3,6,9-trioxaundecane-1,11-diol

Endpoint summary

Description of key information

The dermal irritation of tetraethylene glycol was examined in humans and in animals.  In rabbit, there was no dermal irritation observed in key studies. A group of 103 humans received 0.2 ml applied occlusively to the infrascapular area of the back, either to the right or left of the midline for 48 hours. Subjects were examined at the end of the 48 hour period and 24 hours later. The primary irritation index was 15.5, indicating minimal irritation. 
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. Conjunctiva score was 1.7 one hour after dosing and was reversible within 24 hours in one study, in a second study, conjunctival irritation resolved within 8 days (no evidence that the animals were examined between 24 hours and 8 days). 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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

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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

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 conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

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

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:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

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 conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The dermal irritation of tetraethylene glycol was examined in humans and in animals. In the rabbit, there was no dermal irritation observed (scores of 0.0) in key studies. A group of 103 humans received 0.2 ml of TTEG that was applied occlusively to the infrascapular area of the back, either to the right or left of the midline for 48 hours. Subjects were examined at the end of the 48 hour period and 24 hours later. The primary irritation index was 15.5 out of 118, indicating minimal irritation.

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. Conjunctival irritation resolved within 24 hours in one study, in a second study, within 8 days (no evidence that the animals were examined between 24 hours and 8 days).

Although dermal and eye irritation was noticed, the effects were very minimal.

Justification for selection of skin irritation / corrosion endpoint:
Well conducted study with enough experimental detail and in accordance to guidelines.

Justification for selection of eye irritation endpoint:
Well conducted study with enough experimental detail and in accordance to guidelines.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

As both dermal and eye irritation effects were minimal, if any, classification according to GHS and the Directive 67/548/EEC (DSD) regarding skin or eye irritation is not warranted.