Isotridecanol, ethoxylated

Endpoint summary

Description of key information

Skin irritation / corrosion: not irritating

Read-across (Weight-of-Evidence approach) based on the analogue source substances isotridecanol, ethoxylated, 3 EO (CAS No. 69011-36-5), alcohol, C13, branched, ethoxylated 3-4 EO (CAS No. 24938-91-8), alcohols, C12-13, ethoxylated, < 2.5 EO (CAS No. 66455-14-9, EC No. 500-165-3) and alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0).

Eye irritation / serious eye damage: not irritating

Read-across (Weight-of-Evidence approach) based on the analogue source substances isotridecanol, ethoxylated, 3 EO (CAS No. 69011-36-5), alcohol, C13, branched, ethoxylated 3-4 EO (CAS No. 24938-91-8), alcohols, C12-13, ethoxylated, < 2.5 EO (CAS No. 66455-14-9, EC No. 500-165-3) and alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0).

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:

weight of evidence

Justification for type of information:

Please refer to the Analogue Approach Justification provided in 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 source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Irritation parameter:

edema score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

No potential to induce skin irritation is predicted for the target substance in a Weight-of-Evidence approach considering adequate analogue source substances.

Executive summary:

The skin irritation potential of the target substance is predicted based on adequate and reliable in vivo studies with several structural analogue source substances in a Weight-of-Evidence approach. An irritating potential is observed only in studies using occlusive and/or excessive exposure conditions and for those analogue source substances with three or more ethoxy (EO) groups. Based on the results of the available studies for the analogue source substances and accounting for an average ethoxylation degree of the target substance of < 2.5 EO, no skin irritation potential is predicted for the target substance. As explained in the analogue read-across justification, the differences in composition and molecular structure between the target and the source substances are unlikely to lead to differences in the skin irritation potential.

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:

weight of evidence

Justification for type of information:

Please refer to the Analogue Approach Justification provided in 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 source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Irritation parameter:

iris score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Irritation parameter:

conjunctivae score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Irritation parameter:

chemosis score

Basis:

other: all animals based on WoE

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Remarks:

Hazard conclusion based on Weight-of-Evidence approach using data obtained with adequate analogue source substances.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

No potential to induce eye irritation is predicted for the target substance in a Weight-of-Evidence approach considering adequate analogue source substances.

Executive summary:

The eye irritation potential of the target substance is predicted based on adequate and reliable in vivo studies with several structural analogue source substances in a Weight-of-Evidence approach. A potential to induce eye irritation is identified only for those source substances with three or more ethoxy (EO) groups. Since the target substance is characterised by an ethoxylation degree < 2.5 EO, no eye irritation potential is predicted. As explained in the analogue read-across justification, the differences in composition and molecular structure between the target and the source substances are unlikely to lead to differences in the eye irritation potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data on skin or eye irritation of isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6) are available. In order to assess the irritating potential, studies performed with adequate source substances are considered in an analogue read-across approach in accordance with Annex XI, Section 1.5, of the REACH Regulation (EC) No. 1907/2006. The available source data allow for an accurate hazard assessment of the target substance. A detailed justification of the read-across approach is provided in IUCLID section 13.

Skin irritation / corrosion

The source substances and their respective study results used for assessing the skin irritation potential of the target substance isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6) are summarised in the following table.

Source substance	CAS / EC No.	Condition	Result
Isotridecanol, ethoxylated, 3 EO	69011-36-5 / -	Occlusive	Irritating
Alcohol, C13, branched, ethoxylated 3-4 EO	24938-91-8 / -	Occlusive	Irritating
Alcohol, C13, branched, ethoxylated 3-4 EO	24938-91-8 / -	Semi-occlusive	Not irritating
Alcohols, C12-13, ethoxylated, < 2.5 EO	66455-14-9 / 500-165-3	Occlusive	Not irritating
Alcohols, C12-13, branched and linear, < 2.5 EO	160901-19-9 / 500-457-0	Occlusive	Not irritating

In a skin irritation study according to OECD guideline 404 performed with isotridecanol, ethoxylated, 3 EO (CAS No. 69011-36-5) (Sasol, 1986b), three albino rabbits were exposed for 4 h to 0.5 mL of the test item under occlusive conditions. Observations of local skin effects were made 1, 24, 48, 72 h and 6, 8, 10 and 14 days after the exposure period and scored according to the Draize scoring system. Slight to moderate erythema and oedema were observed as early as 1 h after removal of the patch. Erythema and oedema scores increased until the 72 h reading. At the 48-h reading time point dry skin was seen in 2/3 rabbits. Eschar formation was observed in all animals beginning 6 days after exposure. Beginning scale-off of eschar was observed 8 days after exposure. No scoring was performed 8, 10 and 14 days (3/3, 3/3 and 2/3 animals) after exposure. After 14 days no eschar and no erythema and oedema were seen in 1/3 rabbits. Findings of the other rabbits comprised of eschar, which was not completely scaled off. Mean erythema and oedema scores over 24/48/72 h and for all animals were 3.2 and 3.9, respectively.

In a study with alcohol, C13, branched, ethoxylated 3-4 EO (CAS No. 24938-91-8) (BASF, 1981) the skin irritation and the corrosive potential was assessed according to Federal Register 38, No. 187, PARA 1500.41 (1973-09-27) in a set of two separate experiments. For the assessment of the primary irritation, the animals were exposed for 24 h to the test substance under occlusive conditions. Thereafter, the patches were removed and the resulting reactions evaluated. Observations were made again at the end of a total of 72 h (48 h after the first reading). Scoring was done according to Draize. Marked erythema and oedema were seen directly after the 24 h exposure period as well as 48 h thereafter. Based on the necrosis seen in the skin irritation the test substance would need to be classified as corrosive. However, the effect is presumably due to the 24-h exposure period, which is longer than for the current OECD guideline 404 (4 h) and the occlusive condition (semi-occlusive is required in the OECD guideline 404). Moreover, within the skin corrosion experiment (‘BASF, 1984a’ summarised below), no necrosis was seen and erythema and oedema that occurred after the 4 h exposure period were reversible. Thus, the test substance showed corrosive effects but under conditions more severe than required in the current guideline. In consequence, the substance was evaluated to be irritating to skin.

Another study with alcohol, C13, branched, ethoxylated 3-4 EO (CAS No. 24938-91-8) performed according to OECD guideline 404 (BASF, 1984a) investigated the skin irritation potential under semi-occlusive conditions. Three white rabbits were exposed to 0.5 mL of the test item for 4 h and observed for 72 h afterwards. In contrast to the findings of the previous study (BASF, 1981), there were almost no irritating effects observed. There was one animal (1/3) showing very slight erythema at the 4-h, 24-h and 48-h reading. The erythema was not observed at the 72-h reading time point. All other animals (2/3) showed no indications of skin irritation.

Alcohols, C12-13, ethoxylated, < 2.5 EO (CAS No. 66455-14-9, EC No. 500-165-3) has been investigated in a study similar to OECD guideline 404 (Shell, 1979) in which 3 rabbits were exposed under very stringent conditions to 0.5 mL of the test item for 24 h under occlusive conditions. In contrast, the current OECD guideline 404 requires an exposure period of 4 h and semi-occlusive conditions. Since harsher exposure conditions are expected to result in more severe effects, the results reported in this study probably over-estimated the real skin irritation potential of the test substance. Additionally, the observation period in this study has been restricted to 7 days, as opposed to the 14-day period in the current OECD guideline 404 (which can be extended if necessary to investigate reversibility). Hence, classification that is based on the criteria of the current guideline was considered not justified although skin-irritating effects were observed (mean erythema and oedema scores over all animals at 24, 48 and 72 h were 1.9 and 1.2, respectively).

In another study (Sasol, 1984a), alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0) was tested for its skin irritation potential. Following a protocol similar to OECD guideline 404, six rabbits were exposed to 0.5 mL of the test item for 4 h under occlusive conditions and were observed for 7 days. Skin reactions were scored after 30-60 min, and 24, 48 and 72 h as well as after 5 and 7 days. Only minor erythema scores (max. 0.67, fully reversible within 72 h) and an oedema score 0 (zero) was observed, indicating no skin irritating potential of the test item.

Conclusion on skin irritation / corrosion

The alkyl chains of the four analogue source substances considered for the assessment of the skin irritation potential are both linear and branched and vary in carbon-chain length between C12 and C13. Hence, they are reflecting the target substance properly. In addition, the ethoxylation degree (i.e. the mean number of ethoxy (EO) groups attached to the alcohol moiety) is in the range   < 2.5 to 3-4. An irritating potential was only observed under occlusive and/or excessive exposure conditions and for those analogue source substances with three or more ethoxy (EO) groups. Based on the results of the available studies for the analogue source substances and accounting for an average ethoxylation degree of the target substance of < 2.5 EO, no skin irritation potential is predicted for the target substance isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6).

Eye irritation / serious eye damage

The source substances and their respective study results used for assessing the eye irritation potential of the target substance isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6) are summarised in the following table.

Source substance	CAS / EC No.	Classification according to CLP
Isotridecanol, ethoxylated, 3 EO	69011-36-5 / -	Eye Damage 1, H318
Alcohol, C13, branched, ethoxylated 3-4 EO	24938-91-8 / -	Eye Damage 1, H318
Alcohols, C12-13, ethoxylated, < 2.5 EO	66455-14-9 / 500-165-3	Not irritating
Alcohols, C12-13, branched and linear, < 2.5 EO	160901-19-9 / 500-457-0	Not irritating

In a study according to OECD guideline 405 with isotridecanol, ethoxylated, 3 EO (CAS No. 69011-36-5) (Sasol, 1986c) three male albino rabbits were treated with 0.1 mL of undiluted test substance. The eyes of all three animals were washed 72 h after application with lukewarm physiological NaCl solution. Mean calculations over all animals and all relevant time points for classification resulted in the following scores: cornea 1.6; iris 0.6; conjunctivae 2.2; chemosis 0.7. Since damages in all areas were not fully reversible within 21 days, the substance was considered to be corrosive to the eye.

A study with alcohol, C13, branched, ethoxylated 3-4 EO (CAS No. 24938-91-8) (BASF, 1984b) was performed according to OECD guideline 405. Two male and one female albino rabbits were treated with 0.1 mL of undiluted test substance. Mean calculations over all animals and all relevant time points for classification resulted in the following scorings: cornea 1.0; iris 0.1; conjunctivae 1.7; chemosis 0.6. Since scores were not fully reversible within 8 days, the substance was classified as corrosive to the eye.

Alcohols, C12-13, ethoxylated, < 2.5 EO (CAS No. 66455-14-9, EC No. 500-165-3) has been tested in a study similar to OECD guideline 405 for its eye irritating potential (Shell, 1979). Three New Zealand White rabbits were exposed to 0.2 mL of the undiluted test item and subsequently observed for 7 days. The mean scores for all observational endpoints (cornea opacity, iris, conjunctivae, and chemosis) and all classification-relevant time points were 0. Hence, the test substance was not irritating to the eye.

The fourth relevant eye irritation investigation was performed with alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0) using a protocol similar to OECD guideline 405 (Sasol, 1984b). 0.1 mL of the undiluted test substance was instilled into the eye of six New Zealand White rabbits. The animals were observed for 7 days. The mean scores after 24, 48 and 72 h determined were: cornea opacity: 0 (no effect observed in any animal); iris: 0 (no effect observed in any animal); conjunctivae: 0.83; chemosis: 0.5. The results/scores did not meet the criteria for classification and therefore the test substance was considered not to be irritating to the eye.

Conclusion on eye irritation / serious eye damage

The alkyl chains of the four source substances considered for the assessment of the eye irritation potential are both linear and branched and vary in carbon-chain length between C12 and C13. Hence, they are reflecting the target substance properly. In addition, the ethoxylation degree (i.e. the mean number of ethoxy (EO) groups attached to the alcohol moiety) is in the range < 2.5 to 3-4. The available studies indicate that eye irritation or serious eye damage is determined by the ethoxylation degree rather than by the nature of the alkyl chain, i.e. its carbon-chain length or branching pattern. Whereas source substance alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0) does not show eye irritation, the source substance isotridecanol, ethoxylated, 3 EO (CAS No. 69011-36-5) induces eye damage. It should be noted that the alkyl moieties in both source substances are very similar since alcohols, C12-13, branched and linear, < 2.5 EO (CAS No. 160901-19-9, EC No. 500-457-0) contains predominantly branched constituents. Taking all available data of the analogue source substances into consideration, eye irritation is relevant only for those alcohol ethoxylates with three or more ethoxy (EO) groups. Since the target substance isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6) has an ethoxylation degree < 2.5 EO, no eye irritation potential is predicted.

Justification for classification or non-classification

The available data on skin and eye irritation obtained with adequate structural analogue substances do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification. Based on an analogue read-across (Weight-of-Evidence approach) considering structural analogue source substances, isotridecanol, ethoxylated, < 2.5 EO (CAS No. 69011-36-5, EC No. 500-241-6) is predicted not to fulfil the classification criteria and is consequently not classified for skin and eye irritation.