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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Data on the components of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol, triethylene glycol (TEG) and tetraethylene glycol (TTEG), and on a similar ethylene glycol mixture, Crude Penta, containing 55.32% w/w TTEG and 29.82% w/w pentaethylene glycol, were used to assess its irritation potential.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Principles of method if other than guideline:
Draize test
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
6
Details on study design:
Male and female animals are dosed with 0.5 ml. The dose is applied to the clipped, intact skin under a gauze patch and is loosely covered with impervious sheeting. The test material is applied to each of 6 rabbits, which are restrained for the 4 h contact period. Excess sample is removed after contact. Skin reaction is scored by the method of Draize at 1 hour, 1 day, 2 days, 3 days and 7 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 5 hr, 1, 2, 3, 7 days
Score:
0
Max. score:
0
Reversibility:
other: none observed
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 5 hr, 1, 2, 3, 7 days
Score:
0
Max. score:
0
Reversibility:
other: none observed
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No erythema & eschar or edema in any animal at 5 hrs or 1, 2, 3, or 7 days.
Other effects:
None observed.

No erythema or eschar formation, no edema formation. Other irritation or effects: none

Interpretation of results:
GHS criteria not met
Conclusions:
Skin Irritation, Rabbit (4-hr occluded): No erythema, edema or other reactions on any of 6 rabbits from 0.5 ml TEG
Executive summary:

Skin Irritation, Rabbit (4-hr occluded): No erythema, edema or other reactions on any of 6 rabbits from 0.5 ml TEG

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
prior to or in 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented irritation study in human volunteers.
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Principles of method if other than guideline:
Human Patch Test Study
GLP compliance:
no
Species:
human
Details on test animals or test system and environmental conditions:
12 males and 91 females were used. Participants ranged in age from 18-74 years old. Participants by age range: age 18-25: 7, age 26-35: 23, age 36-45: 31; age 46-55: 15, age 56-65: 18, over 65: 9. Participants by sex: 12 males, 91 females. Participants by race: Caucasoid: 27, Negroid: 1, Hispanic 72, Mongoloid: 0, Asian: 0, Other: 3.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.2 ml of each test substance
Duration of treatment / exposure:
48 hour
Observation period:
At the end of the 48 hour exposure period and 24 hours later.
Number of animals:
12 male, 91 female
Details on study design:
0.2 ml test material applied to the infrascapular area of the back, either to the right or left of the midline.

Occlusive patch covering application site for 48 hours was non-porous film adhesive bandage with a 2cm x 2cm Webril affixed with Scanpor tape as needed.

Grading scale for each individual: No reaction = 0; doubtful response, barely perceptible erythema, only slightly different from surrounding normal skin = 0.5; definite erythema, no edema = 1; definite erythema, minimal or doubtful edema, = 1.5; definite erythema, definite edema = 2.0; definite erythema, definite edema and vesiculation = 3.0. Grading scale overall: irritancy score (I) equal to sum of numerical equivalents, normalized to 100 subjects. I = 0 interpreted as no irritation. 0 50 interpreted as evidence of irritation. 
The strongest reaction score (at patch removal or 24 hours following patch removal) was used in calculating the irritancy score.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: Not stated
Score:
35.9
Reversibility:
no data
Remarks on result:
other: Results are evidence of minimal irritation to humans from TEG
Irritant / corrosive response data:
Primary irritation index (score) for TEG: 35.9—minimal irritation
Other effects:
No additional information available.

Primary irritation index (score) for TEG: 35.9—minimal irritation

Interpretation of results:
other: slightly irritating
Conclusions:
Primary irritation index (score) for TEG: 35.9—minimal irritation
Executive summary:

The dermal irritation of triethylene glycol was examined in humans. A group of 103 humans received 0.2 ml of test material applied occlusively to the infrascapular area of the back, either to the right or left of the midline for 48 hours. Humans were examined at the end of the 48 hour period and 24 hours later. The primary irritation index was 35.9, indicating minimal irritation, for TEG.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
prior to or in 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented irritation study in human volunteers.
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Principles of method if other than guideline:
Human Patch Test Study
GLP compliance:
no
Species:
human
Details on test animals or test system and environmental conditions:
12 males and 91 females were used. Participants ranged in age from 18-74 years old. Participants by age range: age 18-25: 7, age 26-35: 23, age 36-45: 31; age 46-55: 15, age 56-65: 18, over 65: 9. Participants by sex: 12 males, 91 females. Participants by race: Caucasoid: 27, Negroid: 1, Hispanic 72, Mongoloid: 0, Asian: 0, Other: 3.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.2 ml of each test substance
Duration of treatment / exposure:
48 hour
Observation period:
At the end of the 48 hour exposure period and 24 hours later.
Number of animals:
12 male, 91 female
Details on study design:
0.2 ml test material applied to the infrascapular area of the back, either to the right or left of the midline.

Occlusive patch covering application site for 48 hours was non-porous film adhesive bandage with a 2cm x 2cm Webril affixed with Scanpor tape as needed.

Grading scale for each individual: No reaction = 0; doubtful response, barely perceptible erythema, only slightly different from surrounding normal skin = 0.5; definite erythema, no edema = 1; definite erythema, minimal or doubtful edema, = 1.5; definite erythema, definite edema = 2.0; definite erythema, definite edema and vesiculation = 3.0. Grading scale overall: irritancy score (I) equal to sum of numerical equivalents, normalized to 100 subjects. I = 0 interpreted as no irritation. 0 50 interpreted as evidence of irritation. 
The strongest reaction score (at patch removal or 24 hours following patch removal) was used in calculating the irritancy score.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: Not stated
Score:
15.5
Reversibility:
no data
Remarks on result:
other: Results are evidence of minimal irritation to humans from TTEG
Irritant / corrosive response data:
Primary irritation index (score) for TTEG: 15.5—minimal irritation
Other effects:
No additional information available.

Primary irritation index (score) for TTEG: 15.5—minimal irritation

Interpretation of results:
other: slightly irritating
Conclusions:
Primary irritation index (score) for TTEG: 15.5—minimal irritation
Executive summary:

The dermal irritation of tetraethylene glycol was examined in humans. A group of 103 humans received 0.2 ml of test material applied occlusively to the infrascapular area of the back, either to the right or left of the midline for 48 hours. Humans were examined at the end of the 48 hour period and 24 hours later. The primary irritation index was 15.5, indicating minimal irritation, for TTEG.

Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
Not specified but between 9 Dec 1985 and 6 April 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The report does not specify about GLP/Guideline but sufficient data is available for interpretation of results
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Male or female rabbits may be used. The animals are maintained on appropriate commercial diet and municipal water.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hr
Observation period:
10 days.
Number of animals:
6
Details on study design:
Male or female New Zealand White rabbits are dosed with 0.5 ml. The dose is applied to the clipped, intact skin under a gauze patch and is loosely covered with impervious sheeting. The test material is applied to each of 6 rabbits, which are restrained for the 4-hr contact period. Excess sample is removed after contact. Skin reaction is scored, by the method of Draize, at one hour, one day, 2 days, 3 days, 7 days, and 10 days after dosing.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 hr post dosing
Score:
0
Max. score:
0
Remarks on result:
other: same score observed after 1, 2, 3, 7 and 10 days.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 hr post dosing
Score:
0
Max. score:
0
Remarks on result:
other: same score observed after 1, 2, 3, 7 and 10 days.
Irritant / corrosive response data:
There was no erythema, eschar and edema observed in any of the rabbits exposed for 4 hours for tetraethylene glycol.
Other effects:
There were no other effects noted in rabbits exposed for 4 hours for tetraethylene glycol.

No additional information available.

Interpretation of results:
GHS criteria not met
Conclusions:
A 4-hour application of tetraethylene glycol to covered rabbit skin resulted in no irritation.
Executive summary:

The effects of 4 hour dermal exposure of tetraethylene glycol to rabbit skin was examined. There was no irritation or any other effects noted in rabbits dermally exposed to tetraethylene glycol for 4 hours.

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
March 15, 1994 - March 22, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
This substance is another reaction mass of ethylene glycols that is similar but not identical to the Reaction mass of 2,2’-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol. Because of the same constituents, it is considered appropriate to read across.
Reason / purpose for cross-reference:
read-across source
Principles of method if other than guideline:
Rabbits were exposed to 0.5 ml of undiluted Crude Penta for 4 hours under occluded conditions and observed for skin irritation at 1, 24, 48, 72 hours, and 7 days after the end of the contact period.
GLP compliance:
yes
Specific details on test material used for the study:
A 1-quart container of Crude Penta (gross weight: 1418.2 g), Lot No. TS-2561109, CAS No. 25322-68-3, was received on November 11, 1993, from UCC, Texas City, TX, and assigned BRRC Sample No. 56-411. The test substance was a black, slightly viscous liquid. It was stored at room temperature.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Male and female New Zealand White rabbits were received from HRP, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age), The females were nulliparous and nonpregnant.

Animals were housed in Room 122 from arrival to termination of the study. Periodically, a clinical veterinarian examined rabbits housed in Room 122 for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing.

The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm). DACB (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermographo Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co,, Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-708, Any minor exceptions to these specified ranges can be found in the raw data.

Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier and Chester Lab and RJ Lee Group, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAP* PROLAB* Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.

The animals were acclimated for at least 5 days before dosing. Clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights, were rejected for use on this study.

The animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Only rabbits demonstrating weight gain were used. Rabbits weighing between 2.0 and 3.0 kg (approximately 13 to 18 weeks of age) were considered suitable for the definitive tests. As necessary, rabbits weighing up to 3.5 kg were used for irritancy testing. The body weight range (on day of dosing) for males was 2.5 to 3.3 kg. For females, the body weight range was 2.3 to 3.3 kg. A total of 10 males and 10 females were used for the rabbit tests.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of undiluted test material
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3/sex
Details on study design:
The fur was removed from the dorsal area of the trunk of each rabbit using veterinary clippers a few days before dosing and the dose area was trimmed carefully (avoiding skin abrasion), as necessary, up to the day before application of the test substance. A 1-inch square gauze patch was placed over 1 intact (nonabraded) site/rabbit. A dose of 0.5 ml of the undiluted test substance was applied under the patch and the patch was then secured by adhesive tape. Polyethylene sheeting was placed loosely around the trunk and secured, The animal was placed in a restraining device for the 4-hour contact period after which the coverings and as much excess test substance as possible were removed.

The test substance was applied to each of 6 rabbits (3 males, 3 females), Readings were made at 1, 24, 48 and 72 hours and at 7 days after the end of the contact period according to Draize (1959). All rabbits were sacrificed at 7 days (ear vein injection using Euthanasia-6 Solution).
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Very slight erythema (score of 1) observed in 6 of 6 rabbits at 1 hour after exposure. Very slight edema (score of 1) observed in 2 of 6 rabbits at 1 hour after exposure. No erythema or edema (score of 0) at 24, 48, 72 hours, or 7 days in any rabbits. no other irritation or effects observed in any rabbits.

Table 1: Individual Animal Irritaton Scores

 

94-429 (M)

94-441 (M)

94-551 (M)

94-445 (F)

94-576 (F)

94-577 (F)

Mean Score (24, 48, 72 hr)

Erythema/Eschar

0

0

0

0

0

0

Edema

0

0

0

0

0

0

Other Irritation or Effects

None

None

None

None

None

None
Interpretation of results:
GHS criteria not met
Conclusions:
Application of 0.5 ml of undiluted Crude Penta to covered rabbit skin for a 4-hour contact period produced minor erythema on 6 of 6 rabbits within 1 hr after the end of the contact period. Minor edema was also observed on 2 rabbits by 1 hr (after the end of contact). Both erythema and edema subsided within 24 hours. There was no irritation apparent on any animal from 24 hours through the end of the 7-day observation period.
Executive summary:

Application of 0.5 ml of undiluted Crude Penta to covered rabbit skin for a 4-hour contact period produced minor erythema on 6 of 6 rabbits within 1 hr after the end of the contact period. Minor edema was also observed on 2 rabbits by 1 hr (after the end of contact). Both erythema and edema subsided within 24 hours. There was no irritation apparent on any animal from 24 hours through the end of the 7-day observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Draize test
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
0
Remarks on result:
other: Four animals exhibited a moderate to substantial amount of ocular discharge. By 24 hours, all 6 eyes had a normal appearance.

No corneal injury in any of 6 eyes, iritis in 6, minor (transient) conjunctival irritation in 6 (with moderate to substantial discharge in 5) with 0.1 ml; all healed at 24 hours.

Summary of eye scores:

     Observation times  1 h  4 h  24 h  48 h  72 h  7 days
   Animal No.  1  2  3  4  5  6
 Cornea  Opacity  Range  All 0  All 0  All 0  All 0  All 0  All 0
     Mean  0.0  0.0  0.0  0.0  0.0  0.0
   Area  Range  All 0  All 0  All 0  All 0  All 0  All 0
     Mean  0.0  0.0  0.0  0.0  0.0  0.0
 Iris  Injury  Range  All 1  0 - 1  All 0  All 0  All 0  All 0
     Mean  1.0  0.2  0.0  0.0  0.0  0.0
 Conjunctivae  Redness  Range All 1  All 1  All 0  All 0  All 0  All 0
     Mean  1.0  1.0  0.0  0.0  0.0  0.0
   Chemosis  Range  0 - 1  All 1  All 0  All 0  All 0  All 0
     Mean  0.8  1.0  0.0  0.0  0.0  0.0
   Discharge  Range  1 - 3  All 1  All 0  All 0  All 0  All 0
     Mean  2.2  1.0  0.0  0.0  0.0  0.0
Interpretation of results:
GHS criteria not met
Conclusions:
No corneal injury in any of 6 eyes, iritis in 6, minor (transient) conjunctival irritation in 6 (with moderate to substantial discharge in 5) with 0.1 ml; all healed at 24 hours. TEG is not irritating to the rabbit eye.
Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
Not specified but between 9 Dec 1985 and 6 April 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The report does not specify about GLP/Guideline but sufficient data is available for interpretation of results
Justification for type of information:
Read across is based on the category approach. Please refer to attached category document.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No additional information available.
Vehicle:
unchanged (no vehicle)
Controls:
other: Yes, other eye
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
Since fluorescein is used 24 hours after dosing, the eye is washed at that time. Thus duration is for 24 hours
Observation period (in vivo):
Up to 7 days.
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
Male or female New Zealand White rabbits are dosed with volumes of 0.1 ml. The dose is instilled into the lower conjunctival sac of one eye per animal or is placed directly on the eye. The eyelids are held together for one second. Six eyes are dosed per test volume. The eyes are scored at one hour, approximately 4 hours, one day, 2 days, 3 days and 7 days after dosing. Fluorescein (2%) staining is used to determine corneal injury before dosing and at readings after one day.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 hr
Score:
0
Max. score:
0
Remarks on result:
other: Following application of 0.1 ml test material into the eye of rabbits, minor, transient irritation which did not involve the cornea was observed..
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 hr
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 4 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score represents mean discharge value. See Table 1 for other conjunctival endpoints examined.
Irritant / corrosive response data:
In 6 rabbit eyes, 0.1 ml of sample produced no corneal injury. Iritis developed in all 2 eyes by one hour but did not persist at 4 hours. Minor conjunctival irritation was observed in all 6 eyes. After 24 hours, there was no ocular irritation evident in any rabbit.
Other effects:
No additional information available.

Table 1 Primary Eve Irritation-Rabbit

                  Observation Times, Mean (Range)
   1 hr  4 hr  24 hr  48 hr  72 hr  7 days
 Cornea - Opacity

 0.0

(All 0)

  0.0

(All 0)

  0.0

(All 0)

 

0.0

(All 0)

 

  0.0

(All 0)

0.0

(All 0)

 - Area

  0.0

(All 0)

  0.0

(All 0)

 

0.0

(All 0)

 

  0.0

(All 0)

 

0.0

(All 0)

 

 

0.0

(All 0)

 

 Iris - Injury

0.3

(0 to 1)

0.0

(All 0)

0.0

(All 0)

0.0

(All 0)

0.0

(All 0)

 0.0

(All 0)

 Conjunctivae - Redness

 1.0

(All 1)

 

1.0

(All 1)

 

0.0

(All 0) 

0.0

(All 0) 

0.0

(All 0) 

 

0.0

(All 0) 

 

 - Chemosis

 0.7

(0 to 2)

 0.3

(0 to 1)

 0.0

(All 0)

0.0

(All 0) 

 

0.0

(All 0) 

 

0.0

(All 0) 

 - Discharge

 1.7

(1 to 3)

 1.0

(All 1)

 0.0

(All 0)

 

0.0

(All 0) 

 

0.0

(All 0) 

0.0

(All 0) 
Interpretation of results:
GHS criteria not met
Conclusions:
Instillation of 0.1 ml of sample into rabbit eyes produced minor, transient irritation which did not involve the cornea.
Executive summary:

The eye irritation potential of tetraethylene glycol was examined in rabbits. Instillation of 0.1 ml of sample into rabbit eyes produced minor, transient irritation which did not involve the cornea.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
February 1, 1994 - February 11, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
This substance is another reaction mass of ethylene glycols that is similar but not identical to the Reaction mass of 2,2’-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol. Because of the same constituents, it is considered appropriate to read across.
Reason / purpose for cross-reference:
read-across source
Principles of method if other than guideline:
One eye of each of 4 rabbits was dosed with 0.1 ml of undiluted Crude Penta. Eyes were examined at 1, 24, 48, 72 hours, and at 7 and 10 days. Scoring was performed according to Draize (1959).
GLP compliance:
yes
Specific details on test material used for the study:
A 1-quart container of Crude Penta (gross weight: 1418.2 g), Lot No. TS-2561109, CAS No. 25322-68-3, was received on November 11, 1993, from UCC, Texas City, TX, and assigned BRRC Sample No. 56-411. The test substance was a black, slightly viscous liquid. It was stored at room temperature.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male and female New Zealand White rabbits were received from HRP, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age), The females were nulliparous and nonpregnant.

Animals were housed in Room 122 from arrival to termination of the study. Periodically, a clinical veterinarian examined rabbits housed in Room 122 for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing.

The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm). DACB (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermographo Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co,, Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-708, Any minor exceptions to these specified ranges can be found in the raw data.

Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier and Chester Lab and RJ Lee Group, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAP* PROLAB* Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.

The animals were acclimated for at least 5 days before dosing. Clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights, were rejected for use on this study.

The animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Only rabbits demonstrating weight gain were used. Rabbits weighing between 2.0 and 3.0 kg (approximately 13 to 18 weeks of age) were considered suitable for the definitive tests. As necessary, rabbits weighing up to 3.5 kg were used for irritancy testing. The body weight range (on day of dosing) for males was 2.5 to 3.3 kg. For females, the body weight range was 2.3 to 3.3 kg. A total of 10 males and 10 females were used for the rabbit tests.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml of undiluted test material
Duration of treatment / exposure:
No washing
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
2/sex
Details on study design:
Both eyes of each rabbit to be dosed were examined, using fluorescein stain, within 24 hours before application. If any preexisting eye injury was apparent, the rabbit was rejected for use in the test. The test substance (as received) was applied to 1 eye/rabbit. The other eye of each animal served as the control.

A total of 4 rabbit eyes (2 males and 2 females) were each dosed with 0.1 ml of the undiluted test substance. This dose was instilled into the lower conjunctival sac. Eye examinations were made at 1, 24, 48 and 72 hours and at 7 and 10 days following instillation. Fluorescein staining was performed at 1 day and each subsequent examination day. Grading and scoring were performed by the system of Draize (1959). All rabbits were sacrificed by ear vein injection (Euthanasia-6 Solution) at 10 days.
Irritation parameter:
overall irritation score
Remarks:
Draize Weighted Score
Basis:
mean
Time point:
24/48/72 h
Score:
3.665
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
Iritis was observed in 1 rabbit within 1 hour but subsided by 24 hours. Minor conjunctival redness and swelling were apparent in all 4 rabbits within 1 hour, At this time, all 4 rabbits also had a substantial ocular discharge. Within 72 hours, 3 eyes had a normal appearance; only minor conjunctival redness persisted in the remaining dosed eye. In addition to redness, minor conjunctival chemosis and discharge were again apparent in the affected eye at 7 days. All eyes healed within 10 days.

Table 1: Individual Animal Irritation Scores (24, 48, 72 hr)

 

94-281 (M)

94-282 (M)

93-10675 (F)

94-273 (F)

Mean Score (24, 48, 72 hr)

Cornea

Opacity

0

0

0

0

Area

0

0

0

0

Iris

Inflammation

0

0

0

0

Conjunctivae

Redness

0.67

0.67

0.67

1

Chemosis

0.33

0.67

0.33

0.67

Discharge

0.67

0.67

0.67

0.67

Fluorescein Examination

0%

0%

0%

0%
Interpretation of results:
GHS criteria not met
Conclusions:
A dose of 0.1 ml of Crude Penta (as received) instilled into rabbit eyes did not produce corneal injury in any of 4 rabbits. Iritis was observed in 1 rabbit within 1 hour but subsided by 24 hours. Minor conjunctival redness and swelling were apparent in all 4 rabbits within 1 hour, At this time, all 4 rabbits also had a substantial ocular discharge. Within 72 hours, 3 eyes had a normal appearance; only minor conjunctival redness persisted in the remaining dosed eye. In addition to redness, minor conjunctival chemosis and discharge were again apparent in the affected eye at 7 days. All eyes healed within 10 days.
Executive summary:

A dose of 0.1 ml of Crude Penta (as received) instilled into rabbit eyes did not produce corneal injury in any of 4 rabbits. Iritis was observed in 1 rabbit within 1 hour but subsided by 24 hours. Minor conjunctival redness and swelling were apparent in all 4 rabbits within 1 hour, At this time, all 4 rabbits also had a substantial ocular discharge. Within 72 hours, 3 eyes had a normal appearance; only minor conjunctival redness persisted in the remaining dosed eye. In addition to redness, minor conjunctival chemosis and discharge were again apparent in the affected eye at 7 days. All eyes healed within 10 days.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation

The dermal irritation of TEG, TTEG, and Crude Penta was examined in rabbits, and TEG and TTEG were also assessed in humans. In three weight of evidence dermal irritation/Draize test studies in rabbits, TEG (Bushy Run Research Center, 1990), TTEG (Bushy Run Research Center, 1986), and Crude Penta (Bushy Run Research Center, 1994) produced no irritation (scores of 0.0) at 24, 48, and 72 hours from exposure. Available supporting studies in rabbits show similar negative results for TTEG induced skin irritation.

In a weight of evidence study in humans, a single 48 hour occlusive exposure to TEG or TTEG produced slight skin irritation at the end of the exposure period and at 24 hours from exposure (TKL Research, Inc., 1989a). The primary irritation indices for TEG and TTEG were 35.9 and 15.5, respectively, both indicative of minimal irritation. Additionally, a 21 day cumulative irritation patch test of TEG and TTEG in humans did not produce evidence of significant irritation (TKL Research, Inc., 1989b). Finally, no evidence of skin irritation potential was observed when TEG was tested in the in vitro EpiSkin model (Li et al., 2017). Based on these data, skin irritation is not expected for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Eye Irritation

The eye irritation potential of TEG, TTEG, and Crude Penta was examined in rabbits. In two weight of evidence studies, minor conjunctival irritation and/or iritis was observed initially in response to 0.1 ml of TEG (Bushy Run Research Center, 1990) or TTEG (Bushy Run Research Center, 1986); however, in both cases no eye irritation was observed by 24 hours. The available supporting studies also showed no eye irritation in rabbits after exposure to TTEG. According to GHS classification, TEG and TTEG are not irritating as both substances produced no irritation at 24, 48, or 72 hours after exposure.

Minor conjunctival irritation and/or iritis was also observed in rabbit eyes in response to Crude Penta in a weight of evidence study by Bushy Run Research Center (UCC, 1994). This resolved by 72 hours in 3 of 4 rabbits and by 10 days in the 4thrabbit. The observed irritation was below levels requiring classification according to GHS.

Based on data for TEG, TTEG, and Crude Penta, the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol is not expected to produce significant eye irritation.

Respiratory Irritation

Acute and sensory inhalation studies have been used to assess respiratory irritation of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol. Acute inhalation toxicity studies and 9 day repeated exposure inhalation toxicity studies with TEG suggest that respiratory irritation does not occur as a result of exposure to TEG, TTEG, or Crude Penta, though minor irritation was noted on occasion in TEG and TTEG inhalation studies. Some respiratory irritation was noted as a result of exposure to high temperature vapors not typically found with uses of this substance.

For example, in an acute inhalation study with rats exposed to saturated vapor of TTEG heated to 110ºC for 7 hours, lung congestion and hemorrhage was observed after 1 to 3 days (Dow, 1961). In another Dow study (1967), rats exposed to saturated vapor of TTEG heated to approximately 200ºC for 1 or 2 hours showed signs of mild irritation and occasional hemorrhagic pin-points were also noted in the lungs of several animals. However, exposure to similarly heated TTEG or the reaction mixture is not expected in typical use scenarios.

Additionally, periocular and perinasal irritation were observed in males and female Sprague-Dawley rats exposed to 2000 mg/m3 TEG and in males exposed to 500 mg/m3 TEG in a 9 day whole body inhalation study by Ballantyne et al. (2006). However, no irritation was observed in a 9 day nose-only inhalation study by Ballantyne et al. (2006) at doses up to and including 1036 mg/m3 (Central Toxicology Laboratory, 2001).

Sensory irritation from exposure to TEG was examined by Bushy Run Research Center (UCC, 1994). Groups of 4 male Swiss Webster mice were exposed head only to an aerosol of TEG at measured concentrations of 3.601, 4.545, 4.744, and 5.099 mg/L. The mean respiratory rate decreases were 15.2, 27.3, 58.1, and 43.7 for these groups, respectively. Based on the concentration-response curve, the RD50 for TEG was determined to be 5.14 mg/L.

These data suggest a low potential for respiratory or sensory irritation for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Justification for classification or non-classification

Skin Irritation

TEG and TTEG produce up to only minimal skin irritation in humans while no irritation was observed in animals exposed TEG, TTEG, and Crude Penta. Available data show that criteria for classification as skin irritants according to GHS is not met for TEG, TTEG, or Crude Penta. Based on these components and similar materials, skin irritation is not expected for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol and classification is not warranted.

Eye Irritation

None to very slight irritation of rabbit eyes was observed in response to TEG, TTEG, or Crude Penta instillation at 24, 48, or 72 hours; therefore, criteria for classification according to GHS was not met. Based on these components and similar materials, eye irritation of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol is not expected and classification is not warranted.

Respiratory irritation

No studies specifically addressing respiratory irritation are available for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol. Available data from acute and repeated dose inhalation studies on TEG, TTEG, and Crude Penta suggest at most minimal irritation. Similarly, an available sensory irritation study for TEG suggests low potential for sensory irritation. Therefore, respiratory irritation for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol is not expected and classification for STOT-SE for respiratory irritation is not warranted.