2,4,7,9-Tetramethyldec-5-yne-4,7-diol, ethoxylated

Endpoint summary

Description of key information

not irritating to skin (no classification) 
irreversible effects to the eyes (Category 1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rabbit

Type of coverage:

semiocclusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

six

Irritation parameter:

erythema score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

< 1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Number of animals or in vitro replicates:

6 rabbits

Irritation parameter:

chemosis score

Basis:

animal: 1-6

Time point:

24/48/72 h

Reversibility:

not fully reversible within: 7 d (=end of observation period)

Remarks on result:

other: please refer to "any other information on results"

Irritation parameter:

cornea opacity score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

>= 26.7 - <= 30

Reversibility:

fully reversible within: 7 d (= end of observation period)

Remarks on result:

other: results obtained with source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated

Irritation parameter:

iris score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

5

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Remarks on result:

other: results obtained with source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated

Irritation parameter:

conjunctivae score

Basis:

animal: 1-6

Time point:

24/48/72 h

Score:

>= 14.7 - <= 16

Reversibility:

not fully reversible within: 7 d (= end of observation period)

Remarks on result:

other: results obtained with source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated

Irritation parameter:

overall irritation score

Basis:

animal: 1-6

Time point:

24/48/72 h

Reversibility:

not reversible

Remarks:

not fully reversible within 7 d or 21 d observation period

Remarks on result:

probability of severe irritation

Remarks:

based on both source substances, 2,4,7,9-tetramethyldec-5-yne-4,7-diol and 2,4,7,9-tetramethyldec-5-yne-4,7-diol, utilised

Results obtained with source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated

	1 hour			24 hours			48 hours			72 hours			5 days			7 days
Rabbit Number	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae
1	20	5	18	30	5	16	30	5	16	30	5	12	20	0	10	20	0	6
2	20	5	18	30	5	18	30	5	14	30	5	12	30	5	10	30	5	6
3	20	5	18	30	5	18	30	5	16	30	5	14	30	5	12	30	0	10
4	20	5	18	30	5	16	30	5	16	20	5	14	20	5	12	20	0	6
5	20	5	18	30	5	16	30	5	14	30	5	14	30	5	10	20	0	8
6	20	5	18	30	5	18	30	5	16	30	5	14	20	5	12	20	5	10

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

Reversibility cannot be finally evaluated, since effects were still present at the last observation time point (7 d).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Experimental data on the skin and eye irritating potential of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) are not available. However, studies were conducted with the structurally related source substances 2,4,7,9-Tetramethyl-5-decyne-4,7-diol and 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8). Since the composition of the target substance lies in between the two source substances (based on strucutral, physicochemical and toxicological aspects), interpolation of the results is considered appropriate. A justification for read-across is attached to iuclid section 13.

 

Skin irritation

In a primary skin irritation study according to OECD TG 404 0.5 g of the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol was applied to 3 New Zealand White rabbits for 4 h under semiocclusive conditions. Animals were observed for 72 h. Slight erythema was noted at the 1 h observation, which was still present in 2/3 animals at the 24 h observation, but fully reversible within 48 h. Edema was absent at all observation intervals. There were no abnormal clinical signs noted during the observation period. In this study, substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol was not irritating to skin.

 

In a primary skin irritation study according to Hazardous Substances and Articles, Section 1500.41 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) was applied to 6 albino rabbits for 24 h under semiocclusive conditions to intact and abraded skin. Animals were observed for 72 h, however, no observation was made at 48 h. Slight erythema was noted at the 24 h observation, but was fully reversible within 72 h on intact as well as on abraded skin. Edema was absent at all observation time points. In this study, substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) was not irritating to skin.

 

Eye irritation

In an eye irritation study according to EPA OTS 798.4500 0.1 mL of the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol was applied to the conjunctival sac of one eye of 9 New Zealand White rabbits. The eyes of 3 animals were rinsed with lukewarm water for one minute, 30 seconds after application. Six eyes remained unwashed.  The eyes were examined and scored by the Draize technique at one hour and at 24, 48, and 72 hours postdose. In order to determine reversibility, the eyes were examined again on Days 7, 14, and 21. Sodium fluorescein was used to determine corneal effects following the 24-hour scoring interval.

Unwashed eyes:  Corneal opacity, noted in 6/6 eyes, persisted to Day 21 in 3/6 eyes. Iritis, noted in 6/6 eyes, cleared by Day 7.  Conjunctival irritation, noted in 6/6 eyes, cleared by Day 14. 

Washed eyes:  Corneal opacity, noted in 3/3 eyes, cleared by Day 14. Iritis, noted in 3/3 eyes, cleared by Day 7. Conjunctival irritation, noted in 3/3 eyes, cleared by Day 14.

Based on these results, 2,4,7,9-Tetramethyl-5-decyne-4,7-diol caused irreversible damage to the eyes and requires classification as Category 1.

 

In an eye irritation study according to Hazardous Substances and Articles, Section 1500.42 0.1 mL of the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) was applied to the conjunctival sac of the right eye of 6 albino rabbits. Animals were observed for 7 days. All six animas showed irritating effects to cornea, iris and conjunctivae, which were still present at the last observation time point (7 d). Thus, reversibility cannot be finally evaluated.

 

Respiratory irritation

No data on the respiratory irritation of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) are available.

 

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to conclude that these results would not be applicable to humans.

 

 

Overall, both source substances were not irritating to skin and severely irritating to the eyes (irreversible effects). Based on structural similarity, this outcome is interpolated to the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3), which is also considered to be not irritating to skin and to cause irreversible damage to the eyes.

Justification for classification or non-classification

Skin irritation

Based on reliable, adequate and relevant data, 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) does not need to be classified for skin irritation according to regulation (EC) 1272/2008.

 

Eye irritation

Based on reliable, adequate and relevant data, 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) has to be classified as Category 1, irreversible effects on the eye according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H318 and the signal word “Danger”.