Alcohols, C8-18, ethoxylated

Endpoint summary

Description of key information

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization potential for the target chemical. Alcohols, C8-18, ethoxylated were estimated to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Weight of evidence based on the structurally and functionally similar read across chemicals

Justification for type of information:

Weight of evidence based on the structurally and functionally similar read across chemicals

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: Weight of evidence based on the structurally and functionally similar read across chemicals

Principles of method if other than guideline:

Weight of evidence based on the structurally and functionally similar read across chemicals

GLP compliance:

not specified

Type of study:

other: Weight of evidence based on the structurally and functionally similar read across chemicals

Specific details on test material used for the study:

- Name of test material: Alcohols, C8-18, ethoxylated
- IUPAC name: Alcohols, C8-18, ethoxylated (1 - 2.5 moles ethoxylated)
- Molecular formula: (Cx-y AEn) or (C8-18 AE1- 2.5)
- Substance type: Organic
- Physical state: Liquid (viscous)

Species:

other: humans and guinea pigs

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

no data available

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Concentration / amount:

0.2 ml

Day(s)/duration:

21 days

Adequacy of induction:

not specified

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

Intradermal: 3 pairs of 0.1 mL volume (injection 1: Freund’s complete adjuvant (FCA); injection 2: 0.05% test substance solved in corn oil; injection 3: 0.05% test substance in a 1:1 mixture FCA) on the shoulder region.
Epicutaneous, occlusive: patch containing
50% solution of the test substance

Day(s)/duration:

48 hours

Adequacy of induction:

other: dose range finding studies were conducted to determine the concentration of test material to be used for intradermal induction, topical induction without causing untoward toxicity

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Concentration / amount:

0.2 ml

Day(s)/duration:

21 days

Adequacy of challenge:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

2% of the test substance in corn oil

Day(s)/duration:

24 hours

Adequacy of challenge:

other: Dose range finding studies were conducted to determine the concentration of test material to be used for topical challenge without causing untoward toxicity

No. of animals per dose:

1. 110 human volunteers
2. Test group – 10 males and 10 females
Control group – 5 males and 5 females

Details on study design:

The study is based on weight of evidence approach from the read across values

Challenge controls:

no data available

Positive control substance(s):

not specified

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

no dermal reactions observed

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

On the basis of available studies for the structurally similar read across substances, the weight of evidence approach was applied to assess the dermal sensitization potential for the target chemical. Alcohols, C8-18, ethoxylated were estimated to be not sensitizing to skin.

Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of Alcohols, C8-18, ethoxylated.

 

Draize Repeat Insult Patch Test was performed in 110 volunteers to observe the allergic contact dermatitis caused by the structurally and functionally similar read across chemical. For the induction exposure, 0.2 ml of test material was applied to the scapular region of the back for three times per week for 3 weeks under occlusive patches. After 48 hrs, site was observed after removal of patches. The induction exposure duration was 3 weeks which was followed by 14-day non treatment period. From the 6thweeks challenge exposure was applied to new sites of the scapular region of back and the sites were observed after 48 and 96 hrs. During induction and challenge phases, reactions were scored according to the following scale: 0 (no reaction) to 4 (bullae or extensive erosions involving at least 50% of the test area). Faint to moderate erythema was observed during induction phase in 3 subjects and also at challenge phase but no evidence of allergic contact dermatitis was observed.

From the clinical observation it was considered that no skin sensitization reaction was observed. Therefore, the test chemical was considered to be non sensitizing in humans.

This is supported by the results of Magnusson-Kligman guinea pig maximization test performed to determine the degree of sensitization caused by the structurally and functionally similar read across chemical. The study was conducted conforming to the OECD 406 Guidelines. Dose range finding studies were conducted to determine the concentration of test material to be used for intradermal induction, topical induction and topical challenge without causing untoward toxicity. Group of ten male and ten female and control group of five males and five female guinea pigs were used for the study. In the induction phase, the treatment group was intradermally injected 3 pairs of 0.1 mL volume (injection 1: Freund’s complete adjuvant (FCA); injection 2: 0.05% test substance solved in corn oil; injection 3: 0.05% test substance in a 1:1 mixture FCA) on the shoulder region. A week later, a patch containing 50% solution of the test substance was placed over the injection area for 48 hours in the

treatment group. The control groups were treated in the same manner, but without the test substance. Two weeks after the induction phase, the flanks of the treated and the control animals were shaved and an occlusive ‘challenge’ patch containing 2% of the test substance (or corn oil in case of the control group) was applied to one flank of the animals for 24 hours. Approximately 48 and 72 hours from the start of the challenge application, the skin reaction was evaluated according to the Magnusson-Kligman grading scale.

No dermal reactions were observed. Hence, the test chemical was considered to be not sensitizing to skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not sensitizing to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of Alcohols, C8-18, ethoxylated.

 

Draize Repeat Insult Patch Test was performed in 110 volunteers to observe the allergic contact dermatitis caused by the structurally and functionally similar read across chemical. For the induction exposure, 0.2 ml of test material was applied to the scapular region of the back for three times per week for 3 weeks under occlusive patches. After 48 hrs, site was observed after removal of patches. The induction exposure duration was 3 weeks which was followed by 14-day non treatment period. From the 6thweeks challenge exposure was applied to new sites of the scapular region of back and the sites were observed after 48 and 96 hrs. During induction and challenge phases, reactions were scored according to the following scale: 0 (no reaction) to 4 (bullae or extensive erosions involving at least 50% of the test area). Faint to moderate erythema was observed during induction phase in 3 subjects and also at challenge phase but no evidence of allergic contact dermatitis was observed.

From the clinical observation it was considered that no skin sensitization reaction was observed. Therefore, the test chemical was considered to be non sensitizing in humans.

This is supported by the results of Magnusson-Kligman guinea pig maximization test performed to determine the degree of sensitization caused by the structurally and functionally similar read across chemical. The study was conducted conforming to the OECD 406 Guidelines. Dose range finding studies were conducted to determine the concentration of test material to be used for intradermal induction, topical induction and topical challenge without causing untoward toxicity. Group of ten male and ten female and control group of five males and five female guinea pigs were used for the study. In the induction phase, the treatment group was intradermally injected 3 pairs of 0.1 mL volume (injection 1: Freund’s complete adjuvant (FCA); injection 2: 0.05% test substance solved in corn oil; injection 3: 0.05% test substance in a 1:1 mixture FCA) on the shoulder region. A week later, a patch containing 50% solution of the test substance was placed over the injection area for 48 hours in the

treatment group. The control groups were treated in the same manner, but without the test substance. Two weeks after the induction phase, the flanks of the treated and the control animals were shaved and an occlusive ‘challenge’ patch containing 2% of the test substance (or corn oil in case of the control group) was applied to one flank of the animals for 24 hours. Approximately 48 and 72 hours from the start of the challenge application, the skin reaction was evaluated according to the Magnusson-Kligman grading scale.

No dermal reactions were observed. Hence, the test chemical was considered to be not sensitizing to skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar manner that of the read across substances. Therefore the target chemical was estimated to be not sensitizing to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results of the experimental studies from the structurally, functionally similar read across substances indicate a possibility that Alcohols, C8-18, ethoxylated can be not sensitizing to skin.

Hence by applying the weight of evidence approach, Alcohols, C8-18, ethoxylated can be considered to be not sensitizing to skin. It can be classified under the category “Not Classified” as per CLP regulation.