online at 

http://www.pennzoil.com.au/downloads/tds/Pennzoil_Brake_Fluid_Dot_4.pdf 

Testing 

laboratory 

 Repo

rt no. 

 

Owner 

company 

 

Company 

study no. 

 Repo

rt 

date 

 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier Common name 

Identity Pennzoil (trademark) Brake Fluid (DOT 4) 

Results and discussions 

Melting / freezing point 

Melt./Freez. pt. <= -40 °C 

Atm. pressure 

Decomposition no 

Decomp. temp. 

Sublimation no 

Subl. temp. 

Remarks 

4.3 Boiling point 

Boiling point.001 

UUID IUC5-6492d754-c5c8-4598-b5c2-daa652359436 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:35:24 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's product data sheet. Pentaethylene glycol butyl 

ether is available commercially only as a component in automotive brake and 
clutch fluid. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Pennzoil brake fluid DOT 4 data sheet 

Bibliographic 

source 

Available online at 

http://www.pennzoil.com/documents/Super%20HD%20Dot%203and4%20Bra

ke%20Fluid.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference 

type 

company data 

Author Year 

Title Pennzoil Technical Data Sheet for Pennzoil (trademark) Brake Fluid (DOT 4) 

Bibliograp

hic source 

available online at 

http://www.pennzoil.com.au/downloads/tds/Pennzoil_Brake_Fluid_Dot_4.pdf 

Testing 

laboratory 

 Repo

rt no. 

 

Owner 

company 

 

Company 

study no. 

 Repo

rt 

date 

 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Pennzoil DOT 4 and DOT 3 Motor Vehicle Brake Fluid 

Results and discussions 

Boiling point 

Boiling pt. >= 270 °C 

Atm. pressure 1013 hPa 

Decomposition no 

Decomp. temp. 

Remarks Equilibrium Reflux Boiling Point 

4.6 Vapour pressure 
Vapour pressure.001 

UUID IUC5-b6325ec7-8a6d-436a-aaf7-4171008d3210 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:23:33 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's safety data sheet. Pentaethylene glycol butyl 

ether is available commercially only as a component in automotive brake and 

clutch fluid formulations. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

Available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS No. 

106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene glycol 

monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS No. 

143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 
CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3.. 

Results and discussions 

Vapour pressure 

< 0.005 hPa at 20 °C 

Remarks 

4.7 Partition coefficient 

Partition coefficient.001 

UUID IUC5-71252617-a792-4d34-8c84-dd8adbfb81fa 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-11 15:58:06 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized, approved computer model program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN KOWWIN Program (v.167) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-08 

Materials and methods 

Partition coefficient type 

octanol-water 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 
Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Details on methods 

EPIWIN KOWWIN Model input was CAS No. 23601-39-0, 

Results and discussions 

Partition coefficient 

Type log Pow 

Partition coefficient ca. -0.3228 

Temp. 

pH 

4.8 Water solubility 

Water solubility.001 

UUID IUC5-462550a2-44ef-40e1-a53c-ceb370c8fdb3 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:23:02 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's safety data sheet. Pentaethylene glycol butyl 

ether is available commercially only as a component in automotive brake and 

clutch fluids. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

Available online at 

http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Materials and methods 
Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS No. 

106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene glycol 

monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS No. 

143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 

CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3.. 

Results and discussions 

Water solubility 

> 1000000 mg/L 

Temp. 

pH 

Details on results 

miscible in water 

4.11 Flash point 

Flash point.001 

UUID IUC5-3a8b17bf-6d63-462c-9383-54682284758b 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 11:27:09 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study ( ) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's safety data sheet. Pentaethylene glycol butyl 

ether is available commercially only as a component in automotive brake and 

clutch fluid formulations. 

Data source 

Reference 

Reference type company data 

Author Year 

Title Safety Data Sheet for Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic Available online at 
source http://www.enerquip.com.au/brochures/shell/Shell%20PDFs/Brake%20&%20cl

utch%20fluid%20Dot%204%20super.pdf 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report date 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier Common name 

Identity Shell Brake and Clutch Fluid DOT 4 Super 

Details on test material 

Mixture typically containing 30-50% triethyleneglycol monomethyl ether borate ester (CAS No. 

106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% triethylene glycol 

monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl ether (CAS No. 

143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 2-10% 

tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% minor additives. Borate 

esters have the general molecular formula of B(OR)3, where R = glycol ether, e.g., -O(CH2 

CH2O)nCH3.or -O(CH2 CH2O)n CH2CH2CH2CH3.. 

Results and discussions 

Flash point 

ca. 155 °C 

at 

5 Environmental fate and pathways 

5.1 Stability 

5.1.1 Phototransformation in air 

Phototransformation in air.001 

UUID IUC5-49e2caa6-bd40-4aa5-bc7f-cc8c64c91475 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 12:13:11 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for Data were obtained using a recognized, approved computer model program. 
reliability 

Data source 

Reference 

Reference type other: computer model program output. 

Author Year 

Title EPIWIN V4.00 Suite AOPWIN (v1.92) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-11 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 

Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Study design 

Estimation method (if used) 

PHOTOCHEMICAL REACTION WITH OH RADICALS

- Concentration of OH radicals: 1.5E6 OH/cm3

- Degradation rate constant: 82.4248 E-12 cm3/molecule-sec

- Computer programme: EPIWIN V4.00 Suite AOPWIN (v1.92) 

- Other: Half-life 0.130 day 1.557 hours (12-hour day)

Light source 

sunlight 

5.2 Biodegradation 

5.2.1 Biodegradation in water: screening tests 

Biodegradation in water: Waggy Union Carbide Screening TGBE 1987.001 

UUID IUC5-4eca5cef-8d6f-4f38-aa1b-e45f5c219362 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:01:49 EST 

Remarks 
 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 

Data source 

Reference 

Reference 

type 

study report 

Author Waggy GT. Year 1987 

Title Glycol ethers: Summary of available ecological fate and effects data. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

File Number 35931 Report 

date 

1987-11-19 

Materials and methods 

Test guideline 

Qualifier according to 

Guidelin

e 

other guideline: "Standard Methods for the Examination of Water and Wastewater, 

16th Ed., USPHA, Washington, D. C., 1985) 

Deviatio

ns 

 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity Triethylene glycol butyl ether 
Details on test material 

No details. 

Study design 

Oxygen conditions 

aerobic 

Inoculum or test system 

sewage, domestic, non-adapted 

Details on inoculum 

no data 

Duration of test (contact time) 

20 d 

Details on analytical methods 

No data 

Details on study design 

A modified version of the biochemical oxygen demand (BOD) method published in "Standard 

Methods for the Examination of Water and Wastewater," 16th edition, Am. Public Health 

Association, 1985 was used. Nonacclimated domestic sewage organisms were used as seed in 

the test. The test period was extended to 20 days. Reaeration (if needed) wasaccomplished by 

dividing the BOD bottle contents between 2 BOD bottles, sealing, shaking twenty times, 

returning contents to the original BOD bottle, recording the oxygen level, resealing, and 

returning the BOD bottle to the incubator. A discussion of these modifications appears in Price 

et al., "Brine shrimp bioassay and seawater BOD of petrochemicals", J. Water Poll. Control 

Fed., Jan. 1974. 

Any other information on materials and methods incl. tables 

Biological oxygen demand (BOD) of triethylene glycol monomethyl ether (TGME; CAS No. 112-35-6) 

and triethylene glycol monoethyl ether (CAS No. 112-50-5) were also tested in this study. The 20 day 

BOD of both of these chemicals (71%) was greater than that of triethylene glycol monobutyl ether. The 

concentration of test material and bacteria were not listed in the report.

Results and discussions 

% Degradation of test substance 

%Degr. 47 

St. dev. 

Parameter 

Sampling time 20 d 

Remarks 

Details on results 

The calculated theoretical oxygen demand of TGBE was 2.10 mg/mg. After 10 and 20 days of 

incubation, the percent biooxidation was 5, and 47%. 

Biodegradation in water: screening tests.002 

UUID IUC5-2eb7caf5-b30e-42a2-9c0b-19fc46a2911f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:19:32 EST 
Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

 Study 

period 

1989 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability 

code) came from a previous IUCLID data set produced by the European 

Chemicals Bureau. 

Data source 

Reference 

Reference type company data 

Author Year 1989 

Title Hoechst AG. 1989. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company Hoechst AG 

Company study 

no. 

Unpublished Study (Werk Gendorf; p 07/89). Report date 

Materials and methods 

Test type 

inherent biodegradability 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 302 B (Inherent biodegradability: Zahn-Wellens/EMPA Test) 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 

Identifier Common name 

Identity tetraethylene glycol monomethyl ether 
Study design 

Oxygen conditions 

aerobic 

Inoculum or test system 

sewage, industrial (adaptation not specified) 

Details on inoculum 

industrial activated sludge (Gendorf, Germany sewage treatment plant) 

Duration of test (contact time) 

7 d 

Initial test substance concentration 

Initial conc. 573 mg/L 

Based on test mat. 

Details on analytical methods 

no data 

Any other information on materials and methods incl. tables 

CSB = elimination (time sequence values versus initial concentration value): Elimination 

through non-biological processes = ca. 10% 

Results and discussions 

% Degradation of test substance 

%Degr. 99 

St. dev. 

Parameter 

Sampling time 8 d 

Remarks Includes both biological and non-biological degradation. 

Details on results 

3 hour(s) = 10 %; 1 day = 19%; 3 days = 29%; 5 days = 52%; 7 days = 91% 

Biodegradation in water: screening tests.003 

UUID IUC5-c89be75b-2b44-41fc-bb09-dfa6627bf72a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:24:38 EST 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

20

00 

Reliablility 4 (not assignable) 

Rationale for Limited data from a secondary source 
reliability 

Data source 

Reference 

Reference 

type 

secondary source 

Author Year 2000 

Title European Chemicals Bureau Dossier for Tetraethylene glycol butyl ether CAS No. 

1559-34-8 

Bibliograph

ic source 

Shell Nederland Chemie B.V. Rotterdam EUROPEAN COMMISSION - European 

Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test type 

other: BOD 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 1559-34-8 

Identifier EC number 

Identity 216-322-1 

Identifier Common name 

Identity Tetraethylene glycol butyl ether 

Study design 

Oxygen conditions 

no data 

Inoculum or test system 

no data 

Details on inoculum 

no data 

Results and discussions 

Details on results 

ThOD= 2.05 g O2/g substance. 

5.3 Bioaccumulation 

5.3.1 Bioaccumulation: aquatic / sediment 

Bioaccumulation: aquatic / sediment.001 
UUID IUC5-917fe733-6309-4cca-b850-852e19b511da 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-13 17:27:18 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized computer model program. 

Data source 

Reference 

Reference type other: Computer model program output 

Author Year 2009 

Title EPIWIN (v4.00) BCFBAF (v3.00) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-11 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 

Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Test conditions 

Details on estimation of bioconcentration 

BASIS INFORMATION

- Measured/calculated logPow: calculated, -0.32
BASIS FOR CALCULATION OF BCF

- Estimation software: EPIWIN V4.00 Suite BCFBAF (v3.00) 

- Result based on calculated log Pow of: -0.32 

Results and discussions 

Bioaccumulation factor 

Conc. in environment / dose 

Type other: log BCF 

Value ca. 0.5 

Basis 

Time of plateau 

Calculation basis 

Remarks 

5.4 Transport and distribution 

5.4.2 Henry's Law constant 

Henry's Law constant.001 

UUID IUC5-d665a811-fec0-4356-ae90-07a081ec61a6 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-11 16:25:33 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized, approved computer model program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN v4.00 HENRYWIN (v3.20) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-11 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 
yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 

Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Details on methods 

Input was CAS No. 023601-39-0 to the EPIWIN HENRYWIN program. 

Results and discussions 

Henry's Law constant H 

H ca. 0 atm m3/mol 

Temp. (°C) 

Atm. press. 

5.4.3 Distribution modelling 

Distribution modelling.001 

UUID IUC5-70b780d7-4f83-4484-af16-ac24ee681e56 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 12:21:52 EDT 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type estimated by calculation Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized, approved computer model program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN V4.00 Fugacity 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study Report date 2009-06-11 
no. 

Materials and methods 

Calculation programme 

EPIWIN V4.00 Fugacity 

Release year 

2009 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 

Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Test substance input data 

- Molar mass: 294.39

- Water solubility: 1,000,000 mg/L

- log Pow: -.323

- Melting point: -40 deg C

- Reaction half-life estimates for

- Air: 3.12 hours

- Water: 900 hours

- Soil: 1,800 hours

- Sediment: 8,100 hours

Results and discussions 

Percent distribution in media 

Air (%) 

0 

Water (%) 

35 

Soil (%) 

64.9 

Sediment (%) 

0.08 

6 Ecotoxicological Information 

6.1 Aquatic toxicity 

6.1.1 Short-term toxicity to fish 

Short-term toxicity to fish-Wagy TGBE 1974.001 

UUID IUC5-bcc78767-6824-4cb8-b3ee-a711b6d75d4e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 
States of America 

Date 2009-02-12 08:30:40 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

74 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 

Data source 

Reference 

Reference 

type 

 

Author Waggy GT, Payne JR. Year 1974 

Title Environmental impact product analysis: Acute aquatic toxicity testing. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Union Carbide Corporation 

Company 

study no. 

File number 19133 Report 

date 

1974-01-25 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: as described in "Standard Methods for the Examination of Water 

and Wastewater, 13th Ed., 1971. 

Deviation

s 

 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 
Identifier Common name 

Identity Triethylene glycol butyl ether 

Details on test material 

No details 

Analytical monitoring 

no data 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Test organisms 

Test organisms (species) 

Pimephales promelas 

Details on test organisms 

Gdn fish per concentration 

Study design 

Test type 

static 

Water media type 

no data 

Limit test 

no 

Total exposure duration 

96 h Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

total hardness from 30 to 60 mg/l 

Test temperature 

71 to 76 degrees F 

pH 

7.2 to 7.6 

Dissolved oxygen 

7.5 to 9.0 mg/l. 

Salinity 

total alkalinity from 30-40 mg/l 

Nominal and measured concentrations 

concentrations ranging from 10 to 10000 mg/l 

Details on test conditions 

An initial range-finding test was conducted using 2 fish exposed to concentrations ranging from 

10 to 10000 mg/l. Definitive tests were performed with 10 fish (2.5 to 5 cm) per test 

concentration in vessels containing 18.5 liters of dilution water under minimal controlled 
aeration (after the first four hours of the test). Fish were exposed for up to 96 hours. The 

temperature of the water ranged from 71 to 76 degrees F, the pH from 7.2 to 7.6, the total 

alkalinity from 30-40 mg/l, the total hardness from 30 to 60 mg/l, and the dissolved oxygen 

from 7.5 to 9.0 mg/l. 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. 2400 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Details on results 

The 24-hr, 48-hr and 96-hr LC50 values were 2400 mg/l. 

Any other information on results incl. tables 

Toxicity of triethylene glycol monomethyl ether (CAS No. 112-35-6) and of triethylene glycol monoethyl 

ether (CAS No. 112-50-5) were also tested in this study. LC50 values for both chemicals were > 10000 

mg/l.

Short-term toxicity to fish-Konemann TGBE 1981.002 

UUID IUC5-a32a87a6-bee4-4a70-9571-2528d05fdf5a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:33:31 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

81 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 

Data source 

Reference 

Reference 

type 

publication 

Author Konemann H. Year 1981 

Title Quantitative structure-activity relationships in fish toxicity studies. Part 1. 
Relationship for 50 industrial pollutants. 

Bibliograp

hic source 

Toxicology 19:209-221. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier no guideline followed 

Guideline 

Deviations 

Principles of method if other than guideline 

Typical acute aquatic toxicity method. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Vehicle 

no 

Test organisms 

Test organisms (species) 

Poecilia reticulata 

Details on test organisms 

Two to three month old guppies (8 per group) 

Study design 

Test type 

semi-static 

Water media type 

freshwater 
Limit test 

no 

Total exposure duration 

7 d Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

25 mg/l as CaCO3 

Test temperature 

22 +/- 1 degrees C 

pH 

No data 

Dissolved oxygen 

Oxygen content remained above 5 mg/l 

Salinity 

no data 

Nominal and measured concentrations 

test concentrations increased geometrically in ratios of 3.2 

Details on test conditions 

Two to three month old guppies (8 per group) were exposed to several concentrations of test 

material in 1.5 liter vessels for 7 days. Each vessel was filled with 1 liter of standard water 

(hardness 25 mg/l as CaCO3) and covered with glass. A stock solution of test material was 

made by dissolving it in either acetone or 2-propanol (not specified). Various volumes of stock 

solution were added to the test vessels to increase test concentrations geometrically (in 

increasing ratios of 3.2). Test solution was renewed daily. Guppies were fed 0.5 hours before 

each renewal with commercial fish food. Oxygen content, water temperature, and viability 

offish were monitored. Oxygen content remained above 5 mg/l, and temperature was 22 +/- 1 

degrees C. 

Any other information on materials and methods incl. tables 

LC50's were calculated according to the method of Litchfield and Wilcoxon (J Pharm Exp Ther 96:99, 

1949), or by estimation from a log-probit-plot (if concentration-death relationship was too steep).

Results and discussions 

Effect concentrations 

Duration 7 d 

Endpoint LC50 

Effect conc. 197 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Details on results 

The molecular weight of the test material (206 g/mole) was used to convert the log LC50 (in 

micromoles/liter) to the LC50 (in mg/l).
The log of the LC50 was calculated to be 2.98 micromoles/l. 

Short-term toxicity to fish.003 

UUID IUC5-ccf6f1ee-b67f-46d4-99b1-fc611ba2bcb1 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:35:28 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau. 

Data source 

Reference 

Reference 

type 

secondary source 

Author Year 1988 

Title Unpublished study 

Bibliogra

phic 

source 

Original reference was not available. Information came from a previous IUCLID 

data set produced by the European Chemicals Bureau. 

Testing 

laboratory 

 Repor

t no. 

 

Owner 

company 

Hoechst AG. 

Company 

study no. 

88.1713 Repor

t date 

 

Reference 

type 

 

Author Year 

Title 

Bibliograp

hic source 

Hoechst AG Frankfurt/MainClariant GmbH Frankfurt/MainEUROPEAN 

COMMISSION - European Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 
Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 203 (Fish, Acute Toxicity Test) 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 

Identifier Common name 

Identity tetraethylene glycol monomethyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Brachydanio rerio (new name: Danio rerio) 

Details on test organisms 

no data 

Study design 

Test type 

static 

Water media type 

no data 

Total exposure duration 
48 h Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Short-term toxicity to fish.004 

UUID IUC5-b5fab8ac-ed8a-4786-93e1-8dda0122cfe7 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:40:30 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

 Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for Original reference was not available. Information (including the reliability code) 
reliability came from a previous IUCLID data set produced by the European Chemicals 

Bureau. 

Data source 

Reference 

Reference 

type 

secondary source 

Author Year 1988 

Title 

Bibliographic 

source 

Hoechst AG Frankfurt/Main and European Chemicals Bureau 2000 IUCLID 

Testing 

laboratory 

 Report no. 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Unpublished Study (88.1713). Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 203 (Fish, Acute Toxicity Test) 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 

Identifier Common name 

Identity Tetraethylene glycol methyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 
no data 

Test organisms 

Test organisms (species) 

Brachydanio rerio (new name: Danio rerio) 

Details on test organisms 

no data 

Study design 

Test type 

static 

Water media type 

no data 

Total exposure duration 

96 h Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Short-term toxicity to fish-BASF TGBE 1989.005 

UUID IUC5-a8fb3d6f-8c5d-4c5d-b2b7-a8b454cabe0c 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:41:39 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

89 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not high. 

Data source 

Reference 

Reference type study report 

Author Year 1989 

Title 

Bibliographic 

source 

 

Testing laboratory Department of Toxicology Report no. 

Owner company BASF 

Company study no. Project No. 10F0573/885281 Report date 1989-04-26 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: DIN 38 412 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity Triethylene glycol butyl ether 

Details on test material 

Purity was 87.2% 
Details on properties of test surrogate or analogue material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Idus idus 

Details on test organisms 

The average length and weight of fish were 6.7 cm and 2.8 g, respectively. 

Study design 

Test type 

static 

Total exposure duration 

96 h Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

2.5 mmol/l 

Test temperature 

20 degrees C 

pH 

8.0 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

0, 1000, 2150, 4640 or 10000 mg/l test material 

Details on test conditions 

Ten fish/group were exposed to 0, 1000, 2150, 4640 or 10000 mg/l test material in glass 

aquariums (30 cm x 22 cm x 24 cm) containing 10 liters of water (2.8 g fish/liter water) after a 3 

day acclimation period. Food was withdrawn 1 day before and during exposure. The average 

length and weight of fish were 6.7 cm and 2.8 g, respectively. The water had a total hardness, 

acid capacity, ratio Ca/Mg, ratio Na/K, pH and temperature of 2.5 mmol/l, 0.8 mmol/l, 4:1, 

10:1, 8.0, and 20 degrees C. Water was continuously aerated with oil-free air. 

Reference substance (positive control) 
no data 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint other: LD50 

Effect conc. > 2150 — < 4640 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) 

Details on results 

The 24-hr, 48-hr and 96-hr LD50 values were > 2150 and < 4640 mg/l. All fish exposed to 4640 

mg/l died within 4 hours. No deaths were observed at 2150 mg/l. Apathy and tumbling were 

noted at 2150 mg/l. No symptoms of toxicity were observed at 1000 mg/l. 

Short-term toxicity to fish.006 

UUID IUC5-064a7437-761b-4cc5-8dfb-e3a47e59b115 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:42:25 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original data from which MSDS was written were not available. 

Data source 

Reference 

Reference 

type 

 

Author Year 

Title 

Bibliograph

ic source 

Dow MSDS for CARBOWAX methoxypolyethylene glycol 350 (CAS No. 

9004-74-4), Number 870, Dated 7/5/2000. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Number 870 Report 

date 

2000-07-

05 

Materials and methods 
Test guideline 

Qualifier 

Guideline other guideline: no data on guideline 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier IUPAC name 

Identity Carbowax MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Analytical monitoring 

no data 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no data 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

other: fathead minnow 

Details on test organisms 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

96 h Remarks 

Post exposure observation period 

no data 
Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no datano data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect no data 

Remarks (e.g. 95% CL) 

6.1.3 Short-term toxicity to aquatic invertebrates 

Short-term toxicity to aquatic invertebrates-Waggy TGBE 1987.001 

UUID IUC5-bdd81a61-161c-4e79-bcc6-8fffe18a1102 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:49:58 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 
Data source 

Reference 

Reference 

type 

study report 

Author Waggy GT. Year 

Title Glycol ethers: Summary of available ecological fate and effects data. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

File Number 35931 Report 

date 

1987-11-19 

Materials and methods 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: Test practices followed those recommended by EPA and ASTM. 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6). 

Identifier EC number 

Identity 245-774-2 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 
Daphnia magna 

Details on test organisms 

Daphnia magna stocks were originally obtained from the EPA laboratory at Duluth, MN. They 

were maintained at 20-22 degrees C in a series of 600 ml beakers filled with Kanawha River 

water obtained from the South Side Boat Ramp (Charleston, SC). Daphnia were fed three times 

a week with a laboratory-prepared food consisting of trout food, yeast and alfalfa powder. 

Daphnia used in the test were offspring of 20-50 gravid females isolated for 24 hours. 

Study design 

Test type 

static 

Water media type 

freshwater 

Limit test 

no 

Total exposure duration 

48 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

55 mg/l as CaCO3 

Test temperature 

20-22 deg C 

pH 

6.7 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

A series of from 5-10 equidistant concentrations based on results of fish toxicity studies (plus 

control) were tested 

Details on test conditions 

Tests were conducted in 250 ml beakers containing 100 ml of test solution (in Kanawha River 

water) and 5 Daphnia (less than 24 hours old). Tests were run in duplicate. Dissolved oxygen 

and pH were determined initially and at 48 hours for all test solutions. Total hardness, 

alkalinity, pH and conductivity of the test and holding water were 55 mg/l as CaCO3, 36 mg/l as 

CaCO3, 6.7, and 250 micromhos/cm. Mortalities were recorded at 24 and 48 hours.

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint LC50 

Effect conc. 2210 mg/L 

Nominal/Measured nominal 
Conc. based on test mat. Basis for effect mortality 

Remarks (e.g. 95% CL) 

Remarks on results including tables and figures 

Toxicity of triethylene glycol monomethyl ether (CAS No. 112-35-6) and of triethylene glycol 

monoethyl ether (CAS No. 112-50-5) also were tested in this study. LC50 values for both 

chemicals were > 10000 mg/l. 

Short-term toxicity to aquatic invertebrates.002 

UUID IUC5-4cd42ee1-3e42-4d80-9ff5-7bc8a28ef61c 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:52:52 EST 

Remarks 

 

Administrative Data 

Purpose flag weight of evidence (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Study data were available only from a secondary source 

Data source 

Reference 

Reference 

type 

company data 

Author Year 2000 

Title Dow MSDS for CARBOWAX methoxypolyethylene glycol 350 (CAS No. 

9004-74-4), 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Number 870 Report 

date 

2000-07-05 

Materials and methods 

Principles of method if other than guideline 

No data on guideline followed. Study probably conducted by typical method. 

GLP compliance 

no data 

Test materials 
Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowas MGEP-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Analytical monitoring 

no data 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Daphnia magna 

Details on test organisms 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

48 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 
no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Any other information on materials and methods incl. tables 

no data 

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint LC50 

Effect conc. > 10000 mg/L 

Nominal/Measured no data 

Conc. based on no data Basis for effect 

Remarks (e.g. 95% CL) 

6.1.5 Toxicity to aquatic algae and cyanobacteria 

Toxicity to aquatic algae and cyanobacteria-BASF TGBE 1989.001 

UUID IUC5-4a81a83b-81b1-476b-97bc-c7d5793e0f6e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 08:59:44 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

89 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Test material purity is unknown. Details about study conduct are lacking. 

Data source 

Reference 

Reference type study report 
Author Year 1989 

Title Algentest for Butyltriglykol 

Bibliographic 

source 

 

Testing laboratory Report no. 

Owner company BASF AG 

Company study no. 2/1022/88/t0 Report date 1989-09-25 

Materials and methods 

Principles of method if other than guideline 

No guideline referenced. Study was conducted according to typical procedure for acute toxicity 

to algae. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity Triethylene glycol butyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Test organisms 

Test organisms (species) 

Scenedesmus subspicatus (new name: Desmodesmus subspicatus) 

Details on test organisms 

A SAG 86.81 culture of Scenedesmus subspicatus (10,000 cells/ml) was maintained in OECD 

medium at 20 degrees C. 

Study design 

Test type 

static 

Water media type 

no data 

Limit test 

no 

Total exposure duration 

72 h 

Remarks 

Test conditions 
Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

0 (control), 7.812, 15.625, 31.25, 62.5, 125, 250 or 500 mg/l test material in quadruplicate. 

Details on test conditions 

Ten ml of cells in suspension was treated with 0 (control), 7.812, 15.625, 31.25, 62.5, 125, 250 

or 500 mg/l test material in quadruplicate. Fluorescence of vials containing treated cells was 

determined 0, 24, 48 and 72 hours after treatment in a fluorimeter with a gain setting of 1. 

Fluorescence of 2 blank vials containing test material (at each concentration) and medium 

without cells was subtracted from values obtained for test vials. The values for the four tests 

were averaged and a standard deviation was calculated. The average fluorescence value of each 

concentration was presented as a percentage of control values. 

Results and discussions 

Effect concentrations 

Duration 72 h 

Endpoint EC50 

Effect conc. > 500 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 24 h 

Endpoint EC20 

Effect conc. 235.7 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 48 h 

Endpoint EC20 

Effect conc. 235.4 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 
Duration 72 h 

Endpoint EC20 

Effect conc. 267.1 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC90 

Effect conc. 500 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Details on results 

The EC20 value at 24, 48, and 72 hours was 235.7, 235.4, and 267.1 mg/l. The EC50 value was 

greater than the highest concentration tested (500 mg/l). At time 0, fluorescence values ranged 

from 94.37 % of control for cells treated with 7.812 and 31/25 mg/l to 103.09 % of control for 

cells treated with 500 mg/l. The fluorescence values for cells treated with all concentrations 

except 125 (86.08%) and 250 mg/l (79.21%) were greater than 90% at 24 hours. At 48 hours, 

cells treated with 250 or 500 mg/l began to exhibit slightly lower fluorescence values than 

control. At 72 hours, values for cells treated with 250 or 500 mg/l were 80.3% and 75.91% of 

control, respectively. Most values for the 4 replicates at each concentration varied by < = 5%. 

However, at 48 hours, variance of values for concentrations greater than or equal to 250 mg/l 

ranged from 5-10%. The EC90 value = 500 mg/L. 

Toxicity to aquatic algae and cyanobacteria.001 

UUID IUC5-a5ab8123-81cc-479c-bfc9-95e2302027ee 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 16:52:11 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1989 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau 

Data source 

Reference 
Reference type company data 

Author Year 1989 

Title Algentest for Methyltriglykol 

Bibliographic 

source 

 

Testing laboratory Report no. 2/1017/88/t72 

Owner company BASF AG 

Company study no. Report date 1990-03-09 

Materials and methods 

Principles of method if other than guideline 

Typical acute aquatic toxicity procedure for algae. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity Triethylene Glycol Methyl Ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on analytical methods 

no data 

Vehicle 

no data 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

Scenedesmus subspicatus (new name: Desmodesmus subspicatus) 

Details on test organisms 

no data 

Study design 

Test type 

no data 

Water media type 

no data 
Total exposure duration 

72 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no datano data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 72 h 

Endpoint EC20 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC50 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC90 

Effect conc. > 500 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

6.1.7 Toxicity to microorganisms 
Toxicity to microorganisms-Waggy TGBE 1987.001 

UUID IUC5-fe3e0213-d14d-4407-9024-b69c5d4f5e0d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:01:22 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 

Data source 

Reference 

Reference 

type 

study report 

Author Waggy GT. Year 1987 

Title Glycol ethers: Summary of available ecological fate and effects data. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

File Number 35931 Report 

date 

1987-11-19 

Materials and methods 

Principles of method if other than guideline 

Typical method for acute toxictiy to microorganisms. Details of the test are published in: Alsop 

et al., "Bacterial Growth Inhibition Tests", J. Water Pollution Control Federation, Vol 52: No. 

10, October, 1980. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 
Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity Triethylene glycol butyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

other: "sewer microorganisms" 

Details on inoculum 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Limit test 

no 

Total exposure duration 

16 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

23 degrees C 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 
Nominal and measured concentrations 

no data 

Details on test conditions 

Selected concentrations (not listed) were incubated for 16 hours at 23 degrees C on a shaker 

table in the presence of nutrients, buffer, growth substrate, and sewer-microorganisms. Toxicity 

was indicated when the resulting turbidity was at (or less than) 50% of the control (IC50). 

Details of the test are published in: Alsop et al., "Bacterial Growth Inhibition Tests", J. Water 

Pollution Control Federation, Vol 52: No. 10, October, 1980. 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 16 h 

Endpoint IC50 

Effect conc. > 10000 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth inhibition 

Remarks (e.g. 95% CL) 

Details on results 

no data 

Remarks on results including tables and figures 

Toxicity of triethylene glycol monomethyl ether (TGME, CAS No. 112-35-6) and of triethylene glycol 

monoethyl ether (TGEE, CAS No. 112-50-5) were also tested in this study. The LD50 values for TGME 

and TGEE were > 5000 mg/l and > 10000 mg/l, respectively.

Toxicity to microorganisms.002 

UUID IUC5-f5b68256-a69b-4afe-9364-dd59396f8fd5 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:02:18 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau 
Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title Unpublished Stud 

Bibliographi

c source 

Hoechst AG Frankfurt/Main EUROPEAN COMMISSION- European Chemicals 

Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Werk Gendorf; P 07/89 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 209 (Activated Sludge, Respiration Inhibition Test) 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 

Identifier Common name 

Identity Tetraethylene glycol methyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 
Test organisms (species) 

activated sludge 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

3 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 

no data 

Results and discussions 

Effect concentrations 

Duration 3 h 

Endpoint EC0 

Effect conc. > 12500 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect respiration rate 

Remarks (e.g. 95% CL) 

Toxicity to microorganisms.003 

UUID IUC5-e4be1fc1-a0ae-4110-a0c1-7dfeecafc2ee 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:03:33 EST 
Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title 

Bibliographic 

source 

2000 IUCLID data set produced by the European Chemicals Bureau. 

Testing 

laboratory 

 Report no. 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Unpublished Study (Werk Gendorf; P 07/89). Report 

date 

 

Materials and methods 

Test guideline 

Qualifie

r 

according to 

Guideli

ne 

other guideline: "ETAD Fermentation tube method "Determination of damage to 

effluent bacteria by the Fermentation Tube Method" 

Deviatio

ns 

 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 
Identifier IUPAC name 

Identity tetraethylene glycol monomethyl ether 

Details on test material 

no data 

Analytical monitoring 

no 

Details on sampling 

no data 

Details on analytical methods 

no data 

Vehicle 

no 

Details on test solutions 

no data 

Test organisms 

Test organisms (species) 

anaerobic bacteria from a domestic water treatment plant 

Details on inoculum 

no data 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

24 h 

Remarks 

Post exposure observation period 

no data 

Test conditions 

Hardness 

no data 

Test temperature 

no data 

pH 

no data 

Dissolved oxygen 

no data 

Salinity 

no data 

Nominal and measured concentrations 

no data 

Details on test conditions 

no data 

Reference substance (positive control) 
no data 

Results and discussions 

Effect concentrations 

Duration 24 h 

Endpoint other: SG 

Effect conc. ca. 3000 mg/L 

Nominal/Measured no data 

Conc. based on no data 

Basis for effect 

Remarks (e.g. 95% CL) 

7 Toxicological information 

7.1 Toxicokinetics, metabolism and distribution 

7.1.2 Dermal absorption 

Dermal absorption-Ward & Scott TGBE 1986.001 

UUID IUC5-ef1f9a61-dfcd-43a4-8fa1-8ed33080f2ff 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:06:35 EST 

Remarks 

 

Administrative Data 

Purpose 

flag 

supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

198

6 

Reliablility 2 (reliable with restrictions) 

Rationale 

for 

reliability 

Well designed and conducted study, comparing in vitro human skin absorption 

rates for triethylene glycol butyl ether and three analogous glycol ethers. 

However, no data were provided for radiolabeling test material and documenting 

the analysis. 

Data source 

Reference 

Reference 

type 

 

Author Ward RJ, Scott RC. Year 1986 

Title Triethylene glycol ethers: Absorption through human epidermis in vitro 

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

CTL/P/160

0 

Owner 

company 

. Imperial Chemical Industries 

Company Report 1986-10-31 
study no. date 

Materials and methods 

Type of method 

in vitro 

Principles of method if other than guideline 

Typical in vitro dermal absorption rate determination procedure was followed. 

GLP compliance 

no data 

Test materials 

Radiolabelling 

no data 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity POLYSOLV-TB, triethylene glycol monobutyl ether 

Details on test material 

Purity of test material (POLYSOLV-TB, triethylene glycol monobutyl ether) was 96.91%. 

Test animals 

Species 

human 

Sex 

no data 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Duration of exposure 

12 hours 

No. of animals per group 

Not applicable 

Details on in vitro test system (if applicable) 

Human abdominal whole skin (2.54 cmE2) was mounted in a glass diffusion apparatus (at 30 

+/- 1 degree C) and the diffusion of triethylene glycol monobutyl ether was monitored during a 

12-hr period using gas chromatography (n=6). The integrity of the epidermal membranes was 

first assessed by measuring permeability of membranes to tritiated water. Epidermal membranes 

displaying permeability constants greater than 1.5 x 10E-3 cm/hr were deemed to have been 

damaged during preparation and were rejected. 

Results and discussions 
Signs and symptoms of toxicity 

no effects 

Dermal irritation 

not examined 

Remarks on results including tables and figures 

The mean steady state of absorption for triethylene glycol monobutyl ether was 22.2 micrograms/cm2/hr 

(SD +/- 8.59), which was 100-fold less than that of ethylene glycol monomethyl ether. Test material did 

not increase permeability of the membrane (damage ratio of 1.26).

Overall remarks, attachments 

Overall remarks 

Absorption of ethylene glycol monomethyl ether (EGME), triethylene glycol monomethyl ether (TGME), 

and triethylene glycol monoethyl ether (TGEE) also were tested in this study. The rate of absorption of 

EGME was220 micrograms/cm2/hr. The rate of absorption of TGME was 34.0 micrograms/cm2/hr and 

the mean damage ratio was 3.36 (small increase in permeability). The rate of absorption of TGEE was 

24.1 micrograms/cm2/hr, and the mean damage ratio was 1.37 (no increase in permeability).

7.2 Acute Toxicity 

7.2.1 Acute toxicity: oral 

Acute toxicity: oral Moreno TGBE 1976.001 

UUID IUC5-0044d9c9-7b50-44d9-9e8c-4edf6cd14889 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:08:32 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Predates GLP. Purity of substance not given. 

Data source 

Reference 

Reference type 

Author Moreno OM. Year 1976 

Title Report on oral LD50 in rats. 

Bibliographic 

source 

EPA/OTS File 0206801. 

Testing laboratory MB Research Laboratories, Inc. Report no. 
Owner company Olin Corporation 

Company study no. Project number MB 75-990 Report date 1976-01-25 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

male 

Details on test animals and environmental conditions 

Rats (200-250 g) were fasted for approximately 18 hours prior to test material administration. 

Administration / exposure 

Route of administration 

other: intubation 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

The test animals were fasted for approximately 18 hours prior to test material administration. 

Test material was given by intubation at 3.2, 5.0, 7.73, and 12.18 g/kg to groups of 10 animals. 

Doses 

3.2, 5.0, 7.73, and 12.18 g/kg 

No. of animals per sex per dose 

10 animals per dose. A total of forty animals were used in the study 

Control animals 
no 

Details on study design 

Food and water were freely available after treatment. Rats were observed for toxicity and death 

for 14 days. 

Statistics 

The LD50 value and 95% confidence limits were determined by the method of Litchfield and 

Wilcoxon (J Pharm Exp Ther 96:99, 1949). 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 5300 mg/kg bw 

95% CL >= 4100 — <= 6800 

Remarks 

Mortality 

All animals given 12.18 g/kg died within 3 hours. Eight animals given 7.73 g/kg and 6 given 5.0 

g/kg died within 1 day. There were no other deaths over the course of the experiment. 

Clinical signs 

Signs of toxicity at 5.0 g/kg included loss of righting reflex and flaccid muscle tone; at 7.73 

g/kg included comatose (6/10), flaccid muscle tone, and heavy breathing. There were no signs 

of toxicity in rats given 3.2 g/kg. 

Body weight 

no data 

Acute toxicity: oral Smyth TGBE 1962.002 

UUID IUC5-d045e4a1-9095-406c-9f23-cfe403e38763 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:12:53 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

62 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. Predates current guidelines and GLP 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, Year 1962 
Striegel JA. 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP and Striegel JA. Year 1960 

Title Range finding tests on butoxy triglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report no. Report 23-25 

Owner company 

Company study 

no. 

 Report date 1960-03-31 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Test guideline 

Qualifier no guideline followed 

Guideline 

Deviations 

Principles of method if other than guideline 

Standard acute oral study procedure of the time period 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 
Identity triethylene glycol monobutyl ether 

Details on test material 

no details 

Test animals 

Species 

rat 

Strain 

other: Carworth-Wistar 

Sex 

male 

Details on test animals and environmental conditions 

(4-5 weeks of age; 90-120 g 

Administration / exposure 

Route of administration 

other: intubation 

Vehicle 

other: water, corn oil or semi-solid agar (vehicle specific for test compound was not listed) 

Details on oral exposure 

no data 

Doses 

4, 8, and 16 ml/kg 

No. of animals per sex per dose 

five males per dose 

Control animals 

no data 

Details on study design 

Groups of five non-fasted rats (4-5 weeks of age; 90-120 g) were intubated with log doses with 

test material at dose levels differing by a factor of 2.0 in a geometric series. Test compound was 

diluted in either water, corn oil or semi-solid agar (vehicle specific for test compound was not 

listed). Animals were observed up to 14 days after dosing for mortality. Autopsies were 

performed on rats that died. Surviving rats were weighed at study termination. 

Statistics 

The LD50 value and its fiducial range (plus or minus 1.96 standard deviations) were estimated 

by the method of Thompson (Bacteriol Rev 11: 115, 1947) using the Tables of Weil (Biometrics 

8: 249, 1952). 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 6.73 mL/kg bw 

95% CL 

Remarks Average value. Range of LD50 from 4.13 to 11.0 ml/kg 

Mortality 

The oral LD50 for rats averaged 6.73 ml/kg and ranged from 4.13 to 11.0 ml/kg. All animals 

receiving 16 ml/kg died, 3 out of 5 dosed with 8 ml/kg, and 1 out of 5 dosed with 4 ml/kg died 
within 1 day of dosing. Autopsy of dead rats showed a generalized congestion of the abdominal 

viscera and lungs. 

Clinical signs 

no data 

Body weight 

no data 

Gross pathology 

no data 

Other findings 

no data 

Acute toxicity: oral.003 

UUID IUC5-6d220dd0-0521-4c4f-affd-3b76af914eea 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:16:29 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

88 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted, robust study following recognized procedure. 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Project Report 51-41 Report 

no. 

Project Report 

51-41 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1988-05-23 

Materials and methods 

Test type 

standard acute method 
Limit test 

no 

Principles of method if other than guideline 

No guideline mentioned. Study was conducted using typical standard protocol for acute oral 

test. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Rats were fasted overnight before dosing. Male and female rats weighed approximately 250 and 

200 g at study initiation. 

Administration / exposure 

Route of administration 

other: stomach intubation 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Rats (5/sex/dose) received 8.0 or 16.0 ml/kg test material by stomach intubation. Two male rats 

were also dosed with 4.0 ml/kg. A total of 22 animals were used in the study. 

Doses 

8.0 or 16.0 ml/kg 

No. of animals per sex per dose 

5/sex/dose 

Control animals 
no data 

Details on study design 

Rats (5/sex/dose) received 8.0 or 16.0 ml/kg test material by stomach intubation. Two male rats 

were also dosed with 4.0 ml/kg. Doses were varied by adjusting the volume of test material or 

its dilution. Rats were fasted overnight before dosing. Male and female rats weighed 

approximately 250 and 200 g at study initiation. Animals were weighed before dosing and at 

days 7 and 14 after dosing. At death or sacrifice, each animal was subjected to gross pathologic 

evaluation. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 16 mg/kg bw 

95% CL 

Remarks 

Mortality 

None of the animals treated with any dose of test material died. 

Clinical signs 

no data 

Body weight 

Animals were weighed before dosing and at days 7 and 14 after dosing. None of the animals 

treated with any dose of test material died. 

Gross pathology 

At death or sacrifice, each animal was subjected to gross pathologic evaluation. 

Acute toxicity: oral.004 

UUID IUC5-60d19c56-d5dc-4760-bd61-3d5b8d49a1d8 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:17:55 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

47 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Old study, conducted preguidelines and pre GLP 

Data source 
Reference 

Reference 

type 

study report 

Author Carpenter CP Year 1947 

Title Range finding tests on methoxy polyethylene glycols of approximate molecular 

weights 350, 550 and 750. 

Bibliograp

hic source 

Melon Institute of Industrial Research, University of Pittsburgh. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1947-05-

13 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

Standard acute method conducted pre-guideline. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity MPEG-350 

Details on test material 

Methoxy polyethylene glycol of approximately 350 molecular weight. 

Test animals 

Species 

rat 

Strain 

other: common albino 

Sex 

male 

Administration / exposure 

Route of administration 

other: stomach tube 

Vehicle 

unchanged (no vehicle) 
Details on oral exposure 

no details 

Doses 

10 ml/kg and 50 ml/kg 

No. of animals per sex per dose 

Six male animals per dose. Twelve animals were used in the study. 

Control animals 

no data 

Details on study design 

Groups of 6 rats (91-106 g) were dosed with 10 ml/kg (approximately 1 ml) or 50 ml/kg 

(approximately 4.7-5.3 ml) undiluted test material by stomach tube. Body weight gain and 

deaths were observed over a period of 14 days. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 22 mL/kg bw 

95% CL 

Remarks Method of estimation not given. 

Mortality 

All animals dosed with 50 ml/kg died within 1 day. None of the rats dosed with 10 ml/kg died. 

The LD50 was estimated to be 22 ml/kg (method of extrapolation not given). 

Clinical signs 

no data 

Body weight 

Animals dosed with 10 ml/kg gained from 23 to 68 grams over 14 days. 

Gross pathology 

no data 

Acute toxicity: oral.005 

UUID IUC5-6c4163c9-77b2-43b3-9f94-7f7fa52fdfbc 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:19:15 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 
Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title 

Bibliograp

hic source 

Hoechst AG Frankfurt/MainClariant GmbH Frankfurt/Main EUROPEAN 

COMMISSION-European Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Hoechst AG 

Company 

study no. 

Unpublished Study (77.0196). Report 

date 

 

Materials and methods 

Test type 

standard acute method 

Limit test 

yes 

Principles of method if other than guideline 

Interne Richtlinie der Hoechst AG (Internal protocol of Hoechst AG) 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-774-2 

Identifier Common name 

Identity tetraethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

no data 

Sex 
no data 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: unspecified 

Vehicle 

no data 

Details on oral exposure 

Probably used undiluted test material 

Doses 

no data 

No. of animals per sex per dose 

no data 

Control animals 

no data 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LD50 

Effect level > 15000 mg/kg bw 

95% CL 

Remarks 

Mortality 

none at limit dose 

Clinical signs 

no data 

Body weight 

no data 

Gross pathology 

no data 

Other findings 

no data 

Acute toxicity: oral.006 

UUID IUC5-254614e6-7242-4473-8612-c185f4246d57 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:20:35 EST 

Remarks 
 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability 

code) came from a previous IUCLID data set produced by the European 

Chemicals Bureau. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title 

Bibliograp

hic source 

Hoechst AG Frankfurt/MainClariant GmbH Frankfurt/Main EUROPEAN 

COMMISSION-European Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Unpublished Study (88.1130) Report 

date 

 

Materials and methods 

Test type 

standard acute method 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 401 (Acute Oral Toxicity) 

Deviations 

Principles of method if other than guideline 

Standard acute oral protocol used at the time. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier EC number 

Identity 245-883-5 

Identifier Common name 
Identity tetraethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

no data 

Sex 

no data 

Administration / exposure 

Route of administration 

oral: unspecified 

Details on oral exposure 

no data 

No. of animals per sex per dose 

no data 

Control animals 

no data 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Preliminary study (if fixed dose study) 

no data 

Effect levels 

Sex no data 

Endpoint LD50 

Effect level > 2000 mg/kg bw 

95% CL 

Remarks 

Acute toxicity: oral.007 

UUID IUC5-02d53fa8-f9a6-470c-a8e6-08a99cf55033 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 17:50:16 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

58 
Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Older preguideline and pre GLP study. Purity of test material was not noted. 

Data source 

Reference 

Reference type study report 

Author Carpenter CP. Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 

Test type 

standard acute method 

Limit test 

no 

Principles of method if other than guideline 

Standard acute oral toxicity study procedure. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

other: Carworth Farms-Nelson 

Sex 

male 
Details on test animals and environmental conditions 

5-6 weeks old, 90-120 g 

Administration / exposure 

Route of administration 

other: stomach intubation 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

stomach intubation 

Doses 

4, 8, or 16 ml/kg 

No. of animals per sex per dose 

5 males per dose 

Control animals 

no data 

Details on study design 

Male rats (5-6 weeks old, 90-120 g) were dosed with 4, 8, or 16 ml/kg test material by stomach 

intubation. Rats were observed for 14 days. Surviving rats were weighed on day 14. Autopsies 

were performed on those that died. 

Statistics 

The method of moving average was used to calculate the LD50 value. 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 11300 mg/kg bw 

95% CL 

Remarks 

Mortality 

All rats dosed with 16 ml/kg died within 1 day. None of the other animals died. 

Clinical signs 

no data 

Body weight 

All animals except 1 dosed with 4 ml/kg gained weight. 

Gross pathology 

Autopsies on rats that died revealed congested lungs, mottled livers and kidneys, GI 

tractirritation, and congested adrenals. 

Acute toxicity: oral.008 

UUID IUC5-e5c838af-1099-4d0a-9607-f2cbcb72734c 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 18:57:09 EST 

Remarks 

 
Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

2 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Test substance composition was well characterized, and study followed GLP. 

Few study details provided however. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

 

Owner 

company 

Shell 

Company 

study no. 

DocumentNumber SBGR.92.011 Report 

date 

1992-06-3

0 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard acute oral toxicity procedure. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethyleneglycol monomethyl ether borate ester 

(CAS No. 106008-94-0),3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 
23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 

Test animals 

Species 

rat 

Strain 

Fischer 344 

Sex 

male/female 

Details on test animals and environmental conditions 

no details 

Administration / exposure 

Route of administration 

oral: unspecified 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no data 

Doses 

5000 mg/kg bw 

No. of animals per sex per dose 

10 

Control animals 

no 

Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 5000 mg/kg bw 

95% CL 

Remarks 

7.2.2 Acute toxicity: inhalation 

Acute toxicity: inhalation Smyth TGBE 1962.001 

UUID IUC5-01baf344-0464-4b91-b377-af5dcc9969ee 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:23:18 EST 

Remarks 

 
Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

60 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Limited information on study details and test material provided. 

Data source 

Reference 

Reference 

type 

 

Author Carpenter CP and Striegel JA Year 1960 

Title Range finding tests on butoxy triglycol. Melon Institute of Industrial Research 

Bibliographi

c source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report 

no. 

Report 

23-25 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1960-03-31 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard acute method of the period 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 
Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

female 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

inhalation: vapour 

Type of inhalation exposure 

no data probably whole body, since nose only not mentioned. 

Vehicle 

unchanged (no vehicle) 

Details on inhalation exposure 

no data 

Analytical verification of test atmosphere concentrations 

no 

Duration of exposure 

8 h Remarks From 15 minutes up to 8 h 

Concentrations 

not measured. 

No. of animals per sex per dose 

six females per dose 

Control animals 

no data 

Details on study design 

Concentrated vapor (25 degrees C) was generated by passing air at 2.5 liters/min through a 

fritted glass disc immersed in 50 ml of butoxy triglycol. Rats were exposed for 8 hours to a 

flowing stream of this vapor and observed for 14 days.

Rats were exposed from time periods ranging from 15 minutes to 8 hours (until the inhalation 

period killing about one half of the rats within 14 days was defined). The result is the longest 
inhalation period which permitted all rats to survive the14-day observation period. 

Results and discussions 

Preliminary study (if fixed dose study) 

no data 

Mortality 

All animals survived the eight hour exposure through the 14 day post exposure observation 

period. 

Clinical signs 

no data. No observations mentioned. 

Body weight 

no body weight observations mentioned in study. 

Gross pathology 

no data, probably not conducted. 

Acute toxicity: inhalation Moreno TGBE 1976.002 

UUID IUC5-5e7633c0-29b7-4419-9ef4-12f0e8f3f11c 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:35:07 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Good study, but preguideline and pre GLP and purity of test material was 

not noted. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1976 

Title Report on inhalation toxicity in rats. 

Bibliographic 

source 

EPA/OTS File 0206801. 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. Project number MB 

75-990 

Owner 

company 

Olin Corporation 

Company study 

no. 

 Report date 1976-01-25 

Materials and methods 
Test type 

standard acute method 

Principles of method if other than guideline 

standard acute inhalation toxicity method 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

no data 

Details on test animals and environmental conditions 

200-250 g weight for the test animals 

Administration / exposure 

Route of administration 

inhalation: vapour 

Type of inhalation exposure 

no data 

Vehicle 

unchanged (no vehicle) 

Analytical verification of test atmosphere concentrations 

no data 

Duration of exposure 

1 h Remarks 

Concentrations 

200 mg/liter of test material 

No. of animals per sex per dose 

Ten rats of undetermined sex 

Control animals 

no 
Details on study design 

Ten rats (200-250 g, sex not stated) were placed in a 50 liter chamber and exposed to a nominal 

concentration of 200 mg/liter of test material for one hour. The rats were observed daily over 14 

days for signs of toxicity. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LCLo 

Effect level > 200 mg/L air (nominal) 

95% CL 

Exp. duration 

Remarks 

Mortality 

All animals survived the exposure. 

Clinical signs 

no data 

Body weight 

Bodyweights were recorded prior to and 14 days after treatment. Rats gained weight over the 14 

day period. 

Gross pathology 

There were no signs of toxicity. 

Acute toxicity: inhalation.002 

UUID IUC5-72623c1b-0a05-4549-b38c-357d47598a4e 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 18:07:08 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

62 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. Also older study predating guidelines 

or GLP. 

Data source 

Reference 

Reference type study report 

Author Year 1958 

Title Range finding tests on methoxytriglycol. 
Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA 

Year 1962 

Title Range-finding toxicity data: List VI 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard prodecure of the time for acute inhalation toxicology 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rat 

Strain 

other: Carworth-Wistar 
Sex 

female 

Administration / exposure 

Route of administration 

inhalation: vapour 

Type of inhalation exposure 

no data 

Vehicle 

unchanged (no vehicle) 

Details on inhalation exposure 

Six female rats were exposed to a flowing stream of vapor-ladened air generated by passing 2.5 

l/min of dried air at room temperature through a fritted disc immersed to a depth of at least once 

inch in approximately 50 ml of test material contained in a gas-washing bottle. Rats were 

exposed from time periods ranging from 15 minutes to 8 hours (until the inhalation period 

killing about one half of the rats within 14 days was defined). The result is the longest 

inhalation period which permitted all rats to survive the14-day observation period. 

Analytical verification of test atmosphere concentrations 

no data 

Duration of exposure 

8 h Remarks 

Concentrations 

not measured but probably saturated 

No. of animals per sex per dose 

six females 

Control animals 

no data 

Results and discussions 

Mortality 

All animals survived an 8-hr exposure period to concentrated vapor and had normal weight 

gains. 

Clinical signs 

no data 

Body weight 

All animals had normal weight gains. 

Gross pathology 

no data 

Other findings 

no data 

7.2.3 Acute toxicity: dermal 

Acute toxicity: dermal Smyth TGBE 1962.001 

UUID IUC5-1abed54c-b863-4d49-9d2e-436387b80b92 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 
Date 2009-02-12 09:38:46 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

1

9

6

2 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

1962 study predating guidelines and GLP. Purity of test material not noted. 

Otherwise a good study. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP and Striegel JA. Year 1960 

Title Range finding tests on butoxy triglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report no. Report 23-25 

Owner company 

Company study 

no. 

 Report date 1960-03-31 

Materials and methods 

Test type 

other: variation of one-day cuff method of Draize 

Principles of method if other than guideline 

variation of one-day cuff method of Draize 

GLP compliance 

no 
Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no details 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male 

Details on test animals and environmental conditions 

Groups of 4 male rabbits (3-5 months, weighing between 2.5 to 3.5 kg 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

no data 

Details on dermal exposure 

Groups of 4 male rabbits (3-5 months, weighing between 2.5 to 3.5 kg) were treated with 1.25, 

2.5, 5.0 or 10 ml/kg dermally according to a variation of the one-day cuff method of Draize and 

associates (J Pharmacol Exper Ther 82: 377, 1944). Fur was clipped from the entire trunk. A 

VINYLITE sheeting was used to keep the test material in contact with the skin. Rabbits were 

immobilized during the 24-hour skin contact period. It is likely that no vehicle was used, but 

that was not stated. 

Duration of exposure 

24 hours 

Doses 

Not provided. 

No. of animals per sex per dose 

four male rabbits per dose. Twelve animals total. 

Control animals 

no 

Details on study design 

Groups of 4 male rabbits (3-5 months, weighing between 2.5 to 3.5 kg) were treated with 1.25, 

2.5, 5.0 or 10 ml/kg dermally according to a variation of the one-day cuff method of Draize and 
associates (J Pharmacol Exper Ther 82: 377, 1944). Fur was clipped from the entire trunk. A 

VINYLITE sheeting was used to keep the test material in contact with the skin. Rabbits were 

immobilized during the 24-hour skin contact period. After the dressing was removed, animals 

were observed for 14 days. 

The LD50 value and its fiducial range (plus or minus 1.96 standard deviations) was estimated 

by the method of Thompson (Bacteriol Rev 11: 115, 1947) using the Tables of Weil (Biometrics 

8: 249, 1952).

Statistics 

The LD50 value and its fiducial range (plus or minus 1.96 standard deviations) was estimated 

by the method of Thompson (Bacteriol Rev 11: 115, 1947) using the Tables of Weil (Biometrics 

8: 249, 1952). 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 3.54 mL/kg bw 

95% CL >= 1.06 — <= 11.85 

Remarks 1.96 standard deviations 

Mortality 

Three out of four rabbits treated with 10 ml/kg died within 3 days. The remaining animal in this 

group lost 110 g of weight over the 14-day recovery period. Two out of four rabbits treated with 

5 ml/kg or 2.5 ml/kg, and 1 treated with 1.25 ml/kg died by day 9. Findings upon autopsy were 

cherry red and hemorrhaged lungs, dark livers mottled with prominent acini, and pale and 

mottled kidneys. The LD50 value was 3.54 (1.06 to 11.85) ml/kg. 

Clinical signs 

no data 

Body weight 

Surviving animal in the 10 ml/kg group lost 110 g of weight over the 14-day recovery period. 

Gross pathology 

Findings upon autopsy were cherry red and hemorrhaged lungs, dark livers mottled with 

prominent acini, and pale and mottled kidneys. 

Other findings 

no data 

Acute toxicity: dermal Morena TGBE 1976.002 

UUID IUC5-7e532477-b7c5-4907-b707-6b2c8d77e764 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:45:22 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 
used for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

A good study but non-current guideline. Test purity not provided. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1976 

Title Report on acute dermal toxicity in rabbits. 

Bibliographic 

source 

EPA/OTS Document File 0206801 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. 

Owner company Olin Corporation 

Company study 

no. 

Project Number MB 75-990 Report date 1976-01-25 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard acute inhalation test procedure 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 
no data 

Details on test animals and environmental conditions 

Ten rabbits were used with weights of 2.3 to 3.0 kg. 

Administration / exposure 

Type of coverage 

open 

Vehicle 

no data 

Details on dermal exposure 

The animals were clipped free of abdominal hair. Epidermal abrasions were made longitudinally 

every 2 to 3 cm over the clipped area of 5 rabbits. The abrasions were deep enough to penetrate 

the stratum corneum, but not deep enough to produce bleeding. A single dose of 2.0 g/kg was 

applied to the exposed area. The area was covered with gauze and the trunk wrapped with 

impervious material for 24 hours. The dressing was then removed. It is likely that the test 

material was applied non-diluted, but that was not specified. 

Duration of exposure 

24 hours 

Doses 

A single dose of 2.0 g/kg 

No. of animals per sex per dose 

Ten rabbits 

Control animals 

no 

Details on study design 

Ten rabbits (2.3 to 3.0 kg) were clipped free of abdominal hair. Epidermal abrasions were made 

longitudinally every 2 to 3 cm over the clipped area of 5 rabbits. The abrasions were deep 

enough to penetrate the stratum corneum, but not deep enough to produce bleeding. A single 

dose of 2.0 g/kg was applied to the exposed area. The area was covered with gauze and the 

trunk wrapped with impervious material for 24 hours. The dressing was removed, rabbits were 

cleaned, and animals were evaluated over 14 days. 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex no data 

Endpoint LDLo 

Effect level > 2000 mg/kg bw 

95% CL 

Remarks 

Mortality 

There were no deaths. 

Clinical signs 

No signs of toxicity observed. 

Body weight 

no data 
Gross pathology 

no details 

Acute toxicity: dermal.003 

UUID IUC5-15b639af-7701-4660-9a38-4677544c4e4a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:47:04 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

8 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted study with good documentation. Test material is well 

characterized as to composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

51-41 

Owner 

company 

 

Company 

study no. 

Union Carbide Report 

date 

1988-05-23 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

standard acute inhalation test method 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 
Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350)(CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Ten animals total were used in the study. Five rabbits of each sex (weighing between 2 and 3 

kg). 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

Five rabbits of each sex (weighing between 2 and 3 kg) were subjected to 24 hours of contact 

with the test material (16 ml/kg) , which was retained under impervious sheeting on the clipped, 

intact skin of the trunk. If necessary, gauze was wrapped around the trunk over the sample to 

prevent leakage. Bandaging tape was wrapped over the impervious sheeting. Excess fluid was 

removed after the contact period to diminish ingestion. 

Duration of exposure 

24 hours of skin contact. 

Doses 

16 ml/kg, single dose level 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

no 

Details on study design 

Body weights were determined before and 7 and 14 days following test material application. 

Deaths were monitored for 14 days. 

Statistics 
no data 

Results and discussions 

Preliminary study (if fixed dose study) 

no preliminary study 

Effect levels 

Sex male/female 

Endpoint LDLo 

Effect level > 16 mL/kg bw 

95% CL 

Remarks 

Mortality 

No animals died during the course of the study. 

Clinical signs 

No signs of systemic toxicity or irritation were noted. 

Body weight 

no data 

Gross pathology 

no data 

Acute toxicity: dermal.004 

UUID IUC5-39947494-db73-4033-ab8e-baf784e21445 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 18:55:24 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

92 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

few study details given 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit 

Bibliographi

c source 

 

Testing Shell Research Limited, Sittingbourne Research Centre Report 
laboratory no. 

Owner 

company 

Shell 

Company 

study no. 

DocumentNumber SBGR.92.011 Report 

date 

1992-06-3

0 

Materials and methods 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 

Test animals 

Species 

rat 

Strain 

Fischer 344 

Sex 

male/female 

Administration / exposure 

Type of coverage 

no data 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

no data 

Duration of exposure 

no data 

Doses 

2000 mg/kg bw 

No. of animals per sex per dose 

5 per sex per dose 

Control animals 

no data 
Details on study design 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male/female 

Endpoint LD50 

Effect level > 2000 mg/kg bw 

95% CL 

Remarks 

Acute toxicity: dermal.005 

UUID IUC5-7b14fc92-5c09-4a70-b7b8-ebde14a7b577 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-15 19:21:01 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

58 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted study, but test substance purity was not provided. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP Year 1958 
Title Range finding tests on methoxytriglyco 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 

Test type 

standard acute method 

Principles of method if other than guideline 

Standard acute dermal study procedure 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 23601-39-0 

Identifier EC number 

Identity 245-774-2 

Identifier IUPAC name 

Identity 3,6,9,12,15,18-hexaoxaicosane 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male 

Details on test animals and environmental conditions 

Male rabbits (3-5 months old) weighing between 2.5 to 3.5 kg 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

Male rabbits were treated with 2.5 ml/kg (N=2), 5 ml/kg (N=4), or 10 ml/kg (N=2) test material 

according to a variation of the one-day cuff method of Draize and associates (J Pharmacol 
Exper Ther 82: 377, 1944). Fur was clipped from the entire trunk, and doses were placed 

beneath an impervious plastic film (VINYLITE sheeting). Animals were immobilized for a 

24-hour contact period and the film was removed. Rabbits were then observed for 14 days. The 

LD50 value and its fiducial range (plus or minus 1.96 standard deviations) was estimated by the 

method of Thompson (Bacteriol Rev 11: 115, 1947) using the Tables of Weil (Biometrics 8: 

249, 1952). 

Duration of exposure 

24-hour contact period 

Doses 

2.5 ml/kg (N=2), 5 ml/kg (N=4), or 10 ml/kg (N=2) 

No. of animals per sex per dose 

2 male animals at 2.5 ml/kg, 4 animals at 5.0 ml/kg and 2 animals at 10 ml/kg 

Control animals 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 7400 mg/kg bw 

95% CL 

Remarks 

Mortality 

The two rabbits treated with 10 ml/kg died within 4 days. All other rabbits survived and 

appeared normal. The LD50 value was 7.13 ml/kg (7.4 g/kg). 

Clinical signs 

Marked erythema of skin was noted after removal of the dressing (doses and number affected 

was not noted). 

Gross pathology 

One of the rabbits treated with 10 ml/kg had internal hemorrhage as evidence by bloody exudate 

in the peritoneal cavity atautopsy. 

7.3 Irritation / corrosion 

7.3.1 Skin irritation / corrosion 

Skin irritation / corrosion Smyth TGBE 1962.001 

UUID IUC5-daae3911-5f9b-4b90-bd8f-0ab0653581d9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:48:45 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 
MSDS 

Study result type experimental result Study 

period 

19

60 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Predates current guidelines and GLP. Purity of substance not noted. 

Data source 

Reference 

Reference type study report 

Author Carpenter CP and Striegel JA. Year 1960 

Title Range finding tests on butoxy triglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report no. 

Owner company 

Company study 

no. 

Report 23-25 Report date 1960-03-31 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Standard skin irritation procedure of the period. 

GLP compliance 

no 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 
Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no details 

Test animals 

Species 

rabbit 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

open 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.01 ml (one concentraton) 

Duration of treatment / exposure 

24 hours 

Observation period 

24 hours after dosing 

Number of animals 

five rabbits 

Control animals 

no 

Details on study design 

Undiluted test solution (0.01 ml) was applied to the clipped belly skin of 5 rabbits. Irritation that 

occurred within 24 hours was scored in a graded fashion (from 1 to 10), with Grade 1 = no 

irritation, Grade 2 = the least visible capillary injection, Grade 6 = necrosis when undiluted. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis mean 

Time point 24 hours 

Score 3 

Max. score 

Reversibility 

Remarks 

Irritant/corrosive response data 

An average irritation Grade of 3 was obtained with undiluted test material, indicating mild 

irritation. Marked capillary injection was noted on 4 animals and moderate injection on the 5th. 

Applicant's summary and conclusion 

Interpretation of results 
moderately irritating 

Skin irritation / corrosion Carpenter & Striegel TGBE 1960.002 

UUID IUC5-a3d0946a-40b2-45df-ab66-fd6527ff2bd7 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:50:22 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1

9

6

0 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted, older study predating GLP and current guidelines, and not 

stating purity of test material. 

Data source 

Reference 

Reference type study report 

Author Carpenter CP and Striegel JA. Year 1960 

Title Range finding tests on butoxy triglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report no. Report 23-25 

Owner company 

Company study 

no. 

 Report date 1960-03-31 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Typical standard protocol of the time. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 143-22-6 
Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

male rabbits (3-5 months, 2.5 kg avg) 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

1.25, 2.5, 5.0 or 10 ml/kg 

Duration of treatment / exposure 

24 hours skin contact 

Observation period 

14 days 

Number of animals 

four male rabbits per dose 

Control animals 

no 

Details on study design 

Groups of 4 male rabbits (3-5 months, 2.5 kg avg) were treated with 1.25, 2.5, 5.0 or 10 ml/kg 

dermally (on clipped skin). A VINYLITE sheeting was used to keep the test material in contact 

with the skin. Rabbits were immobilized during the 24-hour skin contact period. After the 

dressing was removed, animals were observed for 14 days. 

Results and discussions 

Irritant/corrosive response data 

Listed here are dermal irritation results from an acute dermal toxicity study performed with high 

doses (1.25 to 10 ml/kg). Marked erythema of skin was found upon removal of the dressing 

(doses causing this effect were not stated). Some small scabs and extensive desquamation were 

present at Day 14. 

Skin irritation / corrosion Moreno TGBE 1976.003 

UUID IUC5-9f06f0f3-1640-46cb-8120-a8bbc4d16825 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:52:08 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Data source 

Reference 

Reference 

type 

study report 

Author Moreno OM. Year 1976 

Title Report on primary dermal irritation in rabbits. 

Bibliographic 

source 

 

Testing 

laboratory 

MB Research Laboratories, Inc. Report no. Project number MB 

75-990 

Owner 

company 

Olin Corporation 

Company 

study no. 

 Report 

date 

1976-01-22 

Materials and methods 

Type of method 

in vivo 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 
Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

abraded 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Six rabbits were clipped over the back and sides with an electric clipper. A site (1" x 1") to the 

left of the spinal column was abraded. Abrasions were minor incisions through the stratum 

corneum that did not disturb the derma or produce bleeding. Test material (0.5 ml) was applied 

to a surgical gauze (1" square, 2 layers thick). The patches were placed on test sites and secured 

with adhesive tape. The trunk was wrapped with impervious material. Patches were removed 

after 24 hours. 

Duration of treatment / exposure 

24 hours 

Observation period 

24 and 72 hours 

Number of animals 

Six animals 

Control animals 

no 

Details on study design 

Six rabbits were clipped over the back and sides with an electric clipper. A site (1" x 1") to the 

left of the spinal column was abraded. Abrasions were minor incisions through the stratum 

corneum that did not disturb the derma or produce bleeding. Test material (0.5 ml) was applied 

to a surgical gauze (1" square, 2 layers thick). The patches were placed on test sites and secured 

with adhesive tape. The trunk was wrapped with impervious material. Patches were removed 

after 24 hours. Dermal reactions were evaluated at 24 and 72 hours in accordance with the 

Consumer Product Safety Act, Title 16 CFR 1500.41. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis animal #1 

Time point 24 hours 

Score ca. 1 

Max. score 1 

Reversibility 
Remarks 

Irritant/corrosive response data 

An erythema score of 1 (barely perceptible) was observed in 1 rabbit at 24 hours (abraded skin) 

and another at 72 hours (intact skin). All others received erythema scores of 0. No edema was 

observed at 24 or 72 hours. 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Skin irritation / corrosion.004 

UUID IUC5-71629c9f-77ab-4e58-ae8c-53e4c9cb9bcb 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:54:55 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

88 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study with strong detail documentation 

Data source 

Reference 

Reference 

type 

study report 

Author Reid ME. Year 1988 

Title Carbowax MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

51-41 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1988-05-23 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

Standard Draize procedure. 

GLP compliance 
no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350, CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

occlusive 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Test material (0.5 ml) was applied to the clipped, intact skin of six rabbits (3 of each sex). The 

material was loosely covered with a gauze patch an impervious sheeting. Rabbits were 

restrained for a 4-hour contact period. Excess material was removed after contact. 

Duration of treatment / exposure 

4-hour contact period 

Number of animals 

three of each sex 

Control animals 

no 

Details on study design 

The skin reaction was scored by the method of Draize at one hour, and 1, 2, 3, and 7 days 

following dosing. 

Results and discussions 

Irritation / corrosion results 
Irritation parameter overall irritation score 

Basis mean 

Time point 1 hr, and 1, 2, 3 and 7 days 

Score ca. 0 

Max. score 0 

Reversibility 

Remarks 

Irritant/corrosive response data 

Scores of 0 were obtained for both erythema (and eschar formation) and edema. The material 

was therefore non-irritating. 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Skin irritation / corrosion.005 

UUID IUC5-9506b2f2-ca7f-4484-a3a2-0032d5db0671 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 09:55:40 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability 

code) came from a previous IUCLID data set produced by the 

European Chemicals Bureau. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title 

Bibliograp

hic source 

Hoechst AG Frankfurt/MainClariant GmbH Frankfurt/Main EUROPEAN 

COMMISSION- European Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Unpublished Study (88.1086). Report 

date 

 
Materials and methods 

Type of method 

in vivo 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 404 (Acute Dermal Irritation / Corrosion) 

Deviations 

GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 23783-42-8 

Identifier IUPAC name 

Identity tetraethylene glycol monomethyl ether 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

no data 

Preparation of test site 

no data 

Vehicle 

no data 

Amount/concentration applied 

no data 

Duration of treatment / exposure 

four hours 

Observation period 

no data 

Number of animals 

no data 

Details on study design 

no data 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis mean 
Time point four hours 

Score ca. 0 

Max. score 

Reversibility 

Remarks 

Irritant/corrosive response data 

Effect after 4 hours: none of recognizable significance.] 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Skin irritation / corrosion.006 

UUID IUC5-d25de863-f1f8-4b24-a48c-07127eb82083 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-16 16:23:06 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1992 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Study well conducted following GLP and providing good data on test material 

purity. Details provided in the study were somewhat limited as to methodology. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

011 

Owner 

company 

Shell 

Company 

study no. 

 Report 

date 

1992-06-3

0 

Materials and methods 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to normally followed procedures for 

this type of study. 
GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CASNo. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

semiocclusive 

Preparation of test site 

no data 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

applied undiluted 

Duration of treatment / exposure 

4 hours 

Observation period 

no data 

Number of animals 

six 

Control animals 

no data 

Details on study design 

no data 

Applicant's summary and conclusion 

Interpretation of results 
not irritating 

Conclusions 

not irritating 

Skin irritation / corrosion.007 

UUID IUC5-cf7333db-76dd-4280-8dc7-1b6acf9b6bdb 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-16 17:00:24 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study ( ) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

6

2 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Some study details of test method animals and TS purity are lacking, but 

otherwise the study was well conducted. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title . Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study Report date 1958-06-12 
no. 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No test guideline specified, but study was conducted according to procedure commonly used. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Type of coverage 

open 

Preparation of test site 

shaved 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

undiluted substance 

Duration of treatment / exposure 

24 hours 

Observation period 

24 hours 

Number of animals 

5 rabbits 

Control animals 

no data 
Details on study design 

Undiluted test solution (0.01 ml) was applied to the clipped belly skin of 5 rabbits. Irritation that 

occurred within 24 hours was scored in a graded fashion (from 1 to 10), with Grade 1 = no 

irritation, Grade 2 = the least visible capillary injection, Grade 6 = necrosis when undiluted. 

Results and discussions 

Irritation / corrosion results 

Irritation parameter overall irritation score 

Basis 

Time point 24 hours 

Score 2 

Max. score 

Reversibility 

Remarks 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Conclusions 

An irritation Grade of 2 was obtained with undiluted test material, indicating minimal irritation. 

7.3.2 Eye irritation 

Eye irritation Moreno TGBE 1976.001 

UUID IUC5-8ac0cca2-5b55-4466-876c-f551d7465383 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 10:08:38 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

76 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

One dose was used. Purity of test substance was not provided. Otherwise 

satisfactory study. 

Data source 

Reference 

Reference type study report 

Author Moreno OM. Year 1976 

Title Report on rabbit eye irritation. 

Bibliographic 

source 

EPA/OTS File 0206801 

Testing MB Research Laboratories, Inc. Report no. Project number MB 75-990 
laboratory 

Owner company Olin Corporation 

Company study 

no. 

 Report date 1976-01-24 

Materials and methods 

Principles of method if other than guideline 

After installation of the undiluted test material in the eye, ocular reactions were graded in 

accordance with the Consumer Product Safety Act, Title 16 CFR 1500.42 at 1, 2, and 3 days 

after instillation of the test material. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

.1 ml 

Duration of treatment / exposure 

Single exposure into the eye, that was presumably not rinsed out (rinse not specified). 

Observation period 

Oocular reactions were graded in accordance with the Consumer Product Safety Act, Title 16 

CFR 1500.42 at 1, 2, and 3 days after instillation of the test material. 

Number of animals 

six animals 

Control animals 
no 

Details on study design 

Test material (0.1 ml) was instilled into the conjunctival sac of one eye of each rabbit on Day 0. 

Ocular reactions were graded in accordance with the Consumer Product Safety Act, Title 16 

CFR 1500.42 at 1, 2, and 3 days after instillation of the test material. 

Results and discussions 

Overall irritation / corrosion results 

Irritation 

parameter

other: total conjunctival: ((redness + chemosis + discharge) x 2) 

Basis 

Time point 72 hours 

10 — 16 

Max. score 20 

Reversibility 

Remarks 

Irritation parameter other: Highest overall 

Basis 

Time point 72 hours 

21 

Max. score 110 

Reversibility 

Remarks 

Irritant/corrosive response data 

Conjunctival redness, chemosis and discharge scores of 2-3 (diffuse crimson to beefy red) were 

noted at all time points in all rabbits (except 1 rabbit that had a chemosis score of 1 at 72 hours). 

Iris scores of 1 (folds above normal, congestion, swelling, corneal injection, sluggish reaction to 

light) were observed in all animals at each time point. The total conjunctival score ((redness + 

chemosis + discharge) x 2) ranged from 10-16 out of a possible 20. The highest overall score 

was 21 out of a possible 110. 

Applicant's summary and conclusion 

Interpretation of results 

irritating 

Eye irritation Smyth TGBE 1962.002 

UUID IUC5-afb41288-60f5-4da8-babb-f44e555e5409 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 10:11:36 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 
Study result type experimental result Study 

period 

19

60 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Good study, but older preguideline. Purity of test substance not noted. 

Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107. 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP and Striegel JA. Year 

Title Range finding tests on butoxy triglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Melon Institute of Industrial Research Report no. 23-25 

Owner company 

Company study 

no. 

 Report date 1960-03-31 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

other method: Carpenter and Smyth (Am J Opthal 29:1363, 1946) 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier IUPAC name 
Identity Triethylene glycol butyl ether 

Identifier EC number 

Identity 205-592-6 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

no data 

Duration of treatment / exposure 

not noted 

Observation period 

not noted 

Number of animals 

not noted 

Control animals 

no data 

Details on study design 

Various volumes and concentrations of test material (probably undiluted) were applied to rabbit 

eyes (number of rabbits and time of exposure was not indicated). Eye injury was scored on a 10 

point scale according to the degree of corneal necrosis that resulted from instillation of the 

various concentrations. Grade 1 = very small area of necrosis from 0.5 ml undiluted material, 

Grade 5 = severe burn from 0.005 ml undiluted material, Grade 10 = severe burn from 0.5 ml of 

a 1% solution in water or propylene glycol. 

Results and discussions 

Overall irritation / corrosion results 

Irritation parameter overall irritation score 

Basis mean 

Time point 

ca. 5 

Max. score 5 

Reversibility 

Remarks 

Irritant/corrosive response data 

Rabbit eyes were necrosed by instillation of 0.02 ml. Minor to moderate injury resulted from the 

instillation of 0.005 ml. 

Overall remarks, attachments 

Attached full study report 

() 
Applicant's summary and conclusion 

Interpretation of results 

highly irritating 

Eye irritation.003 

UUID IUC5-78f71c39-96a5-4663-9e58-1a86cdce80fb 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 10:12:47 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

8 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Study was well conducted with detailed information. Test material was well 

characterized with regard to composition. 

Data source 

Reference 

Reference 

type 

 

Author Reid ME. 1988 Year 1988 

Title MPEG 350 NMW. Acute toxicity and primary irritancy studies. 

Bibliographic 

source 

 

Testing 

laboratory 

Bushy Run Research Center Report no. 51-41 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1988-05-23 

Materials and methods 

Principles of method if other than guideline 

No guideline specified. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 
Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG-350 

Details on test material 

Test material (CARBOWAX MPEG-350, CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.1 ml 

Duration of treatment / exposure 

Not specified whether eye was rinsed at some point after instillation of test material. 

Observation period 

1 and 4 hours, and 1, 2, 3, and 7 days after dosing 

Number of animals 

Six 

Control animals 

yes, concurrent no treatment 

Details on study design 

Six male New Zealand white rabbits were dosed with 0.1 ml of test material. The test material 

was instilled into the lower conjunctival sac or placed directly on one eye per animal. The other 

eye served as a control. The eyes were scored at 1 and 4 hours, and 1, 2, 3, and 7 days after 

dosing. Florescein (2%) was added to the eyes before dosing and after 1 day of exposure to 

assess corneal injury. 

Results and discussions 

Irritant/corrosive response data 

Instillation of test material resulted in no corneal injury or iritis. Minor conjunctival irritation 

developed in all 6 rabbits. Moderate discharge was seen in several of the eyes. These effects 

resolved by 24 hours. 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 
Eye irritation.004 

UUID IUC5-c616a915-b5cd-4ae4-8aa0-1d3d4c7818cd 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 10:14:29 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1988 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Original reference was not available. Information (including the reliability code) 

came from a previous IUCLID data set produced by the European Chemicals 

Bureau. 

Data source 

Reference 

Reference 

type 

company data 

Author Year 1988 

Title 

Bibliograp

hic source 

Hoechst AG Frankfurt/MainClariant GmbH Frankfurt/Main EUROPEAN 

COMMISSION - European Chemicals Bureau Ispra (VA) 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Hoechst AG. 

Company 

study no. 

Unpublished Study 88.1220. Report 

date 

 

Materials and methods 

Type of method 

in vivo 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 405 (Acute Eye Irritation / Corrosion) 

Deviations 

GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 
Identifier CAS number 

Identity 23783-42-8 

Identifier Common name 

Identity tetraethylene glycol monomethyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

no data 

Amount/concentration applied 

no data. Probably undiluted test material applied. 

Duration of treatment / exposure 

no data 

Observation period 

4 hours 

Number of animals 

no data 

Control animals 

no data 

Details on study design 

no data 

Results and discussions 

Irritant/corrosive response data 

Effect after 4 hours: none of recognizable significance]. 

Applicant's summary and conclusion 

Interpretation of results 

not irritating 

Eye irritation.005 

UUID IUC5-dcf774f2-5ca6-41d7-8180-979db71c1ff5 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-17 12:28:06 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 
for MSDS 

Study result type experimental result Study 

period 

19

92 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study following GLP, with the composition of the test 

material well characterized. 

Data source 

Reference 

Reference 

type 

study report 

Author Gardner JR. Year 1992 

Title Brake fluid DOT 4: Acute oral and dermal toxicity in rat, skin and eye irritancy in 

rabbit 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

011 

Owner 

company 

 

Company 

study no. 

 Report 

date 

1992-06-3

0 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to standard procedure for eye 

irritation. 

GLP compliance 

yes 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, (20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CASNo. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives 
Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

.1 ml 

Duration of treatment / exposure 

72 hours 

Observation period 

72 hours 

Number of animals 

six 

Control animals 

no data 

Details on study design 

no data 

Results and discussions 

Irritant/corrosive response data 

sllightly irritating 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Eye irritation.006 

UUID IUC5-20da953b-85c9-483d-bc3c-9822a5b1b5dc 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-17 13:00:07 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1958 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Rabbit strain not given. Details of number of animals exposed to each dose not 

given. GLP not specified. Purity of test substance not noted. Otherwise thie was 

a credible study. 
Data source 

Reference 

Reference type publication 

Author Smyth HF, Carpenter CP, Weil CS, Pozzani U, 

Striegel JA. 

Year 1962 

Title Range-finding toxicity data: List VI. 

Bibliographic 

source 

Am Ind Hyg Assoc J 23:95-107 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company study 

no. 

 Report date 

Reference type study report 

Author Carpenter CP. Year 1958 

Title Range finding tests on methoxytriglycol. 

Bibliographic 

source 

 

Testing 

laboratory 

Mellon Institute of Industrial Research Report no. 21-44 

Owner company 

Company study 

no. 

 Report date 1958-06-12 

Materials and methods 

Type of method 

in vivo 

Principles of method if other than guideline 

No guideline specified, but study was conducted according to typical procedure for eye 

irritation. 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 
no details. 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

no data 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

.5 ml 

Duration of treatment / exposure 

no data 

Observation period 

no data 

Number of animals 

not specified 

Control animals 

no data 

Details on study design 

Various volumes and concentrations of test material were applied to rabbit eyes (number of 

rabbits and time of exposure was not indicated). Eye injury was scored on a 10 point scale 

according to the degree of corneal necrosis that resulted from instillation of the various 

concentrations. Grade 1 = very small area of necrosis from 0.5 ml undiluted material, Grade 5 = 

severe burn from 0.005 ml undiluted material, Grade 10 = severe burn from 0.5 ml of a 1% 

solution in water or propylene glycol. 

Results and discussions 

Overall irritation / corrosion results 

Irritation parameter overall irritation score 

Basis 

Time point 

 

Max. score 1 

Reversibility 

Remarks 

Irritant/corrosive response data 

Five rabbit eyes were not injured by 0.5 ml undiluted test material (grade 1). 

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

7.5 Repeated dose toxicity 

7.5.1 Repeated dose toxicity: oral 

Repeated dose toxicity: oral.001 
UUID IUC5-eefddf90-38fc-44d8-98e5-428a21ee84f8 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 10:57:33 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study performed following GLP 

Data source 

Reference 

Reference 

type 

study report 

Author Gill MW and Negley JE. Year 1990 

Title Triethylene glycol monomethyl ether. Ninety day subchronic drinking water 

inclusion neurotoxicity study in rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

Project Report 

52-607, 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1990-09-21 

Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 1998 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats. 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 
Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

This study is also summarized as a fertility study in Toxicity to reproduction.003 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Test guideline 

Qualifier equivalent or similar to 

Guideline EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents) 

Deviations 

Principles of method if other than guideline 

EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The purity of the material was at least 98.7%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 weeks old 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 
Male and female rats (8 weeks old, 15/sex/group) were treated with triethylene glycol 

monomethyl ether (TGME) for 91 days via drinking water at target doses of 0, 400, 1200 and 

4000 mg/kg/day. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

It is assumed that test material of 98.7% purity was diluted into the drinking water, such that the 

animals drinking an historically expected amount of water daily would ingest the target dose. 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily 

Doses/concentrations 

0, 400, 1200 and 4000 mg/kg/day. 

Basis nominal in water 

No. of animals per sex per dose 

15/sex/group 

Control animals 

yes, concurrent no treatment 

Positive control 

no data 

Examinations 

Observations and examinations performed and frequency 

Rats were observed daily for clinical signs and weekly for body weight and water and food 

consumption. Ten rats/sex/group were observed periodically for behavior (functional 

observational battery) and motor activity. 

Sacrifice and pathology 

After 91 days of treatment, tissues of 10 animals/sex/group were fixed in situ, and brains were 

removed. These animals received complete necropsies, and tissues from 6 animals/sex/group 

were processed for evaluation of the nervous system by light microscopy. The 5 

animals/sex/group not sacrificed and perfused in situ were killed by severing the brachial 

vessels to permitexsanguination. These animals received complete necropsies, and the liver, 

kidneys, brain, lungs, adrenals, and testes (males) were weighed. Liver and testes were 

examined by light microscopy. 

Statistics 

Data for continuous variables were analyzed with Levene's test for homogeneity of variance, 

analysis of variance (ANOVA), and by pooled variance t-tests. If Levene's test indicated 

heterogeneous variances, groups were analyzed with an ANOVA for unequal variances, 

followed by separate variance t-tests. Fisher's exact 2 x 2 groups comparisonswere used to 

analyze functional observational battery data. Motor activity counts were log transformed prior 

to analysis. Motor activity dose-effects, dose-sex interactions, and time-dose interactions were 

determined using repeated measures ANOVAs with dose and sex as grouping factors and time 

as a within-subject factor. Comparisons between treated and control groups were made for total 

test session activity (the sum of the counts across the 90-min test session) using ANOVA. To 

reduce the increased false positives associated with repeated significance testing, the correction 

procedure described by Mantel (Biometrics 36:381-399, 1980) was used when testing for 
overall significance. The frequency data for anatomic pathology were analyzed as described by 

Sokal and Rohlf (Biometry, WHFreeman, 1981). 

Any other information on materials and methods incl. tables 

No post obs. period was conducted.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 400 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Liver weight effects. 

Endpoint LOAEL 

Effect level 1200 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Liver weight effects. 

Endpoint NOAEL 

Effect level 1200 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Testicular effects. 

Endpoint LOAEL 

Effect level 4000 mg/kg bw/day (nominal) 

Sex male 

Basis for effect level / Remarks Testicular effects. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

yes 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

no data 

Urinalysis 

no data 
Neurobehaviour 

yes 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

The actual doses attained in the study (time weighted average) were 0, 420, 1240 and 4300 

mg/kg/day for males and 0, 420, 1290 and 4100 mg/kg/day for females.

One female in the high dose treatment group (approximately 4000 mg/kg/day) died on Day 37. 

Males and females treated with the highest dose consumed less food and had lower body 

weights and body weight gains than control animals. Water consumption decreased in high-dose 

females (by an average of 17%). 

Treatment with triethylene glycol monomethyl ether did not result in any clinical signs of 

toxicity, alterations in the functional observational battery, or gross microscopic lesions in the 

nervous system. Significant, small decreases in total test session motor activity were observed 

in the high-dose treatment group at the Day 60 (males only) and Day 90 (females) evaluation 

periods. Study personnel stated that “the decreases in motor activity were not considered to be 

neurotoxicologically significant based on the small magnitude of the changes, the parallel 

changes in body weights at the evaluation periods, and the lack of corroborative behavioral 

effects from the functional observational battery evaluations or histological changes in central 

or peripheral nervous system tissues.”

Increased relative liver weight was observed in males treated with 4000 mg/kg/day (5.229 ± 

0.3984) and 1200 mg/kg/day (3.951 ± 0.4191) versus control (3.214 ± 0.1519). Absolute liver 

weights of males treated with 4000 mg/kg/day were significantly greater than controls (25.926 ± 

3.1591 versus 18.978 ± 1.4925). Microscopic changes (hepatocellular cytoplasmic 

vacuolization and/or hypertrophy) were noted in livers of high-dose males (14/15). The severity 

of these liver lesions was minimal or mild (with the exception of moderate or marked 

vacuolization for 4 high dose males). Mild cholangiofibrosis was observed around a small 

number of bile ducts in high-dose males (7/15). This was not considered by study personnel to 

be physiologically significant due to the limited number of bile ducts affected and the mild 

nature of the effect (Gill et al., Int J Toxicol. 17:1-22, 1998). Minimal or mild hepatocellular 

hypertrophy was seen in 10/15 high dose females. Three males treated with 400 mg/kg/day and 

4 treated with 1200 mg/kg/day also exhibited minimal-mild hepatocellular cytoplasmic 

vacuolization and/or cellular hypertrophy (not statistically different from the controls). One 

control male had mild hepatocellular cytoplasmic vacuolization. None of the females treated 

with 400 or 1200 mg/kg/day exhibited these changes. Hepatocellular hypertrophy was 

considered by study personnel to be a possible adaptive change to accommodate increased 

demand to metabolize the test substance. 
The testes of males in the high dose group exhibited degeneration (12/15) and/or atrophy (5/5) 

of the seminiferous tubules (spermatocytes or developing spermatids). These effects were 

concluded to be related to treatment. The severity of the lesions was primarily mild to moderate 

for degeneration (11/12) and minimal to moderate for atrophy (5/5), indicating that not all 

tubules were affected and that a limited number of cells was affected within the affected 

tubules. One male treated with 1200 mg/kg had severe seminiferous tubule atrophy, a complete 

loss of cell types in the tubules (except for Sertoli cells) and moderate Leydig cell hypertrophy 

(not significant from control). This was not considered to be related to treatment because of the 

lack of a plausible explanation for the unusual dose-response relationship (the effect at this dose 

was more severe than that of a higher dose) and the low incidence of animals affected at this 

dose level (Gill et al., Int J Toxicol 17:1-22, 1998). No testicular changes were noted in males 

treated with 400 mg/kg/day TGME. 

Remarks on results including tables and figures 

Overall remarks, attachments 

Overall remarks 

The route of administration and maximum dose level was specified in a testing consent order (EPA. 

1989. 40 CFR 799, Fed Reg 54:13470-13477). The highest dose level was initially set at 5000 

mg/kg/day, but was decreased to 4000 mg/kg/day based on results of a 14-day dose range-finding 

drinking water study that demonstrated signs of debilitationat levels greater than 4000 mg/kg/day (Gill 

and Hurley, 1990). 

The authors state that a possible contributing factor in the development of testicular lesions at the high 

dose was low-level contamination of the test substance with the known testicular toxicant 

2-methoxyethanol (EGME). EGME was present in the test substance at a concentration of 0.02  0.04 

%, resulting in a EGME dose up to 1.7 mg/kg/day for animals in the high dose group. Given the length of 

the study, it is possible that EGME contributed to the testicular lesions. A comparison between the doses 

of EGME and TGME required to produce testicular toxicity indicated that TGME is 350 times less potent 

than EGME in producing testicular lesions in the rat.The dose of TGME that caused testicular toxicity 

(4200 mg/kg/day) is 4 times greater than the 1000 mg/kg/day limit dose generally recommended for 

subchronic studies. 

Based on the results of the study, the summary preparer assigned a NOAEL for effects on the liver of 

400 mg/kg/day, and a LOAEL of 1200 mg/kg/day (based on increased relative liver weight of males at 

this dose). The summary preparer-assigned NOAEL and LOAEL for testicular effects are 1200 and 4000 

mg/kg/day, respectively. The EPA has determined the NOAEL for testicular effects is between 400 and 

1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers RM1 

screening document (draft), Feb. 24, 1995). 

Repeated dose toxicity: oral.002 

UUID IUC5-57449644-ba3a-427c-96c4-d077a125d217 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 
America 

Date 2009-02-17 13:56:47 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1993 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted study run according to GLP and with good characterization of 

test material composition. Number of animals per dose not completely specified. 

Data source 

Reference 

Reference 

type 

study report 

Author Taupin PJY Year 1993 

Title Brake fluid DOT 4: A 28 day oral (gavage) toxicity study in the rat. 

Bibliographic 

source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

 

Owner 

company 

Shell 

Company 

study no. 

SBGR.92.180 Report 

date 

1993-10-07 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

Guideline was not specified, but study was conducted according to typical procedures for 28 

day oral repeated dose testing. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 
Identity Brake fluid DOT 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

no data 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

28 days 

Frequency of treatment 

daily 

Doses/concentrations 

25, 150, 1000 mg/kg/day 

Basis 

No. of animals per sex per dose 

not detailed 

Control animals 

yes 

Details on study design 

no data 

Positive control 

no data 

Examinations 

Sacrifice and pathology 
Gross pathology examinations were performed 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOEL 

Effect level 150 mg/kg bw/day (nominal) 

Sex male/female 

Basis for effect 

level / Remarks 

No treatment related effects seen at 150 mg/kg bw per day. Effects were seen 

at the next higher dose 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption and compound intake (if feeding study) 

yes 

Food efficiency 

no data 

Water consumption and compound intake (if drinking water study) 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

no data 

Histopathology: neoplastic 

not examined 

Details on results 

Food intake of males dosed with 1000 mg/kg/day was slightly reduced for first 2 weeks of 

treatment. Livers of all 5 males and some females dosed with 1000 mg/kg/day showed slight 

centrilobular hypertrophy (which was considered by the investigators to be adaptive). None of

the controls exhibited this effect. There was no significant effect of treatment on liver weight. 
No effects on other organs (including ovaries and testes) were noted. A NOEL of 150 

mg/kg/day was assigned by the investigator. 

7.5.2 Repeated dose toxicity: dermal 

Repeated dose toxicity: dermal.001 

UUID IUC5-96d5f766-7416-44bd-8188-b55cb9fb01a9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 11:05:37 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted guideline study per GLP, with purity of test substance 

provided. 

Data source 

Reference 

Reference 

type 

 

Author Corley RA, Ciesslak, Breslin WJ, Lomax LG. 13-Week 

dermal toxicity study in Sprague-Dawley rats 

Year 1990 

Title 13-Week dermal toxicity study in Sprague-Dawley rats 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

Study ID 

K-005610-004 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

 Report 

date 

1990-09-26 

Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats. 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 
Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a fertility study in Sprague-Dawley rats. 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: as specified in a testing consent order (EPA. 1989. 40 CFR 799, 

Fed Reg 54:13470-13477). 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The test substance was triethylene glycol monomethyl ether (CAS 112-35-6). Purity (as 

determined by gas chromatography) was 99.23 % at the onset of the study and 99.24% at 

completion of the in-life phase. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 week-old rats 

Administration / exposure 

Type of coverage 
semiocclusive 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 4000 mg/kg/day for 13 weeks. Test 

material was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

Purity (as determined by gas chromatography) was 99.23 % at the onset of the study and 

99.24% at completion of the in-life phase. 

Duration of treatment / exposure 

Six hours daily, 5 days/week for 13 weeks, 91 days. There was no post exposure observation 

period. 

Frequency of treatment 

5 days/week for 13 weeks 

Doses/concentrations 

0 (sham control), 400, 1200 or 4000 mg/kg/day 

Basis analytical per unit body weight 

No. of animals per sex per dose 

10/sex/dose level 

Control animals 

yes, sham-exposed 

Details on study design 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 4000 mg/kg/day for 13 weeks. Test 

material was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. Parameters evaluated throughout the study included 

clinical and ophthalmic observations, dermal irritation, body weight, food consumption, clinical 

pathology, estrous cyclicity (daily vaginal smears during study weeks 12 and 13), hematology 

(just prior to sacrifice), clinical chemistry (just prior to sacrifice), and urinalysis (just prior to 

dosing and during final week of dosing). Organ weight (standard set), gross pathology and 

histopathology (control and high dose group) were evaluated upon necropsy. The oocytes, 

corpora lutea, and follicles from each ovary were evaluated with regard to their normal 

development. Bone marrow smears were prepared from each animal from the shaft of the femur. 

The testes and epididymes also were examined microscopically for males in the intermediateand low-dose groups. 

Examinations 

Observations and examinations performed and frequency 

Parameters evaluated throughout the study included clinical and ophthalmic observations, 
dermal irritation, body weight, food consumption, clinical pathology, estrous cyclicity (daily 

vaginal smears during study weeks 12 and 13), hematology (just prior to sacrifice), clinical 

chemistry (just prior to sacrifice), and urinalysis (just prior to dosing and during final week of 

dosing). 

Sacrifice and pathology 

Organ weight (standard set), gross pathology and histopathology (control and high dose group) 

were evaluated upon necropsy. The oocytes, corpora lutea, and follicles from each ovary were 

evaluated with regard to their normal development. Bone marrow smears were prepared from 

each animal from the shaft of the femur. The testes and epididymes also were examined 

microscopically for males in the intermediate- and low-dose groups. 

Other examinations 

Additional satellite groups of 5 rats/sex/dose level were administered TGME for 30 days for 

interim hematological (48 hr and 30 days), clinical chemistry (48 hr and 30 days), body weight 

determinations, clinical observations, and dermal irritation. 

Statistics 

For the main study group, the data for continuous variables were evaluated by Bartlett's test for 

equality of variances. Depending on the outcome of the test, data were analyzed using a 

parametric or nonparametric analysis of variance (ANOVA), followed by a Dunnett's test 

(parametric data) or Wilcoxon rank-sum test (nonparametric data) with a Bonferroni correction 

for multiple comparisons when appropriate. Statistical outliers were identified by a sequential 

test, but were not excluded from analyses.

For the satellite group, all data (except those for differential leukocyte count and red blood cell 

parameters) were first tested for equality of variance using Bartlett’s test. Hematologic and 

clinical chemistry parameters were evaluated during a two-way analysis of variance with the 

factors of sex and dose. Examinations were first made for a significant sex-dose interaction. If 

this existed, a one-way ANOVA was preformed separately for each sex. If no sex-dose 

interaction was identified and a dose effect was identified, or if in the subsequent ANOVA 

separated by sex a dose-effect was identified, then separate ANOVAs were used for each 

treatment group with the control. A Bonferroni correction was used to control for multiple 

comparisons.

Any other information on materials and methods incl. tables 

The route of administration and maximum dose level was specified in a testing consent order (EPA. 

1989. 40 CFR 799, Fed Reg 54:13470-13477). The highest dose level (4000 mg/kg/day) represented 

the maximum amount of test substance that could be retained on the back and sides of the rat as 

determined in a preliminary 2-week study (Yano et al. 1987. Dow Chemical Company Study ID: 

K-005610-001, Dated Nov. 25, 1987).The EPA has determined that based on severe testicular toxicity in 

1/10 rats given 4000 mg/kg/day and minimal decreases in developing germ cells (1-5% of seminiferous 

tubules affected) in 1/10 rats given 1,200 mg/kg/day, the NOAEL for systemic toxicity is between 400 

and 1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers 

RM1 screening document (draft), Feb. 24, 1995). This value was reached even though it was recognized 

that the testicular changes in the 1,200 mg/kg/day rat were within historical control limits for 

Sprague-Dawley rats (0-17%).

Results and discussions 

Effect levels 

Endpoint NOAEL 
Effect 

level 

4000 mg/kg bw/day (actual dose received) 

Sex male/female 

Basis for 

effect 

level / 

Remarks 

NOAEL = 4000 mg/kg bw (summary preparer); > 400 and < 1200 mg/kg bw (EPA). 

A significant decrease (15%) in platelet counts was noted in females dosed with 4000 

mg/kg for 13 weeks when compared to control. 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

yes 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

Mean body weight and food consumption were comparable to controls throughout the study. 

There were no treatment-related hematological changes in the interim groups or in males 

administered test material for 13 weeks. A significant decrease (15%) in platelet counts was 

noted in females dosed with 4000 mg/kg for 13 weeks when compared to control (1217 +/- 280 
x 103/cu mm); however, the value (1034 +/- 92 x 103/cu mm) was only slightly below the 

historical control range (1050 to 1262 +/- 93 to 294 x 103/cu m) Therefore, it was not 

considered to be toxicologically significant (Gill et al., Int J Toxicol 17:1-22, 1998). There were 

no other changes in any hematological parameters (hematocrit, hemoglobin, erythrocyte count, 

total leukocyte count, and red blood cell indices). There were no changes in clinical chemistries, 

urinalyses, organ weights, or estrous cyclicity measurements. 

Bilaterally decreased spermatogenesis in seminiferous tubules and decreased spermatozoa in the 

epididymes (both were graded as severe) were noted in the testes of one high dose male rat. 

This animal had a complete lack of mature spermatids in greater than 41% of tubules in each 

testicle, few spermatids beyond stage 12 of development in the seminiferous epithelium, and 

decreased spermatic elements in the head and tail of greater than 41% of the tubules and ducts 

in the epididymides. The testes of one male treated with 1200 mg/kg exhibited different 

testicular changes [bilateral multifocal degeneration of spermatocytes and spermatids from 

germinal epithelium (graded as very slight), and multinucleated spermatids]. In this rat, all 

stages of the cycle of the seminiferous epithelium were observed in morphologically normal 

tubules. The epididymides of this rat had decreased spermatic elements in the head and tail of 

1-5% of ducts. Some of the ducts also contained immature spermatids. 

Remarks on results including tables and figures 

Study personnel concluded that the bilateral microscopic testicular changes observed in one high-dose 

and one mid-dose male rat were unrelated to treatment. Reasons given were that the dissimilarity of the 

lesions for the two animals suggested that they occurred spontaneously, and the incidence of animals 

with lesions (1/10 in each group) was well within that of historical controls (0-17%). Study personnel also 

stated that the degenerative changes in the testes of one mid-dose and one high-dose rat were not 

consistent with the types of lesions that have been attributed to 2-methoxyethanol (2-ME). The cell types 

that are most vulnerable to 2-ME are the pachytene spermatocytes and round spermatids (Chapin et al., 

Fund Appl. Toxicol 5:182-189, 1985). As the dose of 2-ME is increased, the number and types of cells 

affected increase up to the point that the germinal epithelium is significantly degenerated and all stages 

of spermatogenesis are affected (Chapin et al., Fund Appl. Toxicol 5:182-189, 1985; Miller et al., Fund 

Appl Toxicol 3:49-54, 1983.). In contrast, the testicular effects seen with the high dose animal treated 

with TGME consisted of a virtually complete lack of mature spermatids beyond stage 12. All other 

stages, including spermatogonia and spermatocytes, were present and appeared morphologically 

normal. In the mid-dose rat, the only effects noted consisted of very slight degeneration of 

spermatocytes and spermatids similar to those seen in historical control animals. 

Study personnel also stated that the lymphoid tissues and hematologic parameters, which have been 

reported to be affected at doses of 2-methoxyethanol that have been associated with testicular changes 

(Miller et al., Fund. Appl. Toxicol. 3:49-54, 1983) were unattected in this TGME study. Taking all factors 

into considereation, the testicular lesions observed in this dermal study could not be directly attributed to 

TGME exposure. 

Repeated dose toxicity: dermal.002 

UUID IUC5-77e34cdc-e7a6-4d3e-8230-745fe4db1d2b 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 
Date 2009-02-12 11:11:23 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for MSDS 

Study result 

type 

experimental result Study 

period 

198

5 

Reliablility 1 (reliable without restriction) 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1985 

Title Nine-day and ninety-day dermal toxicity studies of CARBOWAX MPEG-350 in 

rabbits 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1985-05-3

0 

Reference 

type 

 

Author Hermansky SJ, Leung HW. Year 1997 

Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a fertility study. This is toxicity to reproduction.002 

Materials and methods 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 
no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG 350 

Details on test material 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) was reported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. This material is a 

mixture of several methylated glycol ethers of differing molecular weight (ranging from 

diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Body weights of males and females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study 

initiation 

Administration / exposure 

Type of coverage 

open 

Vehicle 

other: methyl cellulose in distilled water 

Details on exposure 

Dosing: New Zealand white rabbits (10/sex/dose) were treated dermally on clipped dorsal skin 

with 1.0 ml of vehicle (0.1% (w/v) methyl cellulose in distilled water), 50% CARBOWAX 

MPEG-350 (w/v dilution in 0.1% methyl cellulose in water) or 100% CARBOWAX 

MPEG-350, for six hours/day, five days per week for 90 days. Body weights of males and 

females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study initiation. Rabbits were fitted with 

Elizabethan collars after dosing to prevent ingestion of test material. After each 6-hour exposure 

the application site was wiped with a paper towel dampened with water and then dried using a 

towel. Rabbitswere then uncollared until the next treatment. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) was reported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. 

Duration of treatment / exposure 
six hours/day, five days per week for 90 days. 

Frequency of treatment 

five days per week 

Doses/concentrations 

1 ml of 50% and 100% material (approximately 169 and 338 mg/kg/day) 

Basis analytical per unit body weight 

No. of animals per sex per dose 

10/sex/dose 

Control animals 

yes, concurrent vehicle 

Examinations 

Observations and examinations performed and frequency 

Observations: All rabbits were observed daily (weekdays) for death, clinical signs and dermal 

irritation. Any irritation was scored immediately prior to dosing using the Draize system. Body 

weights were recorded on the morning of the first day of dosing, weekly thereafter and prior 

tosacrifice. Food consumption was measured weekly. Urine was collected from 5 

animals/sex/group during the last two weeks of dosing and subjected to standard analyses. 

Standard hematology and clinical chemistry parameters were evaluated for all animals just prior 

to sacrifice. 

Sacrifice and pathology 

Necropsy: All animals were sacrificed and necropsied after 13 weeks of treatment. Weights 

were recorded for liver, kidneys, brain and adrenals of all animals and testes of males. 

Histopathologic examinations were performed on tissues from high-dose and control animals. 

Statistics 

Statistical Analyses: Body weight, food consumption, organ weight and clinical pathology data 

from the three groups were compared using Levene's test for homogeneity of variance. An 

analysis of variance was performed on the groups when data were homogeneous. If 

significantdifferences were found, group differences were delineated by grouped variance 

Student t-tests. When data were heterogeneous, Welch and Brown-Forsyth analyses were 

performed and significant differences among groups were determined using separate variance 

Student t-tests. Draize skin irritation scores were analyzed using the Kruskal-Wallis test, and 

significant differences in groups were determined using the Wilcoxon rank sum test (as 

modified by Mann-Whitney). Frequency data (i.e. histological) were compared using Fisher's 

exact tests. The p value of 0.05 (two-tailed) was used as the critical level of significance for all 

analyses. 

Any other information on materials and methods incl. tables 

A preliminary range-finding study in 15 rabbits dosed 6 hr/day for 9 days (Carpenter, Range finding tests 

on methoxy polyethylene glycols of approximate molecular weights 350, 550 and 750. Melon Institute of 

Industrial Research, University of Pittsburgh. Report dated 5-13-47.1947) showed that daily 

administration of 1 ml of 50% or 100% test material only caused mild skin irritation. Therefore, these 

doses were chosen for the 90-day study.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 338 mg/kg bw/day (actual dose received) 
Sex female 

Basis for effect level / 

Remarks 

Mild acanthosis (epidermal thickening) 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

Mild acanthosis (epidermal thickening) was found in 3 females dosed with 100% material. 

Transient, dose-related erythema (Grade 1) and desquamation of skin occurred. No systemic 

effects were observed in rabbits treated with either 50% or 100% test material. 

Remarks on results including tables and figures 

The NOAELs for local or systemic effects were not listed by the investigators. Based on the data, these 

values are 50% and 100%, respectively. Based on weights of animals determined at weekly intervals 

and the reported density of test material (1.09 g/ml) doses can be calculated on average mg/kg/day 

basis. These doses are 169 mg/kg/day (for 50%) and 338 mg/kg/day (for 100%).

Repeated dose toxicity: dermal.003 
UUID IUC5-28a8564b-5675-47e2-bd3f-df2751cc0ae1 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 11:13:44 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1987 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP with test substance well characterized as to 

composition. No guideline specified but study was conducted according to 

standard procedures. 

Data source 

Reference 

Reference 

type 

study report 

Author Gray TM. Year 1987 

Title A 28-day dermal toxicity study in rats on PEG-methyl ether (Medical Group 

Number #85-166). 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

Document 

Number 4257, 

Owner 

company 

Armour-Dial, Inc. 

Company 

study no. 

 Report 

date 

1987-05-15 

Reference 

type 

study report 

Author Hermansky SJ, Leung HW. Year 1997 

Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company Report 
study no. date 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

No guideline specified but study was conducted according to standard procedures. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowax MPEG-350 ( 

Details on test material 

Test material was Carbowax MPEG-350 (CAS No. 9004-74-4) from Union Carbide. This 

material is a mixture of several methylated glycol ethers of differing molecular weight (ranging 

from diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3).

Test material also contained 1 ppm of 2-methoxyethanol. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male 

Details on test animals and environmental conditions 

The animals were 52 days old. 

Administration / exposure 

Type of coverage 

open 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Male rats (52 days old) were divided into 4 groups of 15 animals (control, low-, mid-, and 

high-dose groups and were acclimated to Elizabethan collars for 7 days before treatment. One 
mid-dose and 3 high-dose animals were dropped before treatment because they appeared 

dehydrated. Each group was treated with 0 (sham control), 1.25, 2.5 or 5 g/kg/day test material 

on shaved backs. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

four weeks 

Frequency of treatment 

five days per week 

Doses/concentrations 

0 (sham control), 1.25, 2.5 or 5 g/kg/day 

Basis no data 

No. of animals per sex per dose 

15 male animals per dose 

Control animals 

yes, sham-exposed 

Details on study design 

Rats were sacrificed 3 days after the last treatment. 

Positive control 

no data 

Examinations 

Observations and examinations performed and frequency 

Signs of irritation, body weights of animals 

Sacrifice and pathology 

Organ weights, gross pathology 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1250 mg/kg bw/day 

Sex male 

Basis for effect 

level / Remarks 

This value is based on significant effects on body weight or weight gain at 

higher doses. 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

no effects 

Food efficiency 

no data 
Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

no data 

Clinical chemistry 

no data 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

no data 

Histopathology: neoplastic 

not examined 

Details on results 

Minor, transient irritation was noted at the application site of all treated animals. Body weights 

of animals given 5.0 g/kg/day and body weight gains of animals given 2.5 g/kg/day were 

depressed. Absolute weights of the thymus and testes of rats treated with 1.25 g/kg/day were 

83% and 93%, respectively of control weights (significantly different). Relative weights of 

these organs were not significantly different from control. There were no pathological 

abnormalities in either of these organs. 

Remarks on results including tables and figures 

One, 3, and 2 animals in the low-, mid- and high-dose groups slipped their collars and therefore may 

have ingested the material during grooming. Results in these animals were not significantly different 

from those animals that did not slip their collars. Therefore, possible ingestion of material in these 

animals did not appear to affect the results of the study. 

The investigators did not identify a NOAEL for the study. However, they stated that there were no 

indications of systemic toxicity secondary to repeated cutaneous exposure to MPEG-350 in this study. 

Based on the information given, the summary preparer assigned a NOAEL of 1250 mg/kg/day. This 

value is based on significant effects on body weight or weight gain at higher doses (although the authors 

stated that these effects may have been due to use of Elizabethan collars). Although the absolute 

weights of the thymus and testes of rats treated with 1.25 g/kg/day were significantly less than control, 

relative weights of these organs were not different from control, there were no histological changes in 

these organs, and these effects were not noted at higher doses. Therefore, they were considered by the 

summary preparer to be unrelated to treatment.

Repeated dose toxicity: dermal IRDC TGBE 1986.005 

UUID IUC5-f6fc6210-aefc-4b84-b058-1787e38841bc 

Dossier UUID 0 
Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 11:16:15 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

86 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted, documented study, but duration less than 28 days. 

Data source 

Reference 

Referenc

e type 

study report 

Author Year 1986 

Title 21-Day dermal toxicity study in rabbits-limit test on triethylene glycol monobutyl 

ether, triethylene glycolmonoethyl ether and triethylene glycol monomethyl ether 

Bibliogr

aphic 

source 

 

Testing 

laborator

y 

International Research and Development Corporation (IRDC). Rep

ort 

no. 

 

Owner 

company 

 

Compan

y study 

no. 

 Rep

ort 

date 

1986-0

7-22 

Materials and methods 

Test type 

subacute 

Limit test 

yes 

Principles of method if other than guideline 

Typical procedure followed for subacute dermal study. 

GLP compliance 

yes 

Test materials 
Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

no data 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Rabbits were observed over a 51-52 day pretest period for clinical abnormalities. Prior to 

randomization, rabbits were fasted (19-23 hours), and blood samples were taken from the 

central ear artery for control hematological and biochemical evaluations. Healthy rabbits (4- 4.5 

months of age) were randomly divided into groups of 5 per sex. 

Administration / exposure 

Type of coverage 

semiocclusive 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Prior to study initiation, hair was removed from the back of each rabbit with an electric clipper. 

Rabbits were shaved as necessary during the course of the study to prevent the test material 

from becoming matted in the hair and to facilitate accurate observations. One group of rabbits 

was left untreated and the other was treated with 1000 mg/kg test material, five days per week 

for 3 weeks. Dose volumes were calculated based on the specific gravity of test material (as 

determined at the study site) and the body weight of animals (determinedweekly). Test material 

was placed on the back using a 5 cc plastic syringe. A glass rod was used to evenly distribute 

the dose over the test site. Following dosing, test sites (of all animals, including controls) were 

wrapped with gauze bandaging and Dermiform tape and plastic restraint collars were attached 

to the rabbits. Collars were removed after 6 hours, and test sites (of all animals, including 

controls) were washed with tepid tap water and dried with paper towels. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 
Duration of treatment / exposure 

21 days 

Frequency of treatment 

6 hr/day, 5 days/week for 3 weeks 

Doses/concentrations 

limit dose of 1000 mg/kg 

Basis nominal per unit body weight 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

yes, sham-exposed 

Details on study design 

All animals were fasted for 19-23 hours before study termination.

Positive control 

no data 

Examinations 

Observations and examinations performed and frequency 

Animals were observed once daily for clinical signs and twice daily for mortality. Food 

consumption was estimated daily based on a visual assessment of remaining food. Body weights 

were recorded weekly. Rabbits were scored immediately prior to each dosing for dermal 

irritation in accordance with the Draize method. Blood samples taken from the central ear artery 

of animals at study termination were analyzed for standard hematological (total and differential 

leukocyte count, erythrocyte count, hemoglobin, hematocrit, platelet count, reticulocyte count, 

mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin 

concentration) and biochemical (sodium, potassium, chloride, calcium, phosphorus, total 

bilirubin, gamma glutamyltranspeptidase, aspartate aminotransferase, alanine aminotransferase, 

ornithine carbamoyltransferase, urea nitrogen, creatinine, total protein, albumin, globulin, 

cholesterol and glucose) parameters. 

Sacrifice and pathology 

All animals were examined grossly upon study termination. 

Weights of adrenals, brain, kidneys, liver, ovaries and testes were taken. A full complement of 

tissueswas examined microscopically. Body weights (weeks 1, 2, 3, and 4), clinical pathology 

parameters and organ weights (absolute and relative) were analyzed. 

Statistics 

Body weights (weeks 1, 2, 3, and 4), clinical pathology parameters and organ weights (absolute 

and relative) were analyzed. using Bartlett’s test for homogeneity of variance and analysis of 

variance (one-way). The treatment groups were compared to the controls using the appropriate 

t-statistic (for equal or unequal variance). Dunnett’s multiple comparison tables were used to 

judge the significance of the differences. Total bilirubin data were transformed to ranks and 

analyzed using a non-parametric test. All tests were two-tailed, with p < 0.05 and p < 0.01 as 

levels of significance. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1000 mg/kg bw/day 
Sex male/female 

Basis for effect level / 

Remarks 

No adverse effects seen at the limit dose of 1000 mg/kg bw 

Observations 

Clinical signs and mortality 

yes 

Dermal irritation 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

There were no deaths or signs of overt toxicity over the study period. There were no significant 

differences in body weights or food consumption between treated or control groups. Some 

hematological and biochemical values from treated animals were different from controls at 

termination. However, since the same changes were noted in blood samples taken from the 

animals prior to treatment, they were not considered by the investigators to be related to 

treatment. Mild to moderate desquamation and fissuring of skin was noted in most rabbits after 

2 to 3 weeks of treatment with test material. This was confirmed microscopically and consisted 

of trace acanthosis and trace to moderate dermatitis. Testicular degeneration (scored as trace in 

severity) , occurred in one rabbit each from the TGEE and TGME-treated groups. This lesion 

was characterized by the presence of spermatid giant cells, focal tubular hypospermatogenesis, 
or cytoplasmic vacuolization. The pathologist stated that “random occurrence of this lesion was 

suggestive of its spontaneous nature and was not test article related. A high incidence of similar 

changes of spontaneous nature in normal New Zealand White rabbits has been reported by 

Morton et al. in "Vet Pathol 23: 176-183, 1986 and Vet Pathol 23: 210-217, 1986.” 

Based on the results, the investigators concluded that in this study, there was no systemic 

toxicity induced by treatment with 1000 mg/kg/day test material. Therefore, the NOAEL is 

1000 mg/kg/day. 

Remarks on results including tables and figures 

Toxicity of triethylene glycol monomethyl (TGME, CAS No. 112-35-6) and monoethyl ethers (TGEE, 

CAS No. 112-50-5) at 1000 mg/kg also was tested in this study. The skin effects noted for triethylene 

glycol butyl ether were more severe than those for TGME and TGEE.

Repeated dose toxicity: dermal.006 

UUID IUC5-97e117c7-391c-488b-8f68-5364d9ce0a2e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 11:19:32 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted study, but of only 2 week duration. Purity of test substance 

not stated. 

Data source 

Reference 

Reference 

type 

study report 

Author Yano BL, Phillips JE, Battjes JE. Year 1987 

Title Triethylene glycol monomethyl ether: 2-week dermal toxicity study in male and 

female Sprague-Dawley rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company Study ID:K-005610-001, Report 1987-11-
study no. date 25 

Materials and methods 

Test type 

subacute 

Limit test 

no 

Principles of method if other than guideline 

Standard procedure used at the time for a two week repeat dose dermal study. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6). 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity is unknown. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

200 to 350 g weight 

Administration / exposure 

Type of coverage 

semiocclusive 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Groups of five rats/sex (200 to 350 g)were dosed with 0, 1000, 2500, or 4000 mg/kg/day of test 

material on clipped back skin, 6 hours/day for a total of 9 applications during a 12 day period. 

Test material was held in place with a gauze patch and elastic bandage. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 
Duration of treatment / exposure 

two weeks, 9 dose applications 

Frequency of treatment 

daily 

Doses/concentrations 

0, 1000, 2500, 4000 mg/kg/day 

Basis nominal per unit body weight 

No. of animals per sex per dose 

five rats/sex 

Control animals 

yes, concurrent no treatment 

Examinations 

Observations and examinations performed and frequency 

Parameters evaluated included clinical observations (including skin evaluations), body weight, 

feed consumption, clinical chemistry, hematology, urinalysis, and fasted body weights.

Sacrifice and pathology 

Organ weight measurement, gross pathology, and histopathology were conducted. 

Other examinations 

no data 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 4000 mg/kg bw/day (nominal) 

Sex male/female 

Basis for effect 

level / 

Remarks 

No significant obverse effects were observed at this or lower doses that were 

considered treatment related. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption 

yes 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 
yes 

Urinalysis 

yes 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

There were no treatment-related adverse systemic effects. A few males and females treated with 

either 1000 or 2500 mg/kg/day had a few small scabs or crusts at the test site. These alterations 

were slight in degree and did not adversely affect the rats.

A number of clinical chemistry, hematological and urinalysis variables were significantly 

different from control. The lower albumin concentration in females from the 1000 mg/kg/day 

group and higher urea nitrogen concentration in males from the 2500 mg/kg/day group were not 

considered by study personnel to be related to treatment because the effects were not noted at 

higher concentrations. The lower albumin concentration in males treated with 4000 mg/kg/day 

also was not attributed to treatment by study personnel because the value was within the range 

of individual animal values in the control group. A slightly higher alanine aminotransferase 

activity was also statistically identified in rats from the 4000 mg/kg/day group. As the value was 

only marginally different from control and was not associated with any histologic changes in the 

liver, study personnel did not consider this to be related to treatment. A slightly higher red 

blood cell count and hemoglobin concentration was observed in rats given 4000 mg/kg/day. 

Since these were only slightly higher than control values, study personnel did not consider them 

to be related to treatment. A few of therats given 2500 or 4000 mg/kg/day had watery cecal 

contents and/or hemolyzed blood in the stomach. These gross pathologic observations were not 

associated with any histologic abnormalities in these tissues or alterations in hematologic and 

clinical chemistry parameters. Therefore, they were not attributed by study personnel to be 

related to treatment. 

7.5.4 Repeated dose toxicity: other routes 

Repeated dose toxicity: other routes.001 

UUID IUC5-303a73fc-8959-46fb-acd3-c853a3fecb22 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:06:20 EST 

Remarks 

 
Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

97 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted, thorough study following GLP. Test substance was well 

defined. 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1997 

Title Subchronic intravenous toxicity study in the rat. Carbowax Sentry M-PEG 350-NF 

and Carbowax Sentry PEG 400 NF and FCC. 

Bibliograp

hic source 

 

Testing 

laboratory 

North American Science Associates, Inc (NAMSA). Repor

t no. 

Report 

TS064-900/S

. 

Owner 

company 

 

Company 

study no. 

 Repor

t date 

 

Materials and methods 

Test type 

subchronic 

Limit test 

no 

Principles of method if other than guideline 

One i.v. dose plus concurrent control. Typical battery of observations for a two week study. 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX Sentry MPEG-350 

Details on test material 

Test material was CARBOWAX Sentry MPEG-350 (CAS No. 9004-74-4), NF grade. This 
material is a mixture of several methylated glycol ethers of 

differing molecular weight (ranging from diethylene glycol monomethyl ether (C2) to 

heptadecaethylene glycol monomethyl ether (C17)). The 

majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) 

tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 1.303% triethylene glycol monomethyl ether (CAS No. 112-35-6), 0.181% 

diethylene glycol monomethyl ether (CAS No. 111-77-3). 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Groups of six rats/sex (6-8 weeks of age, 114 g to 189 g 

Administration / exposure 

Route of administration 

intraveneous 

Vehicle 

other: 

Details on exposure 

Groups of six rats/sex (6-8 weeks of age, 114 g to 189 g) were dosed intravenously for 14 

consecutive days with either vehicle (0.9% sodium chloride, USP), or 1 g/kg/day test material. 

Analytical verification of doses or concentrations 

yes 

Duration of treatment / exposure 

fourteen days 

Frequency of treatment 

daily for fourteen consecutive days 

Doses / concentrations 

either vehicle (0.9% sodium chloride, USP), or 1 g/kg/day test material. 

No. of animals per sex per dose 

six rats/sex 

Control animals 

yes, concurrent vehicle 

Examinations 

Observations and examinations performed and frequency 

Animals were observed daily for general health. Body weights were recorded on days 1, 8 and 

15 of treatment. 

Sacrifice and pathology 

All animals were euthanized on day 15. Blood was collected from the posterior vena cava and 

standard hematological and clinical chemistries were performed. The heart, liver, spleen, 

kidneys, adrenal glands and gonads were weighed, fixed, and processed for microscopic 

evaluation. The data were analyzed using a standard BMDP Statistical Software Package. 
Statistics 

The data were analyzed using a standard BMDP Statistical Software Package. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect level 1000 mg/kg bw/day (actual dose received) 

Sex male/female 

Basis for effect level / 

Remarks 

No adverse effects were observed at the single dose tested. 

Observations 

Clinical signs and mortality 

yes 

Body weight and weight gain 

yes 

Food consumption 

no data 

Food efficiency 

no data 

Water consumption 

no data 

Ophthalmoscopic examination 

no data 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

no data 

Neurobehaviour 

no data 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

not examined 

Details on results 

There was no effect of treatment on body or organ weights or hematological values. Tissues 

(including testes) from treated animals were histologically similar to those of controls. There 

was a significant difference in aspartate aminotransferase activity in control (95 +/- 13 IU/L) 

and treated males (81 +/- 6 IU/L) that was not considered by the investigators to be related to 

treatment since the values for both groups were within the normal expected range. An increase 

in aspartate aminotransferase activity, rather than a decrease would be indicative of liver 
toxicity. 

7.6 Genetic toxicity 

7.6.1 Genetic toxicity in vitro 

Genetic toxicity in vitro BASF TGBE 1989.001 

UUID IUC5-978d151e-c7ca-41a4-be56-3ee011a61a3a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:10:39 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

8

9 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

This was an OECD guideline study, but only 4 strains were tested. Purity of 

test material is not high. 

Data source 

Reference 

Reference type study report 

Author Year 1989 

Title 

Bibliographic 

source 

 

Testing laboratory Department of Toxicology Report no. 

Owner company BASF AG 

Company study no. Project No. 40M0573/884365 Report date 1989-02-24 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 471 (Bacterial Reverse Mutation Assay) 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 
no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity Triethylene glycol butyl ether 

Details on test material 

Test material purity was 87.2%. 

Method 

Species/strain 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Details on mammalian cell 

lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation system S-9 

Test concentrations 

20-5000 micrograms/plate 

Controls 

Negativ

e 

controls 

yes 

Solvent 

/ 

vehicle 

controls 

 

True 

negativ

e 

controls 

 

Positive 

controls 

yes 

Positive 

control 

substan

ce 

other: Positive controls were N-methyl-N’-nitro-N-nitroso-guanidine MNNG), 

4-nitro-o-phenylenediamine, 9-aminoacridine chloride monohydrate (AACM) and 

2-aminoanthracene (AA) 

Remark 
s 

Details on test system and conditions 

Standard test: Test tubes containing 2 ml of soft agar, bacteria (0.1 ml of > = 10E8 S. 

typhimurium TA98, TA100, TA1535, or TA1537), test chemical (0.1 ml of test solution, 

positive control, or aqua dest. solvent) and either buffer or S-9 mix from Aroclor 1254-induced, 

male, Sprague Dawley rats (0.5 ml) were prepared. After mixing, the samples were poured onto 

minimal glucose agar plates within 30 seconds. 

Preincubation test: Test tubes containing bacteria (0.1 ml of > = 10E8 S. typhimurium TA98, 

TA100, TA1535, or TA1537), test chemical (0.1 ml of test solution, positive control, or aqua 

dest. solvent) and either buffer or S-9 mix from Aroclor 1254-induced, male, Sprague Dawley 

rats (0.5 ml) were incubated at 37 degrees C for 20 minutes. Supplemented top agar (2 ml) was 

then added. After mixing, the overlay was poured onto minimal glucose agar plates. Plates were 

incubated at 37 degrees C for 48 hours in the dark. All dose levels (including positive and 

negative controls) were assayed in triplicate. The method of colony counting was not specified. 

Positive controls were 5 micrograms N-methyl-N’-nitro-N-nitroso-guanidine MNNG) for 

strains TA100 and TA1535, 10 micrograms 4-nitro-o-phenylenediamine for strain TA98, and 

100 micrograms 9-aminoacridine chloride monohydrate (AACM) for strain TA 1537 (all in the 

absence of S-9), and 10 micrograms 2-aminoanthracene (AA) for all strains in the presence of 

S-9. All positive control chemicals were dissolved in DMSO. 

Evaluation criteria 

Evaluation Criteria: The test material was considered a mutagen if both the mean number of 

revertant colonies was at least 2 times higher than the mean of the negative (solvent) control and 

it induced a reproducible dose-response relationship over several concentrations. If the 

dose-response was not definitive, it was considered to be a presumptive mutagen. If the 

reversion rates were between 2 and 3 times that of negative controls, the results were considered 

equivocal or inconclusive. 

Results and discussions 

Test results 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid no data 

Negative controls valid no data 

Positive controls valid yes 

Additional information on results 

Standard test: The average number of revertant in the controls for strains TA98, TA100, 

TA1535, and TA1537 in the absence of S-9 were 23, 114, 16, and 9. Addition of S-9 to strain 

TA98 increased the control mutation frequency to 34. S-9 had no effect on the frequency of 

mutations in the other strains. Positive controls induced an average of from 152 revertants in 

TA1535 to 1690 revertants in TA100. The number of revertants induced by test material was 

not increased from that of control at any concentration. The average number of revertants in 

cultures treated with test material (in the absence or presence of S-9) ranged from 109-140 in 

TA100, 12-21 in TA1535, and 8-11 in TA1537. Similar to control TA98 cultures, the average 
number of revertants in TA98 cultures treated with test material in the presence of S-9 (33-36) 

were higher than in the absence of S-9 (19-24).

Preincubation test: The average number of revertant in the controls for strains TA98, TA100, 

TA1535, and TA1537 in the absence of S-9 were 24, 111, 17, and 8. Addition of S-9 to strains 

TA98 and TA1535 increased the control mutation frequency to 33 and 23, respectively. S-9 had 

nosubstantial effect on the frequency of mutations in the other strains. Positive controls induced 

an average of from 94 revertants in TA1537 to 1127 revertants in TA100. The number of 

revertants induced by test material was not increased from that of control at any concentration. 

The average number of revertants in cultures treated with test material (in the absence or 

presence of S-9) ranged from 108-135 in TA100 and 7-11 in TA1537. Similar to control TA98 

cultures, the average number of revertants in TA98 and TA1535 cultures treated with test 

material in the presence of S-9 (35-41 and 18-26, respectively) were higher than in the absence 

of S-9 (19-24 and 14-18, respectively).

The tests were valid, as positive controls induced at least a two-fold increase in frequency of 

mutations. 

Remarks on results including tables and figures 

Cytotoxic concentration: > 5000 micrograms/plate

Applicant's summary and conclusion 

Interpretation of results 

negative 

Genetic toxicity in vitro.002 

UUID IUC5-40906c59-da97-4ed9-9440-38381aa79661 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:12:27 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Only four strains of bacteria were used in the test. 

Data source 

Reference 

Referenc

e type 

study report 
Author Samson YE and Gollapudi BB. Yea

r 

1990 

Title Evaluation of triethylene glycol monomethyl ether (TGME) in the Ames 

Salmonella/mammalian-microsome bacterial mutagenicity assay. 

Bibliogr

aphic 

source 

 

Testing 

laborator

y 

 Rep

ort 

no. 

Study ID 

TXT:K-00561

0-005, 

Owner 

company 

Dow Chemical Company 

Compan

y study 

no. 

 Rep

ort 

date 

1990-03-07 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: Test Standard 40 CFR 798.5265 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Method 

Species/strain 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Details on mammalian cell 
lines (if applicable) 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation system not stated 

Test concentrations 

up to 5000 micrograms/plate 

Vehicle 

DMSO and water 

Controls 

Negative controls yes 

Solvent / vehicle 

controls 

 

True negative 

controls 

 

Positive controls yes 

Positive control 

substance 

other: 2-nitrofluorene, ICR-191, 2-anthramine and sodium azide 

Remarks 

Details on test system and conditions 

Test Concentrations: The test material was dissolved in distilled water at stock concentrations of 

50, 16.67, 5, 1.667, and 0.5 mg/ml. Concentrations were verified by HPLC to be: 51.4, 18.3, 

4.91, 1.75 and 0.523 mg/ml. All positive control solutions (1 mg/ml 2-nitrofluorene, 100 

micrograms/ml ICR-191, 30 micrograms/ml 2-anthramine) were prepared in DMSO (with the 

exception of 250 micrograms/ml sodium azide dissolved in water). 

Test: Bacteria (0.1 ml of 10E8 or 10E9 S. typhimurium TA 98, TA100, TA1535, or TA1537), 

test chemical (0.1 ml of test solution, positive control, or solvent) and either buffer or S-9 mix 

(0.5 ml) were pre-incubated in sterile 12 x 75 mm tightly-capped culture tubes in a gyratory 

incubator (300rpm) at 30 degrees C for 30 minutes. Supplemented top agar (2 ml) was then 

added, the overlay was poured onto plates, and plates were incubated at 37 degrees C for 2 days. 

All dose levels (including positive and negative controls) were assayed in triplicate. 

Revertant colonies were counted manually or with an automatic colony counter. The counter 

was calibrated periodically. A correction factor was used to compensate for the area not scanned 

by the counter (i.e. dish edge) and overlapping colonies. 

Evaluation criteria 

Evaluation Criteria: The test material was considered a mutagen if both the mean number of 

revertant colonies was at least 3 times higher than the mean of the negative (solvent) control and 

it induced a reproducible dose-response relationship over several concentrations. If the 

dose-response was not definitive, it was considered to be a presumptive mutagen. If the 

reversion rates were between 2 and 3 times that of negative controls, the results were considered 

equivocal or inconclusive. 

Statistics 

no data 

Results and discussions 
Test results 

Species/strain S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid 

Positive controls valid yes 

Additional information on results 

Concentrations up to 5000 micrograms/plate did not cause toxicity or cause an increase in 

mutagenicity above that of negative controls. 

The study was valid, as the positive controls induced at least 3 times the number of revertants as 

the negative controls in each tested strain. 

Remarks on results including tables and figures 

Cytotoxic concentration = > 5000 micrograms/plate

Genetic toxicity in vitro.003 

UUID IUC5-ce827574-5411-44b5-8a40-c69cc933392e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:13:31 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

19

84 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Well conducted study per GLP and with test substance well characterized as 

to composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1984 

Title Carbowax methoxy polyethylene glycol 350 Salmonella/microsome (Ames) 

bacterial mutagenicity assay. 

Bibliograph 
ic source 

Testing 

laboratory 

Bushy Run Research Center. Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1984-10-2

3 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Principles of method if other than guideline 

No guideline was referenced in the study, but the study method followed conventional 

procedure for Ames studies. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity Carbowax MPEG-350 

Details on test material 

The test material (CARBOWAX MPEG-350; CAS No. 9004-74-4) is a mixture of several 

methylated glycol ethers of differing molecular weight (ranging from diethylene glycol 

monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether (C17)). The majority of 

the material is in the C5-C11 range (87.445%). It contains 4.347 % (by weight) tetraethylene 

glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene glycol monomethyl ether 

(CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether (CAS No. 111-77-3).Purity 

of test material was 99.8%. Impurities included 0.1% water, 0.05% ethylene glycol, 0.05% 

diethylene glycol, and 50-150 ppm BHT. 

Method 

Species/strain 

Species/strain other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 

Details on 

mammalian cell 

lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic 

activation 

with and without 

Metabolic 0.5 ml of S9 mix containing 50 microliters of S9 liver homogenate from 
activation system Aroclor 1254-induced, Sprague-Dawley male rats 

Test concentrations 

1, 3, 10, 30 and 110 mg/plate 

Vehicle 

water 

Controls 

Negative controls yes 

Solvent / vehicle 

controls 

yes 

True negative 

controls 

no 

Positive controls yes 

Positive control 

substance 

other: 4-nitro-o-phenylenediamine, sodium azide, 9-aminoacridine and 

2-aminoanthracene 

Remarks 

Details on test system and conditions 

Test material was dissolved in water to a concentration of 300 mg/ml for doses of 30 mg/plate 

and below. All subsequent dilutions were made in the same solvent. Dilutions of test substance 

were made fresh each day and were gravimetrically analyzed. The volume of test material used 

in each test was 100 microliters. If necessary, phosphate buffered saline was added to adjust the 

volume.

A preliminary toxicity test was performed in strain TA100 to determine concentrations to use on 

other strains (TA98, TA1535, TA1537, TA1538). None of the doses used (up to 100 mg/plate) 

were toxic. Test material was tested in the Ames assay in triplicate at five doses (1, 3, 10, 30 

and 110 mg/plate). Testing was performed with and without metabolic activation (0.5 ml of S9 

mix containing 50 microliters of S9 liver homogenate from Aroclor 1254-induced, 

Sprague-Dawley male rats). Concurrent water and positive controls 

(4-nitro-o-phenylenediamine for TA98 and TA 1538, sodium azide for TA100 and TA1535 and 

9-aminoacridine for TA1537 in the absence of S9 and 2-aminoanthracene for all stains in the 

presence of S9) were run with each test. 

Evaluation criteria 

The test was considered valid, if positive controls caused mutagenicity and negative controls 

exhibited spontaneous reversion rates that were within historical range. 

Statistics 

no data 

Results and discussions 

Test results 

Species/strain other: S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid 
Positive controls valid yes 

Additional information on results 

The test was valid, as positive controls caused mutagenicity and negative controls exhibited 

spontaneous reversion rates that were within historical range.

Cycotoxic concentration: > 110 mg/plate 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Conclusions 

Mutagenic activity was not observed with any concentration in any of the strains (with or 

without bacterial activation). 

Genetic toxicity in vitro.004 

UUID IUC5-648e5cf6-6065-4214-96ec-1e4eb36f9cbd 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:14:48 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) 

used for MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP. Purity of test substance stated. 

Data source 

Reference 

Reference 

type 

study report 

Author Liscombe VA, Gollapudi BB. Year 1990 

Title Evaluation of triethylene glycol monomethyl ether in the Chinese hamster ovary 

cell/hypoxanthine-guanine-phosphoribosyl-transferase(CHO/HGPRT) forward 

mutation assay 

Bibliographi

c source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company ID TXT:K-005610-006 Report 1990-03-0
study no. date 7 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

mammalian cell gene mutation assay 

Test guideline 

Qualifier according to 

Guideline other guideline: Test Standard 40 CFR 798.5300 

Deviations 

Principles of method if other than guideline 

HGPRT Assay using Chinese hamster ovary cell 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Method 

Target gene 

the gene locus for the enzyme (hypoxanthine-guanine phosphoribosyl transferase) 

Species/strain 

Species/strain Chinese hamster Ovary (CHO) 

Details on mammalian cell lines (if 

applicable) 

 

Additional strain characteristics 

Metabolic activation with and without 

Metabolic activation system S-9 

Test concentrations 

2000 to 5000 micrograms/plate 

Vehicle 

water and DMSO 

Controls 

Negative controls yes 

Solvent / vehicle controls yes 

True negative controls no data 
Positive controls yes 

Positive control substance other: EMS or 20-MC 

Remarks 

Details on test system and conditions 

Indicator cells: The CHO-K1-BH4 cell line was used in the study. Periodic examinations 

revealed no mycoplasma contamination. Cells were grown as a monolayer in Ham's F-12 

nutrient mix supplemented with 5% heat-inactivated, dialyzed fetal bovine serum, 25 mM 

HEPES, 0.25 micrograms/ml Fungizone, 100 units/ml penicillin G and 0.1 mg/ml streptomycin 

sulfate. The selection medium used for the detection of mutants was Ham's F-12 nutrient mix 

without hypoxanthine, and supplemented with 10 micromolar 6-thioguanine, 5% serum, 25 mM 

HEPES, 2 mM L-glutamine and the antibiotics mentioned above.

Test materials: Test material was dissolved in water and further diluted (1:100) in culture 

medium. The concentrations of test material in stock solutions (200, 300, 400, 500 mg/ml)were 

verified by analytical methods.20-methylchlolanthrene (20-MC) was initially dissolved in 

DMSO, and further diluted in culture medium. Ethyl methanesulfonate (EMS) was dissolved in 

culture medium.

Preliminary test : The cytotoxicity of the test material was assessed by determining the ability of 

the treated cells to form colonies. The cultures (3 per dose level) were treated with test material 

in the absence or presence of S-9, incubated for up to 7 days, fixed with methanol and stained 

with crystal violet. The number of colonies/dish was counted and the mean 

colonies/dish/treatment were expressed relative to the negative control value. The test material 

was not cytotoxic at up to 5000 micrograms/ml. Based on this result, this was the highest 

concentration used for the genemutation assay.

Mutation test: Cells in logarithmic growth phase were trypsinized and plated in medium 

containing 5% serum at a standard density (200 cells/100 mm dish for toxicity assay and 1 x 

10E6 cells/100 mm dish for gene mutation assay) prior to treatment. Approximately 24 hours 

after plating,the medium was replaced with Ham's medium without serum, S-9 mix prepared 

from liver homogenate of Aroclor-1254 treated (500 mg/kg) male, Sprague Dawley rats (when 

applicable) and test material (2000 to 5000 micrograms/ml), positive control (either 621 

micrograms/ml EMS or 4 micrograms/ml 20-MC) or water. The total volume of the treatment 

medium was 10 ml/100 mm dish. The number of dishes treated at each dose level was based on 

the expected degree of toxicity that would yield at least 1 x 10E6 surviving cells. Cells were 

treated for 4 hours at 37 degrees C. Exposure was terminated by washing the cells with 

phosphate-buffered saline. Cells were trypsinized 18-24 hours after termination of the treatment 

and replated at a density of 1 x 10E6 cells/100 mm dish. This step was repeated on the third and 

sixth days following treatment. On Day 8, cultures were trypsinized and plated at a density of 2 

x 10E5 cells/100 mm dish (5 dishes per treatment) in selection medium for the determination of 

HGPRT-mutants and 200 cells/60 mm dish (5 dishes/treatment) in Ham's medium without 

hypoxanthine for determination of cloning efficiency. Dishes were incubated for 7-9 days, fixed 

with methanol and stained with crystal violet. The mutation frequency per 10E6 clonable cells 

was calculated as the total number of mutant colonies/cloning efficiency(number of colonies per 

number of cells plated). 

Evaluation criteria 
The assay was considered valid, if the positive control chemicals induced significant increased 

in mutation frequencies in assays with and without S-9 (EMS: 142.0-153.6; 20-MCA: 

64.7-86.3). 

Statistics 

Statistical analysis: The frequencies of mutants per 10E6 clonable cells were statistically 

evaluated by pairwise tests (treatment vs. negative control) and by linear and quadratic trend 

analysis over the dose range. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity yes 

Vehicle controls valid yes 

Negative controls valid yes 

Positive controls valid yes 

Additional information on results 

The mutation frequencies observed in cultures treated with the test chemical in the absence (1.4 

to 7.1) and presence of S-9 (0 to 7.1) were not significantly different from the concurrent 

negative control values (1.4 to 9.6) and were within the laboratory historical negative control 

range. 

Cytotoxic concentration: > 5000 micrograms

The assay was valid, since the positive control chemicals induced significant increased in 

mutation frequencies in assays with and without S-9 (EMS: 142.0-153.6; 20-MCA: 64.7-86.3). 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Genetic toxicity in vitro.005 

UUID IUC5-83cfdf6e-9c06-4310-b95d-65c1363a0e78 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-17 14:18:00 EST 

Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result type experimental result Study 

period 

1

9

9

2 
Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

well conducted study run according to glp, with good characterization of test 

material composition. 

Data source 

Reference 

Reference type study report 

Author Brooks TM, Wiggins DE. Year 1992 

Title Brake fluid Dot 4: Bacterial mutagenicity studies 

Bibliographic 

source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research 

Centre 

Report no. SBGR.92.022 

Owner 

company 

Shell 

Company study 

no. 

 Report date 1992-04-09 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

bacterial reverse mutation assay (e.g. Ames test) 

Principles of method if other than guideline 

Guideline not specified, but study was run according to standard Ames study procedure 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake fluid Dot 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Method 

Species/strain 

Species/strain other: TA98, TA100, TA1535, TA1537, TA1538 and E. coli 

WP2uvrA pKM101 

Details on mammalian 
cell lines (if applicable) 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation 

system 

 

Test concentrations 

up to 5000 micrograms per plate 

Vehicle 

no vehicle 

Controls 

Negative controls no data 

Solvent / vehicle controls no data 

True negative controls no data 

Positive controls no data 

Positive control substance no data 

Remarks 

Details on test system and conditions 

no data 

Evaluation criteria 

no data 

Statistics 

no data 

Any other information on materials and methods incl. tables 

Results and discussions 

Test results 

Species/strain other: TA98, TA100, TA1535, TA1537, TA1538 

Metabolic activation with and without 

Test system 

Genotoxicity negative 

Cytotoxicity no, but tested up to limit concentrations 

Vehicle controls valid no data 

Negative controls valid no data 

Positive controls valid no data 

Remarks on results including tables and figures 

Cytotoxic concentration = > 5000 micrograms per plate 

Genetic toxicity in vitro.006 

UUID IUC5-95832cad-6a4b-4a42-8aec-f6afdd347855 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 
Date 2009-02-17 20:26:54 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust well conducted study following GLP, with good characterization of the 

test substance composition. 

Data source 

Reference 

Reference 

type 

study report 

Author Brooks TM, Wiggins DE Year 1992 

Title Brake fluid Dot 4: In vitro chromosome studies using cultured Chinese hamster 

ovary cells. 

Bibliograph

ic source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.

090 

Owner 

company 

Shell 

Company 

study no. 

 Report 

date 

1992-07-2

3 

Materials and methods 

Type of genotoxicity 

chromosome aberration 

Type of study 

in vitro mammalian chromosome aberration test 

Principles of method if other than guideline 

Guideline was not specified, but study was carried out following standard procedures for this 

type of study. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 
Identifier Common name 

Identity Brake fluid Dot 4 

Details on test material 

Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Method 

Species/strain 

Species/strain Chinese hamster Ovary (CHO) 

Details on mammalian cell lines (if 

applicable) 

no details 

Additional strain characteristics 

Metabolic activation with and without 

Metabolic activation system S-9 

Test concentrations 

The concentrations of test material used (from 10 to 5000 micrograms/ml without S-9 and 100 

to 5000 micrograms/ml with S-9). 

Vehicle 

no vehicle 

Controls 

Negative controls yes 

Solvent / vehicle controls yes 

True negative controls 

Positive controls yes 

Positive control 

substance 

other: methyl methanesulphonate and benzo(a)pyrene 

Remarks 

Details on test system and conditions 

Cells (2 x 10E5) were incubated with medium containing the test compound or relevant controls 

[untreated control, solvent control and positive controls methyl methanesulphonate (20 

micrograms/ml without S-9) and benzo(a)pyrene (25 micrograms/ml with S-9)] for either 3 

hours in the presence of S9 mix (from Aroclor 1254-induced rat liver) or 24 hours in the 

absence of S9 mix. The concentrations of test material used (from 10 to 5000 micrograms/ml 

without S-9 and 100 to 5000 micrograms/ml with S-9) were chosen based on the results of 

preliminary miscibility and mitotic index studies. Duplicate cultures were prepared for each test 

condition. Two separate experiments were conducted using different concentrations. Metaphase 

cells were prepared on glass microscope slides for the analysis of chromosome aberrations 24 

hours following exposure for the cultures with or without S9 mix. All slides were coded. Where 

possible, 200 metaphases were scored for each dose group. Only those cells showing the modal 

chromosome number (20) +/- 2 were analyzed for chromosome damage. Chromosome 

aberrations were classified according to the scheme described by Savage (J Med Genetics 

12:103-122, 1976). 
Evaluation criteria 

Not specified. 

Statistics 

The mitotic index of each group was assessed by counting the number of metaphases in a total 

of 1000 cells. Data were assessed for heterogeneity using the Fisher’s exact test. The number of 

aberrations excluding gaps, aberrations including gaps, isogaps and/or chromatid gaps and 

polyploidy and/or endoreduplication of treated cells was compared to controls using the Fisher’s 

exact test. A Cochran-Armitage trend test was carried out on the dose/response. The test was 

performed twice, once excluding control data and the other including the solvent control. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity no, but tested up to limit concentrations 

Vehicle controls valid 

Negative controls valid 

Positive controls valid 

Additional information on results 

Cells exposed to test material at concentrations up to 5000 micrograms/ml showed no increase 

in chromosome damage or no linear trend compared to negative controls in either experiment. 

The positive control induced significantly more cells with aberrations compared to the negative 

controls (for untreated control and for solvent control). In the first experiment with S-9 (up to 

1875 micrograms/ml test material), there was no effect of treatment on the incidence of type of 

aberration observed. However, there was a significant difference in the number of cells with 

chromatid gaps and/or isogaps between the untreated control (7/200) and solvent control 

cultures (1/200). In the second experiment with S-9 (cells were treated with 1500, 3000 or 5000 

micrograms/ml test material), there was a significant difference in the number of cells with 

aberrations including gaps (11/200) and cells with chromatid gaps and/or isogaps (8/200) at the 

1500 micrograms/ml compared to the solvent control (2/199 and 0/199, respectively). There 

also was a significant increase in the number of cells with chromatid gaps and/or isogaps at the 

high concentration (5/200) compared to control, and between both controls (untreated control 

had 7/200). No linear trend was observed either by including or excluding the solvent control 

from the analysis. The positive control caused increases in aberrations with and without gaps 

compared to the solvent control in both studies. 

The cytotoxic concentration was > 5000 micrograms/ml. 

Remarks on results including tables and figures 

The small random increases in the number of chromatid gaps and/or isogaps in one experiment 

with S-9, which were not dose-dependent and not different from the untreated controls were not 

considered to be compound-related effects by study personnel. 

Overall remarks, attachments 

Overall remarks 
Applicant's summary and conclusion 

Interpretation of results 

negative 

Conclusions 

Study personnel concluded that under the test conditions, the test material did not induce 

chromosomal aberrations either in the presence or absence of S9 mix. 

7.6.2 Genetic toxicity in vivo 

Genetic toxicity in vivo.001 

UUID IUC5-96adfb9f-af92-454b-a840-6b78eea9c1ae 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:16:12 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP with test substance purity noted. 

Data source 

Reference 

Reference 

type 

study report 

Author McClintock ML and Gollapudi B. Year 1990 

Title Evaluation of triethylene glycol monomethyl ether in the mouse bone marrow 

micronucleus test. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Dow Chemical Company 

Company 

study no. 

Study ID TXT:K-005610-007 Report 

date 

1990-03-0

7 

Materials and methods 

Type of study 

micronucleus assay 
Test guideline 

Qualifier according to 

Guideline EPA OPPTS 870.5200 (Mouse Visible Specific Locus Test) 

Deviations 

Principles of method if other than guideline 

Study reference for protocol used is: Test Standard 40 CFR 798.5395 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity was 99.23%. 

Test animals 

Species 

mouse 

Strain 

CD-1 

Sex 

male/female 

Details on test animals and environmental conditions 

Strain specifically denoted to be CD-1 (ICR)BR. The animals were approximately 8 weeks old. 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle(s) 

water 

Details on exposure 

Test material was dissolved in water and administered to mice (approximately 8 weeks old) by 

single oral gavage at dose levels of 0 (water), 500, 1667 and 5000 mg/kg body weight (10 

ml/kg). A previous study revealed that 5000 mg/kg did not affect survival. Concentrations of 

test material in dosing solutions were verified by HPLC. Groups of animals(5/sex/dose/sacrifice 

time) were sacrificed by cervical dislocation 24, 48 and 72 hours after treatment. Mice (5/sex) 

treated with 120 mg/kg cyclophosphamide and sacrificed after 24 hours of treatment served as 

positive controls. 

Duration of treatment / exposure 

Single dose 
Frequency of treatment 

Single dose 

Post exposure period 

up to 72 hours 

Doses / concentrations 

500, 1667, 5000 mg/kg bw 

Basis nominal in water 

No. of animals per sex per dose 

5 animals per sex per dose 

Control animals 

yes, concurrent vehicle 

Positive control(s) 

Mice (5/sex) treated with 120 mg/kg cyclophosphamide and sacrificed after 24 hours of 

treatment served as positive controls. 

Examinations 

Tissues and cell types examined 

Bone marrow samples were obtained from both femurs at sacrifice. Cell smears were prepared 

from cell suspensions. 

Details of tissue and slide preparation 

The slides were air dried, fixed in methanol and stained in 5% Giemsa. Slides were coded and 

scored blindly. One thousand polychromatic erythrocytes (PCE) were evaluated from each 

surviving animal and the frequencies of micronucleated polychromatic erythrocytes (MN-PCE) 

were recorded. Micronuclei were identified as darkly stained bodies with sharp contours and 

varying shapes such as round, almond, or ring. The ratio of PCE-NCE (normochromatic 

erythrocytes) in the bone marrow was determined by examining 100 erythrocytes. 

Evaluation criteria 

The test was valid if positive controls had significantly more MN-PCE than controls (62.2 in 

males and 34.6 in females). 

Statistics 

Statistical Analysis: The raw data on the counts of MN-PCE for each animal were transformed 

by adding 1 to each count and then taking the natural log of the adjusted number. The 

transformed MN-PCE data and the data on percent PCE were analyzed by a three-way analysis 

of variance looking only at main effects. Pairwise comparisons between treated vs. negative 

controls were done (if necessary) by a t-test usingBonferroni correction for multiple 

comparisons. 

Results and discussions 

Test results 

Sex male/female 

Genotoxicity negative 

Toxicity 

Vehicle controls valid yes 

Negative controls valid 

Positive controls valid yes 

Additional information on results 

One female dose with 1667 mg/kg test material died prior to scheduled sacrifice. The cause of 
death was not determined. There were no significant increases in the frequencies of 

micronucleated polychromatic erythrocytes (MN-PCE) in groups treated with test material 

(range from 0.2 to 1.6) versus negative controls (range 0.4 to 1.2). The ratios of polychromatic 

erythrocytes (PCE) to normochromatic erythrocytes (NCE) (% PCE) in test animals (67.3 to 

82.0) also were similar to those of negative controls (70.6 to 78.7). 

The test was valid as positive controls had significantly more MN-PCE than controls (62.2 in 

males and 34.6 in females). 

Applicant's summary and conclusion 

Interpretation of results 

negative 

7.8 Toxicity to reproduction 

7.8.1 Toxicity to reproduction 

Toxicity to reproduction.001 

UUID IUC5-8cc5d3b2-1dd1-4d9b-b4f3-db6f453d4482 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-17 21:07:51 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1

9

9

0 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Effect on mating was not characterized. Otherwise study was robust per 

current protocol following GLP. 

Data source 

Reference 

Reference type study report 

Author Corley RA, Ciesslak, Breslin WJ, Lomax LG. Year 1990 

Title 13-Week dermal toxicity study in Sprague-Dawley rats. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner 

company 

Dow Chemical Company 

Company study 

no. 

Study ID K-005610-004 Report date 1990-09-26 
Reference 

type 

publication 

Author Gill MW, Fowler EH, Gingell R, Lomax LG, Corely RA. Year 1998 

Title Subchronic dermal toxicity and oral neurotoxicity of triethylene glycol 

monomethyl ether in CD rats 

Bibliograph

ic source 

Int J Toxicol 17:1-22. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

The same study is summarized as a 91 day dermal repeat dose study in Sprague-Dawley rats. 

This is repeated dose toxicity dermal.001 

Materials and methods 

Test type 

fertility 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477). 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

Purity (as determined by gas chromatography) was 99.23 % at the onset of the study and 

99.24% at completion of the in-life phase. 

Test animals 

Species 

rat 

Strain 
Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

8 week-old rats 

Administration / exposure 

Route of administration 

dermal 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Triethylene glycol monomethyl ether (TGME) was administered dermally to 8 week-old rats 

(10/sex/dose level) at 0 (sham control), 400, 1200 or 400 mg/kg/day for 13 weeks. Test material 

was applied to shaved areas of skin on the back and sides of each rat (12 cm2 in area), 

uniformly spread, and covered with a semiocclusive dressing for 6 hours. After removal of the 

dressing, the application site was wiped with a dampened towel. Material was applied in this 

manner daily, 5 days/week for 13 weeks. 

Details on mating procedure 

No mating 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

Purity of test substance as administered (as determined by gas chromatography) was 99.23 % at 

the onset of the study and 99.24% at completion of the in-life phase. 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily, 6 hr/day, 5 days/week 

Doses / concentrations 

0 (sham control), 400, 1200 or 400 mg/kg/day 

Basis analytical conc. 

No. of animals per sex per dose 

10/sex/dose level 

Control animals 

yes, sham-exposed 

Examinations 

Parental animals: Observations and examinations 

Upon necropsy the test animals were examined. The oocytes, corpora lutea, and follicles from 

each ovary were evaluated with regard to their normal development. The testes and epididymes 

also were examined microscopically for males in the intermediate- and low-dose groups. 

Postmortem examinations (Parental animals) 

See Repeated dose dermal study.001 for details 

Results and discussions 

Effect levels 

Endpoint NOAEL 
Generation P 

Sex male/female 

Effect level 4000 mg/kg bw/day (actual dose received) 

Basis for 

effect level / 

Remarks 

NOAEL for systemic effects on test animals. Conclusion of summary preparer; 

no adverse systemic effects seen at highest dose. 

Endpoint NOAEL 

Generatio

n 

P 

Sex male/female 

Effect 

level 

>= 400 — < 1200 mg/kg bw/day (actual dose received) 

Basis for 

effect 

level / 

Remarks 

Interpretation of EPA, based on bilaterally decreased spermatogenesis observed in 

one male treated with the highest dose (4000 mg/kg bw) and testicular changes 

observed in one male treated with 1200 mg/kg. 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

yes 

Reproductive function: sperm measures (parental animals) 

yes 

Reproductive performance (parental animals) 

not examined 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

There were no indications of systemic toxicity at any dose. Mean body weight and food 

consumption were comparable to controls throughout the study. Bilaterally decreased 

spermatogenesis in seminiferous tubules and decreased spermatozoa in the epididymes (both 

were graded as severe) were noted in the testes of one high dose male rat. This animal had a 

complete lack of mature spermatids in greater than 41% of tubules in each testicle, few 

spermatids beyond stage 12 of development in the seminiferous epithelium, and decreased 

spermatic elements in the head and tail of greater than 41% of the tubules and ducts in the 

epididymides. The testes of one male treated with 1200 mg/kg exhibited different testicular 

changes [bilateral multifocal degeneration of spermatocytes and spermatids from germinal 

epithelium (graded as very slight), and multinucleated spermatids]. In this rat, all stages of the 

cycle of the seminiferous epithelium were observed in morphologically normal tubules. The 
epididymides of this rat had decreased spermatic elements in the head and tail of 1-5% of ducts. 

Some of the ducts also contained immature spermatids. There were no effects on estrous 

cyclicity or ovaries of females. 

Observations: offspring 

Remarks on results including tables and figures 

Study personnel concluded that the bilateral microscopic testicular changes observed in one high-dose 

and one mid-dose male rat were unrelated to treatment. Reasons given were that the dissimilarity of the 

lesions for the two animals suggested that they occurred spontaneously, and the incidence of animals 

with lesions (1/10 in each group) was well within that of historical controls (0-17%). Study personnel also 

stated that the degenerative changes in the testes of one mid-dose and one high-dose rat were not 

consistent with the types of lesions that have been attributed to 2-methoxyethanol (2-ME). The cell types 

that are most vulnerable to 2-ME are the pachytene spermatocytes and round spermatids (Chapin et al., 

Fund Appl. Toxicol 5:182-189, 1985). As the dose of 2-ME is increased, the number and types of cells 

affected increase up to the point that the germinal epithelium is significantly degenerated and all stages 

of spermatogenesis are affected (Chapin et al., Fund Appl. Toxicol 5:182-189, 1985; Miller et al., Fund 

Appl Toxicol 3:49-54, 1983.). In contrast, the testicular effects seen with the high dose animal treated 

with TGME consisted of a virtually complete lack of mature spermatids beyond stage 12. All other 

stages, including spermatogonia and spermatocytes, were present and appeared morphologically 

normal. In the mid-dose rat, the only effects noted consisted of very slight degeneration of 

spermatocytes and spermatids similar to those seen in historical control animals. 

Study personnel also stated that the lymphoid tissues and hematologic parameters, which have been 

reported to be affected at doses of 2-methoxyethanol that have been associated with testicular changes 

(Miller et al., Fund. Appl. Toxicol. 3:49-54, 1983) were unaffected in this TGME study. Taking all factors 

into consideration, the testicular lesions observed in this dermal study could not be directly attributed to 

TGME exposure. 

Overall remarks, attachments 

Overall remarks 

Additional details for this study can be found in the Repeated dose dermal study.001 summary. 

The EPA has determined that based on severe testicular toxicity in 1/10 rats given 4000 mg/kg/day and 

minimal decreases in developing germ cells (1-5% of semiferous tubules affected) in 1/10 rats given 

1,200 mg/kg/day, the NOAEL for testicular toxicity is between 400 and 1200 mg/kg/day (Anderson, L. 

Triethylene glycol monomethyl, monoethyl and monobutyl ethers RM1 screening document (draft), Feb. 

24, 1995). This value was reached even though it was recognized that the testicular changes in the 

1,200 mg/kg/day rat were within historical control limits for Sprague-Dawley rats (0 1 7 %).

Toxicity to reproduction.002 

UUID IUC5-276c6a8f-4917-473b-93d3-cef7c9bc2e2f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:20:24 EST 

Remarks 
 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used 

for MSDS 

Study result 

type 

experimental result Study 

period 

1985 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Well conducted, robust study with test substance well characterized as to 

composition. Study conducted following GLP. No guideline specified 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1985 

Title Nine-day and ninety-day dermal toxicity studies of CARBOWAX MPEG-350 in 

rabbits. 

Bibliographi

c source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

 Report 

date 

1985-05-3

0 

Reference 

type 

 

Author Hermansky SJ, Leung HW. Year 1997 

Title Cutaneous toxicity studies with methoxy polyethylene glycol-350 (MPEG-350) in 

rats and rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Cross-reference to same study 

This study is also summarized as a 90 day repeated dose dermal study. See repeated dose 

toxicity dermal.002 for further details. 

Materials and methods 

Test type 

fertility 

Limit test 
no 

Principles of method if other than guideline 

No guideline specified, but study was conducted following standard procedures and principles. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 9004-74-4 

Identifier Common name 

Identity CARBOWAX MPEG 350 

Details on test material 

The test material (CARBOWAX MPEG 350, CAS No. 9004-74-4) wasreported to be 

chemically inert (stable for > 6 months at room temperature) and 99.8% pure. This material is a 

mixture of several methylated glycol ethers of differing molecular weight (ranging from 

diethylene glycol monomethyl ether (C2) to heptadecaethylene glycol monomethyl ether 

(C17)). The majority of the material is in the C5-C11 range (87.445%). It contains 4.347 % (by 

weight) tetraethylene glycol monomethyl ether (CAS No. 23783-42-8), 1.303% triethylene 

glycol monomethyl ether (CAS No. 112-35-6), 0.181% diethylene glycol monomethyl ether 

(CAS No. 111-77-3). 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Body weights of males and females ranged from 2.5 to 3.2 kg and 2.5 to 3.1 kg at study 

initiation. 

Administration / exposure 

Route of administration 

dermal 

Vehicle 

other: methyl cellulose in distilled water 

Details on exposure 

Dosing: New Zealand white rabbits (10/sex/dose) were treated dermally on clipped dorsal skin 

with 1.0 ml of vehicle (0.1% (w/v) methyl cellulose in distilled water), 50% CARBOWAX 

MPEG-350 (w/v dilution in 0.1% methyl cellulose in water) or 100% CARBOWAX 

MPEG-350, for six hours/day, five days per week for 90 days. Rabbits were fitted with 

Elizabethan collars after dosing to prevent ingestion of test material. After each 6-hour exposure 

the application site was wiped with a paper towel dampened with water and then dried using a 

towel. Rabbits were then uncollared until the next treatment.
Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

90 days 

Frequency of treatment 

daily, six hours/day, five days per week 

Doses / concentrations 

1 ml of 50% and 100% material (approximately 169 and 338 mg/kg/day) 

Basis nominal conc. 

No. of animals per sex per dose 

10/sex/dose 

Control animals 

yes, concurrent vehicle 

Further details on study design 

A preliminary range-finding study in 15 rabbits dosed 6 hr/day for 9 days showed that daily 

administration of 1 ml of 50% or 100% test material only caused mild skin irritation. Therefore, 

these doses were chosen for the90-day study.

Based on weights of animals determined at weekly intervals and the reported density of test 

material (1.09 g/ml) doses can be calculated on average mg/kg/day basis. These doses are 169 

mg/kg/day (for 50%) and 338 mg/kg/day (for 100%). 

Examinations 

Parental animals: Observations and examinations 

Observations: All rabbits were observed daily (weekdays) for death, clinical signs and dermal 

irritation. Body weights were recorded on the morning of the first day of dosing, weekly 

thereafter and prior to sacrifice. Food consumption was measured weekly. Urine was collected 

from 5 animals/sex/group during the last two weeks of dosing and subjected to standard 

analyses. Standard hematology and clinical chemistry parameters were evaluated for all animals 

just prior to sacrifice. 

Estrous cyclicity (Parental animals) 

no data 

Sperm parameters (Parental animals) 

no data 

Postmortem examinations (Parental animals) 

Necropsy: All animals were sacrificed and necropsied after 13 weeks of treatment. Weights 

were recorded for liver, kidneys, brain and adrenals of all animals and testes of males. 

Histopathologic examinations were performed on tissues (including testes, epididymes, prostate, 

accessorysex glands, uterus, ovaries and mammary gland) from high-dose and control animals. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect 

level 

338 mg/kg bw/day (nominal) 
Basis for 

effect level 

/ Remarks 

The NOAEL listed is for reproductive organ toxicity. The NOAEL for systemic 

effects was not listed by the investigators. Based on the data, this value is 100% 

(338 mg/kg/day). 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Test substance intake (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

no data 

Reproductive function: sperm measures (parental animals) 

yes 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

No effects on any test animal sex organ were observed 

Observations: offspring 

Remarks on results including tables and figures 

The NOAEL listed is for reproductive organ toxicity. Further details of this study can be found in the 

summary for repeated dose toxicity dermal.002. The NOAEL for systemic effects was not listed by the 

investigators. Based on the data, this value is 100% (338 mg/kg/day).

Toxicity to reproduction.003 

UUID IUC5-24f457bd-0cd8-42e3-ae5f-c4397b1732b1 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:22:10 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 2 (reliable with restrictions) 
Rationale for 

reliability 

Well conducted, robust study, following GLP, but the effect on mating was 

not characterized. 

Data source 

Reference 

Reference 

type 

 

Author Gill MW and Negley JE. Year 1990 

Title Triethylene glycol monomethyl ether. Ninety day subchronic drinking water 

inclusion neurotoxicity study in rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide 

Company 

study no. 

Project Report 52-607, Report 

date 

1990-09-

21 

Cross-reference to same study 

This study is also summarized as a repeated dose study in Repeated dose study oral.001 

Materials and methods 

Test type 

fertility 

Limit test 

no 

Principles of method if other than guideline 

The route of administration and maximum dose level was specified in a testing consent order 

(EPA. 1989. 40 CFR 799, Fed Reg 54:13470-13477). 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol monomethyl ether 

Details on test material 

The purity was at least 98.7%. 

Test animals 

Species 

rat 
Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: drinking water 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Rats were treated with triethylene glycol monomethyl ether (TGME) for 91 days via drinking 

water at target doses of 0, 400, 1200 and 4000 mg/kg/day. 

Details on mating procedure 

Study did not include mating. Study examined male reproductive organs. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

91 days 

Frequency of treatment 

daily 

Doses / concentrations 

0, 400, 1200 and 4000 mg/kg/day. 

Basis nominal in water 

No. of animals per sex per dose 

15/sex/group 

Control animals 

other: concurrent water 

Positive control 

no data 

Examinations 

Parental animals: Observations and examinations 

Rats were observed daily for clinical signs and weekly for body weight and water and food 

consumption. Rats were also observed periodically for behavior (functional observational 

battery) and motor activity. 

Estrous cyclicity (Parental animals) 

no data 

Sperm parameters (Parental animals) 

Yes, see results section. 

Litter observations 

no 

Postmortem examinations (Parental animals) 

Gross lesions and organ weights were recorded at necropsy. Microscopic analyses of liver, 

testes and the nervous system also were performed. 
Postmortem examinations (Offspring) 

no 

Statistics 

no data 

Reproductive indices 

no data 

Offspring viability indices 

no data 

Any other information on materials and methods incl. tables 

The authors state that a possible contributing factor in the development of testicular lesions at the high 

dose was low-level contamination of the test substance with the known testicular toxicant 

2-methoxyethanol (EGME). EGME was present in the test substance at a concentration of 0.02  0.04 

%, resulting in a EGME dose up to 1.7 mg/kg/day for animals in the high dose group. Given the length of 

the study, it is possible that EGME contributed to the testicular lesions. A comparison between the doses 

of EGME and TGME required to produce testicular toxicity indicated that TGME is 350 times less potent 

than EGME in producing testicular lesions in the rat.The dose of TGME that caused testicular toxicity 

(4000 mg/kg/day) is 4 times greater than the 1000 mg/kg/day limit dose generally recommended for 

subchronic studies.

Results and discussions 

Effect levels 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect level 1200 mg/kg bw/day (nominal) 

Basis for effect level / 

Remarks 

Interpretation by summary preparer for reproduction organ toxicity. 

Endpoint NOAEL 

Generation P 

Sex male/female 

Effect level > 400 — < 1200 mg/kg bw/day (nominal) 

Basis for effect 

level / Remarks 

Interpretation by the Environmental Protection Agency for testicular 

effects. 

Observations: parental animals 

Clinical signs (parental animals) 

yes 

Body weight and food consumption (parental animals) 

yes 

Test substance intake (parental animals) 

yes 

Reproductive function: estrous cycle (parental animals) 

no data 

Reproductive function: sperm measures (parental animals) 

yes 

Reproductive performance (parental animals) 
no data 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 

yes 

Details on results (parental animals) 

The testes of males in the high dose group exhibited degeneration (12/15) and/or atrophy (5/5) 

of the seminiferous tubules (spermatocytes or developing spermatids). The authors concluded 

that these effects were related to treatment. The severity of the lesions was primarily mild to 

moderate for degeneration (11/12) and minimal to moderate for atrophy (5/5), indicating that 

not all tubules were affected and that a limited number of cells was affected within the affected 

tubules. One male treated with 1200 mg/kg had severe seminiferous tubule atrophy, a complete 

loss of cell types in the tubules (except for Sertoli cells) and moderate Leydig cell hypertrophy 

(not significant from control). This was not considered to be related to treatment because of the 

lack of a plausible explanation for the unusual dose-response relationship (the effect at this dose 

was more severe than that of a higher dose) and the low incidence of animals affected at this 

dose level (Gill et al., Int J Toxicol 17:1-22, 1998) One male treated with 1200 mg/kg had 

severe seminiferous tubule atrophy and moderate Leydig cell hypertrophy (not significant from 

control). No testicular changes were noted in males treated with 400 mg/kg/day TGME. 

Observations: offspring 

Viability (offspring) 

not examined 

Clinical signs (offspring) 

not examined 

Body weight (offspring) 

not examined 

Sexual maturation (offspring) 

not examined 

Organ weights (offspring) 

not examined 

Gross pathology (offspring) 

not examined 

Histopathology (offspring) 

not examined 

Details on results (offspring) 

91 Day repeated dose study did not include mating, but examined male testes. 

Remarks on results including tables and figures 

The NOAEL listed is for reproductive organ toxicity. Other results are shown in section 5.4. The 

summary preparer-assigned NOAEL and LOAEL for testicular effects is 1200 and 4000 mg/kg/day, 

respectively. By contrast, the EPA has determined that the NOAEL for testicular effects is between 400 

and 1200 mg/kg/day (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers 

RM1 screening document (draft), Feb. 24, 1995).

7.8.2 Developmental toxicity / teratogenicity 
Developmental toxicity / teratogenicity Leber TGBE 1990.001 

UUID IUC5-82fde93b-9ed8-454d-9884-2393680f4a38 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:25:07 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

86 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Established protocol followed with GLP. 

Data source 

Reference 

Referenc

e type 

publication 

Author Leber A.P. et al. Year 1990 

Title Triethylene glycol ethers. Evaluation of in vitro absorption through human 

epidermis, 21-dermal toxicity in rabbits and a developmental toxicity screen in rats. 

Bibliogra

phic 

source 

J Am Coll Toxicol 9:507-515, 1990. 

Testing 

laborator

y 

 Repo

rt no. 

 

Owner 

company 

 

Compan

y study 

no. 

 Repo

rt 

date 

 

Reference 

type 

study report 

Author Wason SM, Hodge MCE Year 1986 

Title Triethylene glycol ethers: An evaluation of teratogenic potential and developmental 

toxicity using an in vivo screen in rats. 

Bibliograp

hic source 

 
Testing 

laboratory 

 Repor

t no. 

CTL/P/

1584 

Owner 

company 

Imperial Chemical Industries PLC. 

Company 

study no. 

 Repor

t date 

 

Materials and methods 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: modified Chernoff-Kavlok assay (Schuler RL et al. Environ Health 

Persp 57:141-146, 1984) 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 143-22-6 

Identifier EC number 

Identity 205-592-6 

Identifier Common name 

Identity triethylene glycol monobutyl ether 

Details on test material 

Purity was 96.91% according to manufacturer (Olin Corporation). 

Test animals 

Species 

rat 

Strain 

other: other:Alpk:AP (Wistar) 

Details on test animals and environmental conditions 

approximately 11-13 weeks of age 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Analytical verification of doses or concentrations 
no data 

Duration of treatment / exposure 

days 7-16 of gestation 

Frequency of treatment 

daily 

Duration of test 

until Day 5 of parturition 

Doses / concentrations 

deionized water, 250 mg/kg triethylene glycol monobutyl ether (TGBE), 1000 mg/kg TGBE, 50 

mg/kg ethylene glycol monomethyl ether (EGME), or 250 mg/kg EGME. 

Basis nominal conc. 

No. of animals per sex per dose 

Not stated. 

Control animals 

other: both negative (water) and positive (50 and 250 mg/kg ethylene glycol monomethyl ether) 

Further details on study design 

Female rats were mated with males of the same strain when they were approximately 11-13 

weeks of age. The first day spermatozoa were detected in vaginal smears was counted as Day 1 

of gestation. Ten gestating animals per group were dosed with deionized water, 250 mg/kg 

triethylene glycol monobutyl ether (TGBE), 1000 mg/kg TGBE, 50 mg/kg ethylene glycol 

monomethyl ether (EGME), or 250 mg/kg EGME. Dose levels of TGBE were selected based on 

the results of a previous range finding study. EGME was administered at levels known to 

produce toxicity in the assay. All animals were dosed by gavage from Days 7-16 (inclusive) of 

gestation with 1 ml of dosing solution per 100 g body weight using a 5ml glass syringe and 

stainless steel (16 gauge cannula). Dosing solutions were prepared immediately prior to dosing 

and stored in a refrigerator until use. The volume given to each animal was adjusted daily 

according to body weight. 

Examinations 

Maternal examinations 

Rats were observed each day for clinical condition and signs of illness. Body weights were 

recorded on Days 1, 7 through 17, 19, and 22 of gestation and on Day 5 post partum. 

Maternal body weight gains were measured during treatment and pregnancy. 

Ovaries and uterine content 

The uteri of females which failed to litter were grossly examined for implantation sites on or 

shortly after Day 25 of gestation to ascertain if the animals had been pregnant. 

Fetal examinations 

Litters were weighed and sexed on Days 1 (within 24 hours of birth) and 5 post partum. Dead 

pups were not weighed. Mortality on Day 1 and Day 5 post partum was recorded. 

Animals which littered and their offspring were killed and discarded without postmortem 

examination after Day 5 post partum. 

Statistics 

Litters produced/number pregnant, number of viable litters on Days 1 and 5, total number of 

live pups/litter, total number of dead pups/litter, mean total litter size (live and dead pups), 

survival percentage, number of dead pups per group, mean pup weight (Days 1 and 5), mean 
pup weight gain and mean % weight gain/litter datafrom treated and control animals were 

compared using the Student's t-test. All comparisons were two-tailed. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 1000 mg/kg bw/day (nominal) 

Basis for effect level / 

Remarks 

Data are for trieth;ylene glycol butyl ether 

Endpoint NOAEL 

Effect type teratogenicity 

Effect level 1000 mg/kg bw/day (nominal) 

Basis for effect level / 

Remarks 

Data are for trieth;ylene glycol butyl ether 

Details on maternal toxic effects 

Maternal Data: Dams dosed with either dose of TGBE appeared normal throughout the study 

and gained a similar amount of weight as negative controls. Administration of 50 or 250 mg/kg 

EGME was associated with piloerection. Four animals in the 250 mg/kg EGME group had 

slight vaginal bleeding between Days 17 and 19 of gestation. 

Details on embryotoxic / teratogenic effects 

Litter Data: The pregnancy rate was high with 9/10 pregnancies in the negative control group, 

and 10/10 pregnancies in the groups dosed with TGBE. No litters were produced in either 

EGME group (although implantation sites were present in all animals). There were no effects on 

any litter parameter measured in rats treated with either dose of TGBE. 

Remarks on results including tables and figures 

At the dose levels tested (250 or 1000 mg/kg/day), TGBE was not embryotoxic or teratogenic (in 

contrast to EGME). 

Triethylene glycol monomethyl ether and triethylene glycol monoethyl ether also were not teratogenic at 

1000 mg/kg. The EPA also concluded that there were no remarkable treatment-related effects in this 

study (Anderson, L. Triethylene glycol monomethyl, monoethyl and monobutyl ethers RM1 screening 

document (draft), Feb. 24, 1995). The NOAEL listed under teratogenicity is the NOAEL for 

developmental toxicity.

Developmental toxicity / teratogenicity.002 

UUID IUC5-c5b9b170-73a7-4c97-a270-8e2bf1b8ab45 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:29:11 EST 

Remarks 

 
Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP and standard protocol. 

Data source 

Reference 

Reference 

type 

study report 

Author Hoberman AM. Year 1990 

Title Triethylene glycol monomethyl ether (TGME): oral developmental toxicity study in 

Crl:CD(SD)BR pregnant rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Argus Research Laboratories, Inc. Report 

no. 

StudyNumber 

503-005. 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Limit test 

no 

GLP compliance 

no 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol methyl ether 

Details on test material 

no details 

Test animals 

Species 

rat 

Strain 
Sprague-Dawley 

Details on test animals and environmental conditions 

203 to 256 g 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Groups of 25 mated female rats (203 to 256 g) were given daily dosages of 4.8 ml of deionized 

water (control), or 0.6, 1.2, 2.4, and 4.8 ml/kg/day of triethylene glycol monomethyl ether 

(TGME) by gavage. These doses corresponded to 0, 625, 1250, 2500 or 5000 mg/kg/day. All 

doses were adjusted daily according to body weights recorded immediately prior to intubation. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

Days 6 to 15 of gestation 

Frequency of treatment 

daily 

Duration of test 

15 days 

Doses / concentrations 

0, 625, 1250, 2500 or 5000 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

25 females per dose 

Control animals 

yes, concurrent vehicle 

yes, sham-exposed 

Examinations 

Maternal examinations 

Rats were observed at least twice daily during the dosage and postdosage periods for clinical 

signs, signs of resorption, premature deliveries and death. Body weight and feed consumption 

were recorded on Day 0 of presumed gestation and from days 6 through 20 of gestation. Dams 

that were found dead were necropsied on day of death and subjected to the same procedures 

described for scheduled sacrifice. 

Ovaries and uterine content 

Rats were sacrificed on Day 20 of presumed gestation, and the thoracic and abdominal viscera 

were examined for gross lesions. The uterus was excised from each rat and weighed. The 

number and placement of implantations were recorded and sites were categorized as early or 

late resorptions, or live or dead fetuses. Each ovary was examined for the number of corpora 

lutea. 

Fetal examinations 

Fetuses were weighed, sexed, and examined for external alterations. One-half were examined 

for soft tissue alterations, and the remaining half were examined for skeletal alterations. 
Statistics 

Maternal and fetal incidence data were analyzed suing the variance test for homogeneity of the 

binomial distribution. Maternal body weight and feed consumption data, organ weight data, and 

litter averages for percent male fetuses, percent dead or resorbed conceptuses per litter, fetal 

body weights, fetal ossification sites, and percent fetal alterations were analyzed using Bartlett's 

Test of homogeneity of variances and the analysis of variance (when data were homogeneous). 

If the analysis of variance was significant, Dunnett's Test was used to identify the statistical 

significance of individual groups. If data were not homogeneous, the Kruskal-Wallis test was 

used when less than or equal to 75% ties were present; when more than 75% ties were present 

the Fisher's Exact Test was used. In cases where the Kruskal-Wallis Test was statistically 

significant, Dunn's Method of Multiple Comparisons was used to identify the statistical 

significance of individual groups.

All other Caesarean-sectioning data were evaluated using the procedures previously described 

for the Kruskal-Wallis Test. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 1250 mg/kg bw/day (nominal) 

Basis for effect 

level / Remarks 

Reduced food consumption was observed at the next higher dose (2500 

mg/kg bw). 

Endpoint NOAEL 

Effect type teratogenicity 

Effect 

level 

625 mg/kg bw/day (nominal) 

Basis for 

effect level 

/ Remarks 

Groups given 1250 mg/kg/day and higher doses of TGME had significant increases 

in the litter and/or fetal incidences of reversible delays in fetal ossification. 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

One nonpregnant animal in the high dose group (5000 mg/kg/day) was found dead on day 13 of 

presumed gestation. This was considered by the authors to be treatment-related. Significant 

numbers of rats treated with the high dose exhibited decreased motor activity, excess salivation, 

ataxia, and impaired righting reflex. Food consumption of high dose animals were reduced over 

the entire dosage period. Average maternal body weight gains of rats in the high dose group 

were reduced on days 6-9, 6-12, 12-16, and 6-16 of gestation. Consequently, average body 

weights of these animals were reduced on days 9, 12, and 16. Average gravid uterine weights of 

high-dose animals were also reduced. 

Food consumption of rats receiving 2500 mg/kg/day was reduced during days 6-16, 6-18, and 

12-16. Food consumption and average maternal body weights and body weight gains in rats 

receiving 1250 mg/kg/day were not significantly different from controls. Therefore, 1250 
mg/kg/day was considered by study personnel to be the NOAEL for maternal toxicity.

There was no effect of TGME on the number of pregnant dams or number of copora lutea, 

implantations, live litter size or fetal sex ratios. 

Embryotoxic / teratogenic effects 

yes 

Details on embryotoxic / teratogenic effects 

Fetal: Significant increases in embryo-fetal lethality (litter averages for total resorptions (1.6 

versus 0.6 in control), late resorptions (0.3 versus 0 in controls), percentage of resorbed 

conceptuses (12.0 versus 4.4 incontrol) and dams with at least one resorption (81.8% versus 

47.8 in control) occurred in the 5000 mg/kg group. Fetuses from rats treated with 2500 or 5000 

mg/kg had lower body weights than controls (3.04 and 2.56 g (respectively) versus 3.32 in 

controls). 

There was no effect of TGME on the incidences or types of gross external or internal soft tissue 

malformations. Groups given 1250 mg/kg/day and higher doses of TGME had significant 

increases in the litter and/or fetal incidences of reversible delays in fetal ossification. Fetuses 

from rats given 2500 or 5000 mg/kg/day also had a significant increase in the incidence of 

cervical ribs. The NOAEL for developmental toxicity was considered by study personnel to be 

625 mg/kg/day. 

Remarks on results including tables and figures 

The authors remarked that the skeletal variations noted were common observations in fetuses with 

reduced body weights. Since only reversible delays in fetal ossification were observed in the 1250 

mg/kg/day group, the actual NOAEL may be close to this concentration. The NOAEL listed under 

teratogenicity is the NOAEL for developmental toxicity.

Developmental toxicity / teratogenicity.003 

UUID IUC5-94891cda-5cf6-4094-add8-da47f26c92d4 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:32:11 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

19

90 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following GLP and standard methodology 

Data source 

Reference 
Reference 

type 

study report 

Author Hoberman AM. Year 1990 

Title Triethylene glycol monomethyl ether (TGME): oral developmental toxicity study 

in New Zealand White rabbits. 

Bibliograp

hic source 

 

Testing 

laboratory 

Argus Research Laboratories, Inc. Report 

no. 

503-004

. 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Limit test 

no 

Principles of method if other than guideline 

Study followed standard methodology 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity Triethylene glycol methyl ether (TGME) 

Details on test material 

no details 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: gavage 

Details on exposure 

Groups of 20 artificially inseminated female rabbits were given daily dosages of 0 (same 
volume of deionized water as the highest dose), 250, 500, 1000 or 1500 mg/kg/day of 

triethylene glycol monomethyl ether (TGME) by gavage. All doses were adjusted daily 

according to body weights recorded immediately prior to intubation. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

artificial insemination 

Duration of treatment / exposure 

days 6 to 18 of gestation 

Frequency of treatment 

daily 

Duration of test 

24 days 

Doses / concentrations 

0, 250, 500, 1000 or 1500 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

20 artificially inseminated female rabbits 

Control animals 

yes, concurrent vehicle 

Examinations 

Maternal examinations 

Rabbits were observed daily during the course of the study for clinical signs, abortions, 

premature deliveries and death. Body weights were recorded on Day 0, and Days 6 through 29 

of presumed gestation. Food consumption was recorded daily. 

Ovaries and uterine content 

Rabbits were sacrificed on Day 29 of presumed gestation, and the thoracic and abdominal 

viscera were examined for gross lesions. The uterus was excised from each animal and weighed. 

The number and placement of implantations were recorded and sites were categorized as early 

or late resorptions, or live or dead fetuses. Each ovary was examined for the number of corpora 

lutea. 

Fetal examinations 

Fetuses were weighed, sexed, and examined for external and soft tissue or skeletal alterations. 

Statistics 

no data 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 500 mg/kg bw/day (nominal) 

Basis for 

effect level / 

Remarks 

Mortallity and maternal toxicity was observed for dose groups above 500 mg/kg 

bw, but effects and mortality did not occur at 500 mg/kg bw. 
En

dpo

int 

NOAEL 

Eff

ect 

typ

e 

teratogenicity 

Eff

ect 

lev

el 

1000 mg/kg bw/day (nominal) 

Bas

is 

for 

eff

ect 

lev

el / 

Re

ma

rks 

The authors concluded that the NOAEL for fetal toxicity was 1500 mg/kg/day because the 

skeletal abnormalities observed at this dose were not unique. However, in a similar study 

performed by the same laboratory in rats (see previous record), common skeletal 

abnormalities were considered to be adverse. On this basis, the NOAEL for developmental 

toxicity in rabbits should be the dose that did not produce an increase in any skeletal 

abnormalities (1000 mg/kg/day). The NOAEL listed under teratogenicity is the NOAEL for 

developmental toxicity. 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

Maternal: Eight rabbits treated with the 1500 mg/kg/day dose died, and three aborted. A 

significant number of rabbits treated with this dose exhibited decreased motor activity, labored 

breathing, a red substance in the cage pan, dehydration, no feces, ataxia, gastric 

ulceration,anogenital staining, mottled gallbladders, thin-walled stomach, reddened stomach, 

and fluid-filled or empty small intestines, and lower average gravid uterine weight. There was 

one death in the 1000 mg/kg/day group. This was considered to be possibly related to treatment. 

One rabbit in the low dose group aborted. Study personnel did not consider this to be related to 

test material because it was not dose-dependent. 

There was no effect of treatment on the number of pregnant rabbits, average number of corpora 

lutea, implantations, live fetuses, resorptions, or fetal sex ratios. 

Rabbits treated with all doses except 250 mg/kg/day gained more weight during the postdosage 

period than controls, reflecting increased food consumption during this period. Study personnel 

did not consider this weight gain to be an adverse effect, as it is commonly seen in 

developmental studies after dosing is terminated. 

Details on embryotoxic / teratogenic effects 

Fetal: There was no effect of treatment on fetal body weight, or incidences or types of gross 

external or internal soft tissue malformations. The fetal and/or litter incidences of angulated 

hyoid alae and reversible delays in ossification of the xiphoid were increased in the 1500 

mg/kg/day group. 

Developmental toxicity / teratogenicity.004 
UUID IUC5-579f4ed8-027a-4ce4-ad1e-8db85368274d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-12 14:46:18 EST 

Remarks 

 

Administrative Data 

Purpose flag key study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result type experimental result Study 

period 

1

9

9

2 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Robust study following standard procedure and following GLP. Purity of test 

substance was provided. 

Data source 

Reference 

Referen

ce type 

 

Author Bates HK and de Serres FJ. Yea

r 

1992 

Title Developmental neurotoxicity evaluation of triethylene glycol monomethyl ether (CAS 

112-35-6) administered by gavage to time-mated CD rats on gestational day 6 through 

postnatal day 21. 

Bibliogr

aphic 

source 

CMA Reference Ge-43.0-DEV/NEU-RTI 

Testing 

laborato

ry 

 Rep

ort 

no. 

 

Owner 

compan

y 

 

Compan

y study 

no. 

 Rep

ort 

date 

1992-

03-03 

Materials and methods 

Limit test 

no 

GLP compliance 

yes 
Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-35-6 

Identifier EC number 

Identity 203-962-1 

Identifier Common name 

Identity triethylene glycol methyl ether 

Details on test material 

The analyzed chemical purity was 99.2%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Details on test animals and environmental conditions 

Timed pregnant CD" (Sprague-Dawley) rats, 64 sperm plug-positive females per group 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Timed pregnant CD" (Sprague-Dawley) rats, 64 sperm plug-positive females per group, were 

gavaged with the neat test material, triethylene glycol monomethyl ether (TGME), once daily, 

on gestational day (GD) 6 through postnatal day (PND) 21 at doses of 0, 300, 1650 or 3000 

mg/kg/day. The volume of TGME administered was adjusted based on each animal's most 

recent body weight. 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

no details other than the females were plug-positive females per group 

Duration of treatment / exposure 

day 6 of gestation through postnatal Day 21 

Frequency of treatment 

daily 

Duration of test 

38 days 

Doses / concentrations 

300, 1650, 3000 
Basis nominal conc. 

No. of animals per sex per dose 

64 pregnant females per dose. 

Control animals 

yes, concurrent vehicle 

Examinations 

Maternal examinations 

Clinical observations were made at least twice daily during the dosing period and daily 

otherwise. Maternal body weights were measured on GD 0, 6, 9, 12, 15, 18, 20, and on PND 0, 

4, 7, 13, 17, and 21. Food consumption was measured for the intervals GD 0-6, 6-9, 9-12, 

12-15, 15-18, 18-20, and PND 0-3, 3-6, 6-9, and 9-12. Maternal animals were allowed to deliver 

and rear their young. 

On PND 22 the dams were evaluated for body weight, liver and kidney weight and the number 

of uterine implants (metrial glands).

Fetal examinations 

Pups were counted, examined externally, weighed, and sexed on PND 0 and PND 4. After 

examination on PND 4, litter size was standardized by random culling to either a 4:4 or 5:3 sex 

ratio. Litters with insufficient numbers of pups were removed from the study after culling. 

Litters with sufficient numbers of pups remained on study, and pups wereexamined and 

weighed on PNDs 7, 13, 17, 21,35, 49, and 68. Male pups were examined daily starting at PND 

17 for testicular descent, and females were examined daily starting on PND 30 for vaginal 

opening. One male and one female pup from each litter were assigned to each of three 

behavioral tests. Motor activity was assessed for one hour in a Figure-8 maze on PNDs 13, 17, 

21, 47, and 58. Auditory startle response was assessed on PNDs 22 and 60, and learning and 

memory were assessed with an active avoidance paradigm run on PNDs 60-64. Three 

euthanizations occurred during the course of this study. The first took place after culling and 

involved those dams that had failed to deliver as well as the dams and pups from litters of 

insufficient size or sex ratio. The second took place on PND 22 and the third on PND 68.

On PND 22 and PND 68 one male and one female pup from each litter were weighed and killed. 

A total of 24 of these pups were perfused in situ at each euthanization (PND 22 and PND 68 

i.e., 48 animals total) and were examined for histopathologic lesions of the central and 

peripheral nervous system. The brains of the remaining animals at each sacrifice were removed 

and separated into the telencephalon, diencephalon, medulla oblongata/pons, and the 

cerebellum. These sections were all weighed separately. 

Statistics 

Data were analyzed using the FREQ, GLM, NPAR1WAY and LIFETEST procedures in the 

SAS software package, in conjunction with a set of custom-designed analysis procedures. 

Results and discussions 

Effect levels 

En

dpo

int 

NOAEL 

Eff

ect 

maternal toxicity 
typ

e 

Eff

ect 

lev

el 

1650 mg/kg bw/day (nominal) 

Bas

is 

for 

eff

ect 

lev

el / 

Re

ma

rks 

Conclusion of summary preparer, EPA. The authors stated that “TGME administered by 

gavage to pregnant and lactating CD" (Sprague- Dawley) rats resulted in no overt signs of 

maternal toxicity”. However, they also stated that the increased kidney weights in the high 

dose animals occurred as a result of exposure to TGME. Based on this comment, a 

maternal NOAEL of 1650 was assigned by the summary preparer. This is in agreement 

with the maternal NOAEL derived by the EPA (Anderson, L. Triethylene glycol 

monomethyl, monoethyl and monobutyl ethers RM1 screening document (draft), Feb. 24, 

1995). 

Endpoi

nt 

NOAEL 

Effect 

type 

teratogenicity 

Effect 

level 

300 mg/kg bw/day (nominal) 

Basis 

for 

effect 

level / 

Remar

ks 

Conclusion of summary preparer, EPA. The authors arrived at a no observable effect 

level (NOEL) of “equal to or greater than 300 mg/kg/day” based on decreased postnatal 

weight gains at 1650 and 3000 mg/kg/day. The reviewer does not believe that a 

NOAEL can be assigned from this study due to the unclear significance of minor 

reductions in body weight gains of animals at various time points and changes in startle 

response at 1650 and 3000 mg/kg. A NOAEL for teratogenicity of 300 mg/kg/day has 

been derived by the EPA (Anderson, L. Triethylene glycol monomethyl, monoethyl and 

monobutyl ethers RM1 screening document (draft), Feb. 24, 1995). The NOAEL listed 

under teratogenicity is the NO(A)EL for developmental toxicity. 

Maternal toxic effects 

yes 

Details on maternal toxic effects 

Of the 256 mated animals assigned to this study 33, 27, 28, and 31 litters in the control to 

high-dose group, respectively, had sufficient pups of both sexes to be used for the behavioral 

evaluations. Evaluation of data from the maternal animals revealed no dose- related patterns of 

clinical signs of toxicity or lethality. Maternal body weights were equivalent across all groups 

and for all time points. No statistically significant effects on maternal weight gain or food 

consumption were noted. The length of gestation was significantly increased in the high-dose 

group animals compared to control although this finding was “of questionable biological 

significance since the difference between the groups was smaller than the 14-hour breeding 

time.” Necropsy of maternal animals in the high- dose group revealed significantly heavier 

kidneys than controls. Kidney weights increased in a dose-dependent manner.
Necropsy of maternal animals revealed that kidneys from the maternal animals exposed to 3000 

mg/kg/day of TGME were significantly heavier than controls 

Details on embryotoxic / teratogenic effects 

Analysis of pup in life data revealed no significant effects for PND 0/4 pup sex ratio or for pup 

survival during any period. Female pups from the mid- and high-dose groups (6.7 and 6.8 +/- 

0.1 g) and male pups from the high- dose group (7.0 and 7.1 +/- 0.1 g) were significantly 

heavier than their control cohorts on PND O (6.2 and 6.7 +/- 0.1 g for females and males, 

respectively). Pups from these same groups gained significantly less weight in the period from 

PND 4 to PND 21. Although born heavier, the male pups from the high-dose group were 

significantly lighter than the control pups at the end of the study on PND 68 (440.7 +/- 6.0 vs. 

462.4 +/- 4.8 g). Final body weights (PND 68) of mid and high dose females and mid-dose 

males were not significantly different from control.

Evaluation of pup development through the determination of vaginal opening revealed no 

differences between groups. Male pup development, as gauged by time of testes descent, was 

shown to be significantly advanced in the pups from the mid- and high-dose groups. Evaluation 

of the behavioral data generated during the course of this study indicated no dose-related effects 

on motor activity or active avoidance data. Significant effects on auditory startle response 

parameters were noted. In particular, the auditory startle amplitude (magnitude of the startle 

reflex) was increased in male and female pups in the high-dose group on PND 22. Auditory 

startle amplitude was also increased for male pups on PND 60 and a similar trend of smaller 

magnitude was observed in PND 60 females. When startle latency (time to maximum startle 

reflex) was examined, the pups showed no consistent effect on PND 22, but both male and 

female pups demonstrated a decrease in the startle latency on PND 68.

Necropsy of weanling and adolescent pups revealed no findings that could be related to 

treatment. Histopathological assessment of the peripheral and central nervous systems of the 

pups showed no treatment related lesions in any group. 

Applicant's summary and conclusion 

Conclusions 

“In conclusion, TGME administered by gavage to pregnant and lactating CD" (SpragueDawley) rats resulted in no overt signs of maternal toxicity. In addition, no discernible effects 

were noted in the offspring on motor activity, active avoidance, or neuropathology at exposures 

up to 3000 mg/kg/day. Exposure to TGME at 3000 mg/kg/day resulted inincreases in auditory 

startle amplitude and decreases in latency to maximum startle, but no changes in the habituation 

process evaluated in the auditory startle test. The significance of these auditory startle 

observations with regard to the condition of the test animals is notclear. Exposure to TGME at 

levels of 1650 and 3000 mg/kg/day produced developmental toxicity evidenced by decreased 

postnatal weight gains. Therefore, the no observable effect level" (NOEL) for this study is 

considered to be equal to or greater than 300 mg/kg/day.” 

Developmental toxicity / teratogenicity.005 

UUID IUC5-cfa3ed72-3cd2-4989-9ab8-d528ddd2cd40 

Dossier UUID 0 

Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-02-17 21:02:50 EST 
Remarks 

 

Administrative Data 

Purpose flag supporting study (X) robust study summary ( ) used for classification ( ) used for 

MSDS 

Study result 

type 

experimental result Study 

period 

1993 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Pups were not examined for malformations. Statistical analyses were not 

performed. Otherwise the study was well conducted according to GLP and 

standard procedures. 

Data source 

Reference 

Reference 

type 

study report 

Author Taupin PJY Year 1993 

Title Brake Fluid DOT 4: Chernoff and Kavlock (CKA) developmental toxicity screen 

in the rat 

Bibliographi

c source 

 

Testing 

laboratory 

Shell Research Limited, Sittingbourne Research Centre Report 

no. 

SBGR.92.2

33 

Owner 

company 

Shell 

Company 

study no. 

 Report 

date 

1993-02-02 

Materials and methods 

Limit test 

no 

Test guideline 

Qualifier according to 

Guideline other guideline: Chernoff-Kavlok teratogenicity screening test 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 106008-94-0 

Identifier Common name 

Identity Brake Fluid DOT 4 

Details on test material 
Test material is a mixture containing 30-50% triethylene glycol monomethyl ether borate ester 

(CAS No. 106008-94-0), 3-30% triethylene glycol monobutyl ether borate ester, 20-30% 

triethylene glycol monomethyl ether (CAS No. 112-35-6), 2-10% triethylene glycol monobutyl 

ether (CAS No. 143-22-6), 20-30% tetraethylene glycol monomethyl ether (CAS No. 

23783-42-8), 2-10% tetraethylene glycol monobutyl ether (CAS No. 1559-34-8), and < 1% 

minor additives. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Details on test animals and environmental conditions 

no data 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Groups of 10 female rats were dosed by oral gavage with 25, 150 or 1000 mg/kg/day test 

material on days 7-17 of gestation. Additional groups of females were sham dosed (negative 

control) or dosed with 1000 mg/kg/day ethylene glycol diethyl ether (positive control). 

Analytical verification of doses or concentrations 

no data 

Details on analytical verification of doses or concentrations 

no data 

Details on mating procedure 

no data 

Duration of treatment / exposure 

days 7-17 of gestation 

Frequency of treatment 

daily 

Duration of test 

From Day 7 of gestation to Day 5 of lactation. 

Doses / concentrations 

25, 150, 1000 mg/kg/day 

Basis nominal conc. 

No. of animals per sex per dose 

10 female rats. 

Control animals 

other: sham dosed (negative control) or dosed with 1000 mg/kg/day ethylene glycol diethyl 

ether (positive control). 

Further details on study design 

Groups of 10 female rats were dosed by oral gavage with 25, 150 or 1000 mg/kg/day test 

material on days 7-17 of gestation. Additional groups of females were sham dosed (negative 
control) or dosed with 1000 mg/kg/day ethylene glycol diethyl ether (positive control). Animals 

were allowed to litter naturally, and any that did not deliver by day 25 of gestation were killed. 

Dams and surviving pups were killed on day 5 of lactation. 

Examinations 

Maternal examinations 

Body weights were recorded on days 1, 7 and 21 of gestation and on day 5 of lactation (or at 

termination for animals that did not reproduce). Food intake was recorded over days 1 to 7 and 

7 to 17 of gestation, day 17 of gestation to day 1 of lactation and days 1-5 of lactation. 

Ovaries and uterine content 

Uteri of all dams were examined for implantation sites. 

Fetal examinations 

The birth index [total number of pups born (live and dead) x 100/ number of implantation sites], 

live birth index (number of pups alive at day 1 of lactation/ total number of pups born x 100) 

and viability index (number of pups alive on day 5 of lactation/ number of pups alive on day 1 

of lactation x 100) were calculated for each litter and group. Litter weights were recorded on 

days 1 and 5 of lactation and the uteri of all dams were examined for implantation sites. Pups 

were not necropsied. 

Statistics 

Statistical analyses were not performed. 

Results and discussions 

Effect levels 

Endpoint NOAEL 

Effect type maternal toxicity 

Effect level 1000 mg/kg bw/day 

Basis for effect 

level / Remarks 

1000 mg/kg bw was highest dose tested and showed no adverse effects. 

Endpoint NOAEL 

Effect type teratogenicity 

Effect level 1000 mg/kg bw/day 

Basis for effect level 

/ Remarks 

1000 mg/kg bw was highest dose tested and showed no adverse effects. 

Maternal toxic effects 

no effects 

Details on maternal toxic effects 

There was no effect of Brake Fluid DOT4 on maternal body weight of food intake. 

Embryotoxic / teratogenic effects 

no effects 

Details on embryotoxic / teratogenic effects 

Mean litter weights of low dose (25 mg/kg/day) animals were slightly lower than negative 

controls at birth (79 +/- 24 g vs. 90 +/- 23 g in sham control) and on day 5 of lactation (109 +/- 

29 g vs. 133 +/- 34 g in sham control). In contrast, mean litter weights of high dose animals 

were higher than negative controls at birth (97 +/- 10 g) and on day 5 of lactation (150 +/- 24 g). 

The authors stated that the reduction at 25 mg/kg/day could be related to slightly smaller litter 

sizes (the birth index was 85 +/- 15 vs. 95 +/- 7 in the sham control). Two rats in this group had 

a lower number of implant sites (8 and 6) than the others (ranged from 15-19), which led to a 
decrease in the number of pups delivered(5 in each of the animals vs. 13-18 in the others). 

Another low dose animal that had 16 implant sites only delivered 9 pups. The birth index of 

animals treated with 150 (94 +/- 6) or 1000 mg/kg/day test material (95 +/- 6) was similar to the 

sham control (95 +/- 7). There was no effect of treatment on the number of dead pups (4 in 

control vs. 1 in each treated group). There were no treatment-related necropsy findings. There 

was no effect of treatment with Brake Fluid DOT 4 of the duration of gestation, the number of 

females littering, the mean number of implant sites, or the live birth index or viability index. 

Based on these data, the authors concluded that 1000 mg/kg/day Brake Fluid DOT4 did not 

cause fetal growth retardation or embryolethality.

By contrast, the positive control animals lost weight from days 7 to 21 of gestation. All nine 

pregnant animals treated with ethylene glycol diethyl ether (EGDE) resorbed their litters. Most 

animals treated with EGDE had enlarged livers and/or spleens. 

Remarks on results including tables and figures 

It is not known whether the decreased mean litter weights or birth index at 25 mg/kg/day or the 

increased mean litter weights at 1000 mg/kg/day are significantly different from control, since 

statistical analyses were not performed. However, these findings do not appear to be related to 

treatment since they are not dose-dependent. Since the investigators concluded that 1000 

mg/kg/day Brake Fluid DOT4 did not cause fetal growth retardation or embryo or fetal lethality, 

the NOAEL for these effects is 1000 mg/kg/day. The NOAEL listed under teratogenicity is the 

NOAEL for developmental toxicity. 

Overall remarks, attachments 

Overall remarks 

Reference substance: 3,6,9,12,15,18-hexaoxaicosane 

UUID ECB5-4fff17de-eb4d-4f3e-8517-5b27f7fa7a16 

Dossier UUID 0 

Author European Commision/Joint Research Centre/European 

Chemicals Bureau 

Date 2007-05-10 05:00:00 EDT 

Remarks Created 

General information 

Reference substance name 3,6,9,12,15,18-hexaoxaicosane 

EC inventory 

EC number 245-774-2 CAS number 23601-39-0 

EC name 3,6,9,12,15,18-hexaoxaicosane 

Molecular formula C14H30O6 

Reference substance information 

CAS information 

CAS number 23601-39-0 

IUPAC name 

IUPAC name 3,6,9,12,15,18-hexaoxaicosane 
Synonyms 

Name 3,6,9,12,15,18-hexaoxaeicosane 

Name 3,6,9,12,15,18-Hexaoxaeicosane 

Name 3,6,9,12,15,18-Hexaoxaeicosane 

 DSL Category: Organics

USEPA Category: Ethylene Glycol Ethers;Neutral Organics 

Molecular and structural information 

Molecular formula C14H30O6 

Molecular weight range 294.3844 

SMILES notation CCOCCOCCOCCOCCOCCOCC 

InChI InChI=1/C14H30O6/c1-3-15-5-7-17-9-11-19-13-14-20-12-10

-18-8-6-16-4-2/h3-14H2,1-2H3 

Structural formula 

Legal entity: PCA Services, Inc. 

UUID IUC5-627340ec-79cf-4d47-86f0-902729c7a

dc2 

Dossier UUID 0 

Author rgerwe / (No legal entity) 

Date 2008-11-16 11:49:37 EST 

Remarks 

General information 

Legal entity name PCA Services, Inc. 

Identifiers 

Other IT system identifiers 

IT system LEO 
ID 8869 

Contact information 

Contact address 

Address 2704 Trail Wood Drive 

Postal code 27705 

Town Durham 

Region / State North Carolina 

Country United States of America 

Phone (919) 382-8787 

Fax (919) 382-8788 

E-mail r.gerwe2@verizon.net 

Web site www.pcaserve.com 

Contact persons 

Organisation PCA Services, Inc. 

Title President 

First name Roderick 

Last name Gerwe 

Phone (919) 382-8787 

Fax (919) 382-8788 

E-mail r.gerwe2@verizon.net 

Address 2704 Trail Wood Drive 

Postal code 27705 

Town Durham 

Region / State North Carolina 

Country United States of America