2-ethylhexane-1,3-diol

Endpoint summary

Description of key information

Undiluted EHD is a mild skin irritant and causes severe eye irritation in rabbits.  When dermally tested in human volunteers under exaggerated conditions, undiluted EHD resulted in barely perceptible skin irritation.  The substance has a long history of safe use as a dermal human insect repellent.   It is considered potentially hazardous to the eyes for occupational exposure.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data obtained from a peer-reviewed publication

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Primary Cutaneuous irritaion study was conducted with a 4 hr occlusive contact time.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
3 male and 3 female rabbits
Dorsal skin was clipped prior to exposure.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml of undiluted EHD
VEHICLE - None

Duration of treatment / exposure:

Four hours of occluded contact

Observation period:

14 Days

Number of animals:

6 Rabbits

Details on study design:

TEST SITE: - Type of wrap if used: Occlusive dressing
REMOVAL of occlusive dressing: at the end of 4 h. Excess material was removed gently with moist tissue.
The exposure site was inspected for signed of inflammation at 1 h, and 1, 2, 3, and 7 days after removal of the occlusive dressing.
Erythema and edema were scored according to the method of Draize (McCreesh AH and Steinberg M. Skin Irritation Testing in Animals. In: Dermatoxicology and Pharmacology, Marzulli FN and Maibach HI, (Eds.) Hemisphere Publishing Corp. Washington, 1977, p. 196) and the skin was closely examined for other dermal reactions.

Irritation parameter:

other: descriptive

Basis:

mean

Time point:

other: 4 h

Score:

> 0 - < 2

Max. score:

4

Reversibility:

fully reversible within: 24-48 h

Remarks on result:

other: mild irritation, mostly resolved by 24 h.

Irritant / corrosive response data:

At the end of a 4-h occlusive contact period with 0.5 ml of undiluted EHD applied to the clipped dorsal trunk skin, five animals had slight local erythema and one also had well-defined local edema. These effects resolved within 24–48 h

Scores not provided in publication.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

After a 4-hour exposure (occluded), undiluted 2-Ethylhexane-1,3-Diol showed mild erythema in five of six rabbits, which resolved in 24-48 h. The substance is considered mildly irritating to rabbits under these conditions.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data published in a peer reviewed journal.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Six rabbits had 0.1 ml of undiluted EHD instilled into the inferior conjunctival sac, and further groups of six rabbits had 0.01 or 0.005 ml of EHD applied directly to the cornea

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Body weights: 2.0 to 3.0 kg.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Six rabbits had 0.1 ml of undiluted EHD applied to the conjunctival sac.
Six rabbits had 0.01 or 0.005 ml of EHD applied directly to the cornea of the eye.

Duration of treatment / exposure:

14 days

Observation period (in vivo):

Eyes were inspected periodically: 1 and 24 h, and 2, 3 and 7 to 14 days after dosing, for signs of ocular and periocular inflammation and injury up to 14 days post-dosing.

Number of animals or in vitro replicates:

12 Animals. 6 had EHD instilled into the inferior conjunctival sac and six rabbits had EHD applied directly to the cornea

Details on study design:

The Draize scale was used for evaluation (Draize J.H., Woodard G., Calvery H.O. (1944). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharmacol. And Exp. Therapeutics 82: 377–390.)

Irritation parameter:

other:

Basis:

mean

Time point:

other: 1 h

Score:

>= 80

Max. score:

110

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

Following 0.1 ml of EHD there was a rapid development of mild to severe conjunctivitis (moderate to marked injection, mild to severe chemosis, mild to marked discharge), which took up to 7 days to resolve. A moderate iritis was seen that persisted for 24–48 h. A just detectable to moderate corneal injury was seen in five out of six rabbits, which persisted for 3–7 days. With the smaller volume of EHD applied to the cornea there was a moderate to severe conjunctivitis for 24 h post-instillation but the effects required 2–7 days to resolve. Scores for irritation were not provided. These were estimated based on the conclusions of the study.

Other effects:

In one animal the conjuntivitis resolved rapidly, and the eye appeared normal by 24 hr post instillation. However,
in the remaining 5 animals the conjunctival infection persisted from 3-7 days.

Summary of Scores for Eye Lesion Observed After the Instillation of Various Volumes of EHD into the Eyes of Rabbits

		Effect as Average (and range)
Volume	Observation	Cornea		Iris	Conjunctivae
(ml)		Opacity	Area		Redness	Chemosis	Discharge
0.1	1 h	0.7 (0-1)	2.7 (0-4)	0.8 (0-1)	2.8 (2-3)	2.8 (1-4)	2.7 (1-3)
	4 h	0.8 (0-1)	2.8 (0-4)	0.8 (0-1)	2.5 (1-3)	2.5 (1-3)	2.5 (1-3)
	1 day	1.0 (0-2)	2.7 (0-4)	0.8 (0-1)	2.0 (0-3)	1.2 (0-2)	1.5 (0-3)
	2 days	1.0 (0-2)	2.3 (0-4)	0.0	1.8 (0-3)	0.8 (0-1)	0.3 (0-2)
	3 days	0.8 (0-2)	2.3 (0-4)	0.2 (0-1)	1.3 (0-2)	0.5 (0-1)	0.3 (0-2)
	7 days	0.2 (0-1)	0.3 (0-2)	0.0	0.0	0.2 (0-1)	0
	14 days	0.0	0.0	0.0	0.0	0.0	0.0
0.01	1 h	0.3 (0-1)	0.8 (0-3)	1.0 (1-1)	2.8 (2-3)	2.7 (2-3)	2.7 (2-3)
	4 h	1.3 (0-2)	2.0 (0-4)	1.0 (1-1)	2.8 (2-3)	2.8 (1-4)	2.7 (1-3)
	1 day	1.5 (0-2)	1.0 (1-2)	0.8 (0-1)	2.7 (2-3)	1.3 (0-2)	1.8 (0-3)
	2 days	1.5 (0-2)	0.8 (0-1)	0.5 (0-1)	1.8 (0-3)	1.2 (0-2)	1.0 (0-2)
	3 days	0.7 (0-2)	0.5 (0-1)	0.5 (0-1)	1.2 (0-2)	1.2 (0-2)	0.3 (0-1)
	7 days	0.0	0.0	0.0	0.0	0.0	0.0
0.005	1 h	0.7 (0-1)	0.7 (0-1)	0.5 (0-1)	3.0 (3-3)	2.3 (2-3)	3.0 (3-3)
	4 h	0.3 (0-1)	0.3 (0-1)	1.0 (0-1)	3.0 (3-3)	3.2 (2-4)	3.0 (3-3)
	1 day	0.8 (0-1)	0.8 (0-1)	0.3 (0-1)	2.5 (2-3)	2.0 (2-2)	1.3 (2-3)
	2 days	0.8 (0 -1)	1.0 (0-2)	0.0	1.5 (1-2)	1.5 (1-2)	0.7 (1-2)
	3 days	0.5 (0-2)	0.3 (0-1)	0.2 (0-1)	0.8 (0-2)	0.8 (1.2)	0.7 (0-2)
	7 days	0.0	0.0	0.0	0.0	0.0	0.0

Interpretation of results:

Category I

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

EHD causes severe eye damage when administered undiluted into the eyes of rabbits, which resolved within 7 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Exposure of the skin of rabbits to undiluted EHD under occlusive patches results in a slight erythema which resolved quickly (24-48 h) after patch removal. When tested in human volunteers under semi-occlusive and occlusive conditions, undiluted EHD resulted in barely perceptible skin irritation. The substance has a long history of safe use as a dermal human insect repellent. It is not classified as a skin irritant.

Exposure of the eyes of rabbits to undiluted EHD resulted in severe conjunctival irritation which did not resolve until 7 days post-treatment. Additionally, moderate iritis (reversible within 48 h) and mild-to-moderate corneal injury (reversible within 7 days) were observed. Draize scores were not presented in the publications.

Justification for selection of skin irritation / corrosion endpoint:
experimental result

Justification for selection of eye irritation endpoint:
experimental result

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

The substance is not classified as a skin irritant according to CLP000 of Regulation EC No. 1272/2008. It has a long history of safe use as a dermal human insect repellent.

The substance is classified as causing severe eye damage, Category 1, Index # 603-087-00-9, according to CLP000 of Regulation EC No. 1272/2008.