Registration Dossier

Administrative data

Description of key information

Read-across, key, guinea pig, OECD 406, GLP: negative

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:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH

The basis for this read-across is the “Read-Across Assessment Framework” (RAAF) (ECHA 2017). The analogue approach is applied. The read-across hypothesis is that the target and the source substances have similar (eco)toxicological and fate properties as a result of structural similarity. According to the RAAF this approach is covered by scenario 2: “Different compounds have the same type of effect(s)”.
“This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds with qualitatively similar properties. For the REACH information requirement under consideration, the property investigated in a study conducted with one source substance is used to predict properties that would be observed in a study with the target substance if it were to be conducted. Qualitatively similar properties or absence of effect are predicted. The predicted property may be similar or based on a worst-case approach” (ECHA 2017) (for details see read-across statement in section 13).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

The target and the source substances are waxy solids. Their physical and chemical properties are in the same range. The target and the source substances are of highest purity. Thus, there are no impurities to consider in this read-across approach (for details see read-across statement in section 13).

3. ANALOGUE APPROACH JUSTIFICATION

Read-across is intended for the endpoints skin and eye irritation and skin sensitisation using data on the source substance. This is based on a similar toxicokinetic pattern and congruent results in toxicological studies. In addition, no toxicological mode of action is indicated by a profiling with the OECD QSAR Toolbox v4.3 (for details see read-across statement in section 13).

The source substance was tested for skin sensitisation in a guinea pig maximisation test according to OECD Guideline 406 and GLP. 5 females were treated with the vehicles liquid paraffin and polyethylene glycol 400 (group 1) and 10 females were treated with the test material (group 2). Induction included intradermal injection of test material preparation in liquid paraffin (25 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene glycol 400 (7.5 g/L) for 48 hours on experimental day 8. Challenge by topical application of the test material preparation in polyethylene glycol 400 (2.5 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 hours and 72 hours after start of treatment. The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. After challenge no positive reactions were seen 48 or 72 hours after treatment with the test material. As a conclusion of the study the source substance is considered to be not skin sensitising. This study is also valid for the target substance based on the given justification. Therefore, the target substance is also considered to be not skin sensitising.

4. DATA MATRIX
for details see read-across statement in section 13
Reason / purpose:
read-across source
Positive control results:
50% positive reactions with control substance
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
25 g/L (induction I), 7.5 g/L (induction II), 2.5 g/L (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
25 g/L (induction I), 7.5 g/L (induction II), 2.5 g/L (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of toxicity
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
PEG400 undiluted
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no signs of toxicity
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
PEG400 undiluted
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no signs of toxicity
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
10 g/L alpha-Hexylcinnamaldehyde
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
10 g/L alpha-Hexylcinnamaldehyde
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Pretest data

For the main study the following concentrations were chosen:

Vehicle:       Liquid paraffin (for intradermal induction)

Polyethylene glycol 400 (for topical induction and challenge)

Test material

Intradermal induction:        25 g/L slightly irritant

Topical induction:               7.5 g/L slightly irritant (48 hours exposure)

Topical challenge:              2.5 g/L not irritant (24 hours exposure)

Main test:

Findings in the induction phase

After intradermal injection, the common signs of irritation after injection of Freund's complete adjuvant were observed. The injection sites were swollen and red, later on, scabs developed.

Findings after challenge

Group 1: negative control group

After challenge with polyethylene glycol 400 (PEG400), no erythema or edema were observed at the readings.

A single treatment was performed with the test material (2.5 g/L PEG400) to exclude the primary irritation potential of the test material. No positive reactions were observed in the treated areas at any reading.

Group 2: test material group

The challenge was performed on the right flank with the test material preparation in PEG400.

No positive skin reactions were observed in the areas treated with PEG400 alone at any reading.

After challenge with the test material (2.5 g/L preparation in PEG400) no positive skin reactions were observed at the readings. This results in 0 % positive reactions at challenge.

Clinical findings and mortality

The clinical behavior of the guinea pigs was normal during the experimental part. All animals survived the experimental part.

Body weight

The body weight development corresponded to that of the animals of the vehicle group.

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
Under the given experimental conditions, the test material induced no reactions. According to Regulation (EC) No 1272/2008, the test material is not classified as a skin sensitiser. The read-across analogue approach is based on similarity in chemical structure, physical-chemical properties, toxicokinetic behaviour and toxicological study results. As a conclusion, it is scientifically justified to fill toxicological data gaps for the target substance with data on the respective source substance. Therefore the same result can be applied to the target substance.
Executive summary:

The source substance was tested for skin sensitisation in a guinea pig maximisation test according to OECD Guideline 406 following GLP.

Purpose

The purpose of this GPMT assay was to identify the contact allergenic potential of the test material. This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man.

Study Design

The test material was investigated for skin sensitising properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969).

5 females were treated with the vehicles liquid paraffin and polyethylene glycol 400 (group 1) and 10 females were treated with the test material (group 2).

Induction included intradermal injection of test material preparation in liquid paraffin (25 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene glycol 400 (7.5 g/L) for 48 hours on experimental day 8.

Challenge by topical application of the test material preparation in polyethylene glycol 400 (2.5 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 hours and 72 hours after start of treatment.

Results

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. After challenge no positive reactions were seen 48 or 72 hours after treatment with the test material.

Conclusion

Under the given experimental conditions, the test material induced no reactions. According to Regulation (EC) No 1272/2008, the test material is not classified as a skin sensitiser. The read-across analogue approach is based on similarity in chemical structure, physical-chemical properties, toxicokinetic behaviour and toxicological study results. As a conclusion, it is scientifically justified to fill toxicological data gaps for the target substance with data on the respective source substance. Therefore the same result can be applied to the target substance.

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

Read-across, Guinea pig maximisation test, OECD 406

The source substance was tested for skin sensitisation in a guinea pig maximisation test according to OECD Guideline 406 following GLP.

Purpose

The purpose of this GPMT assay was to identify the contact allergenic potential of teh test material. This study should provide a rational basis for risk assessment to the sensitising potential of the test item in man.

Study Design

The test material was investigated for skin sensitising properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969).

5 females were treated with the vehicles liquid paraffin and polyethylene glycol 400 (group 1) and 10 females were treated with the test material (group 2).

Induction included intradermal injection of test material preparation in liquid paraffin (25 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene glycol 400 (7.5 g/L) for 48 hours on experimental day 8.

Challenge by topical application of the test material preparation in polyethylene glycol 400 (2.5 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 hours and 72 hours after start of treatment.

Results

The animals did not show any clinical signs during the course of the study and no cases of mortality were observed. After challange no positive reactions were seen 48 or 72 hours after treatment with the test material.

Conclusion

Under the given experimental conditions, the test material induced no reactions. According to Regulation (EC) No 1272/2008, the test material is not classified as a skin sensitiser. The read-across analogue approach is based on similarity in chemical structure, physical-chemical properties, toxicokinetic behaviour and toxicological study results. As a conclusion, it is scientifically justified to fill toxicological data gaps for the target substance with data on the respective source substance. Therefore the same result can be applied to the target substance.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of the read-across key study for in vivo skin sensitisation, no classification for skin sensitisation is triggered in accordance with Regulation (EC) No 1272/2008.