Amines, C12-16 alkyl dimethyl, reaction products with ethyl chloroacetate, 2-(2-aminoethylamino)ethanol and 2-propenoic acid

Endpoint summary

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:

September / October 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

At the time the study was conducted the Guinea Pig Maximation was the accepted standard test for skin sensitisation.

Species:

guinea pig

Strain:

other: Pirbright White

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Fa. Winkelmann Versuchstierzucht
- Age at study initiation: -
- Weight at study initiation: male 359 - 447 g, female 334 - 425 g
- Housing: collective housing up to a maximum of 5 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): -
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:-

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Pilot experiment:
Intradermal: 0.1 ml of 5.0 %, 1 %, 0.5 % and 0.1 % dilution in water.
Dermal: soaked patch with 100 %,50 %, 25 % , 10%, 5%, 1% and 0.5 % of the test substance in water.
Main study:
Intradermal: 0.1 ml of 1 % dilution in water.
Dermal: soaked patch with the undiluted test substance.
Challenge: soaked patch with 5 % and 1 % dilution in water.

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Pilot experiment:
Intradermal: 0.1 ml of 5.0 %, 1 %, 0.5 % and 0.1 % dilution in water.
Dermal: soaked patch with 100 %,50 %, 25 % , 10%, 5%, 1% and 0.5 % of the test substance in water.
Main study:
Intradermal: 0.1 ml of 1 % dilution in water.
Dermal: soaked patch with the undiluted test substance.
Challenge: soaked patch with 5 % and 1 % dilution in water.

No. of animals per dose:

10 male / 10 female

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2: intradermal and epicutaneous
- Exposure period:
- Test groups: 10 male / 10 female
- Control group: 10 male / 10 female
- Site: shoulders




B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 24 h
- Test groups: 2
- Control group: 1
- Site: flanks
- Concentrations: 5 % and 1 % dilutions in water
- Evaluation (hr after challenge): 24h and 48h after patch removal

OTHER:

Challenge controls:

2 control groups (1 % and 5 % test substance concentration)

Positive control substance(s):

yes

Remarks:

2.4 dinitrochlorobenzene and benzocaine

Positive control results:

The reaction to the positive control substances 2.4 dinitrochlorobenzene (strong sensitizer) and benzocaine (moderate sensitizer) is tested periodically. The last test with an acceptable level of response to each of these substances was performed in October 1991.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5 % dilution

No. with + reactions:

18

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 % dilution. No with. + reactions: 18.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5 % dilution

No. with + reactions:

19

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 % dilution. No with. + reactions: 19.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1 % dilution

No. with + reactions:

2

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1 % dilution. No with. + reactions: 2.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1 % dilution

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 % dilution. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5 % dilution

No. with + reactions:

17

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5 % dilution. No with. + reactions: 17.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5 % dilution

No. with + reactions:

14

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 % dilution. No with. + reactions: 14.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1 % dilution

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1 % dilution. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1 % dilution

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1 % dilution. No with. + reactions: 0.0. Total no. in groups: 20.0.

The intensity and severity of responses to the test article (concentration 5 %) in the test group were compared to the responses in controls and therefore the effects refer to severity may be attributable in a value of 0.70 only to the sensitizing potential of the test article (1.25 mean value in the control group vs. 1.95 in the test group). The comparison refer to intensity was nearly indiscriminately.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

According to the grading scheme of Magnusson and Kligman, the test article “REWOTERIC QAM 50” is classified as a “mild sensitizer”. The sensitisation rate at 24 h was 10 % with the 1 % dilution. The 5 % dilution caused skin reactions in 90 % of the test group animals and in 85 % of the control group animals. From the results it is assumed that the sensitization rate is < 30 % for both concentrations and the test substance is regarded as non-sensitising.

Executive summary:

The test substance was tested regarding its skin sensitisation potential. The test was performed according to the protocol of Magnusson and Kligman, in which adjuvant is used to elicit an immunologic reaction. The test protocol is in compliance with the OECD Guideline for the Testing of Chemicals No. 406 Skin Sensitisation (1992). The maximum compatible doses for the intradermal and dermal application as well as the subirritative dose for the challenge were determined in a pilot experiment. In the main experiment two test groups of ten (10) male and ten (10) female guinea pigs of the strain "Pirbright White" were treated intradermally with 0.1 ml of a 1 % dilution of the test substance in water. Two control groups of ten (10) male and ten (10) female animals received the vehicle only. For the dermal induction the undiluted test substance or the vehicle only (control group) was used. In the challenge application 5 % or 1 % dilutions of the test substance in water were applied to the flanks of the animals. Body weight development of the animals was positive and within normal ranges.

 In the challenge visible changes of the skin ( erythema and swelling grading 1 -3 ) were observed 24 hours after patch removal in

90 % (18/20) of the 5 % test group and in 85 % (17/20) of the 5 % control group animals indicating a distinct irritating potential of the 5 % concentration of the test substance. In the 1 % test group 10 % (2/20) of the animals showed only very slight erythema at the treated skin site after 24 hours. 48 h after the challenge these skin reactions were not observed anymore. In the corresponding 1 % control group no skin reaction was observed 24 hours and 48 hours after the challenge.

According to the grading scheme of Magnusson and Kligman, the test substance is classified as a “mild sensitizer”. The sensitisation rate was 10 % at 24 h and 0 % at 48 h with the 1 % dilution. The 5 % dilution caused skin reactions both in the test group animals and in the corresponding control group. From the results it is assumed that overall the sensitization rate is < 30 % and the test substance is regarded as non-sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The test substance was tested regarding its skin sensitisation potential according to the protocol of Magnusson and Kligman. The test protocol is in compliance with the OECD Guideline for the Testing of Chemicals No. 406 Skin Sensitisation (1992). In the main experiment two test groups of ten (10) male and ten (10) female guinea pigs were treated intradermally with a 1 % dilution of the test substance in water. Two control groups received the vehicle only. For the dermal induction the undiluted test substance or the vehicle only (control group) was used. In the challenge application 5 % or 1 % dilutions of the test substance in water were applied to the flanks of the animals. In the challenge visible changes of the skin (erythema and swelling grading 1 -3) were observed 24 hours after patch removal in 90 % (18/20) of the 5 % test group and in 85 % (17/20) of the 5 % control group animals indicating a distinct irritating potential of the 5 % concentration of the test substance. In the 1 % test group 10 % (2/20) of the animals showed only very slight erythema at the treated skin site after 24 hours. 48 h after the challenge these skin reactions were not observed anymore. In the corresponding 1 % control group no skin reaction was observed 24 hours and 48 hours after the challenge.

According to the grading scheme of Magnusson and Kligman, the test substance is classified as a “mild sensitizer”. The sensitisation rate was 10 % at 24 h and 0 % at 48 h with the 1 % dilution. The 5 % dilution caused skin reactions both in the test group animals and in the corresponding control group. From the results it is assumed that the sensitization rate is < 30 % and the test substance is regarded as non-sensitising according to the current CLP criteria.

Migrated from Short description of key information:
In the GPMT test with the test substance in a concentration of 1 % only very slight skin reactions were observed in two animals. The sensitisation rate was 10 %. Skin irritation effects were observed with the test substance in a concentration of 5 % in the test group and in the corresponding control group. The test substance is regarded as non-sensitising.

Justification for selection of skin sensitisation endpoint:
Acceptable, well-documented GLP guideline study report

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitisation is conclusive but not sufficient for classification according to DSD (67/548/EEC) and GHS (CLP

1272/2008/EC).