2,6-dimethyloct-7-en-2-ol

Endpoint summary

Description of key information

Skin irritation

The analogue chemical, dimyrcetol, is a skin irritant in rabbits when tested undiluted.

 

Eye irritation

In an in vivo eye irritation study in rabbits, the test article was classified as moderately irritating to the eye of the albino rabbit under the conditions of the study.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Test substance identified by name only. The observation period was only 7 days.

Qualifier:

according to guideline

Guideline:

other: Annex V, EEC Directive 79/831

Version / remarks:

The system described in the Official Journal of the European Communities No. L257, 16th September 1983 was used to classify materials (Commission Directive of 29th July 1983 adapting technical progress for the 5th time, Council Directive 67/548/EEC).

Deviations:

yes

Remarks:

The observation period was only 7 days.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Animals were individually housed in anodised aluminum cages with grid floors and no bedding materials were provided in the cages.
- Diet: Ad libitum (commercially available pelleted rabbit diet (Product Ref. 680, Dalgety-Spillers Ltd.))
- Water: Ad libitum (tap water)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-67
- Air changes (per hr): Not indicated, but room was air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Tested either undiluted or as 50% solution in DEP

Controls:

no

Amount / concentration applied:

A 0.5 mL aliquot of the test material was placed evenly over a 2.5 cm square of surgical lint B.P. The lint square was then placed onto the animals skin, on the left flank and immediately caudal to the last rib, with the test material in contact with the skin. In the test, a second test material was applied in the same manner to the right flank. Lint patches were held in place with Elastoplast bandages (10 cm wide). The test material was applied a group of four animals either neat (undiluted) or as a 50% solution.

Duration of treatment / exposure:

4 hours. After the treatment period, the adhesive tapes was removed and the treated sites cleansed by gently swabbing with cotton wool soaked in warm water.

Observation period:

One hour after removeal and at 4, 24, 48, 72 and 168 hours after patch removal, animals were assessed for signs of reaction to treatment. Animals were examined under a standard light source designed to comply with the requirements of B.S. 950 Part 1 (Artificial Daylight for the Assessment of Colour). Irritation was assessed numerically as defined in Table 1.

Number of animals:

4

Details on study design:

The day before treatment, rabbits were restrained and the dorsal surfaces of the trunk clipped free of hair using a Oster Model A2 clipper with Angra blade. Groups of 4 healthy animals with intact skin were selected for the study.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 100% Dimyrcetol

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.6

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: 100% dimyrcetol

Irritant / corrosive response data:

Sample 8A (50% Dimyrcetol, See Table 2)

Well defined erythema and very slight oedema of the skin were apparent in 3/4 rabbits and very slight erythema in 1/4 rabbits 1 hour after dosing. Some increase in severity of oedematous response was exhibited by 2/4 animals at 24 hours, with slight reaction observed. Further increases in response were apparent at the 48 hour examination with well defined erythema noted in all 4 rabbits. Oedema of the skin ranged from very slight in one rabbit, slight in two rabbits, and moderate in one rabbit. Slight desquamation of the surface of treated skin was also observed in one rabbit. The irritant response seen in one rabbit had declined by the 72 hour observation, with very slight erythema remaining. There were no remaining reactions at treated sites on any rabbit by day 7 after dosing.

Sample 8B (100% Dimyrcetol, See Table 3)

Well defined erythema was observed in all 4 rabbits and very slight oedema of the treated skin in three rabbits was apparent at the one hour observation. Oedematous responses increased and at 24 hours after dosing slight reaction was observed in three rabbits and very slight reaction was noted in the remaining rabbit of the group. Well defined erythema and slight oedema were present at the treated site of all four rabbits 48 and 72 hours after dosing. This response had declined within 7 days with very slight erythema remaining in 3 rabbits and very slight oedema in all 4 rabbits. Slight desquamation from the treated skin was also observed in one rabbit.

Table 2:  Sample 8A Results

 

Rabbit No. /Observation Time	Erythema Score	Oedema Score	Comments
909
1 hour	2	1
24 hour	2	2
48 hour	2	3
72 hour	2	3
168 hour	0	0
914
1 hour	1	0
24 hour	1	0
48 hour	2	1	Slight desquamation
72 hour	1	0	Very slight desquamation
168 hour	0	0
915
1 hour	2	1
24 hour	2	1
48 hour	2	2
72 hour	2	2
168 hour	0	0
917
1 hour	2	1
24 hour	2	2
48 hour	2	2
72 hour	2	2
168 hour	0	0

 

Table 3:  Sample 8B Results

 

Rabbit No. /Observation Time	Erythema Score	Oedema Score	Comments
909
1 hour	2	0
24 hour	2	2
48 hour	2	2
72 hour	2	2
168 hour	0	1
914
1 hour	2	1
24 hour	2	1
48 hour	2	2
72 hour	2	2
168 hour	1	1	Slight desquamation
915
1 hour	2	1
24 hour	2	2
48 hour	2	2
72 hour	2	2
168 hour	1	1
917
1 hour	2	1
24 hour	2	2
48 hour	2	2
72 hour	2	2
168 hour	1	1

 

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Undiluted dimyrcetol is rated as a skin irritant in the rabbit.

Executive summary:

In a key study in rabbits, the undiluted analogue chemical, dimyrcetol, applied under semi-occlusive wrap was rated a skin irritant according to Annex V of EEC Directive 78/831 based on a group mean erythema irritation score of 2 or higher for the 24-, 48- and 72-hour observations. Minimal erythema and edema (scores of 0 to 1) persisted to the 168 hour observation. A 50% dilution in diethyl phthalate was not an irritant under the same conditions. All irritant effects noted in the study with 50% test material were resolved by the 168-hour observation point.

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:

1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Principles of method if other than guideline:

The study was conducted according to the procedure originally suggested by Draize (Draize, H.J. "Appraisal of the Safety of Chemical in Foods, Drugs and Cosmetics", Assoc. of Food and Drug Officials of the U.S., Austin, Texas, 1959).

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Not stated
- Weight at study initiation: 2.0 to 3.5 kg at the preliminary eye examination
- Housing: Singly under standard laboratory conditions; suspended pans beneath cages were littered with prepared bedding (Easi Litter)
- Diet: Daily 100 g of Purina Rabbit Chow supplemented by whole oats
- Acclimation period: Yes, but the period not stated
- Assurance of animal health: Animals were examined by a veterinarian during quarantine and all animals assigned to the study were in good health prior to the start of the study and were selected to be free of apparent ocular defects

ENVIRONMENTAL CONDITIONS
The criteria used for housing and maintenance were those specified in the "Guide for the Care and Use of Laboratory Animals", DHEW Publication No. (NIH) 78-23, Revised 1978.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of each rabbit served as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

single application

Observation period (in vivo):

10 days

Number of animals or in vitro replicates:

6

Details on study design:

METHOD

24 hours prior to dosing, both rabbit eyes were examined using a hand held ophthalmoscope and then by fluorescein staining. One drop of Fluorescein Sodium Ophthalmic Solution USP was dropped onto the cornea which was then irrigated with Sodium Chloride Solution USP. Eyes were examined for corneal ulceration using an ultraviolet light.

On the day of dosing, the lower lid was everted from the eyeball of the right eye of each animal to form a cup into which the test article was instilled. The eyelids were then gently held shut for one second. The eye was not washed after instillation. Any untoward reaction to instillation of the test substance was recorded and the animal returned to its cage.

Both eyes of each rabbit were scored according to the method of Draize (table 1) at 24, 48 and 72 hours and at 4 and 7 days after dosing. In addition, at 24 hours and 7 days, both eyes were examined with fluorescein stain under an ultra violet light.

Any persistent changes observed on Day 7 were re-evaluated on Day 10 using a hand-held ophthalmoscope and the fluorescein method described previously.

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

All of the six animals developed corneal opacity within 24 hours of being dosed. Opacity had cleared in one of the six animals at 72 hours, and in four of the six animals by Day 7. The eyes of the last two animals had cleared by Day 10.

See the table below for individual animal irritation results.

Table 2: Primary eye irritation data for individual animals and observation times

 

Rabbit		Cornea			Iris		Conjunctivae				Total
Number	Hr/Day	A (Opacity)	B (Area)	(A x B x 5)	A	A X 5	A (Redness)	B (Chemosis)	C (Discharge)	(A + B + C) x 2	Score
A-1126	24 hours	2	4	40	0	0	2	1	2	10	50
	48 hours	2	4	40	0	0	1	0	0	2	42
	72 hours	2	3	30	0	0	0	0	0	0	30
	day 4	1	3	15	0	0	0	0	0	0	15
	day 7	1	2	10	0	0	0	0	0	0	10
	day 10	0	0	0	0	0	0	0	0	0	0
	Mean=	1.33	2.67		0.00		0.50	0.17	0.33
Mean	(24,48 and 72 hr)	2.00	3.67		0.00		1.00	0.33	0.67
A-1127	24 hours	2	3	30	1	5	3	2	3	16	51
	48 hours	2	3	30	0	0	1	0	0	2	32
	72 hours	2	1	10	0	0	1	0	0	2	12
	day 4	2	1	10	0	0	0	0	0	0	10
	day 7	0	0	0	0	0	0	0	0	0	0
	day 10	0	0	0	0	0	0	0	0	0	0
	Mean=	1.33	1.33		0.17		0.83	0.33	0.50
Mean	(24,48 and 72 hr)	2.00	2.33		0.33		1.67	0.67	1.00
A-1128	24 hours	2	4	40	0	0	2	1	2	10	50
	48 hours	2	4	40	0	0	2	0	0	4	44
	72 hours	2	4	40	0	0	1	0	0	2	42
	day 4	2	4	40	0	0	1	0	0	2	42
	day 7	0	0	0	0	0	0	0	0	0	0
	day 10	0	0	0	0	0	0	0	0	0	0
	Mean=	1.33	2.67		0.00		1.00	0.17	0.33
Mean	(24,48 and 72 hr)	2.00	4.00		0.00		1.67	0.33	0.67
A-1129	24 hours	2	3	30	0	0	3	2	2	14	44
	48 hours	2	3	30	0	0	2	0	0	4	34
	72 hours	1	1	5	0	0	2	0	0	4	9
	day 4	1	1	5	0	0	1	0	0	2	7
	day 7	0	0	0	0	0	0	0	0	0	0
	day 10
	Mean=	1.2	1.6		0		1.6	0.4	0.4
Mean	(24,48 and 72 hr)	1.67	2.33		0.00		2.33	0.67	0.67
A-1139	24 hours	1	2	10	0	0	2	2	1	10	20
	48 hours	1	2	10	0	0	1	0	0	2	12
	72 hours	0	0	0	0	0	0	0	0	0	0
	day 4	0	0	0	0	0	0	0	0	0	0
	day 7	0	0	0	0	0	0	0	0	0	0
	day 10	0	0	0	0	0	0	0	0	0	0
	Mean=	0.33	0.67		0.00		0.50	0.33	0.17
Mean	(24,48 and 72 hr)	0.67	1.33		0.00		1.00	0.67	0.33
A-1140	24 hours	1	4	20	0	0	1	1	0	4	24
	48 hours	1	4	20	0	0	1	0	0	2	22
	72 hours	1	4	20	0	0	1	0	0	2	22
	day 4	1	3	15	0	0	0	0	0	0	15
	day 7	1	1	5	0	0	0	0	0	0	5
	day 10	0	0	0	0	0	0	0	0	0	0
	Mean=	0.83	2.67		0.00		0.50	0.17	0.00
Mean	(24,48 and 72 hr)	1.00	4.00		0.00		1.00	0.33	0.00
Mean by sample time =
	24 hours	1.67	3.33		0.17		2.17	1.50	1.67		39.83
	48 hours	1.67	3.33		0.00		1.33	0.00	0.00		31.00
	72 hours	1.33	2.17		0.00		0.83	0.00	0.00		19.17
	day 4	1.17	2.00		0.00		0.33	0.00	0.00		14.83
	day 7	0.33	0.50		0.00		0.00	0.00	0.00		2.50
	day 10	0.00	0.00		0.00		0.00	0.00	0.00		0.00

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The primary ocular irritation scores were 39.83 at 24 hours, 31.00 at 48 hours, 19.17 at 72 hours, 14.83 at 4 days, 2.5 at 7 days and 0 at 10 days. Under the conditions of this study, the test article was classified as moderately irritating to the eye of the albino rabbit.

Executive summary:

In a study in rabbits, 0.1 mL of undiluted test item was applied to six rabbit eyes followed by examinations at 24-, 48 and 72-hours and at days 4 and 7 days following treatment. Eyes were examined with fluorescein stain under ultraviolet light at 24-hours and 7 days. Any persistent changes noted at day 7 were re-evaluated on day 10. All animals developed corneal opacity by 24 hours (scores of 1 to 2). Opacity had cleared in one animal at 72 hours and in 4 of 6 animals by day 7. The eyes of the last 2 animals cleared by day 10. Based on the Draize scoring system, the material would be rated as moderately irritating to eyes. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 1.56; iris, 0.06; conjunctival redness, 1.44; conjunctival chemosis, 0.50; and conjunctival discharge, 0.56. In a supporting study in rabbits, undiluted dimyrcetol was rated an eye irritant based on the Draize scoring system. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 0.33; iris, 0.17; conjunctival redness, 0.83; conjunctival chemosis, 0.56; and conjunctival discharge, 0.56. Under the conditions of this study, the test article was classified as moderately irritating to the eye of the albino rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read-across, skin irritation in vivo, RL2

In a study in rabbits, the undiluted analogue chemical, dimyrcetol, applied under semi-occlusive wrap was rated a skin irritant according to Annex V of EEC Directive 78/831 based on a group mean erythema irritation score of 2 or higher for the 24-, 48- and 72-hour observations. Minimal erythema and edema (scores of 0 to 1) persisted to the 168 hour observation. A 50% dilution in diethyl phthalate was not an irritant under the same conditions. All irritant effects noted in the study with 50% test material were resolved by the 168-hour observation point.

 

Eye Irritation in vivo, RL1

In a key study in rabbits, 0.1 mL of undiluted test item was applied to six rabbit eyes followed by examinations at 24-, 48 and 72-hours and at days 4 and 7 days following treatment. Eyes were examined with fluorescein stain under ultraviolet light at 24-hours and 7 days. Any persistent changes noted at day 7 were re-evaluated on day 10. All animals developed corneal opacity by 24 hours (scores of 1 to 2). Opacity had cleared in one animal at 72 hours and in 4 of 6 animals by day 7. The eyes of the last 2 animals cleared by day 10. Based on the Draize scoring system, the material would be rated as moderately irritating to eyes. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 1.56; iris, 0.06; conjunctival redness, 1.44; conjunctival chemosis, 0.50; and conjunctival discharge, 0.56. In a supporting study in rabbits, undiluted dimyrcetol was rated an eye irritant based on the Draize scoring system. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 0.33; iris, 0.17; conjunctival redness, 0.83; conjunctival chemosis, 0.56; and conjunctival discharge, 0.56.

 

Please refer to Section 13 of this IUCLID file for read-across documentation and rationale for the selection of representative analogue chemicals.

 

Skin irritation/corrosion: irritating

Eye irritation: irritating

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
Skin Irritation

The substance is assessed in a read-across approach, using the analogue substance dimyrcetol. The available experimental test data for the substances are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the available data, the source substance is classified for skin irritation (category 2). Thus, the target substance is also classified for skin irritation (category 2) according to Regulation (EC) No 1272/2008 (CLP), as amended for sixteenth time in Regulation (EU) No 2021/743.

 

Eye irritation

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the available data, the test substance was an eye irritant and is thus classified for eye irritation (category 2) according to Regulation (EC) No 1272/2008 (CLP), as amended for sixteenth time in Regulation (EU) No 2021/743.

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