Registration Dossier

Administrative data

Description of key information

The skin sensitisation potential of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 429 using the Local Lymph Node Assay (LLNA).Preliminary investigations were performed at 50% w/v to establish the highest concentration of test substance which did not lead to systemic toxicity or excessive local irritation. The study comprised three treated groups, each comprising four female mice receiving the test substance at concentrations of 10, 25 or 50% w/v. Similarly constituted groups received the vehicle (acetone:olive oil (4:1 v/v)) or positive control substance (25% v/v hexyl cinnamic aldehyde). The mice were treated by daily application of 25 μl of the appropriate concentration or control (vehicle or positive), to the dorsal surface of both ears for three consecutive days. The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation of 3H-methyl Thymidine (3HTdR) by β-scintillation counting of LNC suspensions. The response was expressed as radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into LNC of test nodes relative to that recorded for control nodes (test/control ratio, termed as Stimulation Index (SI)). The results of preliminary investigations indicated that 50% w/v would be a suitable high concentration for use on the main study. The SI obtained for 10, 25 and 50% w/v were 1.2, 1.6 and 2.3 respectively which indicates that the test substance did not show the potential to induce skin sensitization. The EC3 value was greater than 50% w/v. The SI for the positive control substance hexyl cinnamic aldehyde was 9.0, which demonstrates the validity of this study. The test substance is not regarded as a potential skin sensitizer.

The LLNA was performed before 11th October 2016.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Healthy female CBA/Ca mice (a total of 22 females) were obtained from Harlan UK Limited. The mice were in the weight range 16.2 to 18.7 g and approximately eight to twelve weeks of age prior to dosing on Day 1. They were acclimatised to the experimental environment for at least 5 days prior to the start of the study. Each animal was assigned an alpha-numeric code and identified uniquely within the study by tail marking. Each cage label was colour-coded and was identified uniquely with the study number, test substance concentration and animal mark(s).
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
10, 15 and 50 % w/v
No. of animals per dose:
4.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
911.78 Dpm. Test/control ratio = 9, where a result of greater than 3 indicates a positive response.
Key result
Parameter:
SI
Value:
2.3
Test group / Remarks:
50% w/v
Parameter:
SI
Value:
1.6
Test group / Remarks:
25% w/v
Parameter:
SI
Value:
1.2
Test group / Remarks:
10% w/v

Group

Concentration % w/v

Dpm/node

Test/control ratio†

Result

2

3

4

5

6

Control – AOO

10

25

50

HCA 25%

101.24

123.94

162.22

233.56

911.78

N/a

1.2

1.6

2.3

9.0

n/a

-

-

-

+

AOO = Acetone/olive oil (vehicle control)

HCA = Hexyl cinnamic aldheyde (positive control)

NB Group 1 was the preliminary phase

Interpretation of results:
GHS criteria not met
Conclusions:
Propoxylated Phenol Derivative is not regarded as a potential sensitizer.
Executive summary:

The skin sensitisation potential of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 429 using the Local Lymph Node Assay (LLNA). Preliminary investigations were performed at 50% w/v to establish the highest concentration of test substance which did not lead to systemic toxicity or excessive local irritation. The study comprised three treated groups, each comprising four female mice receiving the test substance at concentrations of 10, 25 or 50% w/v. Similarly constituted groups received the vehicle (acetone:olive oil (4:1 v/v)) or positive control substance (25% v/v hexyl cinnamic aldehyde). The mice were treated by daily application of 25 μl of the appropriate concentration or control (vehicle or positive), to the dorsal surface of both ears for three consecutive days. The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation of 3H-methyl Thymidine (3HTdR) by β-scintillation counting of LNC suspensions. The response was expressed as radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into LNC of test nodes relative to that recorded for control nodes (test/control ratio, termed as Stimulation Index (SI)). The results of preliminary investigations indicated that 50% w/v would be a suitable high concentration for use on the main study. The SI obtained for 10, 25 and 50% w/v were 1.2, 1.6 and 2.3 respectively which indicates that the test substance did not show the potential to induce skin sensitization. The EC3 value was greater than 50% w/v. The SI for the positive control substance hexyl cinnamic aldehyde was 9.0, which demonstrates the validity of this study. The test substance is not regarded as a potential skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information on respiratory sensitisation. However, no concerns are expected. As chemical respiratory sensitisers also elicit positive results in predictive tests for contact sensitisation, a negative outcome for dermal sensitisation is also predictive for non respiratory sensitisation of the substance. Additionally, the likelihood for exposure via inhalation and thus becoming sensitised to the registered substance, is very low, based on the high boiling point and very low vapour pressure and use that is limited to industrial and professional users and which does not involve the forming of aerosols, particles or droplets of an inhalable size.

As suggested in REACH Guidance Document R7a. (R.7.3.5 Information and its sources on respiratory sensitisation), the negative results on skin sensitisation from an adequately performed appropriate test can indicate that the substance lacks the potential to cause allergic sensitisation of the respiratory tract.

Justification for classification or non-classification

Propoxylated Phenol Derivative is not regarded as a potential sensitizer.