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Subject #3 of 3 EHPV High Boiling EGEs

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Date: Fri, 3 Jul 2009 16:25:11 -0400

Subject: Substance: pentaethylene glycol methyl ether / 3,6,9,12,15-pentaoxahexadecanol / 

2,5,8,11,14-pentaoxahexadecan-16-ol / 23778-52-1 / PCA Services, Inc. / Durham / United 

States of America

Content-Type: multipart/related;

boundary="_005_7479667966666770687971717168697576688065787676687074768_";

type="multipart/alternative"

Thread-Topic: Substance: pentaethylene glycol methyl ether / 3,6,9,12,15-pentaoxahexadecanol / 

2,5,8,11,14-pentaoxahexadecan-16-ol / 23778-52-1 / PCA Services, Inc. / Durham / United 

States of America

Thread-Index: AcrBZQ71d4jG35qUToaXa4xascqrDQ==

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Printing Date 2009-07-03 16:24:22 EDT 

Restriction of specific regulatory purposes 

 

Confidentiality 

 

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

Substance: pentaethylene glycol methyl ether 

UUID IUC5-6705699e-fdd7-4137-9bc7-c36ebea60fb9 

Dossier UUID 0 

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

America 

Date 2009-06-14 10:48:25 EDT 

Remarks Created endpoint study record 4.1 Appearance/physical 

state/colour 

0 Related Information 

0.1 Templates 

0.2 Categories 

0.3 Mixtures 

1 General Information 

1.1 Identification 

Substance identification 

Chemical name pentaethylene glycol methyl ether 

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

Reference substance 

Reference substance 3,6,9,12,15-pentaoxahexadecanol /

2,5,8,11,14-pentaoxahexadecan-16-ol / 23778-52-1

 EC number EC name 

245-874-6 3,6,9,12,15-pentaoxahexadecanol 

CAS number CAS name 

23778-52-1 

IUPAC name 

2,5,8,11,14-pentaoxahexadecan-16-ol 

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 IUC5-9406f24b-cf91-4b89-9d6b-56c97fab0c69 

Dossier UUID 0 

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

America 

Date 2009-06-14 11:02:20 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 product specification 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data come from manufacturer's product data sheet. Pentaethylene glycol methyl 

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&%20c

lutch%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 

Substance type 

organic 

4.2 Melting point/freezing point 

Melting point/freezing point.001 

UUID IUC5-40e99664-d05d-4681-9af0-722b69ee5862 

Dossier UUID 0 

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

America 

Date 2009-06-14 10:16:42 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 brake fluid manufacturer's data sheet. Pentaethylene glycol 

methyl ether is commercially available only in automotive brake and clutch 

fluid formulations. 

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 

yes 

Test material identity 

Identifier Common name 

Identity Pennzoil 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 IUC5-8b2810e6-6cb8-44bc-af10-b02006d33f85 

Dossier UUID 0 

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

America 

Date 2009-06-14 11:34:41 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 methyl 

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 

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 

 Rep

ort 

no. 

 

Owner 

company 

 

Company 

study no. 

 Rep

ort 

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 

Results and discussions 

Boiling point 

Boiling pt. >= 270 °C 

Atm. pressure ca. 1013 hPa 

Decomposition no 

Decomp. temp. 

Remarks Equilibrium Reflux Boiling Point 

4.6 Vapour pressure 

Vapour pressure.001 

UUID IUC5-c9872ff5-102e-4c35-8104-96b3dc73d1db 

Dossier UUID 0 
Author rgerwe2 / PCA Services, Inc. / Durham / United States of 

America 

Date 2009-06-14 10:33:07 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 methyl 

ether is available commercially only in a formulation of automotive brake or 

clutch 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&%20c

lutch%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 

yes 

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 IUC5-142d3cb4-841d-455f-bf7c-05ea51b81595 

Dossier UUID 0 

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

America 

Date 2009-06-13 16:56:36 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 computer program. 

Data source 

Reference 

Reference type other: computer model program output. 

Author Year 2009 

Title EPIWIN 4.00, KOWWIN (v1.67) 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-13 

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 23778-52-1 

Identifier EC number 

Identity 245-874-6 
Identifier IUPAC name 

Identity 2,5,8,11,14-pentaoxahexadecan-16-ol 

Results and discussions 

Partition coefficient 

Type log Pow 

Partition coefficient ca. -2 

Temp. 

pH 

4.8 Water solubility 

Water solubility.001 

UUID IUC5-a0e50590-dffd-4d1d-8961-9ca6b9474b1f 

Dossier UUID 0 

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

America 

Date 2009-06-14 10:39:48 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 methyl 

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 

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. 

Any other information on materials and methods incl. tables 

Results and discussions 

Water solubility 

> 1000000 mg/L 

Temp. 

pH 

Details on results 

miscible in water 

4.11 Flash point 

Flash point.001 

UUID IUC5-6524160d-2072-4984-bf3f-67c9d8b8852f 

Dossier UUID 0 

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

America 

Date 2009-06-14 10:44:04 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 methyl 

ether is availaibe commercialy 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 

yes 

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 IUC5-2a0de322-fb6a-4abf-b2ab-b34e44b100b9 

Dossier UUID 0 

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

America 

Date 2009-06-14 12:07:21 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 20
period 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 2009 

Title EPIWIN 4.00, AOPWIN (v1.92) 

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 23778-52-1 

Identifier EC number 

Identity 245-874-6 

Identifier IUPAC name 

Identity 2,5,8,11,14-pentaoxahexadecan-16-ol 

Study design 

Estimation method (if used) 

PHOTOCHEMICAL REACTION WITH OH RADICALS

- Concentration of OH radicals: 1.5E6 OH/cm3

- Degradation rate constant: 68.0607 E-12 cm3/molecule-sec

- Computer programme: AOPWIN (v1.92)

- Half-life: 1.886 hours or .157 day (12-hour day) 

Light source 

sunlight 

5.2 Biodegradation 

5.2.1 Biodegradation in water: screening tests 

Biodegradation in water: screening tests Hoechst TetraEGME 1989.002 

UUID IUC5-ab340aa2-0f24-4d61-b0bb-1bab9ea86ebe 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 
Date 2009-02-19 09:00:29 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% 

5.3 Bioaccumulation 

5.3.1 Bioaccumulation: aquatic / sediment 

Bioaccumulation: aquatic / sediment.001 

UUID IUC5-12b763e1-654e-4871-af8e-11edbf5b7b50 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:25:55 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 4.00 BCFBAF (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 23778-52-1 

Identifier EC number 

Identity 245-874-6 

Identifier IUPAC name 

Identity 2,5,8,11,14-pentaoxahexadecan-16-ol 

Test conditions 

Details on estimation of bioconcentration 

BASIS INFORMATION

- Measured/calculated logPow: estimated, -2.00

BASIS FOR CALCULATION OF BCF

- Estimation software: EPIWIN 4.00 BCFBAF (v3.00)

- Result based on calculated log Pow of: -200 

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 IUC5-7f20dd0c-f1ba-44ee-8671-7d41d544e993 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:08:11 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 

reliability 

Data were obtained using a recognized, approved computer model 

estimation program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN 4.00 HENRYWIN (v3.20) 

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 23778-52-1 

Identifier EC number 

Identity 245-874-6 

Identifier IUPAC name 

Identity 2,5,8,11,14-pentaoxahexadecan-16-ol 

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 IUC5-500fc26d-3478-4847-9da9-2b8efa6eef97 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:18:37 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 computer model 

program. 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN 4.00 Fugacity Level III Model 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-13 

Materials and methods 

Model 

Calculation according to Mackay, Level III 

Calculation programme 

EPIWIN 4.00 Fugacity Level III 

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 23778-52-1 
Identifier EC number 

Identity 245-874-6 

Identifier IUPAC name 

Identity 2,5,8,11,14-pentaoxahexadecan-16-ol 

Test substance input data 

- Molar mass: 252.31

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

- Vapour pressure:

- log Pow: -2.00

- Melting point: -40

- Reaction half-life estimates for

- Air: 3.77 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 Hoechst TetraEGME 1968.003 

UUID IUC5-b86470d5-267a-4521-bbf4-88f306a9282a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:30 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 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 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/Main EUROPEAN 

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 Hoechst TetraEGME 1988.004 

UUID IUC5-7c12c52d-4897-4b78-8ccd-d755e6302c43 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:30 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 

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 

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 DOW MPEG.006 

UUID IUC5-d98b1133-eead-4775-877b-3e0f2b3d1760 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:04 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 

Bibliograp Dow MSDS for CARBOWAX methoxypolyethylene glycol 350 (CAS No. 
hic source 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) 

Short-term toxicity to fish DOW MPEG.006 

UUID IUC5-07266c2c-aaa8-423c-8cde-c2b03424fbe5 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:00 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 DOW MPEG 2000.002 

UUID IUC5-88bfbb51-504e-43cb-ab6e-b0a44322183f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:04 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) 

Short-term toxicity to aquatic invertebrates DOW MPEG 2000.002 

UUID IUC5-cb476ba8-bae4-4123-9d49-324b7d314232 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:00 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 Report 
laboratory 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 TGME 1989.001 

UUID IUC5-1570d756-1b30-4968-9f70-fcbef7255f6f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:11 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 Hoechst TetraEGME 1988.002 

UUID IUC5-80d82213-c1ec-4c7f-9404-9e3f02d0bce2 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:31 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 

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 Hoechst-2 TetraEGME 1988.003 

UUID IUC5-4b98dff9-7711-4818-b211-546f391c245d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:31 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 

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 

7.2 Acute Toxicity 

7.2.1 Acute toxicity: oral 

Acute toxicity: oral Carpenter Rat TGME 1958.007 

UUID IUC5-96651e8b-c0cd-4dba-98a8-91ea1b2f11e8 

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

States of America 

Date 2009-02-19 08:53:12 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 Gardner Rat Brake Fluid 1992.008 

UUID IUC5-9e0c1719-009a-4cd5-abf1-1ece2dfbeb19 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:38 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 

Acute toxicity: oral Hoechst Rat TetraGME 1988.005 

UUID IUC5-c009b412-1974-4971-b07e-813efe4b1c6f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:31 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 

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 Hoechst Rat TetraGME 1968.006 

UUID IUC5-0d3e6424-9776-4596-bf44-f07083b2ca38 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:31 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 

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 Reid Rat MPEG.003 

UUID IUC5-90af10c1-ffd7-4e54-a571-b00c74d56df5 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:05 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

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-e951683f-a681-4210-8cdd-1dfefceb5cab 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:05 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

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 Reid Rat MPEG.003 

UUID IUC5-1b763994-668d-47d3-8a7e-5d99c2077677 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:01 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 Carpenter Rat MPEG 1947.004 

UUID IUC5-2b4ea376-e15c-4b3a-a19c-0cfb52ac3d68 

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

States of America 

Date 2009-02-19 09:06:01 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 

7.2.2 Acute toxicity: inhalation 

Acute toxicity: inhalation Smyth TGME Rat 1962.002 

UUID IUC5-29730531-5cf1-444f-856e-61c431dc6fef 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:12 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 Gardner BF DOT 4 1992.004 

UUID IUC5-5edb8311-eb33-4277-a8c2-d7daa0b0af1a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:39 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 

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 

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-ae2667c3-adb4-48f3-a9d7-0dc2dfa2fac1 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:05 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 Union Carbide Report 1988-05-23 
study no. date 

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 Reid MPEG Rabbit 1988.003 

UUID IUC5-62c5c185-5fdc-4287-bbe9-f89535c20281 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:01 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 
7.3 Irritation / corrosion 

7.3.1 Skin irritation / corrosion 

Skin irritation / corrosion Smyth TGME 1962.007 

UUID IUC5-a7816e5f-3d98-4f06-ad06-b1f1a66ec146 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:13 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 

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 Gardner BF DOT 4 1992.006 

UUID IUC5-9d88aa84-0ae2-4a51-a6fb-08ebb2d68e26 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:39 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 Hoechst TetraEGME 1988.005 

UUID IUC5-bd0e93f3-5312-49d5-ad0d-fb1a3f3d3459 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:32 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 

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 Unpublished Study (88.1086). Report 
study no. 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 Reid MPEG 1988.004 

UUID IUC5-f0c7d5e1-b231-4a94-b3e4-7392b0897431 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:06 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 Reid MPEG 1988.004 

UUID IUC5-f2c3e9ed-8c73-4b5e-abc3-a7ce10262bde 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:02 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 

7.3.2 Eye irritation 

Eye irritation Smyth TGME 1962.006 

UUID IUC5-2d753088-2fa9-47d7-ba28-704e44d39e2e 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:13 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 

Eye irritation Gardner BF DOT 1992.005 

UUID IUC5-cb217d63-5eb5-4bce-a462-a0c7c27f787c 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:39 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 

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 Hoechst TetraEGME 1988.004 

UUID IUC5-7c4a4fc1-3a83-4af2-91ed-f289bbc0af6a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:00:32 EST 

Remarks 

 

Administrative Data 

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

MSDS 

Study result experimental result Study 1988 
type period 

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 Reid MPEG 1988.003 

UUID IUC5-0ee9f388-2e7b-48ae-8130-e81f82b582d9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:06 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 Reid MPEG 1988.003 

UUID IUC5-0cc5e9ea-e483-41ea-875a-05ef46a5206f 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:03 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 

7.5 Repeated dose toxicity 

7.5.1 Repeated dose toxicity: oral 

Repeated dose toxicity: oral Gill and Negley TGME 1990.001 

UUID IUC5-1b521fea-5c97-4376-a487-abd7b6cc4e69 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:13 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. 

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 Taupin BF DOT 1993.002 

UUID IUC5-540c0586-c4a6-4768-860a-7d0199f4fe04 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:40 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 

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 Shell 
company 

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-ec3af847-5a6e-4bf7-b3be-2eee6d39e0f7 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:14 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 Year 1990 
dermal toxicity study in Sprague-Dawley rats 

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-a30c3f76-b3c9-443b-8234-94f038570589 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:14 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. 

Repeated dose toxicity: dermal UC MPEG 1985.002 

UUID IUC5-53589035-b3c8-4a64-806b-44cbfd597674 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:06 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 Gray MPEG 1987.003 

UUID IUC5-eb7bc564-bb4b-4221-bf7f-367ea9b481b6 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 
Date 2009-02-19 09:05:07 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 

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 

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.

Repeated dose toxicity: dermal UC MPEG 1985.002 

UUID IUC5-414f9efd-bd52-4fec-90f4-2dca6a38bba9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:03 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 / Mild acanthosis (epidermal thickening) 
Remarks 

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-f211be5f-140a-4040-83e3-ee81d24f190a 

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

States of America 

Date 2009-02-19 09:06:06 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 

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 

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-a12bb192-13e7-4e03-a2a0-5783365d17ce 

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

States of America 

Date 2009-02-19 09:05:07 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

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. 

Repeated dose toxicity: other routes NAMSA MPEG 1997.001 

UUID IUC5-e09029f1-36e1-4970-a8bd-e310403a8379 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:06 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

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 IUC5-3a0738e3-e2af-41d1-bd61-0807c726f6bb 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:14 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 Liscombe & Gollapudi TGME 1990.004 

UUID IUC5-4efae387-0d5e-4d5e-838c-554e7dd2e6a5 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:15 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

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 Brooks & Wiggins AMES BF DOT 1992.005 

UUID IUC5-810f8ae8-e396-4fe2-ac9f-d9d764114480 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:40 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 

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 IUC5-1deb0c72-48b3-4fbe-8e3d-f09b3e24754a 

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

States of America 

Date 2009-02-19 08:56:40 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 

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 IUC5-7974950b-cfbb-4438-8de7-eebd7cc3a6e6 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:05:07 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

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-

23 

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 yes 
controls 

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 UC MPEG 1984.003 

UUID IUC5-408f72b1-fb4a-4d84-9c06-37723cbfbbfe 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:07 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

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-

23 

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-e915ed5c-a131-4872-8049-79e042cf6dc6 
Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:15 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 Corley 13-Week TGME 1990.001 

UUID IUC5-f3310206-d82e-40b3-a647-300ed069cc65 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:16 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 Report 
study no. 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 IUC5-0b20f079-7d4e-4132-8ed7-6eed72fa76ec 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:16 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).

Toxicity to reproduction UC MPEG 1985.002 

UUID IUC5-41c90466-abe3-41b2-b28a-0eb777fee804 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 
States of America 

Date 2009-02-19 09:05:08 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 

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 UC MPEG 1985.002 

UUID IUC5-fdfbec51-9f88-4732-9058-ef580e185b84 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 09:06:07 EST 

Remarks 

 

Administrative Data 

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

for MSDS 

Study result experimental result Study 1985 
type period 

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 IUC5-04f2ae73-6961-424b-98a0-31d4d5c3a443 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:17 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 Hoberman TGME Rabbits 1990.003 

UUID IUC5-2a8e01ca-3570-43d3-94f6-0807b98c6a74 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:17 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

dp

oin

t 

NOAEL 

Eff

ect 

typ

e 

teratogenicity 

Eff

ect 

lev

1000 mg/kg bw/day (nominal) 
el 

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 IUC5-298194f1-b0b1-4efb-b7f7-23f1e39fda41 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:53:17 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

dp

oin

t 

NOAEL 

Eff

ect 

typ

e 

maternal toxicity 

Eff

ect 

lev

el 

1650 mg/kg bw/day (nominal) 

Ba

sis 

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 
for 

eff

ect 

lev

el / 

Re

ma

rks 

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 

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 Taupin BF DOT 1993.005 

UUID IUC5-a4c4b344-0ebc-4eb2-8ae3-6cfb34716529 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-19 08:56:41 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 

1993-02-0

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: 3,6,9,12,15-pentaoxahexadecanol 

UUID ECB5-02601508-3eb3-426e-a6ad-9484faa5b70f 

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-pentaoxahexadecanol 

EC inventory 

EC number 245-874-6 CAS number 23778-52-1 

EC name 3,6,9,12,15-pentaoxahexadecanol 

Molecular formula C11H24O6 

Reference substance information 

CAS information 

CAS number 23778-52-1 

IUPAC name 

IUPAC name 2,5,8,11,14-pentaoxahexadecan-16-ol 

Synonyms 

Name 2,5,8,11,14-pentaoxahexadecan-16-ol 

Name 2,5,8,11,14-Pentaoxahexadecan-16-ol 

Name 2,5,8,11,14-Pentaoxahexadecan-16-ol 

 DSL Category: Organics

OECD Category: High boiling EGE's
USEPA Category: Ethylene Glycol Ethers;Neutral Organics;Nonionic Surfactants 

Molecular and structural information 

Molecular formula C11H24O6 

Molecular weight range 252.3047 

SMILES notation COCCOCCOCCOCCOCCO 

InChI InChI=1/C11H24O6/c1-13-4-5-15-8-9-17-11-10-16-7-6-14-3-

2-12/h12H,2-11H2,1H3 

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 16:29:56 -0400

Subject: Substance: triethylene glycol hexyl ether / 2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol / 

2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol / 25961-89-1 / PCA Services, Inc. / Durham / United 

States of America

Content-Type: multipart/related;

boundary="_005_6979787672757766756971656572697173718080656776666679666_";

type="multipart/alternative"

Thread-Topic: Substance: triethylene glycol hexyl ether / 

2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol / 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol / 

25961-89-1 / PCA Services, Inc. / Durham / United States of America

Thread-Index: AcrBZQ8SYkES2CFxRnWsCFugMiMTgw==

X-MS-Has-Attach: yes

X-MS-TNEF-Correlator:

MIME-Version: 1.0
Printing Date 2009-07-03 16:28:52 EDT 

Restriction of specific regulatory purposes 

 

Confidentiality 

 

Name triethylene glycol hexyl ether 

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

Substance: triethylene glycol hexyl ether 

UUID IUC5-7455d46e-38d6-4dc1-bc8f-60b005cccebb 

Dossier UUID 0 

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

America 

Date 2009-06-11 15:13:01 EDT 

Remarks Created endpoint study record 5.3.1 Bioaccumulation: aquatic / 

sediment 

0 Related Information 

0.1 Templates 

0.2 Categories 

0.3 Mixtures 

1 General Information 

1.1 Identification 

Substance identification 

Chemical name triethylene glycol hexyl ether 

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

Reference substance 

Reference 

substance 

2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol /

2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol / 25961-89-1

 EC number EC name 

247-372-2 2-[2-[2-(hexyloxy)ethoxy]ethoxy]et

hanol 

CAS number CAS name 

25961-89-1 
IUPAC name 

2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

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-b664234c-5786-424a-863f-4161a6826421 

Dossier UUID 0 

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

America 

Date 2009-06-14 11:06:10 EDT 

Remarks 

 

Administrative Data 

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

used for MSDS 

Study result type other: observation of appearance of substance 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

result is based only on observation of physical state. 

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 

Substance type 

organic 

Overall remarks, attachments 

Overall remarks 

Substance exists commercially only as a component in a high boiling ethylene glycol ether 

byproduct stream, which consists of a mixture of verious high boiling glycol ethers. 

Applicant's summary and conclusion 

Executive summary 
4.2 Melting point/freezing point 

Melting point/freezing point.001 

UUID IUC5-97b0d7fd-b472-443e-9ab9-974ab55f7369 

Dossier UUID 0 

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

America 

Date 2009-06-09 15:14:54 EDT 

Remarks 

 

Administrative Data 

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

MSDS 

Study result 

type 

experimental result 

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 

Pennzoil 

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 Super Heavy-Duty DOT 4 and DOT 3 Motor Vehicle brake fluid 

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-eddeaf6a-9257-48f2-90b3-abf0e5a62aef 

Dossier UUID 0 

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

America 

Date 2009-06-14 11:33:50 EDT 

Remarks 

 

Administrative Data 

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

Study result 

type 

experimental result 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data are associated with automotive brake fluid, of which triethylene glycol 

hexyl ether is a component. Triethylene glycol hexyl ether is not available 

commercially as a neat material. 

Data source 

Reference 

Reference type publication 

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 

Pennzoil Company 

Company study 

no. 

 Report date 

Reference 

type 

publication 

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 

GLP compliance 

no data 

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. >= 272 °C 

Atm. pressure 1013 hPa 

Decomposition no 

Decomp. temp. 

Remarks Equilibrium Reflux Boiling Point for typical product 

4.6 Vapour pressure 

Vapour pressure.001 

UUID IUC5-71fad078-d7ed-4ca0-b794-e5b44913ee65 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:41:59 EDT 

Remarks 

 

Administrative Data 

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

MSDS 

Study result type no data 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data obtained from manufacturer material safety data sheet 

Data source 

Reference 

Reference company data 
type 

Author Year 

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

Bibliographic 

source 

 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

Shell Company 

Company 

study no. 

 Report 

date 

2006-06-28 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier other: Trade 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 

Remarks 

4.7 Partition coefficient 

Partition coefficient.001 

UUID IUC5-b1cca0fa-7943-405e-a048-b3ebe2e27e6e 

Dossier UUID 0 

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

America 

Date 2009-06-09 15:21:24 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 June 
period 2009 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were obtained using a recognized estimation program. 

Data source 

Reference 

Reference type other: estimation program 

Author Year 2009 

Title EPIWIN KOWWIN (v1.67) 

Bibliographic 

source 

 

Testing laboratory Report no. 

Owner company 

Company study no. Report date 2009-05-08 

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 25961-89-1 

Identifier EC number 

Identity 247-372-2 

Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Results and discussions 

Partition coefficient 

Type log Pow 

Partition coefficient ca. 1 

Temp. 

pH 

4.8 Water solubility 

Water solubility.001 

UUID IUC5-219e0b75-6656-4b89-9758-739373611494 

Dossier UUID 0 

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

America 

Date 2009-06-09 15:23:03 EDT 

Remarks 

 

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

MSDS 

Study result type other: study type not known 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data obtained from manufacturer's Safety Data Sheet 

Data source 

Reference 

Reference 

type 

company data 

Author Year 

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

Bibliographic 

source 

Shell Safety Data Sheet 

Testing 

laboratory 

 Report no. 

Owner 

company 

 

Company 

study no. 

 Report 

date 

2006-06-28 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier other: Trademark 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. 20 °C 

pH 

Details on results 

Test material is miscible in water. 

4.11 Flash point 

Flash point.001 
UUID IUC5-44491923-2fb2-4a30-aaeb-b91d89871dcf 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:58:44 EDT 

Remarks 

 

Administrative Data 

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

MSDS 

Study result type other: no data 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data obtained from manufacturer's safety data sheet 

Data source 

Reference 

Reference type company data 

Author Year 

Title Shell Brake and Clutch Fluid DOT 4 Super 

Bibliographic 

source 

Safety Data Sheet 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2006-06-28 

Materials and methods 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier other: Trademark 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-f49bb2df-fc8f-49b2-a4fe-1473567e611c 

Dossier UUID 0 

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

America 

Date 2009-06-14 11:52:46 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 

June 8, 

2009 

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 AOP (v.1.92) 

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 25961-89-1 

Identifier EC number 

Identity 247-372-2 
Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Study design 

Estimation method (if used) 

PHOTOCHEMICAL REACTION WITH OH RADICALS

- Concentration of OH radicals: 1.5E6 OH/cm3

- Degradation rate constant: 54.3707 E-12 cm3/molecule-sec

- Computer programme: EPIWIN AOP (v1.92)

- Half-life = 2.361 hours or 0.197 day (12-hour day) 

Light source 

sunlight 

5.2 Biodegradation 

5.2.1 Biodegradation in water: screening tests 

Biodegradation in water: screening tests.001 

UUID IUC5-b4a95b03-10eb-4013-87a2-4567d1062222 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 10:26:58 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

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to guideline study with acceptable restrictions. 

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 Corporation 

Company 

study no. 

File No. 35931 Report 

date 

 

Materials and methods 
Test type 

ready biodegradability 

Test guideline 

Qualifi

er 

according to 

Guideli

ne 

other guideline: other: as described in "Standard Methods for the Examination of 

Water and Wastewater", 16th ed., USPHA, Washington, D. C., 1985 

Deviati

ons 

 

Principles of method if other than guideline 

A modified version of the biochemical oxygen demand (BOD) method was used. A discussion 

of the modifications appears in Price et al., "Brine shrimp bioassay and seawater BOD of 

petrochemicals", J. Water Poll. Control Fed., Jan. 1974. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Identifier EC number 

Identity 203-988-3 

Details on test material 

The test material was the tradename product Hexyl CARBITOL. The purity was not listed. 

Study design 

Oxygen conditions 

aerobic 

Inoculum or test system 

sewage, domestic, non-adapted 

Duration of test (contact time) 

>= 20 d 

Any other information on materials and methods incl. tables 

Nonacclimated domestic sewage organisms were used as seed in the test. Domestic wastewater 

was filtered through glass wool and added (3 ml/bottle) as seed material to clean BOD bottles. 

A buffered, aerated solution containing minerals was then added. Small amounts of test material 

were added from a 0.1 % stock solution to yield concentrations of 3, 7 and 10 mg/l. A control 

with no test material also was run. At least two of the concentrations were tested in duplicate. 

Dissolved oxygen (DO) was monitored five times during the course of the 20-day test. The 

solution was reaerated when the DO dropped below 4.0 mg/l. Reaeration (if needed) was 

accomplished by dividing the BOD bottle contents between 2 BOD bottles, sealing, shaking 
them twenty times, returning contents to the original BOD bottle, recording the oxygen level, 

resealing, and returning the BOD bottle to the incubator. Samples were analyzed routinely for 

nitrites and nitrates. Results of the tests were expressed in terms of % biooxidation calculated as 

the cumulative oxygen uptake for the test material minus a control x 100 / initial concentration 

of test material x theoretical oxygen demand. 

Results and discussions 

% Degradation of test substance 

%Degr. >= 80 

St. dev. 

Parameter 

Sampling time 20 d 

Remarks 

Details on results 

The calculated theoretical oxygen demand was 2.35 mg/mg. After 5, 10 and 20 days of 

incubation, the percent biooxidation was 23, 69 and 80% (respectively). 

Biodegradation in water: Waggy Union Carbide Screening TGBE 1987.001 

UUID IUC5-84d62373-4fd9-4d7e-8308-29f953b29aa9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 12:55:28 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 

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 Union Carbide 
company 

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%. 

5.3 Bioaccumulation 

5.3.1 Bioaccumulation: aquatic / sediment 

Bioaccumulation: aquatic / sediment.001 

UUID IUC5-e9e9dfac-dad5-4012-b36b-0b9d2ff18cde 

Dossier UUID 0 

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

America 

Date 2009-06-13 17:29:28 EDT 

Remarks 

 

Administrative Data 

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

MSDS 

 Study 

period 

20

09 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Data were estimated using a recognized, approved computer program 

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 2009-06-08 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 25961-89-1 

Identifier EC number 

Identity 247-372-2 

Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Study design 

Water media type 

freshwater 

Test conditions 

Details on estimation of bioconcentration 

BASIS INFORMATION

- Measured/calculated logPow: 1.0

BASIS FOR CALCULATION OF BCF

- Estimation software: EPIWIN BCF (v3.00)

- Result based on calculated log Pow of: 1.0 

Any other information on materials and methods incl. tables 

Results and discussions 

Bioaccumulation factor 

Conc. in environment / dose 

Type other: log BCF 

Value ca. 0.33 

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 IUC5-6ce91d5b-8faf-4e2d-ac21-4a50ca8dc309 

Dossier UUID 0 

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

Date 2009-06-13 15:56:28 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 program output 

Author Year 2009 

Title EPIWIN HENRY (v3.20) 

Bibliographic 

source 

 

Testing laboratory Report no. 

Owner company 

Company study 

no. 

 Report date 2009-05-09 

Materials and methods 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 25961-89-1 

Identifier EC number 

Identity 247-372-2 

Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Details on methods 

Input to HENRY model was CAS No. 25961-89-1 

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-c75e0df0-d5e0-43fb-9536-ae15d3fe0824 

Dossier UUID 0 

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

America 

Date 2009-06-13 16:04:01 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 

Date were obtained by a recognized computer model program 

Data source 

Reference 

Reference type other: computer model program output 

Author Year 2009 

Title EPIWIN 4.0 Fugacity Level III 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner company 

Company study 

no. 

 Report date 2009-06-09 

Materials and methods 

Model 

Calculation according to Mackay, Level III 

Calculation programme 

EPIWIN Fugacity Level III 

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 25961-89-1 

Identifier EC number 
Identity 247-372-2 

Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Test substance input data 

- Molar mass: 234.34

- Data temperature: 25 deg C

- Water solubility: 1000000 mg/L

- Vapour pressure: 0

- log Pow: 1

- Melting point: -40 deg C

- Boiling point 270 deg C

- Reaction half-life estimates for

- Air: 4.721 hr

- Water: 360 hr

- Soil: 720 hr

- Sediment: 3240 hr

Any other information on materials and methods incl. tables 

Inputs to Fugacity program were CAS No. 25961 -89 -1, melting point -40 deg C, and boiling 

point 270 deg C. 

Results and discussions 

Percent distribution in media 

Air (%) 

0 

Water (%) 

30.6 

Soil (%) 

69.4 

6 Ecotoxicological Information 

6.1 Aquatic toxicity 

6.1.1 Short-term toxicity to fish 

Short-term toxicity to fish.001 

UUID IUC5-0ba7c585-587a-46fd-85ad-51b03a7668a0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 10:41:20 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

87 

Reliablility 4 (not assignable) 

Rationale for 

reliability 

Insufficient study detail in the report. 

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 Corporation 

Company 

study no. 

File No. 35931 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: EPA/ASTM procedures were followed. 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Identifier EC number 

Identity 203-988-3 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial product). The purity was not 

stated. 

Analytical monitoring 

no data 

Vehicle 

no data 
Test organisms 

Test organisms (species) 

Pimephales promelas 

Study design 

Test type 

static 

Water media type 

freshwater 

Total exposure duration 

96 h Remarks 

Test conditions 

Any other information on materials and methods incl. tables 

EPA/ASTM procedures were followed. Ten test fish (fathead minnows) were tested per test 

concentration (not listed). The method for calculating the LD50 value (and 95% confidence 

limits) was not stated. 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. 220 mg/L 

Nominal/Measured nominal 

Conc. based on no data 

Basis for effect mortality 

Remarks (e.g. 95% CL) (200 - 244 mg/l) 95% CL 

Short-term toxicity to fish.002 

UUID IUC5-59d3b4df-9138-48ac-9841-fc60ef533edc 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 11:08:53 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

84 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP 

Data source 

Reference 
Reference 

type 

study report 

Author Year 1994 

Title Acute toxicity study on the zebra fish of n-hexylglykol in a static system (96 

hours). 

Bibliographi

c source 

 

Testing 

laboratory 

BASF AG, Abteilung Toxikologie. Report 

no. 

 

Owner 

company 

BASF AG 

Company 

study no. 

Project No. 17F0238/915102BASF AG Report 

date 

1994-04-1

1 

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 112-25-4 

Identifier Common name 

Identity ethylene glycol hexyl ether 

Details on test material 

Purity was 98.23% by gas chromatography. The stability of the test material over the study 

period was proved by reanalysis. 

Analytical monitoring 

yes 

Vehicle 

no 

Test organisms 

Test organisms (species) 

Brachydanio rerio (new name: Danio rerio) 

Details on test organisms 

Fish: The ranges for body length and weight of the zebra fish were 2.7 - 3.1 cm and 0.17 - 0.3 g, 

respectively. The approximate age of the fish was 4 months. Fish were fed standard feed for 

aquarium fish. Food was withdrawn 1 day before exposure. Mortality during the last 2 weeks of 

housing was 0%. 

Study design 

Test type 
static 

Water media type 

freshwater 

Limit test 

no 

Total exposure duration 

96 h Remarks 

Test conditions 

Test temperature 

Steady at 23 deg. C 

pH 

8.3 – 8.4 

Dissolved oxygen 

7.7 – 8.2 mg/l 

Nominal and measured concentrations 

46.4, 100, 215, 464 and 1000 mg/l (nominal) 

Details on test conditions 

Test water: The fish were housed in a flow-through tank containing unchlorinated, 

carbon-filtered tap water with a total hardness of 250 mg/l CaCO3, pH of 8.0 - 8.6 and 

temperature of 20-27 degrees C approximately 1.5 months before being used in the test. The 

water was aerated with oil-free air to > 60% saturation. The water was regularly tested for the 

presence of contaminants and microbes. Test conduct: Glass aquaria (30 x 22 x 24 cm3) 

containing 10 liters of test water were loaded with 10 zebra fish each (0.23 g test fish/ liter of 

water). Concentrations tested were based on the results of 2 preliminary studies. Zebra fish were 

exposed over a 96-hour period to a range of concentrations spaced by a factor of about 2.2 

(46.4, 100, 215, 464 and 1000 mg/l). An untreated control was included. Fish were placed in the 

aquaria within 25 minutes of addition of test material. They were not fed during the test. The 

water was maintained at 23 degrees under slight aeration. Fish were observed 1, 4, 24, 48, 72 

and 96 hours after exposure. The pH, temperature and oxygen content were measured 1, 24, 48, 

72 and 96 hours after exposure. The LC0, LC50 and LC100 concentrations and the NOEC were 

to be determined for each time point. The concentrations of test material present at 1 and 96 

hours 

were analytically confirmed. If possible, the LC5 and LC95 were to be calculated using probit 

analysis. 

Results and discussions 

Effect concentrations 

Duration 96 h 

Endpoint LC50 

Effect conc. >= 94 — <= 215 mg/L 

Nominal/Measured meas. (not specified) 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) Range of LC50 values for all measured time points. 

Duration 96 h 

Endpoint NOEC 
Effect conc. 41 mg/L 

Nominal/Measured meas. (not specified) 

Conc. based on test mat. 

Basis for effect no data 

Remarks (e.g. 95% CL) Value for all time points. 

Duration 96 h 

Endpoint LC0 

Effect conc. 94 mg/L 

Nominal/Measured meas. (not specified) 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) Value for all time points. 

Duration 96 h 

Endpoint LC100 

Effect conc. 215 mg/L 

Nominal/Measured meas. (not specified) 

Conc. based on test mat. 

Basis for effect mortality 

Remarks (e.g. 95% CL) Value for all time points. 

Details on results 

All fish exposed to 46.4 mg/l (nominal) and 100 mg/l (nominal) survived exposure for 96 hours. 

All fish exposed to concentrations > = 215 mg/l died within 1 hour. Apathy was noted in fish 

exposed to 100 mg/l (nominal concentration) at all time points.Analytically detected 

concentrations at 1 and 96 hours were within 85.1-102.6% of nominal.

The analytical concentrations corresponding to the No Observed Effect Concentrations 

(NOEC), LC0 and LC100 (46.4, 100 and 215 mg/l nominal concentrations) at all time points 

were 41, 94 and 215 mg/l, respectively. The LC50 values were between 94 and 215 mg/l at all 

time points. 

Short-term toxicity to fish-Wagy TGBE 1974.001 

UUID IUC5-0d50828e-64aa-47c2-a4f4-15c8ba01f087 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:31 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-cf4e0fc4-dbbd-47f6-9a2a-ba1be88332c5 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:32 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

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-BASF TGBE 1989.005 

UUID IUC5-07df2d99-5379-4603-9e50-a50c43221fde 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:32 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

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. 

6.1.3 Short-term toxicity to aquatic invertebrates 

Short-term toxicity to aquatic invertebrates.001 

UUID IUC5-1b43e788-08dd-4807-94e6-51fee826e492 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 11:20:14 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

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to a guideline study with acceptable restrictions. 

Data source 

Reference 

Reference type company data 

Author Waggy GT. Year 1987 

Title Summary of available ecological fate and effects data. 

Bibliographic 

source 

 

Testing 

laboratory 

 Report no. 

Owner 

company 

Union Carbide 

Company 

study no. 

File No. 35931 Report date 

Materials and methods 

Test guideline 

Qualifier according to 
Guideline other guideline: EPA/ASTM 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial material). The purity was not 

listed. 

Analytical monitoring 

no 

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 

Test conditions 

Hardness 

Total hardness for the test and holding water were 55 mg/l as CaCO3, 36 mg/l as CaCO3, 6.7, 

and 250 micromhos/cm, respectively. 
pH 

6.7 

Salinity 

Conductivity of test water was 250 micromhos/cm 

Details on test conditions 

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

control) were tested. 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 (values 

were not listed). Mortalities were recorded at 24 and 48 hours. 

Any other information on materials and methods incl. tables 

Lighting conditions, method of calculating the LC50 value, numbers of deaths at each 

concentration, condition of controls and purity and solubility/insolubility of the test material 

were not listed. 

Results and discussions 

Effect concentrations 

Duration 48 h 

Endpoint LC50 

Effect conc. 433 mg/L 

Nominal/Measured no data 

Conc. based on test mat. Basis for effect 

Remarks (e.g. 95% CL) 

Short-term toxicity to aquatic invertebrates-Waggy TGBE 1987.001 

UUID IUC5-19d08a20-8d54-4e29-9ae1-b6b99644519a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:33 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 

19

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Purity of test material was not noted. 

Data source 

Reference 

Reference study report 
type 

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. 

6.1.4 Long-term toxicity to aquatic invertebrates 

Long-term toxicity to aquatic invertebrates.001 

UUID IUC5-400dd0aa-fc00-4b28-89a2-b6165f62b21a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 14:19:06 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 

200

3 

Reliablility 2 (reliable with restrictions) 

Rationale 

for 

reliability 

Meets national standard methods with the acceptable following restrictions:

The method of preparation of test solutions, types of exposure vessels and 

volumes tested were not given. Raw data were not provided. Concentrations were 

not analytically determined. Results for time points other than 7 days were not 

deternined. 

Data source 

Reference 

Reference 

type 

publication 

Author Devillers J, Chezeau A, Poulsen V and Thybaud E Year 2003 

Title Effects of glycol ethers on the reproduction of Ceriodaphnia dubia 

Bibliographic 

source 

Chemosphere 50: 373-376. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: AFNOR NF T 90-376 

Deviations 

GLP compliance 
no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

The test material was 95% pure 

Analytical monitoring 

no 

Details on analytical methods 

Concentrations of test material were not analytically determined. 

Vehicle 

no 

Details on test solutions 

The method of preparation of the test solutions, types of exposure vessels, and volumes tested 

were not given. 

Test organisms 

Test organisms (species) 

other: Ceriodaphnia dubia 

Details on test organisms 

Young organisms (< 24 hours old) and from the second to fifth brood of healthy adults reared in 

the laboratory 

Study design 

Test type 

static 

Water media type 

freshwater 

Limit test 

no 

Total exposure duration 

7 d Remarks 

Test conditions 

Hardness 

250 +/- 20 mg/l as CO3 

Test temperature 

25 +/- 2 deg C. 

pH 

8.0 +/- 0.3 
Dissolved oxygen 

8.6 - 9.2 mg/L 

Salinity 

Na = 5 mg/l, K = 1 mg/l, SO4 = 10 mg/l and 

Cl = 4.5 mg/l). 

Details on test conditions 

Organisms were individually introduced in 100 ml glass vials containing 50 ml of test solution 

(mineral water with Ca = 78 mg/l, Mg = 24 mg/l, Na = 5 mg/l, K = 1 mg/l, SO4 = 10 mg/l and 

Cl = 4.5 mg/l). Hardness and pH of the test solutions were measured daily (except weekends). 

Values were within the guidelines of pH = 8.0 +/- 0.3 and hardness = 250 +/- 20 mg/l as CO3. 

Daily measurements of dissolved oxygen ranged between 8.6 and 9.2 mg/l. Temperature was 

monitored continuously. The test was conducted at 25 +/- 2 degrees C. A 16:8 light:dark 

photoperiod was employed. Light intensity at the air/water interface ranged between 300 and 

500 lx. Test solutions were changed daily (with the exception of weekends). The organisms 

were fed with Chorella vulgaris (6 x 10E6 cells/50 ml), Raphidocelis subcapitata (3 x 10E6 

cells/50 ml) and 25 microliters/50 ml of a stock solution (5 g/l) of commercial fish food. Ten 

replicates (one individual per each) were used per treatment and control. A range of 5 

concentrations spanning those causing 0-100% inhibition of reproduction were used. The 

criterion for estimating the effect of the material on the reproduction of the organism was the 

EC10 at 7 days. The EC10 value was calculated according to the method of Hill (Garrie et al., 

Water Res. 24:59-65, 1990 and Vindimian et al., J Appl Biochem 5:261-268, 1983). The 

following criteria had to be met in order for the test to be considered valid: control survival of > 

80%, < 20% of males at Day 7 in each batch, > 60% of control females having three broods, and 

control females having at least 15 offspring in 7 days. 

Any other information on materials and methods incl. tables 

Results and discussions 

Effect concentrations 

Duration 7 d 

Endpoint EC10 

Effect conc. 19.63 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect reproduction 

Remarks (e.g. 95% CL) 5.8 - 45.61 mg/l confidence range 

6.1.5 Toxicity to aquatic algae and cyanobacteria 

Toxicity to aquatic algae and cyanobacteria.001 

UUID IUC5-60b28600-8091-4565-af2c-3bddeaa478e2 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 14:37:31 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

89 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Basic data provided, well conducted, and not by a current guideline 

Data source 

Reference 

Reference 

type 

study report 

Author Year 1989 

Title Prufung auf Okotoxizitat: Hemmung der Algen-Zellvermehrung nach DIN 

38412L9 (unpublished study). 

Bibliograph

ic source 

 

Testing 

laboratory 

BASF AG, Laboratorium fur Angewandte Biologie Report 

no. 

 

Owner 

company 

BASF AG 

Company 

study no. 

Journal number 01038, 15.12.1989. Report 

date 

1989-12-

15 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline other guideline: Scenedesmus-cell reproduction inhibition test DIN 38412 L 9 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-25-4 

Identifier Common name 

Identity ethylene glycol monohexylether 

Details on test material 

Purity >98%

impurities/coproducts: up to 0.2% Diethylenglycol-monobutylether, 0.1% Diethylenglycol, 

0.1% Diethylenglycol-monohexylether 

Analytical monitoring 

no 
Vehicle 

no 

Details on test solutions 

Test concentrations: 0, 5, 10, 25, 50, 100 or 250 mg/l 

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 to 16,000 cells/ml) was maintained 

at 21 to degrees C. 

Study design 

Test type 

static 

Water media type 

freshwater 

Total exposure duration 

96 h 

Remarks An exposure duration of 72 hours was also included in the study. 

Test conditions 

Test temperature 

21.6 deg C 

Details on test conditions 

A SAG 86.81 culture of Scenedesmus subspicatus (10,000 to 16,000 cells/ml) was maintained 

at 21 to degrees C. Cells in suspension were treated with 0 (control), 10, 25, 50, 100 or 250 mg/l 

test material in quadruplicate. Test concentrations were chosen based on the results of a 

preliminary test. Fluorescence of vials containing treated cells was determined 0, 24, 48, 72 and 

96 hours after treatment in a fluorimeter (at wavelengths from 300 to 780 nm). 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 pH of solutions was determined before and at the end of 

the test. Fluorescence was converted to cell number (N) using the equation fluorescence = N/ml 

- 4748.47/220.024. The data were analyzed according to the method of Tallarida and Jacob (The 

Dose-Response Relation in Pharmacology, p. 98- 103, Springer Verlag, 1979). 

Any other information on materials and methods incl. tables 

The study was translated into English from German by the reviewer. Test substance purity data 

came from an IUCLID document for CAS No. 112-25-4 prepared by the European Chemicals 

Bureau, dated 11-FEB-2000. 

Fluorescence measures chlorophyll content, and chlorophyll content is a measure of biomass. In 

a study described by Herman et al. (Aquatic Toxicol 18:87-100, 1990), 4 different ways of 

measuring biomass were checked for sensitivity (cell number, absorbance, chlorophyll content 

and dry weight). Measuring cell number was the most sensitive means of assessing algal cell 

growth, followed by absorbance and chlorophyll content, which were of equal utility. Since 
most test methods use absorbance for calculating biomass, and results of tests measuring 

chlorophyll content and absorbance are similar, tests employing fluorescence to measure 

chlorophyll content should be as sensitive as those employing absorbance as a means of 

assessing algal biomass. 

Growth medium chemistry (other than pH), source of dilution water, size of exposure vessels 

and volumes of solution, method of preparation of test solutions and light conditions were not 

described. 

Results and discussions 

Effect concentrations 

Duration 72 h 

Endpoint EC10 

Effect conc. 23 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth rate 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC50 

Effect conc. 198 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth rate 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC10 

Effect conc. 11 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 72 h 

Endpoint EC50 

Effect conc. 98 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 96 h 

Endpoint EC10 
Effect conc. 89 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth rate 

Remarks (e.g. 95% CL) 

Duration 96 h 

Endpoint EC50 

Effect conc. 147 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth rate 

Remarks (e.g. 95% CL) 

Duration 96 h 

Endpoint EC10 

Effect conc. 12 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 96 h 

Endpoint EC50 

Effect conc. 70 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect biomass 

Remarks (e.g. 95% CL) 

Duration 96 h 

Endpoint EC0 

Effect conc. 25 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect growth rate 

Remarks (e.g. 95% CL) 

Details on results 

In algae exposed to 0, 5, 10, 25, 50, 100 or 250 mg/l test material for 72 hours, the reported 

growth rates were 1.18, 1.14, 1.12, 1.10, 1.04, 0.95 and0.24, and the biomass inhibition was 6.8, 

11.4, 13.8, 22.1, 41.8 and 85.4 percent, respectively. Based on these data EC10 and EC50 

values at 72 hours for growth inhibition (GI) and biomass inhibition (BI) were 23 and 198 mg/l 

(GI) and 11 and 98 mg/l (BI). There was no EC0 value for either inhibition of growth rate or 

biomass.In algae exposed to 0, 5, 10, 25, 50, 100 or 250 mg/l test material for 96 hours, the 

reported growth rates were 1.08, 1.09, 1.08, 1.08, 1.06, 0.94 and 0.11, and the biomass 

inhibition was 6.4, 10.4, 12.0, 23.2, 46.5 and 94.6 percent, respectively. Based on these data 
EC10 and EC50 values at 96 hours for GI and BI were 89 and 147 mg/l (GI), and 12 and 70 

mg/l (BI). The EC0 value for growth rate inhibition was 25 mg/l. There was no EC0 value for 

biomass inhibition. Values for the 4 replicates at each concentration less than 250 mg/l varied 

by <= 5.19%. Values were more variable for organisms exposed to 250 mg/l for 72 or 96 hours. 

pH of the medium increased during the test, with larger increases observed in flasks with lower 

concentrations. The highest final pH was 9.15 (at 10 mg/l), and the lowest final pH was 7.55 (at 

250 mg/l). 

Temperature of all media remained constant at 21.6 degrees C. Fluorescence of blank vials was 

zero for all concentrations of test material at all time points. 

Toxicity to aquatic algae and cyanobacteria-BASF TGBE 1989.001 

UUID IUC5-f38c01a2-2a08-4b0b-ba29-2992de089963 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:33 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

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. 

6.1.7 Toxicity to microorganisms 

Toxicity to microorganisms.001 

UUID IUC5-4bb63938-b9a0-49d6-9ef6-acbfadc5ebd0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 14:42:48 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

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Basic data given 

Data source 

Reference 

Reference 

type 

company data 

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. 

Union Carbide Corporation File No. 35931 Report 

date 

 

Materials and methods 

Principles of method if other than guideline 
No information on guideline followed. Study used standard methodology for the time. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Analytical monitoring 

no data 

Details on test solutions 

no details 

Test organisms 

Test organisms (species) 

other: not specified 

Study design 

Test type 

no data 

Water media type 

no data 

Total exposure duration 

16 h 

Remarks 

Test conditions 

Test temperature 

23 degrees C 

pH 

Not provided 

Dissolved oxygen 

Not provided 

Salinity 

Not provided 

Nominal and measured concentrations 

Not given 

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 

Any other information on materials and methods incl. tables 

Results and discussions 

Effect concentrations 

Duration 16 h 

Endpoint EC10 

Effect conc. >= 1000 mg/L 

Nominal/Measured nominal 

Conc. based on test mat. 

Basis for effect other: turbidity 50% less than control 

Remarks (e.g. 95% CL) 

Toxicity to microorganisms-Waggy TGBE 1987.001 

UUID IUC5-630effff-21b6-4493-883b-363f49cdd689 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:33 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 

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 Union Carbide 
company 

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.

7 Toxicological information 

7.1 Toxicokinetics, metabolism and distribution 

7.1.2 Dermal absorption 
Dermal absorption-Ward & Scott TGBE 1986.001 

UUID IUC5-c404e7dc-b4f6-4b4a-970c-0e60df6dca1d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:34 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 

study no. 

 Report 

date 

1986-10-31 

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.001 

UUID IUC5-e23466ee-0fb2-4567-a545-585806f65fac 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 15:03:52 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

7 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to guideline study with acceptable restrictions. Purity of the test 

material was not listed. 

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B, Myers RC Year 1987 

Title The comparative acute toxicity and primary irritancy of the monohexyl ethers of 

ethylene and diethylene glycol. 

Bibliograp

hic source 

Vet Human Tox 29:361-366 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test type 

standard acute method 

Limit test 
no 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: Standard acute toxicity testing method 

Deviations 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Test animals 

Species 

rat 

Strain 

Wistar 

Sex 

male/female 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Animals were fasted prior to gavage dosing. 

Doses 

Undiluted test material was administered by gavage to each group at the following 

concentrations: 1, 2, 4, 8 or 16 ml/kg (males) and 2, 4, or 8 ml/kg (females) 

No. of animals per sex per dose 

Five per sex per dose 

Control animals 

no 

Details on study design 

Fasted male and female rats (200 to 260 g) were divided into 5 groups of five animals each 

(males) and 3 groups of 5 animals each (females). Undiluted test material was administered by 

gavage to each group at the following concentrations: 1, 2, 4, 8 or 16 ml/kg (males) and 2, 4, or 

8 ml/kg (females). Animals were inspected twice daily for signs of toxicity for 14 days. Body 

weights were taken before dosing, and 7 and 4 days after dosing. Animals that died and all 
animals surviving the 14 day period werenecropsied. LD50 values and their slopes were 

calculated by the moving average method. 

Results and discussions 

Effect levels 

Sex female 

Endpoint LD50 

Effect level 3.73 mL/kg bw 

95% CL 2.52 — 5.52 

Remarks 95%CL for females 

Sex male 

Endpoint LD50 

Effect level 4.92 mL/kg bw 

95% CL 3.09 — 7.84 

Remarks 95% CL for males 

Mortality 

Mortality rates for males treated with 4, 8 or 16 ml/kg were 2/5, 4/5 and 5/5 and for females 

treated with 4 or 8 ml/kg were 3/5 and 5/5. All animals treated with 1 or 2 ml/kg survived. All 

deaths occurred within 1 day of dosing. 

Clinical signs 

Signs of toxicity included sluggishness, unsteady gait, and prostrated appearance. Animals that 

died had red or dark pink lungs. 

Body weight 

All survivors gained weight over the 14 day period and had normal pathology. 

Remarks on results including tables and figures 

The LD50 values (with 95% confidence limits) were 4.92 ml/kg (3.09-7.84) for males and 3.73 

ml/kg (3488 mg/kg/bw) (2.52 - 5.52) for females. The slope of the dose-mortality curve was 

higher for females (4.96) than males (3.00). 

The LD50 value in ml/kg was converted to 3488 mg/kg using a density of 0.935 g/ml. 

The acute oral toxicity of ethylene glycol monohexyl ether (EGHE) in Sprague-Dawley rats 

also was tested in this study. The LD50 values for EGHE were lower than the values for 

diethylene glycol monohexyl ether and the slope of the dose-mortality curve was steeper. 

Acute toxicity: oral Moreno TGBE 1976.001 

UUID IUC5-5d77e8eb-d802-4a99-b578-d5f08a15d897 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:34 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 IUC5-80c3c3c0-ea09-4dd6-ba20-d2c4b86f8d92 

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

States of America 

Date 2009-02-13 13:01:34 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, 

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 

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 

7.2.2 Acute toxicity: inhalation 

Acute toxicity: inhalation.001 

UUID IUC5-c01213e8-8b70-4ab8-933b-5029cff12d7a 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 15:07:43 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 

1987 

Reliablility 2 (reliable with restrictions) 

Rationale for Comparable to guideline study with acceptable restrictions. Purity of the test 
reliability material was not listed. Concentration of material in the atmosphere was

not analyzed. 

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B, Myers RC. 1987 Year 1987 

Title The comparative acute toxicity and primary irritancy of the monohexyl ethers of 

ethylene and diethylene glycol. 

Bibliograp

hic source 

Vet Human Tox 29:361-366. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test type 

standard acute method 

Limit test 

yes 

Test guideline 

Qualifier no guideline followed 

Guideline 

Deviations 

Principles of method if other than guideline 

Followed standard acute inhalation toxicity study procedure of the time. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier IUPAC name 

Identity Diethylene glycol hexyl ether 

Test animals 

Species 

rat 

Strain 
Wistar 

Sex 

male/female 

Details on test animals and environmental conditions 

Five Wistar rats of each sex (210 to 270 g) 

Administration / exposure 

Route of administration 

inhalation: vapour 

Type of inhalation exposure 

no data 

Vehicle 

unchanged (no vehicle) 

Details on inhalation exposure 

Five rats of each sex (210 to 270 g) were exposed to a statically generated saturated vapour 

atmosphere of test material. The atmosphere was produced by introducing a sample of material 

into a sealed 120-liter chamber and allowing the vapour to equilibrate for 18 hours at 26 degrees 

C. 

Analytical verification of test atmosphere concentrations 

no data 

Duration of exposure 

>= 6 h Remarks 

Concentrations 

saturated vapour atmosphere 

No. of animals per sex per dose 

Five rats of each sex 

Control animals 

no 

Details on study design 

Rats were introduced into separate chambers through gasketted drawers designed to minimize 

vapour loss. Oxygen content was continuously monitored and maintained at 20%. Animals were 

removed from the chamber after 6 hours of exposure and were observed for 14 days. Body 

weights were measured before exposure and 7 and 14 days following exposure. All rats were 

subjected to necropsy after the 14 day observation period. 

Any other information on materials and methods incl. tables 

A saturated vapour of ethylene glycol monohexyl ether also was tested in Sprague Dawley rats 

and was found to produce no adverse effects after a 6-hour exposure. All animals survived the 6 

hour exposure. 

Results and discussions 

Mortality 

All animals survived the 6 hour exposure. 

Clinical signs 

There were no signs of toxicity or irritancy during or after exposure. 

Body weight 

Animals gained weight over the fourteen day observation period. 
Gross pathology 

normal pathology. 

Remarks on results including tables and figures 

A saturated vapour of ethylene glycol monohexyl ether also was tested in Sprague Dawley rats 

and was found to produce no adverse effects after a 6-hour exposure. 

Acute toxicity: inhalation Smyth TGBE 1962.001 

UUID IUC5-7da525ef-da73-4e89-bbaf-ba5640e60bc4 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:35 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 

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 Am Ind Hyg Assoc J 23:95-107. 
source 

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 IUC5-62149eb3-c245-469d-be71-82843f613cb9 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:35 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 

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. 

7.2.3 Acute toxicity: dermal 

Acute toxicity: dermal.001 

UUID IUC5-c39303ee-fb96-4a76-9d56-43565e67683e 

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

States of America 

Date 2009-02-05 15:13:12 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 

1

9

8

7 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to guideline study with acceptable restrictions. Purity of the test 

material was not listed. 

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B, Myers RC Year 1987 

Title The comparative acute toxicity and primary irritancy of the monohexyl ethers of 

ethylene and diethylene glycol. 

Bibliograp

hic source 

Vet Human Tox 29:361-366. 

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 

Standard dermal acute study procedure of the period. 

GLP compliance 

no data 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-59-4 
Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

male and female rabbits (2 to 3 kg weight) 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on dermal exposure 

Undiluted test material was applied to the clipped trunk skin of groups of 5 male or female 

rabbits 

Duration of exposure 

24 hours 

Doses 

1, 2 or 4 ml/kg (males), and 1, 2, 2.8 or 4 ml/kg (females). 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

no 

Details on study design 

Undiluted test material was applied to the clipped trunk skin of groups of 5 male or female 

rabbits (2 to 3 kg) at the following concentrations: 1, 2 or 4 ml/kg (males), and 1, 2, 2.8 or 4 

ml/kg (females). An occlusive dressing consisting of polyethylene sheeting, adhesive tape and 

plastic ties was used to keep the material in contact with the skin. Animals were immobilized 

during the 24 hour contact period. Test material was then removed with moist tissue. Animals 

were examined twice daily for 14 days for signs of local irritation and systemic toxicity. Body 

weights were taken before dosing and 7 and 14 days following dosing. Necropsies were 

performed on animals that died and all animals surviving the 14-day observation period. LD50 

values and their slopes were calculated by the moving average method. 

Results and discussions 

Effect levels 

Sex male 

Endpoint LD50 

Effect level 2.14 mL/kg bw 
95% CL 1.45 — 3.17 

Remarks 

Sex female 

Endpoint LD50 

Effect level 2.37 mL/kg bw 

95% CL 2.03 — 2.76 

Remarks 

Mortality 

All animals treated with 2.8 or 4.0 ml/kg died within 6 days of exposure. Two out of five male 

rats dosed with 2.0 ml/kg died within 2 days. None of the females treated with 2.0 ml/kg died. 

There were no deaths in males or females treated with 1 ml/kg. 

Clinical signs 

Signs of toxicity included salivation, sluggishness, unsteady gait and comatose appearance. 

These signs occurred during exposure and survivors recovered within 3 to 4 days. Erythema, 

edema, necrosis and ecchymoses were found at the application site up to study termination 

(doses not stated). 

Body weight 

Females treated with 2.0 ml/kg lost weight over the first week of recovery but then recovered. 

Gross pathology 

Animals that died had dark red or pink lungs. These effects were also noted in some of the 

animals that survived (doses, sex and number not stated). 

Remarks on results including tables and figures 

The LD50 values (with 95% confidence limits) were 2.14 ml/kg (1.45 - 3.17) for males and 2.37 

ml/kg (2.03 - 2.76) ml/kg for females. The slope of the dose-mortality curve was steeper for 

females (13.3) than males (4.96).

Ethylene glycol monohexyl ether (EGHE) also was tested in this study. The LD50 values for 

EGHE were lower than the values for diethylene glycol monohexyl ether. 

Acute toxicity: dermal Smyth TGBE 1962.001 

UUID IUC5-26e233e3-719d-4952-8539-2aed733061f0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:36 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 

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 IUC5-2eba6256-489c-4b53-8b4d-cbd9cc5507e7 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:36 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

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 

7.3 Irritation / corrosion 

7.3.1 Skin irritation / corrosion 

Skin irritation / corrosion.001 

UUID IUC5-785efe42-34f6-42be-a5bf-86dd2db3c0f0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 
States of America 

Date 2009-02-05 15:22:08 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

7 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to guideline study with acceptable restrictions. Purity of the test 

material was not listed. 

Data source 

Reference 

Reference 

type 

 

Author Ballantyne B, Myers RC. Year 1987 

Title The comparative acute toxicity and primary irritancy of the monohexyl ethers of 

ethylene and diethylene glycol. 

Bibliograp

hic source 

Vet Human Tox 29:361-366. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Test guideline 

Qualifier according to 

Guideline EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion) 

Deviations 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 
Identifier Common name 

Identity Diethylene glycol hexyl ether 

Test animals 

Species 

rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

2 to 3 kg body weight, strain not specified. 

Test system 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

0.5 ml 

Duration of treatment / exposure 

4 hours 

Observation period 

1 hour, and 1, 2, 3, 7 and 14 days after dosing 

Number of animals 

Six, sex not noted 

Control animals 

no data 

Details on study design 

Test material (0.5 ml) was applied to the shaved, dorsal skin of 6 rabbits (2 to 3 kg, sex not 

noted). The application site was covered for 4 hours with a gauze patch and impervious 

polyethylene sheeting. After 4 hours, the material was gently removed with a moist tissue. The 

application site was inspected for local inflammation at 1 hour, and 1, 2, 3, 7 and 14 days after 

dosing. Erythema and edema were scored according to the method of Draize et al. (J Pharmacol 

Exp Ther 82:377, 1944). 

Results and discussions 

Irritation / corrosion results 

Irritation parameter erythema score 

Basis mean 

Time point 14 days 

Score 0.5 

Max. score 

Reversibility fully reversible within: 2 hours 

Remarks 

Irritation parameter edema score 

Basis mean 

Time point 14 days 

Score 0.3 
Max. score 

Reversibility fully reversible within: 24 hours 

Remarks 

Irritant/corrosive response data 

Three animals were not affected by treatment. Three animals developed a mild erythema which 

lasted for 2 hours, and two had minimal edema over a24 hour period. The average scores for 

erythema and edema were 0.5 and 0.3, respectively. No other signs of inflammation or tissue 

injury were present. 

Remarks on results including tables and figures 

Ethylene glycol monohexyl ether (EGHE) also was tested in this study. EGHE was found to be 

more irritating than diethylene glycol monohexyl ether.

Applicant's summary and conclusion 

Interpretation of results 

slightly irritating 

Skin irritation / corrosion Smyth TGBE 1962.001 

UUID IUC5-3639f2f7-9d07-4695-806b-14931240cdb2 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:36 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-a303ba4e-f713-4bad-ae63-298dd531a06d 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:37 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 

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 IUC5-5b700b3a-6785-4e2d-a57d-1eb4b4175fa6 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:37 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 

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 

7.3.2 Eye irritation 

Eye irritation.001 

UUID IUC5-a93d5eb0-5ba3-4aca-b84e-cbd4f77a1d57 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 15:49:13 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

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Comparable to guideline study with acceptable restrictions.

Purity of the test material was not listed.

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B, Myers RC Year 1987 

Title The comparative acute toxicity and primary irritancy of the monohexyl ethers of 

ethylene and diethylene glycol. 

Bibliograp

hic source 

Vet Human Tox 29:361-366 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Type of method 

in vivo 

Test guideline 

Qualifier 

Guideline other guideline: Standard eye irritation procedure for period 

Deviations 

GLP compliance 

no data 

Test material equivalent to submission substance identity 

no 

Test materials 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier IUPAC name 

Identity Diethylene glycol hexyl ether 

Test animals 

Species 
rabbit 

Strain 

no data 

Details on test animals and environmental conditions 

Rabbits (2 to 3 kg) whose eyes did not stain after exposure to 2% fluorescein for 20 seconds 

were used in the study. 

Test system 

Vehicle 

unchanged (no vehicle) 

Amount/concentration applied 

Test material was instilled into the interior conjunctival sac of one eye of 6 rabbits (0.1 ml) or 

the surface of the cornea (0.005 ml) of 6 other rabbits. 

Duration of treatment / exposure 

Test material was not removed after instillation 

Observation period 

Eyes were inspected for signs of local inflammation at 1, 4 and 24 hours and 2,3, 7, 14 and 21 

days after instillation. 

Number of animals 

Six rabbits/treatment 

Control animals 

no data 

Details on study design 

Rabbits (2 to 3 kg) whose eyes did not stain after exposure to 2% fluorescein for 20 seconds 

were used in the study. Test material was instilled into the interior conjunctival sac of one eye 

of 6 rabbits (0.1 ml) or the surface of the cornea (0.005 ml) of 6 other rabbits. Eyes were 

inspected for signs of local inflammation at 1, 4 and 24 hours and 2,3, 7, 14 and 21 days after 

instillation. Particular attention was paid to the development of injection of the conjunctiva and 

nictitating membrane, chemosis, discharge, iritis, and corneal injury (both severity and area 

ofinvolvement). Corneal opacity and area involved were scored from 0 to 4, injury to the iris 

was scored from 0 to 2, conjunctival redness and discharge were scored from 0 to 3, 

andchemosis from 0 to 4. 

Results and discussions 

Overall irritation / corrosion results 

Irritation 

parameter

cornea score 

Basis mean opacity 

Time point 1 hr 

1.3 

Max. score 

Reversibility 

Remarks Corneal injury after application of 0.1 ml/eye. Barely detectable in one animal 

at 21 days. 

Irritation 

parameter

cornea score 

Basis mean area score 
Time point 1 hr 

2.2 

Max. score 

Reversibility 

Remarks Corneal injury after application of 0.1 ml/eye. Barely detectable in one animal 

after 21 days. 

Irritant/corrosive response data 

Within an hour of instillation of 0.1 ml of test material into the interior conjunctival sac, all 

animals developed a moderate to marked conjunctivitis, seen as hyperemia, chemosis and 

discharge (scores of 2 to 3). This started to resolve by Day 2, but 3 animals still had slight 

hyperemia and chemosis at Day 21. Mild iritis was present from 1 hour (all score of 1) until 

about 7 days. By 1 hour of instillation, mild-moderate corneal injury that affected up to 3/4 of 

the cornea was observed in 5 animals (average opacity and area scores of 1.3 and 2.2, 

respectively). By24 hours, the 6th animal also showed evidence of mild corneal injury. All but 

one animal had no evidence of corneal injury after 7 days. Corneal injury was just detectable in 

this animal at 21 days.

Similar effects were seen in animals treated with 0.005 ml test material on the surface of the 

cornea, but they resolved quicker. Conjunctivitis was moderate to marked for the first 24 hours 

(scores of 2 to 3) but was resolved by 7 days in all but one animal. All had normal conjunctiva 

by Day 14. Minimal iritis was observed in all animals within 1 to 24 hours. This cleared after 2 

to 7 days. Mild to moderate corneal injury that affected up to 3/4 of the cornea developed within 

4 hours in all rabbits (average opacity and area scores of 1.5 and 3.0, respectively). No injury 

was observed in any of the animals after 7 days. 

Remarks on results including tables and figures 

Ethylene glycol monohexyl ether (EGHE) also was tested in this study. EGHE was found to be 

as irritating as diethylene glycol monohexyl ether. 

Applicant's summary and conclusion 

Interpretation of results 

highly irritating 

Eye irritation Moreno TGBE 1976.001 

UUID IUC5-ee7c4a10-9a69-4742-8408-1f92658419ac 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:38 EST 

Remarks 

 

Administrative Data 

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

for MSDS 

Study result type experimental result Study 19
period 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 

laboratory 

MB Research Laboratories, Inc. Report no. Project number MB 75-990 

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 IUC5-88fa9fa3-ff1e-4a01-9970-4031d9dba621 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:38 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

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 

7.5 Repeated dose toxicity 

7.5.1 Repeated dose toxicity: oral 

Repeated dose toxicity: oral.001 

UUID IUC5-5ab4793e-969f-46c8-bb24-5eeef79529c2 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 16:21:16 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 

20

04 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP. 

Data source 

Reference 

Referenc

e type 

study report 

Author Carney EW, Zablotny CL, Andrus AK, Marable BR and Thomas J. Year 2004 

Title Diethylene glycol hexyl ether: A combined dietary toxicity study with the 

reproduction/developmental toxicityscreening test in CD rats. 

Bibliogra

phic 

source 

 
Testing 

laborator

y 

Toxicology & Environmental Research and Consulting Repo

rt no. 

 

Owner 

company 

The Dow Chemical Company 

Company 

study no. 

 Repo

rt 

date 

2005-0

5-04 

Materials and methods 

Test type 

combined repeated dose and reproduction / developmental screening 

Limit test 

yes 

Test guideline 

Qualifier according to 

Guidelin

e 

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the 

Reproduction / Developmental Toxicity Screening Test) 

Deviatio

ns 

 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

Purity of the test material was 96.8%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Animals: CD (Crl: CD(SD)IGS BR) rats were obtained from Charles River Laboratories, Inc. 

They were acclimated to the laboratory at least one week prior to treatment, and were 

approximately 8 weeks old at the beginning of the study. 
Animals were housed one per cage (prebreeding) or two per cage (one per sex during breeding) 

in stainles ssteel cages. Dams were housed one per cage (with litter) in plastic cages with 

ground corn cob nesting material from approximately gestation Day 19 through lactation, under 

a 12 hour light/dark photocycle. Room humidity and temperature were maintained at 40-70% 

and 22 +/- 1 degrees C. Room air was exchanged approximately 12-15 times/hour. Animals 

were allowed free access to food and municipal water. There were no contaminants in the feed 

or water that would interfere with the study. 

Administration / exposure 

Route of administration 

oral: feed 

Vehicle 

unchanged (no vehicle) 

Details on oral exposure 

Diet preparation: Diets were prepared by serially diluting a concentrated test material-fee 

mixture (pre-mix) with ground feed. Pre-mixes were prepared periodically throughout the study 

based on stability data. Diets were prepared weekly for two weeks prior to breeding. 

Concentrations of material in the diets were calculated from body weights and feed 

consumption data. To avoid potential overdosing during the breeding period, co-housed animals 

were provided with the female diet, which was of lower concentration. Following breeding. The 

male diet was prepared weekly until necropsy. During gestation and lactation, female were 

provided with the same concentrations as given during breeding. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

Representative samples from the test diets were analyzed at least once to ensure homogeneous 

distribution of test material at the lowest and highest concentrations. All test diets from the first 

mix were analyzed prior to dosing using gas chromatography-mass spectrometry (GC-MS), and 

an internal standard. Reference samples (one/dose/mix) were retained and stored in sealed vials. 

Duration of treatment / exposure 

Females: dosed daily for two weeks prior to breeding, through breeding (two weeks), gestation 

(three weeks), and through postpartum Day 4.

Males: dosed for two weeks prior to breeding and continuing through breeding (two weeks) up 

until necropsy. 

Frequency of treatment 

Continuous 

Doses/concentrations 

100, 300, 1000 mg/kg/day 

Basis nominal in diet 

No. of animals per sex per dose 

Groups of 12 male and 12 female CD rats randomly assigned to four treatment groups and were 

fed diets supplying concentrations of 0 (control), 100, 300 and 1000 mg/kg/day. 

Control animals 

yes, plain diet 

Details on study design 
Study conduct: Groups of 12 male and 12 female CD rats randomly assigned to four treatment 

groups and were fed diets supplying concentrations of 0 (control), 100, 300 and 1000 

mg/kg/day. Females were dosed daily for two weeks prior to breeding, through breeding (two 

weeks), gestation (three weeks), and through postpartum Day 4. The males were dosed for two 

weeks prior to breeding and continuing through breeding (two weeks) up until necropsy. 

Females that delivered were necropsied on post-partum Day 5. Pups were euthanized on 

postnatal Day 4.

During breeding, each female was caged with a male from the same group until pregnancy 

occurred (presence of sperm in vaginal lavage sample evaluated daily or presence of a 

copulatory plug) or two weeks had elapsed. The day on which pregnancy was detected was 

considered lactation Day 0. If mating did not occur after two weeks, the animals were separated 

without further opportunity for mating. 

Examinations 

Observations and examinations performed and frequency 

Cage-side examinations for skin, fur, mucous membranes, respiration, nervous system function 

(including tremors and convulsions), animal behavior, moribundity, mortality, availability of 

feed and water, and litter observations were conducted twice daily. Females were observed for 

signs of parturition on or about gestation Day 20. Females that delivered received clinical 

examinations on lactation Days 0, 1 and 4. Females that failed to mate or deliver were subjected 

to hand-held evaluations weekly.

Detailed clinical observations were conducted on all rats before exposure and weekly 

throughout the study. Mated females underwent these examinations on gestation Day 0, 7, 14, 

and 20, and on lactation Day 3. The examination included cage-side, hand-held and open-field 

observations.

All rats were weighed prior to exposure, twice during the first week of the study and once 

during the second week. Male body weights continued to be recorded weekly throughout the 

study. Presumed pregnant females were weighed on gestation Day 0, 7, 14 and 20. Females that 

delivered litters were weighed on lactation Days 1 and 4. Females that failed to mate or deliver 

a litter were not weighed during the gestation or lactation phases.

Feed consumption was determined prior to exposure on twice during the first week of exposure. 

It was then determined once a week during the pre-breeding phase. It was not determined during 

breeding. After breeding, was determined once a week for males and on gestation Days 0, 7, 14, 

and 20 for mated females. After parturition, feed consumption was measured on lactation Days 

1 and 4. Feed consumption was not recorded for females that failed to mate or deliver a litter. 

Functional tests (sensory evaluation, rectal temperature, grip performance and motor activity) 

were conducted prior to exposure and during the last week of the treatment period (lactation 

Day 4 for females).

A timed urine volume (overnight, 16 hours) was obtained from all male rats (nonfasted) during 

the week prior to scheduled necropsy. Urine was analyzed for colour, appearance, specific 

gravity, volume, pH, bilirubin, glucose, proteins, ketones, blood and urobilinogen. Urine 

collected by manual compression of the bladder was pooled from each group and analyzed 
microscopically for microsediment. 

Sacrifice and pathology 

On the day prior to the scheduled necropsy, all males and females in each group were fasted 

overnight. At necropsy, the animals were anesthetized with CO2 and blood was collected from 

the orbital sinus. Blood samples were not collected from females that failed to deliver. Blood 

was analyzed for hematocrit, hemoglobin concentration, red blood cell count, total and 

differential which blood cell counts, platelet count, red blood cell indices (mean corpuscular 

hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration), and 

prothrombin time. Serum was analyzed for alkaline phosphatase, alanine aminotransferase 

(ALT), aspartate aminotransferase (AST), albumin, cholesterol, creatinine, sodium, potassium, 

phosphate, chloride, calcium, glucose, total bilirubin, total protein and urea nitrogen.

Males were terminated and necropsied on test Day 34. Females that delivered were terminated 

and necropsied on post-partum Day 5. Females that did not deliver were terminated and 

necropsied at least 24 days after the last day of the mating period. Post-mortem examinations 

included a gross necropsy of all adults (which included a gross examination of the brain, 

pituitary and eyes), with collection of organ weights (testes, epdidymides, seminal vesicles with 

coagulating gland, prostate, ovaries, liver, kidneys, adrenals, thymus, spleen, brain, 

thyroid/parathyroid, and heart) and extensive histopathologic examination of tissues (adrenals, 

aorta, auditory sebaceous glands, bone (including joint), bone marrow, brain, cecum, cervix, 

coagulating glands, colon, cranial nerve, duodenum, epididymides, esophagus, eyes, gross 

lesions, heart, ileum, jejunum, kidneys, lacrimal/Harderian glands, larynx, liver, lungs, 

mammary gland, mediastinal lymph node and tissues, mesenteric lymph node and tissues, nasal 

tissues/pharynx, oral tissues, ovaries, oviducts, pancreas, parathyroid glands, peripheral nerve, 

pituitary, prostate, rectum, salivary glands, seminal vesicles, skeletal muscle, skin and subcutis, 

spinal cord, spleen, stomach, testes, thymus, thyroid gland, tongue, trachea, urinary bladder, 

uterus and vagina) from control and high dose animals. The histopathological examination of 

the testes included a qualitative assessment of states of spermatogenesis. 

Statistics 

Statistical analyses: Parental body weights, gestation and lactation body weight gains, litter 

mean body weights, feed consumption, urine volume, urine specific gravity, coagulation, 

clinical chemistry data, hematological data and organ weights were first evaluated by Bartlett's 

test for homogeneity. Parametric and nonparametric data were then analyzed by the appropriate 

analysis of variance (ANOVA). If the ANOVA was significant at alpha = 0.05, a Dunnett's test 

(alpha = 0.05) or the Wilcoxon Rank Sum test with Bonferroni's correction was performed. 

Feed consumption data were excluded if the feed was spilled or scratched. Females failing to 

deliver a litter were excluded from analyses of gestation and lactation body weight, feed 

consumption and organ weights. Detailed clinical observation and sensory evaluation scores 

were analyzed using a z-test of proportions (at alpha = 0.05). Rectal temperature and grip 

performance were analyzed by an analysis of covariance. Motor activity was analyzed by a 

repeated measure design. 

Results and discussions 

Effect levels 

Endpoint NOEL 

Effect level 300 mg/kg bw/day (nominal) 

Sex male/female 
Basis for effect 

level / Remarks 

A NOEL of 300 mg/kg/bw;day for general toxicity. A NOEL of 1000 

mg/kg/bw/day for neurological 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) 

no data 

Ophthalmoscopic examination 

yes 

Haematology 

yes 

Clinical chemistry 

yes 

Urinalysis 

yes 

Neurobehaviour 

yes 

Organ weights 

yes 

Gross pathology 

yes 

Histopathology: non-neoplastic 

yes 

Histopathology: neoplastic 

no data 

Details on results 

Dietary administration of diethylene glycol hexyl ether (DGHE) to CD rats had no effect on 

detailed clinical or sensory observations. All animals survived to termination. There was a slight 

treatment-related decrease in body weights of males and females given 1000 mg/kg/day. 

Decreased maternal body weights persisted throughout the gestation and lactation phases of the 

study. Decreased feed consumption was noted in high dose males and females during the 

prebreeding period and in high dose females during gestation.

Females given 1000 mg/kg/day had treatment-related increases in serum ALT and ALP 

activities, along with increases in relative liver weight. These effects corresponded with 

treatment-related histopathologic changesin the liver that consisted of very slight panlobular 

hepatocyte hypertrophy. Males given 1000 mg/kg/day had treatment-related increases in 

relative liver weight, which corresponded with the histological alteration of very slight 

periportal hepatocyte hypertrophy. At 1000 mg/kg/day, other findings of lesser significance 
included slightly increased blood urea nitrogen and decreased absolute thymus weights in 

females, and decreased urine pH and increased relative kidney weights in males. Additional 

histopathologic findings of minor toxicological significance at 1000 mg/kg/day included very 

slight diffuse acinar hypertrophy of the submandibular salivary gland in males, and very slight 

atrophy of the mesenteric adipose tissue in females.

There were no adverse effects of DGHE on neurological function. There were no adverse gross 

or histopathologic findings in the reproductive organs of high dose males or females.

Based on these results, the no-observed-adverse-effect level (NOAEL) for general toxicity was 

300 mg/kg/day. The NOAEL for neurological effects was 1000 mg/kg/day, the highest dose 

level tested. Analyses of all test diets from the first mix of the main study revealed mean 

concentrations ranging from 92.5 to 104% of targeted concentrations. Analyses of the low dose 

female and high dose male diets indicated that the diets were homogeneous. Analyses 

confirmed that the 10% premix was stable for 14 days and that the test diets were stable for 8 

days at concentrations ranging from 0.120 to 0.359%, which encompass the range of dietary 

concentrations used in the study. 

Remarks on results including tables and figures 

A limit dose of 1000 mg/kg/day was selected as the high dose level based on data obtained in a 

preliminary range-finding study. The authors reported no-observable-effect-levels (NOELs) of 

300 mg/kg/bw/day for general toxicity and 1000 mg/kg/bw/day for neurological effects. Data 

in this summary pertain to exposed adult animals only. Procedures and results relating to the 

reproductive toxicity component of this study are described in the reproductive toxicity 

summary in this dossier. 

7.5.2 Repeated dose toxicity: dermal 

Repeated dose toxicity: dermal.001 

UUID IUC5-afa4acb7-f485-4ed2-b430-c758a6d3d951 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-05 16:37:08 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

87 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

The duration of the test is less than 28 days. 

Data source 
Reference 

Reference 

type 

study report 

Author Frantz SW. Year 1987 

Title Hexyl CARBITOL (R): Nine-day repeated dose percutaneous toxicity study in 

albino rabbits. 

Bibliograph

ic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide Corporation 

Company 

study no. 

 Report 

date 

1987-05-2

9 

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 Diethylene glycol hexyl ether 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial material). The purity of the 

test material (approximately 100%) was listed on a material safety data sheet attached to the 

study report. 

Test animals 

Species 

rabbit 

Strain 

New Zealand White 

Sex 

male/female 

Details on test animals and environmental conditions 

Fifty six rabbits (28 per sex) were received at 12-13 weeks of age. They were acclimated for 2 

weeks before dosing. They were maintained on a restricted diet (4 oz/day/rabbit) during this 

period. Only rabbits with body weights within +/- 20% of the population mean for each sex (2-3 
kg) were used. 

Administration / exposure 

Type of coverage 

occlusive 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Five animals/sex were randomly chosen to receive vehicle (control), or 0.11, 0.32 or 1.07 

ml/kg/day test material (100, 300 or 1000 mg/kg/day). 

Prior to the first dose (and subsequently, as needed), fur was clipped from the dorsal area of the 

trunk of the animals (approximately 10% of body surface area). Care was taken to avoid 

abrading the skin. Test material was applied topically as a neat liquid to the clipped 

intrascapular region of the back. Dosages were determined based on individual body weights 

measured on Days 0 and 7. Control animals were treated with water at a dose of 1.0 ml/kg/day. 

The dose site was covered with an 8-ply gauze patch and a piece of polyethylene sheeting. The 

animals were then wrapped with a Lycra/Spandex jacket held in place with Velcro strips. The 

wrappings were removed after 6 hours of exposure. Animals were dosed daily, Monday through 

Friday of the first week and Monday through Thursday of the second week. Food and water 

were available ad libitum after treatment was initiated. 

Analytical verification of doses or concentrations 

no data 

Duration of treatment / exposure 

6 hrs/day for 9 days beginning on a Monday (except the weekend) 

Frequency of treatment 

daily 

Doses/concentrations 

100, 300, 1000 mg/kg/day 

Basis nominal per unit body weight 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

yes, concurrent vehicle 

Details on study design 

There was no post exposure period. 

Examinations 

Observations and examinations performed and frequency 

Animals were examined daily for signs of toxicity before dosing (with particular attention given 

to the application site). Skin irritation was graded according to a similar scale as Draize (1 = 

very slight, 2 = well-defined, 3 = moderate to severe, 4 = severe). Body weights were measured 

on Days 0, 7, 10, and 11 (at termination). Animals were fasted during the night prior to 

termination. The body weights used for determining body weight gains were those obtained on 

Day 10. Food consumption was determined on Days 2, 4, 6, 7, 9, and 10.

Blood was obtained from all animals via cardiac puncture just prior to termination on Day 11. 

The following hematological parameters were measured: erythrocyte count, hemoglobin, 
hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean 

corpuscular hemoglobin concentration (MCHC), total leukocyte count, platelet count, and 

differential leukocyte count. Clinical chemistry measurements included creatinine, fasted 

glucose, total and direct bilirubin, total protein, albumin, globulin, calcium, phosphorus, 

aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, 

sorbitol dehydrogenase, sodium, potassium, chloride, urea nitrogen.

Sacrifice and pathology 

Complete necropsies were performed after animals were euthanized. The liver, kidneys, 

adrenals, brain, heart and testes (males) were weighed. The following tissues were fixed and 

examined histologically (in the control and high dose groups): all lesions, brain, pituitary, heart, 

thymus, thyroid (with parathyroid), adrenals, liver, kidneys, testes and epididymis (males), 

uterus and ovaries (females), spleen, mesenteric lymph nodes, and sternum with marrow. 

Treated and untreated skin from all groups was fixed and examined. The spinal cord, sciatic 

nerve, eyes, salivary glands (submaxillary), aorta, trachea, lungs with mainstem bronchi, 

esophagus, stomach, small and large intestine, pancreas, gallbladder, prostate, accessory sex 

glands, mammary gland, urinary bladder, mediastinal lymph nodes, and gastrocnemius muscle 

were also fixed and saved for analysis (if necessary). 

Statistics 

Food consumption, body weight and organ weight data analyzed using Levene's test for 

homogeneity of variance, analysis of variance, and pooled variance t-tests (if homogeneous). 

Heterogeneous data were analyzed using an analysis of variance for unequal variance and 

separate variance t-tests. Frequency data were compared with Fisher's exact tests. The fiducial 

limit of 0.05 was used as the critical level 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 Systemic toxicity 

Endpoint no NOAEL identified 

Effect level 100 mg/kg bw/day (nominal) 

Sex male/female 

Basis for effect level / 

Remarks 

Pathological and histological changes of the skin. 

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 

There were no mortalities during the test. Erythema was observed in 5/5 and 4/5 high dose 

(1000 mg/kg/day) males and females (respectively) by Day 4. Edema at the application site was 

observed in all males from the high dose group starting on Day 3. These findings were generally 

of limited severity (Grade 1). However, erythema scores of 3 or 4 were noted in 2 high-dose 

females. Barely perceptible (Grade 1) erythema and/or edema was noted at various times in all 

males and females from the mid dose group (300 mg/kg/day) and occasionally in all males and 

one female in the low dose group (100 mg/kg/day). Fissuring at the skin was noted in males 

from all treatment groups and all females in the mid and high dose groups. Encrustation was 

found in 2 and 3 high dose males and females, respectively. Ecchymosis was found in 1 and 3 

high dose males and females, respectively.

A significant reduction in food consumption was found in high dose males during the first 

week. There was no significant effect of treatment on weight, weight gain, or organ weights 

(except for increased weight gain in males from the low dose at Day 11). There was no effect of 

treatment on any hematological or clinical chemistry variable.Gross pathological and 

histological changes were limited to the skin at the treated area. 

Gross findings included crusting or scaling dermatitis, scratches or fissures. Acanthosis and 

hyperkeratosis were found in all high and mid-dose animals, and in 3 males and 4 females from 

the low dose group. Superative epidermitis was noted in 9/10 animals from the high dose group. 

The underlying dermis showed dose-related changes ranging from acute inflammation with 

edema, hemorrhage, and necrotizing dermatitis to dermal fibrosis. 

The NOAELs for systemic and local toxicity were = 1000 mg/kg/day, and < 100 mg/kg/day, 

respectively. 
Repeated dose toxicity: dermal IRDC TGBE 1986.005 

UUID IUC5-51ffd837-2dd0-4d59-9076-28466fe12292 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:38 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

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.

7.6 Genetic toxicity 

7.6.1 Genetic toxicity in vitro 

Genetic toxicity in vitro.001 

UUID IUC5-b7eeb0d2-7591-42ae-a1b6-5039fa58f2f0 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 16:22:14 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

87 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Test method was comparable to a guideline study and following GLP. 

Data source 

Reference 

Reference 

type 

study report 

Author Deeble R Year 1987 

Title Hexyl CARBITOL. Salmonella/microsome (Ames) bacterial mutagenicity assay. 

Bibliographic 

source 

 

Testing Bushy Run Research Center Report 
laboratory no. 

Owner 

company 

Union Carbide Corporation 

Company 

study no. 

 Report 

date 

1987-07-23 

Reference 

type 

publication 

Author Ballantyne B and Vergnes JS Year 2001 

Title In vitro and in vivo genetic toxicology studies with diethylene glycol monohexyl 

ether. 

Bibliographi

c source 

J Appl Toxicol 21:449-460. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

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 other guideline: internal company protocol 

Deviations 

Principles of method if other than guideline 

Standard Ames study protocol. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

The material tested was Hexyl CARBITOL (tradename for commercial material). The purity 
was 96.8%. 

Method 

Species/strain 

Species/strain other: S. typhimurium strains TA98, TA100, TA1535, TA1537, 

TA1538 

Details on mammalian cell 

lines (if applicable) 

 

Additional strain 

characteristics 

 

Metabolic activation with and without 

Metabolic activation 

system 

S-9 

Test concentrations 

0.03 to 3 mg/plate (without S-9); 0.1 to 10 mg/plate (with S-9) 

Vehicle 

DMSO 

Controls 

Negative controls no data 

Solvent / vehicle 

controls 

yes 

True negative 

controls 

 

Positive controls yes 

Positive control 

substance 

sodium azide Also used 4-nitro-o-phenylenediamine and 

2-aminoanthracene 

Remarks 

Details on test system and conditions 

Test material was diluted in DMSO to a stock concentration of 100 mg/ml. Dilutions of the 

stock solution were made on each day of testing. Dilutions were made such that 100 microliters 

of the dilution would deliver the required dose. Concentrations were verified gravimetrically. 

S-9 liver homogenate was prepared from Aroclor 1254-induced Sprague-Dawley male rats. For 

tests with metabolic activation, 0.5 ml of S-9 mix containing 50 microliters of S-9 was added 

per plate.Preliminary toxicity tests with one plate per test concentration were performed using 

strain TA100 (in the absence and presence of S-9). Ten concentrations were tested. Toxicity 

was assessed by observing growthinhibition of the background lawn and/or a reduction in the 

number of spontaneous mutants. Each test chemical was tested in triplicate at 5 doses that 

spanned a range from relativelynontoxic to moderately toxic (0.03, 0.1, 0.3, 1 and 3 mg in the 

absence of S-9 and 0.1, 0.3, 1, 3, and 10 mg in the presence of S-9). Concurrent solvent 

(DMSO) and positive controls were run without S-9 as follows: 0.01 mg 

4-nitro-o-phenylenediamine in strains TA98 and TA1538, 0.01 mg sodium azide in strains 

TA100 and TA1535, and 0.06 mg 9-aminoacridine in strain TA1537. The positive control used 

in all strains incubated with S-9 was 0.01 mg 2-aminoanthracene.Revertant colonies were 

counted after 48-72 hours of incubation (temperature was not listed). The criterion for 

significance was a greater than 2-fold increase in mutants with respect to the solvent control. 

Evaluation criteria 

The tests were considered valid if all positive controls produced a greater than 2-fold increase in 
the number of mutants over control (both in the absence and presence of S-9). The number of 

spontaneous revertants in the solvent control should be within the historical 95% confidence 

range at the laboratory. 

Results and discussions 

Test results 

Species/strain other: 

Metabolic activation with and without 

Test system all strains/cell types tested 

Genotoxicity negative 

Cytotoxicity 

Vehicle controls valid yes 

Negative controls valid 

Positive controls valid yes 

Additional information on results 

Preliminary toxicity tests showed that concentrations equal to or greater than 5 mg/plate 

produced complete absence of growth and that 3 mg/platecaused a reduction of growth of the 

bacterial lawn. In the presence of S-9, 10 mg/plate affected growth and concentrations equal to 

or greater than 30 mg/plate obliterated growth.

The average number of revertants in the solvent controls were 24 (TA98), 97 (TA100), 18 

(TA1535), 8 (TA1537) and 8 (TA1538). The average number of revertants in cultures incubated 

with test material ranged from 15-26 (TA98), 52-95 (TA100), 17-26 (TA1535), 3-9 (TA1537), 

and 8-11 (TA1538).

In the presence of S-9, the average number of revertants in the solvent controls for strains 

TA98, TA100, TA1535, TA1537 and TA1538 were 24, 79, 9, 8, and 22 (respectively). The 

average number of revertants in cultures incubated with test material and S-9 ranged from 9-35 

(TA98), 28-92 (TA100), 5-13 (TA1535), 2-7 (TA1537), and 3-23 (TA1538).

The test substance was judged to be nonmutagenic. The tests were valid, as all positive controls 

produced a greater than 2-fold increase in the number of mutants over control (both in the 

absence and presence of S-9). The number of spontaneous revertants in the solvent control was 

within the historical 95% confidence range at the laboratory. 

Applicant's summary and conclusion 

Interpretation of results 

negative 

Genetic toxicity in vitro.002 

UUID IUC5-d72cb5f3-0dc7-4e0b-a0cc-c23d15a6ab71 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 16:25:21 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 

20

01 

Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Criteria for a positive response were not fully described. 

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B and Vergnes Year 2001 

Title In vitro and in vivo genetic toxicology studies with diethylene glycol monohexyl 

ether. 

Bibliographi

c source 

J Appl Toxicol 21:449-460. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Type of genotoxicity 

gene mutation 

Type of study 

mammalian cell gene mutation assay 

Test guideline 

Qualifier according to 

Guideline other guideline: Customary protocol for the time period 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 
Identity Diethylene glycol hexyl ether 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial material). The sample was 

96.8% pure. 

Method 

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 

Test concentrations 

0.25 to 2.0 mg/ml without S-9 and 0.1 to 2.5 mg/ml with S-9 

Vehicle 

DMSO 

Controls 

Negative controls no data 

Solvent / vehicle 

controls 

no data 

True negative controls no data 

Positive controls yes 

Positive control 

substance 

N-dimethylnitrosamine 

Remarks Ethylmethanesulfonate was also used as a positive control. 

Details on test system and conditions 

CHO-K1-BH4 (subclone D1) cells were first treated with seven concentrations of test material 

(from 0.01 to 10 mg/ml) to select test concentrations that would not result in excessive toxicity.

In the definitive test without metabolic activation, 5 x 10E6 cells were inoculated into culture 

flasks containing test medium and incubated at 37 degrees C for 20-24 hours before treatment. 

Test material (0.25, 0.75, 1, 1.5 and 2.0 mg/ml), DMSO solvent (20 micrograms/ml), medium, 

or positive control (200 micrograms/ml ethylmethanesulfonate) were added to the cultures and 

cells were incubated for 5 hours. After the 5 hour exposure, each flask was rinsed with buffered 

saline, fresh medium was added, and cells were incubated for an additional 18-24 hours. For the 

tests in the presence of metabolic activation, the same procedure was used with the exception 

that 1.0 ml of S-9 activation mixture (from Aroclor 1254-induced Sprague-Dawley male rats) 

was added to the flasks, serum was omitted from the culture medium, the treatment period was 2 

(instead of 5) hours, test material concentrations were 0.1, 0.25, 0.75, 1.0, 1.5, 2.0 and 2.5 

mg/ml), and dimethylnitrosamine (200 microliters/ml) was the positive control. DMSO vehicle 

and all concentrations of test material were tested in duplicate. 

Cytotoxicity was determined 24 hours after exposure. At 2-3 day intervals after treatment, 5 x 

10E5 cells from each culture were subcultured. After at least 7 days, cells were dissociated and 

replated at 2 x 10E5 cells in 5 dishes (for assessment of mutations) and at 100 cells/dish in 4 

dishes (for assessment of plating efficiency) in medium containing 6-thioguanine (2 
micrograms/ml). These cultures were incubated for 6-8 days. Cells were then fixed and stained 

for counting with a Coulter Counter. 

Evaluation criteria 

Criteria for a positive response were not fully described. 

Statistics 

The numbers of mutants/10E6 total cells and per 10E6 viable cells were calculated. Mutation 

data were analyzed by the method of Irr and Snee (Mut Res 15:109-118, 1979) after Box-Cox 

transformation (J Roy Stat Soc 26:211-252, 1964), before parametric analysis using the 

Student's t test. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system strain/cell type: Chinese hamster Ovary (CHO) 

Genotoxicity other: weakly positive in the presence of S-9. 

Cytotoxicity yes Cytotoxic concentration: 2.0 mg/ml 

Vehicle controls valid no data 

Negative controls valid no data 

Positive controls valid yes 

Additional information on results 

Cell viability was not affected by test material concentration up to approximately 750 mg/ml in 

the absence of S-9 and 1 mg/ml in the presence of S-9. A concentration of 2.0 mg/ml caused 

100% lethality. The plating efficiency for all concentrations was not affected by test material 

concentration(up to 2 mg/ml).

Test material did not produce a dose-related increase in the number of mutants per 10E5 viable 

cells in the absence of S-9. In the presence of S-9, increases in the mutation frequency occurred 

that were not dose-related and were inconsistent between duplicate cultures. A linear regression 

analysis of the data showed a significant trend for the combined data from the two tests (r=0.82, 

p= 0.0035). Both positive controls produced highly significant increases in the number of 

mutants. 

Genetic toxicity in vitro.003 

UUID IUC5-46e9082c-af12-467f-a4e3-33f1ed7988bc 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 16:28:50 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 

20

01 
Reliablility 2 (reliable with restrictions) 

Rationale for 

reliability 

Criteria for a positive response were not fully described. 

Data source 

Reference 

Reference 

type 

publication 

Author Ballantyne B and Vergnes JS. Year 2001 

Title In vitro and in vivo genetic toxicology studies with diethylene glycol monohexyl 

ether. 

Bibliographi

c source 

J Appl Toxicol 21:449-460. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Type of study 

sister chromatid exchange assay in mammalian cells 

Test guideline 

Qualifier according to 

Guideline other guideline: Standard protocol was used for the time period. 

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 203-988-3 

Identifier Common name 

Identity . 112-59-4 (dossier available) for studies 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial material). The sample was 

96.8% pure. 

Method 

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 

0.75 to 2.0 mg/ml without S-9 and 1.0 to 2.5 mg/ml with S-9 

Vehicle 

DMSO 

Controls 

Negative controls no data 

Solvent / vehicle 

controls 

yes 

True negative controls no data 

Positive controls yes 

Positive control 

substance 

N-dimethylnitrosamine 

Remarks Ethylmethanesulfonate was also used as a positive control. 

Details on test system and conditions 

The concentrations tested were determined by the results of a previous HPRT mutation test (see 

above).

In the definitive test without metabolic activation, 2-3 x 10E6 cells were inoculated into culture 

flasks containing test medium and incubated at 37 degrees C for 20 hours before treatment. Test 

material (0.75, 1.0, 1.6 and 2.0 mg/ml), DMSO solvent (5 micrograms/ml), medium, or positive 

control (100 micrograms/ml ethylmethanesulfonate) and bromodeoxyuridine (BrDU; 3 

micrograms/ml) were added to the cultures and cells were incubated for 5 hours. After the 5 

hour exposure, each flask was rinsed with buffered saline, fresh medium containing BrDU was 

added, and cells were incubated for an additional 24 hours to allow 2 cycles of division. For the 

tests in the presence of metabolic activation, the same procedure was used with the exception 

that cells were incubated for 48 hours before treatment, 1.0 ml of S-9 activation mixture (from 

Aroclor 1254-induced Sprague-Dawley male rats) was added to the flasks, serum was omitted 

from the culture medium, the treatment period was 2 (instead of 5) hours, the incubation period 

was 28 (instead of 24 hours), test material concentrations were 1.0, 1.5 and 2.0 mg/ml) and 

dimethylnitrosamine (300 microliters/ml) was the positive control. DMSO vehicle and all 

concentrations of test material were tested in duplicate. 

Colchicine (0.2 micrograms/ml) was added to the flasks 2 hr prior to harvest to produce mitotic 

arrest. Cells were removed and incubated for 20 min at 37 degrees C. Cells were then fixed, 

spread on slides and stained. The number of chromosomes and sister chromatid exchanges 

(SCEs) in 25 cells per culture were counted for each treatment group. 

Evaluation criteria 

Criteria for a positive response were not fully described. 

Statistics 

Data were analyzed using Box-Cox transformation (J Roy Stat Soc 26:211-252, 1964) and 

Levene's test for equality of variance. Homogeneous data were compared using analysis of 
variance (ANOVA) and pooled t-tests and non-homogenous data were compared using 

ANOVA for unequal variances, followed by separate t-tests. 

Results and discussions 

Test results 

Species/strain Chinese hamster Ovary (CHO) 

Metabolic activation with and without 

Test system strain/cell type: Chinese hamster Ovary (CHO) 

Genotoxicity negative 

Cytotoxicity yes Cytotoxic concentration: 2.0 mg/ml 

Vehicle controls valid yes 

Negative controls valid no data 

Positive controls valid yes 

Additional information on results 

There was no effect of treatment on the incidence of sister chromatid exchanges (SCEs) in the 

absence of metabolic activation. In the presence of metabolic activation, a significant increase 

in SCEs was seen in one culture at 1.5 mg/ml (0.77 +/- 0.24 vs. 0.49 +/- 0.14 in DMSO control). 

This effect was not dose-related. There was no mitotic inhibition in the absence of S-9, and only 

the high dose (2 mg/ml) caused mitotic inhibition in the presence of S-9. The test was valid, as 

the positive controls induced significant increases in the frequency of SCEs. 

Genetic toxicity in vitro BASF TGBE 1989.001 

UUID IUC5-9e4b391e-fd9f-4dc6-8499-aa64498744fa 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:39 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 

7.6.2 Genetic toxicity in vivo 

Genetic toxicity in vivo.001 

UUID IUC5-e8ff6925-3f75-4dce-a233-2b115c4a3389 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 
States of America 

Date 2009-02-11 16:54:55 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

91 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Equivalent to guideline study and following GLP 

Data source 

Reference 

Reference 

type 

study report 

Author Vergnes J.S Year 1991 

Title Hexyl CARBITOL(R): In vivo clastogenic potential using the bone marrow 

chromosome aberration assay in rats. 

Bibliograp

hic source 

 

Testing 

laboratory 

Bushy Run Research Center Report 

no. 

 

Owner 

company 

Union Carbide Corporation 

Company 

study no. 

 Report 

date 

1991-11-

01 

Reference 

type 

publication 

Author Ballantyne B and Vergnes JS Year 2001 

Title In vitro and in vivo genetic toxicology studies with diethylene glycol monohexyl 

ether. 

Bibliographi

c source 

J Appl Toxicol 21:449-460 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Type of genotoxicity 

chromosome aberration 

Type of study 
mammalian germ cell cytogenetic assay 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: Internal company protocol 

Deviations 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial material). The sample was 

approximately 95-96% pure. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Rats were acclimated for 7 days before treatment. Only those with body weights within 2 

standard deviations of the mean for each sex were used for the chromosome aberration tests. For 

the first test, the males weighed between 300 and 325 g and the females weighed between 208 

and 235 g. Male rats used for the second test weighed between 328 and 359 g. Animals were 

randomized into groups of 5/sex for the first test and 5 males for the second test. Food and water 

were provided ad libitum except during dosing. 

Administration / exposure 

Route of administration 

oral: gavage 

Vehicle(s) 

corn oil 

Details on exposure 

Test material was dissolved in corn oil on the morning of the test. Doses used in the definitive 

tests were verified by gravimetric analyses. Dilutions were prepared for a dosing volume of 10 

ml/kg.
Preliminary tests with 3 males/dose level (4 from 2560 to 5000 mg/kg) and 5 animals/sex/dose 

level (6 from 1638 to 5000 mg/kg) were conducted to determine the LD50 value. An additional 

group of 5 females was dosed at 1301 mg/kg. The LD50 values were calculated by probit 

analysis.

In the first test, groups of 5 animals/sex/test interval were dosed with test material by gavage at 

25% (750 mg/kg for males, 450 mg/kg for females), 50% (1500 mg/kg for males and 900 mg/kg 

for females), and 80% (2400 mg/kg for males and 1500 mg/kg for females) of the LD50 values. 

An additional dose of 375 mg/kg (12.5% of LD50 value) was given to 5 males/ test interval 

(two of these rats were not within 2 standard deviations of the mean) due to high mortality at the 

high dose. Groups of 5/sex/interval were administered corn oil vehicle by gavage. The positive 

control cyclophosphamide (30 mg/kg) was administered i.p. to one group of 5 animals/sex.

In the second test, five males/test interval were given corn oil vehicle or test material at doses of 

375, 600, 750, 1000 and 1500 mg/kg by gavage. An additional 5 males were given 

cyclophosphamide (30 mg/kg, i.p.). 

Duration of treatment / exposure 

up to 48 hours 

Frequency of treatment 

See details on exposure section. 

Post exposure period 

See details on expsure section. 

Doses / concentrations 

450, 900, 1500 mg/kg (females); 750, 1500, 2400 mg/kg (males); 375, 600, 750, 1000, 1500 

mg/kg (males) 

Basis other: gravimetrically determined 

No. of animals per sex per dose 

five animals per sex per dose 

Control animals 

yes, concurrent vehicle 

Positive control(s) 

The positive control cyclophosphamide (30 mg/kg) was administered i.p. to one group of 5 

animals/sex. 

Examinations 

Tissues and cell types examined 

When possible, 500 cells per animal were scored for the proportion of mitotic cells. When 

possible, 50 metaphase cells per animal were evaluated blindly for chromosome number, 

specific type of chromosome or chromatid-type aberrations, deletions and exchanges, gaps, 

endoreplicated chromosomes and polyploid cells were noted but were not included as 

statistically evaluated aberrations. Severely damaged cells (> = 10 breakage events) and 

pulverized cells were recorded as severely damaged, but no attempt was made to classify the 

types of damage in these cells. 

Evaluation criteria 

The result was considered positive if there was a statistically significant and dose-related 

increase in the frequency of chromosome aberrations. The result was equivocal if one result 

was significantly different from control and there was no dose-response. The result was 
negative if none of the doses produced a significant increase. 

Statistics 

The LD50 values were calculated by probit analysis. Data were analyzed using the Fisher's 

Exact Test (one-tailed). A difference between treated and control cells was considered to be 

significant if p 0.05 (one-tailed). 

Any other information on materials and methods incl. tables 

Animals treated with test material were terminated at preassigned time intervals of 12 hr, 24 hr or 48 hours for the 

first study, and 24 or 48 hours for the second study. Vehicle controls were terminated at 24 hours in the first study 

and at 24 and 48 hours in the second study. Positive control animals were killed at 24 hours in both studies. 

Colchicine (4 mg/kg) was injected i.p. 2-3 hours prior to euthanization. A femur was removed from each animal. 

Bone marrow cells were collected and fixed. Slides were prepared and chromosomes were stained with Giemsa.

When possible, 500 cells per animal were scored for the proportion of mitotic cells. When possible, 50 metaphase 

cells per animal were evaluated blindly for chromosome number, specific type of chromosome or chromatid-type 

aberrations, deletions and exchanges, gaps, endoreplicated chromosomes and polyploid cells were noted but were 

not included as statistically evaluated aberrations. Severely damaged cells (> = 10 breakage events) and pulverized 

cells were recorded as severely damaged, but no attempt was made to classify the types of damage in these cells. 

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 

The preliminary toxicity test indicated that 3200 to 500 mg/kg test material produced mortality 

in 1/3 male rats. Based on these results, 7 dose levels ranging from 1310 to 5000 mg/kg were 

tested in another study. All male and female rats dosed with 5000 mg/kg, 4/5 males dosed with 

4000 mg/kg and 5/5 females dosed with 3200 mg/kg died. The LD50 value was 3016 mg/kg for 

males and 1823 mg/kg for females. 

In the first test, a significant increase in aberrations was observed in male rats treated with 375 

(6.8 vs. 1.2% in control) or 750 mg/kg test material for 48 hours (9.5%), excluding one high 

dose animal that had multiple fragments. The incidence of aberrations in male rats treated with 

750 mg/kg test material was 23.3 % if this animal was included. No significant increase in 

aberrations was noted in males treated with 1500 mg/kg at any interval, males treated with 375 

or 750 mg/kg for 12 or 24 hours, or females treated with any dose for any time interval 

measured. The test was valid, as the positive control induced a significant increase in 
aberrations in both sexes with respect to control (25.2% in males and 24.2% in females). 

A second test was performed to determine if the results seen in the first test were reproducible. 

The mean incidences of aberrations in treated male rats ranged from 0.8 to 1.6% among cells 

harvested 24 hours after dosing (vs. 1.2% in vehicle control) and from 0 to 1.2% for cells 

harvested at 48 hours (vs. 0.8% in vehicle control). No significant or dose-related increases in 

aberrations were noted in treated rats. The positive control induced aberrations in 16.4% of 

cells, indicating that the test system was responsive to a clastogenic agent. 

Since the positive results in males in the first test were not dose dependent and could not be 

confirmed in the second experiment the material was judged to be negative in the test. 

Genetic toxicity in vivo.002 

UUID IUC5-d61de3a6-f75c-4270-930e-f023c9275477 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 17:00:39 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 

19

88 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Comparable to a guideline study following GLP. 

Data source 

Reference 

Reference type study report 

Author Guzzie PJ. Year 1987 

Title Hexyl Carbitol(R): In vivo mouse micronucleus study. 

Bibliographic 

source 

 

Testing 

laboratory 

Bushy Run Research Center, Report no. 

Owner 

company 

Union Carbide Corp. 

Company study 

no. 

 Report date 1988-01-12 

Reference 

type 

publication 

Author Ballantyne B and Vergnes JS. Year 2001 
Title In vitro and in vivo genetic toxicology studies with diethylene glycol monohexyl 

ether. 

Bibliographi

c source 

J Appl Toxicol 21:449-460. 

Testing 

laboratory 

 Report 

no. 

 

Owner 

company 

 

Company 

study no. 

 Report 

date 

 

Materials and methods 

Type of genotoxicity 

chromosome aberration 

Type of study 

micronucleus assay 

Test guideline 

Qualifier equivalent or similar to 

Guideline other guideline: A standard internal company protocol 

Deviations 

Principles of method if other than guideline 

Test material was Hexyl CARBITOL. The purity was 96.8%. 

GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

Test material was Hexyl CARBITOL (tradename for commercial product). The purity was 

96.8%. 

Test animals 

Species 

mouse 

Strain 

Swiss Webster 

Sex 

male/female 

Details on test animals and environmental conditions 
Five-week old mice were used for all preliminary and definitive tests. They were acclimated for 

5 to 6 days before dosing. Animals used for the definitive micronucleus test were randomized 

by weight and those outside a range of two standard deviations were not used. 

Administration / exposure 

Route of administration 

intraperitoneal 

Vehicle(s) 

Fresh suspensions oftest material in corn oil were made on the morning of the test and dilution 

concentrations were verified by gravimetric analysis. 

Details on exposure 

Mice (5/sex/group) were dosed with test material over a range of dose levels from 410 to 1000 

mg/kg in a preliminary test to determine the optimal doses for use in the definite test. The ratio 

of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) was determined 

for the highest group in which at least 3 animals survived for 48 and 72 hours after dosing.

For the definitive test, the body weights for males ranged from 23.8 to 26.9 g, and for females 

from 20.6 g to 22.2 g. Three dose levels of approximately 25, 50 and 80 % of the LD50 value 

(200, 400 and 640 mg/kg), a vehicle control (10 ml/kg), or the positive control 

triethylenemelamine (TEM, 0.3 mg/kg) were given i.p. to groups of 5 mice/sex. An additional 3 

animals/sex were dosed with 640 mg/kg. Bloodsamples were collected from tails 30, 48 and 72 

hours after dosing of vehicle or test material. Positive control animals were sampled at 30 hours 

only. One or two blood smear slides were prepared per animal per sampling time. Slides were 

stained and read blindly. Micronuclei wereidentified as darkly-stained, spherical inclusions in 

polychromatic erythrocytes (cells with pale-blue staining of the cytoplasm). NCE's did not stain 

blue. A minimum of 1000 PCE was examined per animal per sampling time (unless precluded 

by cytotoxicity). The PCE/NCE ratio for approximately 1000 total cells was calculated. Slides 

of several of the high dose animals had low numbers of erythrocytes and reduced ratios of 

PCE/NCE. The lowest 3/sex were eliminated, leaving 5/sex/dose group for evaluation. 

Duration of treatment / exposure 

one time i.p. dosing 

Frequency of treatment 

One time i.p. dosing 

Post exposure period 

72 hours. 

Doses / concentrations 

200, 400, 640 mg/kg 

Basis nominal conc. 

No. of animals per sex per dose 

five per sex per dose 

Control animals 

yes, concurrent vehicle 

Positive control(s) 

The positive control triethylenemelamine (TEM, 0.3 mg/kg) was given i.p. to groups of 5 

mice/sex. 

Examinations 

Tissues and cell types examined 
See details and slide preparation section below. 

Details of tissue and slide preparation 

One or two blood smear slides were prepared per animal per sampling time. Slides were stained 

and read blindly. Micronuclei were identified as darkly-stained, spherical inclusions in 

polychromatic erythrocytes (cells with pale-blue staining of the cytoplasm). NCE's did not stain 

blue. A minimum of 1000 PCE was examined per animal per sampling time (unless precluded 

by cytotoxicity). The PCE/NCE ratio for approximately 1000 total cells was calculated. Slides 

of several of the high dose animals had low numbers of erythrocytes and reduced ratios of 

PCE/NCE. The lowest 3/sex were eliminated, leaving 5/sex/dose group forevaluation. 

Evaluation criteria 

Data from males and females were analyzed separately and collectively. The result was 

considered positive if at least one significant increase (p < = 0.01) above the control was 

observed with an indication of a dose-response. A test was considered inconclusive if a 

significant increase was noted at one dose and no dose-response relationship was apparent. A 

test was negative if there were no significant differences between control and treated animals at 

any dose. 

Statistics 

Data from treated groups were compared to those of the vehicle control using the Fisher's exact 

test. 

Results and discussions 

Test results 

Sex male/female 

Genotoxicity negative 

Toxicity yes A pooled LD50 value of 806.4 mg/kg was calculated. 

Vehicle controls valid yes 

Negative controls 

valid 

no data 

Positive controls valid yes 

Additional information on results 

All five males and three females dosed with 1000 mg/kg in the preliminary study died within 48 

hours of dosing. A dose of 800 mg/kg was lethal to 4/5 males and 2/5 females. No animals 

dosed with 512 mg/kg or less died. Using the moving average method of Thompson and Weil, a 

pooled LD50 value of 806.4 mg/kg was calculated. Doses chosen for use in the study were 25, 

50 and 80% of this value.

There were no significant decreases in the PCE/NCE ratio in females treated with any dose at 

any time. This ratio was reduced in samples taken at 72 hours from males treated with 640 

mg/kg (83.8% of control), indicating a moderate degree of bone marrow cytotoxicity. This 

decrease was not sufficient to preclude evaluation of micronuclei.

Analysis of variance testing indicated that there were no sex-related differences in the 

incidences of micronuclei in males and females treated for 72 hours; therefore, values for 72 

hours were pooled for subsequent analyses. Values at 30 and 48 hours were not pooled because 

there were sex-related differences. 

Remarks on results including tables and figures 
As shown in the table below, no statistically significant increases in micronuclei were noted 

between controls and animals treated with test material at any time period. 

Sa

mpl

e

Tim

e 

(h)

Mate

rial

Dose Gender Total 

MN-PCE 

 Mean 

MN-PC

E/ 

1000PC

E 

Std.

Dev.

 Mean % 

 MN-PCE

Cont

rol

10 

ml/k

g

 M

 F

 13

 6

 2.6

 1.2

 1.52

 0.84

0.26

0.12

TE

M

 

0.3 

mg/k

g

 M

 F

138

154

27.6

30.8

9.42

10.52

2.76*

3.08*

DG

HE

200 

mg/k

g

 M 

 F

12

9

2.4

1.8

0.89

1.30

0.24

0.18

DG

HE

400 

mg/k

g

 M

 F

11

4

2.2

0.8

1.79

1.10

0.22

0.08

30

DG

HE

640 

mg/k

g

 M

 F

6

6

1.2

1.2

1.30

0.84

0.12

0.12

contr

ol

10 

ml/k

g

 M

 F

17

7

3.4

1.4

1.14

0.55

0.34

0.14

48
DG

HE

200 

mg/k

g

 M

 F

9

8

1.8

1.6

1.30

0.89

0.18

0.16

DG

HE

400 

mg/k

g

 M

 F 

14

6

2.8

 1.2

1.64

1.30

0.28

0.12

DG

HE

640 

mg/k

g

 M

 F

12

1

2.4

0.2

1.67

0.45

0.24

0.02

contr

ol

10 

ml/k

g

 M

 F

11

7

2.2

1.4

2.28

0.89

0.22

0.14

DG

HE

200 

mg/k

g

 M

 F

10

18

2.0

3.6

 1.22

 2.51

0.20

0.36

DG

HE

400 

mg/k

g

 M 

 F

10

 7

2.0

1.8

 1.58

 0.96

0.20

0.18

72

DG

HE

640 

mg/k

g

 M 

 F

 9

 4

1.8

0.8

 1.79

 0.45

0.18

 0.08

The test was valid, as the positive control (TEM) produced a significant increase in micronuclei 

and the incidences of micronuclei in the vehicle controls were within an acceptable range for 

the system. 

7.8 Toxicity to reproduction 

7.8.1 Toxicity to reproduction 

Toxicity to reproduction.001 
UUID IUC5-7c0eb0d0-1ea8-49c3-a568-14c52527d987 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 17:15:02 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 

20

04 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study conducted following GLP. 

Data source 

Reference 

Reference 

type 

study report 

Author Carney EW, Zablotny CL, Andrus AK, Marable BR and Thomas J. Year 2004 

Title Diethylene glycol hexyl ether: A combined dietary toxicity study with the 

reproduction/developmental toxicityscreening test in CD rats. 

Bibliogra

phic 

source 

 

Testing 

laborator

y 

 Repo

rt no. 

 

Owner 

company 

The Dow Chemical Company 

Company 

study no. 

 Repo

rt 

date 

1004-0

2-17 

Materials and methods 

Test type 

screening 

Limit test 

yes 

Test guideline 

Qualifier according to 

Guideline OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the 

Reproduction / Developmental Toxicity Screening Test) 

Deviation

s 

 
GLP compliance 

yes 

Test materials 

Test material equivalent to submission substance identity 

no 

Test material identity 

Identifier CAS number 

Identity 112-59-4 

Identifier EC number 

Identity 203-988-3 

Identifier Common name 

Identity Diethylene glycol hexyl ether 

Details on test material 

Purity of the test material was 96.8%. 

Test animals 

Species 

rat 

Strain 

Sprague-Dawley 

Sex 

male/female 

Details on test animals and environmental conditions 

Animals: CD (Crl: CD(SD)IGS BR) rats were obtained from Charles River Laboratories, Inc. 

They were acclimated to the laboratory at least one week prior to treatment, and were 

approximately 8 weeks old at the beginning of the study. Animals were housed one per cage 

(prebreeding) or two per cage (one per sex during breeding) in stainless steel cages. Dams were 

housed one per cage (with litter) in plastic cages with ground corn cob nesting material from 

approximately gestation Day 19 through lactation, under a 12 hour light/dark photocycle. Room 

humidity and temperature were maintained at 40-70% and 22 +/- 1 degrees C. Room air was 

exchanged approximately 12-15 times/hour. Animals were allowed free access to food and 

municipal water. There were no contaminants in the feed or water that would interfere with the 

study. 

Administration / exposure 

Route of administration 

oral: feed 

Vehicle 

unchanged (no vehicle) 

Details on exposure 

Diet preparation: Diets were prepared by serially diluting a concentrated test material-fee 

mixture (pre-mix) with ground feed. Pre-mixes were prepared periodically throughout the study 

based on stability data. Diets were prepared weekly for two weeks prior to breeding. 

Concentrations of material in the diets were calculated from body weights and feed 

consumption data. To avoid potential overdosing during the breeding period, co-housed animals 

were provided with the female diet, which was of lower concentration. Following breeding. The 
male diet was prepared weekly until necropsy. During gestation and lactation, female were 

provided with the same concentrations as given during breeding. Representative samples from 

the test diets were analyzed at least once to ensure homogeneous distribution of test material at 

the lowest and highest concentrations. 

Details on mating procedure 

During breeding, each female was caged with a male from the same group until pregnancy 

occurred (presence of sperm in vaginal lavage sample evaluated daily or presence of a 

copulatory plug) or two weeks had elapsed. The day on which pregnancy was detected was 

considered lactation Day 0. If mating did not occur after two weeks, the animals were separated 

without further opportunity for mating. 

Analytical verification of doses or concentrations 

yes 

Details on analytical verification of doses or concentrations 

All test diets from the first mix were analyzed prior to dosing using gas chromatography-mass 

spectrometry (GC-MS), and an internal standard. Reference samples (one/dose/mix) were 

retained and stored in sealed vials.

Analyses of all test diets from the first mix of the main study revealed mean concentrations 

ranging form 92.5 to 104% of targeted concentrations. Analyses of the low dose female and 

high dose male diets indicated that the diets were homogeneous. Analyses confirmed that the 

10% premix was stable for 14 days and that the test diets were stable for 8 days at 

concentrations ranging from 0.120 to 0.359%, which encompass the range of dietary 

concentrations used in the study. 

Duration of treatment / exposure 

Females were dosed daily for two weeks prior to breeding, through breeding (two weeks), 

gestation (three weeks), and through postpartum Day 4. The males were dosed for two weeks 

prior to breeding and continuing through breeding (two weeks) up until necropsy.

Exposure period was 53 days. Duration of test: to post-partum Day 5 

Frequency of treatment 

Continuous (feed) 

Details on study schedule 

Study conduct: Groups of 12 male and 12 female CD rats randomly assigned to four treatment 

groups and were fed diets supplying concentrations of 0 (control), 100, 300 and 1000 

mg/kg/day. Females were dosed daily for two weeks prior to breeding, through breeding (two 

weeks), gestation (three weeks), and through postpartum Day 4. The males were dosed for two 

weeks prior to breeding and continuing through breeding (two weeks) up until necropsy. 

Females that delivered were necropsied on post-partum Day 5. Pups were euthanized on 

postnatal Day 4. 

Doses / concentrations 

0 (control), 100, 300 and 1000 mg/kg/day 

Basis nominal in diet 

No. of animals per sex per dose 

Groups of 12 male and 12 female CD rats per dose 

Control animals 

yes, plain diet 
Further details on study design 

A limit dose of 1000 mg/kg/day was selected as the high dose level based on data obtained in a 

preliminary range-finding study. The authors reported no-observable-effect-levels (NOELs) of 

300 mg/kg for general toxicity and 1000 mg/kg for reproductive and neurological effects 

Examinations 

Parental animals: Observations and examinations 

Cage-side examinations for skin, fur, mucous membranes, respiration, nervous system function 

(including tremors and convulsions), animal behavior, moribundity, mortality, availability of 

feed and water, and litter observations were conducted twice daily. Females were observed for 

signs of parturition on or about gestation Day 20. Females that delivered received clinical 

examinations on lactation Days 0, 1 and 4. Females that failed to mate or deliver were subjected 

to hand-held evaluations weekly. 

Detailed clinical observations were conducted on all rats before exposure and weekly 

throughout the study. Mated females underwent these examinations on gestation Day 0, 7, 14, 

and 20, and on lactation Day 3. The examination included cage-side, hand-held and open-filed 

observations. 

All rats were weighed prior to exposure, twice during the first week of the study and once 

during the second week. Male body weights continued to be recorded weekly throughout the 

study. Presumed pregnant females were weighed on gestation Day 0, 7, 14 and 20. Females that 

delivered litters were weighed on lactation Days 1 and 4. Females that failed to mate or deliver 

a litter were not weighed during the gestation or lactation phases.

Feed consumption was determined prior to exposure on twice during the first week of exposure. 

It was then determined once a week during the re-breeding phase. It was not determined during 

breeding. After breeding, it was determined once a week for males and on gestation Days 0, 7, 

14, and 20 for mated females. After parturition, feed consumption was measured on lactation 

Days 1 and 4. Feed consumption was not recorded for females that failed to mate or deliver a 

litter.

Functional tests (sensory evaluation, rectal temperature, grip performance and motor activity) 

were conducted prior to exposure and during the last week of the treatment period (lactation 

Day 4 for females).

Females were observed for signs of parturition beginning on or about gestation Day 20. The day 

of delivery was recorded as lactation Day 0. 

A timed urine volume (overnight, 16 hours) was obtained from all male rats (nonfasted) during 

the week prior to scheduled necropsy. Urine was analyzed for colour, appearance, specific 

gravity, volume, pH, bilirubin, glucose, proteins, ketones, blood and urobilinogen. Urine 

collected by manual compression of the bladder was pooled from each group and analyzed 

microscopically for microsediment.

On the day prior to the scheduled necropsy, all males and females in each group were fasted 

overnight. At necropsy, the animals were anesthetized with CO2 and blood was collected from 

the orbital sinus. Blood samples were not collected form females that failed to deliver. Blood 
was analyzed for hematocrit, hemoglobin concentration, red blood cell count, total and 

differential which blood cell counts, platelet count, red blood cell indices (mean corpuscular 

hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration), and 

prothrombin time. Serum was analyzed for alkaline phosphatase, alanine aminotransferase, 

aspartate aminotransferase, albumin, cholesterol, creatinine, sodium, potassium, phosphate, 

chloride, calcium, glucose, total bilirubin, total protein and urea nitrogen.

Males were terminated and necropsied on test Day 34. Females that delivered were terminated 

and necropsied on post-partum Day 5. Females that did not deliver were terminated and 

necropsied at least 24 days after the last day of the mating period. Pups were euthanized on 

postnatal Day 4. 

Estrous cyclicity (Parental animals) 

Mated females underwent these examinations on gestation Day 0, 7, 14, and 20, and on lactation 

Day 3. The examination included cage-side, hand-held and open-filed observations. 

Litter observations 

All litters were examined as soon as possible after delivery. The litter size on lactation Day 0, 

numbers of live and dead pups on postpartum Days 0, 1 and 4, clinical observations, and sex 

and weight of each pup on lactation Days 1 and 4 were recorded. Any pups dead or euthanized 

in moribund condition were examined grossly for external and visceral defects. 

Postmortem examinations (Parental animals) 

Post-mortem examinations included a gross necropsy of all adults (which included a gross 

examination of the brain, pituitary and eyes), with collection of organ weights (testes, 

epididymides, seminal vesicles with coagulating gland, prostate, ovaries, liver, kidneys, 

adrenals, thymus, spleen, brain, thyroid/parathyroid, and heart) and extensive histopathologic 

examination of tissues (adrenals, aorta, auditory sebaceous glands, bone (including joint), bone 

marrow, brain, cecum, cervix, coagulating glands, colon, cranial nerve, duodenum, 

epididymides, esophagus, eyes, gross lesions, heart, ileum, jejunum, kidneys, 

lacrimal/Harderian glands, larynx, liver, lungs, mammary gland, mediastinal lymph node and 

tissues, mesenteric lymph node and tissues, nasal tissues/pharynx, oral tissues, ovaries, 

oviducts, pancreas, parathyroid glands, peripheral nerve, pituitary, prostate, rectum, salivary 

glands, seminal vesicles, skeletal muscle, skin and subcutis, spinal cord, spleen, stomach, testes, 

thymus, thyroid gland, tongue, trachea, urinary bladder, uterus and vagina) from control and 

high dose animals. The histopathological examination of the testes included a qualitative 

assessment of states of spermatogenesis. The uteri of all females were examined and the number 

of implantation sites recorded. The uteri of females that did not deliver were stained with a 10% 

solution of sodium sulfide to verify pregnancy status. 

Statistics 

Statistical analyses: Parental body weights, gestation and lactation body weight gains, litter 

mean body weights, feed consumption, urine volume, urine specific gravity, coagulation, 

clinical chemistry data, hematological data and organ weights were first evaluated by Bartlett's 

test for homogeneity. Parametric and nonparametric data were then analyzed by the appropriate 

analysis of variance (ANOVA). If the ANOVA was significant at alpha = 0.05, a Dunnett's test 

(alpha = 0.05) or the Wilcoxon Rank Sum test with Bonferroni's correction was performed. 

Feed consumption data were excluded if the feed was spilled or scratched. 

Gestation length, average time to mating, and litter size were analyzed using a non-parametric 
ANOVA. If the ANOVA was significant, the Wilcoxon Rank Sum test with Bonferroni's 

correction was performed. Statistical outliers (alpha = 0.02) were identified and excluded from 

the analysis only for documented, scientifically sound reasons. Mating, conception, fertility and 

gestation indices were analyzed by the Fisher exact probability test, with Bonferroni's 

correction. The neonatal sex ratio was analyzed using the binomial distribution test. Genders of 

pups found dead were included in the ratio. Survival indices, post-implantation loss and other 

neonatal incidence data were analyzed using the litter as the experimental unit by the censored 

Wilcoxon test (alpha = 0.05). Females failing to deliver a litter were excluded from analyses of 

gestation and lactation body weight, feed consumption and organ weights. Detailed clinical 

observation and sensory evaluation scores were analyzed using a z-test of proportions (at alpha 

= 0.05). Rectal temperature and grip performance were analyzed by an analysis of covariance. 

Motor activity was analyzed by a repeated measure design. 

Results and discussions 

Effect levels 

Endp

oint 

NOAEL 

Gener

ation 

P 

Sex female 

Effect 

level 

300 mg/kg diet 

Basis 

for 

effect 

level / 

Rema

rks 

Females given 1000 mg/kg/day had treatment-related increases in serum ALT and ALP 

activities, along with increases in relative liver weight. These effects corresponded with 

treatment-related histopathologic changes in the liver that consisted of very slight 

panlobular hepatocyte hypertrophy. These effects were not observed at 300 mg/kg 

bw/day

NOAEL F1 Offspr.: 1000 mg/kg bw (the highest dose tested) 

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) 

yes 

Reproductive function: sperm measures (parental animals) 

yes 

Reproductive performance (parental animals) 

yes 

Organ weights (parental animals) 

yes 

Gross pathology (parental animals) 

yes 

Histopathology (parental animals) 
yes 

Details on results (parental animals) 

Dietary administration of diethylene glycol hexyl ether (DGHE) to CD rats had no effect on 

detailed clinical or sensory observations. All animals survived to termination. There was a slight 

treatment-related decrease in body weights of males and females given 1000 mg/kg/day. 

Decreased maternal body weights persisted throughout the gestation and lactation phases of the 

study. Decreased feed consumption was noted in high dose males and females during the 

prebreeding period and in high dose females during gestation.

Females given 1000 mg/kg/day had treatment-related increases in serum ALT and ALP 

activities, along with increases in relative liver weight. These effects corresponded with 

treatment-related histopathologic changes in the liver that consisted of very slight panlobular 

hepatocyte hypertrophy. Males given 1000 mg/kg/day had treatment-related increases in 

relative liver weight, which corresponded with the histological alteration of very slight 

periportal hepatocyte hypertrophy. At 1000 mg/kg/day, other findings of lesser significance 

included slightly increased blood urea nitrogen and decreased absolute thymus weights in 

females, and decreased urine pH and increased relative kidney weights in males. Additional 

histopathologic findings of minor toxicological significance at 1000 mg/kg/day included very 

slight diffuse acinar hypertrophy of the submandibular salivary gland in males, and very slight 

atrophy of the mesenteric adipose tissue in females.

There were no adverse effects of DGHE on neurological or reproductive function (time to 

mating, female or male mating index, female or male conception index, female or male fertility 

index, gestation index, gestation survival index, post-implantation loss), or prenatal/early 

neonatal growth,survival, or external condition of the offspring. There were no adverse gross or 

histopathologic findings in the reproductive organs of high dose males or females.

Based on these results, the no-observed-adverse-effect level (NOAEL) for general toxicity was 

300 mg/kg/day. The NOAEL for reproductive and neurological effects was 1000 mg/kg/day, the 

highest dose level tested.

Observations: offspring 

Viability (offspring) 

yes 

Clinical signs (offspring) 

yes 

Body weight (offspring) 

yes 

Sexual maturation (offspring) 

no data 

Organ weights (offspring) 

no data 

Gross pathology (offspring) 

no data 

Histopathology (offspring) 

no data 

7.8.2 Developmental toxicity / teratogenicity 
Developmental toxicity / teratogenicity.001 

UUID IUC5-e3d60116-ceb3-4db1-85ac-50d2f93f16f4 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-11 17:24:16 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 

20

04 

Reliablility 1 (reliable without restriction) 

Rationale for 

reliability 

Guideline study following GLP. 

Data source 

Reference 

Reference 

type 

study report 

Author Carney EW, Zablotny CL, Andrus AK, Marable BR and Thomas J. Year 2004 

Title Diethylene glycol hexyl ether: A combined dietary toxicity study with the 

reproduction/developmental toxicityscreening test in CD rats. 

Bibliogra

phic 

source 

 

Testing 

laborator

y 

 Repo

rt no. 

 

Owner 

company 

The Dow Chemical Company 

Company 

study no. 

 Repo

rt 

date 

1004-0

2-17 

Materials and methods 

Limit test 

yes 

Test materials 

Test material equivalent to submission substance identity 

yes 

Test material identity 

Identifier CAS number 

Identity 25961-89-1 
Identifier EC number 

Identity 247-372-2 

Identifier IUPAC name 

Identity 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Developmental toxicity / teratogenicity Leber TGBE 1990.001 

UUID IUC5-bb9a3df3-3f6b-4afe-9586-f4175e5d49be 

Dossier UUID 0 

Author RodB / Boatman Toxicology Consulting LLC / Spencerport / United 

States of America 

Date 2009-02-13 13:01:39 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 

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.

Reference substance: 2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol 

UUID ECB5-47217680-b2fb-4774-a5e8-1314008b3ea6 

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 2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol 

EC inventory 

EC number 247-372-2 CAS number 25961-89-1 

EC name 2-[2-[2-(hexyloxy)ethoxy]ethoxy]ethanol 

Molecular formula C12H26O4 

Reference substance information 

CAS information 

CAS number 25961-89-1 

IUPAC name 

IUPAC name 2-{2-[2-(hexyloxy)ethoxy]ethoxy}ethanol 

Synonyms 

Name Ethanol, 2- 2- 2-(hexyloxy)ethoxy ethoxy - 

Name Ethanol, 2-[2-[2-(hexyloxy)ethoxy]ethoxy]- 

 OECD Category: High boiling EGE's

USEPA Category: Ethylene Glycol Ethers;Neutral Organics;Nonionic Surfactants 

Molecular and structural information 

Molecular formula C12H26O4 

Molecular weight range 234.3324 

SMILES notation CCCCCCOCCOCCOCCO 

InChI InChI=1/C12H26O4/c1-2-3-4-5-7-14-9-11-16-12-10-15-8-6-1

3/h13H,2-12H2,1H3 

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