Alcohols, C16-18, ethoxylated

Endpoint summary

Description of key information

Skin sensitisation (in vivo, guinea pig/Buehler test, OECD 406): not sensitising

Conclusion based on data obtained with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) and considering all available data on skin sensitisation in the Alcohol Ethoxylates (AE) category in a Weight-of-Evidence approach.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Mar - 12 May 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted in 1992

Deviations:

yes

Remarks:

room temperature in the animal room was 22 ± 3 °C instead of 20 ± 3 °C as recommended by the guideline

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Type of study:

Buehler test

Justification for non-LLNA method:

An in vivo skin sensitisation study is available that was performed prior to 1 June 2008. In accordance with Regulation (EC) No. 1907/2006, the data were included to avoid unnecessary testing.

Species:

guinea pig

Strain:

Dunkin-Hartley

Remarks:

Pirbright White Hsd/Win:DH

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Versuchstierzucht, Borchen, Germany
- Age at study initiation: Healthy young adults, not further specified
- Weight at study initiation: < 500 g
- Housing: Conventional housing, max, 5 animals per cage in Macrolon cage (type IV)
- Diet: Ssniff G 4-Alleindiät für Meerschweinchen, Ssniff Spezialfutter GmbH, Soest, Germany, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 6 Mar To: 12 May 1995

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

6 h

Adequacy of induction:

other: Test substance did not cause skin irritation.

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100%

Day(s)/duration:

6 h

Adequacy of challenge:

other: Test substance did not cause skin irritation.

No. of animals per dose:

10 (controls), 20 (in test groups)

Details on study design:

RANGE FINDING TESTS:
The left and right flanks of three animals was clipped 2 - 3 h prior to application. Formulations containing 5, 25 and 50% test substance in maize oil were prepared by heating the test subtance. 0.3 mL of test formulations as well as unchanged test substance (without vehicle) were applied to gauze patches (2 cm x 2 cm). Four gauze patches were then applied to the clipped skin of the animals as follows:

- left flank, anterior part: 5%
- left flank, posterior part: 25%
- right flank, anterior part: 50%
- right flank, posterior part: 100%

Patches were fixed under occlusive conditions for 6 h. After patch removal, the test sites were gently cleaned with vehicle and a soft tissue. Skin reactions were scored 36 and 60 h after start of the application. No skin reactions occured in any animal at any time point. Therefore, a concentration of 100% test substance (unchanged, without vehicle) was chosen for the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: Unchanged test substance
- Control group: Maize oil
- Site: left flank
- Frequency of applications: Every 7 days
- Duration: Days 0-14
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 28
- Exposure period: 6 h
- Test groups: Unchanged test substance and maize oil
- Control group: Unchanged test substance and maize oil
- Site: Posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

no

Remarks:

Historical control data provided in study report

Positive control results:

The results of a positive control test (7 Nov - 2 Dec 1994) are provided in the study report. The positive control substance 2-mercaptobenzothiazol (2-MCBT) induced skin sensitisation in 9/10 test animals.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no systemic effects observed

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no systemic effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction: 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no systemic effects observed

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction: 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no systemic effects observed

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

Induction: 2.5%; challenge: 50%

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

no systemic effects observed

Remarks on result:

positive indication of skin sensitisation

Remarks:

Historical control data provided in study report

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

Induction: 2.5%; challenge: 50%

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

no systemic effects observed

Remarks on result:

positive indication of skin sensitisation

Remarks:

Historical control data provided in study report

No signs of systemic or local toxicity were noted in any animal.

Detailed tables are attached as pdf documents under 'Attached background material'.

Interpretation of results:

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

Conclusions:

The test substance did not induce skin sensitisation in a Buehler test according to OECD guideline 406.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Data on skin sensitisation are available for alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) as well as several member substances of the Alcohol Ethoxylates (AE) category.

 

Study with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5)

The skin sensitising potential of alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) was assessed in a Buehler test according to OECD guideline 406 and GLP (Sasol, 1995a). In a pre-test the highest non-irritant concentration of the test substance was investigated. Since the test substance did not cause skin irritation up to a concentration of 100% (unchanged), the induction and challenge concentrations in the main study were set at 100% (unchanged). In the main study 20 female Dunkin-Hartley (Pirbright White Hsd/Win:DH) guinea pigs were induced epicutaneously for 6 h under occlusive conditions with 100% test substance on Days 0, 7 and 14. A control group of 10 animals was treated with maize oil. Two weeks after the last induction animals were challenged by epicutaneous occlusive exposure for 6 h to 100% test substance and maize oil. 24 and 48 h after patch removal the application sites were assessed for signs of local irritation. No dermal reactions were observed in any test animal at any time point. In a positive control investigation with 2-mercaptobenzothiazol (2-MCBT) documented in the study report, skin sensitisation was induced in 9/10 test animals demonstrating the adequacy of the test design. According to the findings of the present study, the test substance is not considered to be a skin sensitiser.

 

Studies in the AE category

Studies investigating skin sensitisation are available for the following AE substances:

 

CAS No.	EC No.	Substance	Study protocol	Hazard conclusion
27252-75-1	500-058-1	Octan-1-ol, ethoxylated	OECD 442E	Negative in the activation of dendritic cells
			OECD 442D	Positive for keratinocyte activation
68439-50-9	500-213-3	Alcohols, C12-14, ethoxylated	OECD 406	Not sensitising
			Similar OECD 406	Not sensitising
68439-49-6	939-518-5	Alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO	OECD 406	Not sensitising
66455-14-9	500-165-3	Alcohols, C12-13, ethoxylated	Similar OECD 406	Not sensitising

 

Evaluation of skin sensitisation as observed in studies

All available study results indicate that AE substances have no potential to induce skin sensitisation. None of the category member substances turned out to be sensitising to skin in in vivo investigations (GPMT and Buehler test design), thus demonstrating similar toxicological properties. The maximum number of positively induced animals was 5 out of a group of 19 animals in the second study performed with alcohols, C12-14, ethoxylated (CAS No. 68439-50-9, EC No. 500-213-3). No animal showed a positive response in any of the other in vivo studies. The in vitro studies with octan-1-ol, ethoxylated (CAS No. 27252-75-1, EC No. 500-058-1) resulted in an inconclusive picture. A further investigation would be needed to finally conclude on the in vitro skin sensitisation potential of the substance. However, no further testing for the substance is warranted as it is corrosive to skin. In conclusion, the inconclusive assessment for octan-1-ol, ethoxylated (CAS No. 27252-75-1, EC No. 500-058-1) is not considered to invalidate the general findings of the in vivo studies, especially as this substance exhibits corrosive properties. Based on all available data on skin sensitisation in the AE category, it is established that the AE substances are not sensitising to skin.

This evaluation is considered sufficiently conclusive for the hazard assessment and classification and labelling of the AE substances. For a detailed evaluation of the skin sensitisation potential of the substances in the AE category, please refer to the category justification attached to the category object.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitisation obtained with alcohols, C16-18 (even numbered), ethoxylated, < 2.5 EO (CAS No. 68439-49-6, EC No. 939-518-5) and with other members of the Alcohol Ethoxylates (AE) category 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.