Registration Dossier

Administrative data

Description of key information

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:
1984-02-27 To: 1984-03-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD Guideline 406 (Skin Sensitisation), GLP
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Acclimation period is 4 days instead of 5 days. Pre and post study body weight not mentioned in the report
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Inc
- Age at study initiation: Not available
- Weight at study initiation: Not available
- Housing: As per the S.O.P.
- Diet (e.g. ad libitum): As per the S.O.P.
- Water (e.g. ad libitum):As per the S.O.P.
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): As per the S.O.P.
- Humidity (%): As per the S.O.P.
- Air changes (per hr): As per the S.O.P.
- Photoperiod (hrs dark / hrs light):As per the S.O.P.


IN-LIFE DATES: From: 1984-02-27 To: 1984-03-30
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
One group of 20 test animals was treated with 0.4ml of 2% w/v of P1655 in distilled water for a period of 6 hours weekly for 3 induction exposure.
Test group and 10 control animals were challenged with 1% w/v of test material in distilled water .
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
One group of 20 test animals was treated with 0.4ml of 2% w/v of P1655 in distilled water for a period of 6 hours weekly for 3 induction exposure.
Test group and 10 control animals were challenged with 1% w/v of test material in distilled water .
No. of animals per dose:
20 animals in the test substance group and 10 animals in the vehicle control were treated with 0.4ml of 1% w/v of test material in distilled water .
Details on study design:
RANGE FINDING TESTS: Four animals were exposed for 6 hours period to various concentrations of the test substance
Concentration: 10%, 5%, 2% and 1% w/v P1655 in distilled water
Exposure period: 6 hours
Grading: the patch site were scored for irritation 24 and 48 hours following 6 hour patch application


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 induction exposure
- Exposure period: 6 hours
- Test groups: 0.4 ml of 2% w/v aqueous solution
- Control group: none
- Site: left shoulder of each animal
- Frequency of applications: once a week for 3 weeks
- Duration: 6 hours under occlusion
- Concentrations: 0.4 ml of 2% w/v aqueous solution of P1655

B. CHALLENGE EXPOSURE
- No. of exposures: one 6 hour exposure
- Day(s) of challenge: two weeks after third induction exposure
- Exposure period: 6 hours under occlusion
- Test groups: 1% w/v aqueous solution
- Control group: 1% w/v aqueous solution
- Site: left posterior quadrant of the side and back of the test animal
- Concentrations: 1% w/v aqueous solution of P1655
- Evaluation (hr after challenge): 24 and 48 hours after challenge exposure


OTHER: none
Challenge controls:
10 animals treated with 1% w/v of P1655 in distilled water .
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% w/v of test material in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No animal with positive response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% w/v of test material in distilled water . No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No animal with positive response.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% w/v of test material in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no animals with positive responses
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% w/v of test material in distilled water . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no animals with positive responses.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1% w/v of test material in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no animals with positive responses
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% w/v of test material in distilled water . No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no animals with positive responses.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1% w/v of test material in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no animals with positive responses
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1% w/v of test material in distilled water . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no animals with positive responses.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
P1655 (30.4%) C10-16 alkyldimethylamine, N-Oxides did not induce sensitization in the guinea pig model.
Executive summary:

One group of 20 test animals was treated with 2% w/v of P1655 (30.4% active C10 -16 alkyldimethyl amine N-oxides) in distilled water for a period of 6 hours weekly for 3 induction exposures. The test animals and control animals were challenged with 1% w/v of P1655 in distilled water. At primary challenge, no skin reactions were observed in the test and control animals at the concentration of 1% w/v of P1655 in distilled water. Therefore, it was concluded that  30.4% C10-C16 alkyldimethylamine, N-Oxide is not a skin sensitizer.

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

Two reliable animal studies are available. In the key study [Conine DL (1984) ] performed according to OECD TG 406 (Buehler method) under GLP, a group of 10 male and 10 female guinea pigs (Hartley) were treated with 2 % w/v of the test substance (containing 30.4 % AO) in distilled water for a period of 6 hours weekly for 3 induction exposures. The test substance was applied to the shaved left shoulder of each animal and covered occlusively for 6 hours. A group of 10 animals served as controls. The test animals and control animals were challenged with 1 % w/v of the test substance in distilled water two weeks after the final induction. The test substance was applied to the shaved left posterior quadrant of the side and back of the test animal and covered occlusively for 6 hours. Dermal reaction to the challenge was assessed 24 and 48 hours after the challenge exposure. No positive responses were noted at 24 or 48 hours. In the supporting study [Vinegar MB (1978)] also performed according to OECD TG 406 a group of 20 guinea pigs were treated with 0.4 mL of undiluted test substance (containing 27.8% AO) for a period of 6 hours weekly for 3 induction exposures. The test animals (and control animals) were challenged with 10 % w/v of the test substance in distilled water.At challenge, slight confluent or moderate patchy erythema (score 1) was observed in 2/20 test animals at the 24-hour reading. No positive responses were noted in the control animals. At 48 hours no positive responses were noted in the test and control animals.Thus, the responses observed at 24 hours were considered irritative in nature. Conclusion: the test substance is not a skin sensitiser in guinea pigs.

There are four reliable human patch test studies available. In the key study [MacLennan A (1982) ] performed according to good clinical regulations 21CFR parts 50, 56 & proposed ICH guideline, 78 (male and female) subjects were exposed to 9 induction patches containing 0.75% aqueous test substance (30% AO) under occlusion for a period of 3 weeks. Patches were removed 24 hours after each application and patch sites were graded at 48 hour after patch application prior to the next patch application. After a 2 week rest period, subjects were challenged with 0.75% aqueous test substance (30% AO) 24 hour patch exposure. Challenge patch sites were graded at 48 and 96 hours after patch application.31/78 subjects were observed with mild erythema grade1 during the challenge exposure. No positive responses indicative of delayed contact hypersensitivity was observed. A second human patch study [Cuthbert (1982) ] using 0.5% aqueous test substance (27.4% AO) conducted to the same study design also showed mild erythema grade 1 in 39/85 subjects during the challenge exposure. These skin responses resolved at the 96 hour challenge read and mild erythema was observed suggesting that these responses were irritative in nature. In a third human patch study [Yerker (1989) ] using 0.1% aqueous test substance (31.6% AO) conducted to the same study design none of the 106 subjects who completed the test produced visible response during the challenge test. In the fourth human patch study [Stephens & Herndon (1992)] performed to good clinical regulations, 141 (male and female) subjects were exposed to 6 induction patches containing 1.5% aqueous test substance (30 %AO) and 3 induction patches containing 0.75 % aqueous test substance under occlusion for a period of 3 weeks. Patches were removed 24 hours after each application and patch sites were graded at 48 hour after patch application prior to the next patch application. After a 17-23 day rest period, subjects were challenged with 0.75% aqueous test substance (30% AO) 48 hour patch exposure. Challenge patch sites were graded at 48 and 96 hours after patch application. At 48 hours during the challenge phase 2/141 subjects showed erythema grade 2. These skin responses resolved at the 96 hour challenge read and only 6/141 subjects were observed with erythema grade 0.5 with the remainder (135/141) scoring 0. All four reliable human patch test studies concluded that the test substance did not produce skin sensitisation in humans.


Migrated from Short description of key information:
C12-14 amine oxide was not sensitising in three human patch test studies. It was also not sensitising to the skin of Guinea pigs in two Buehler tests.

Justification for selection of skin sensitisation endpoint:
Study performed according to OECD TG 406 under GLP

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data are available regarding the potential of amine oxides to cause respiratory sensitisation.


Migrated from Short description of key information:
No information is available for this endpoint

Justification for classification or non-classification

Three repeat insult patch tests are available in humans. None of these studies showed evidence of sensitisation. In addition, two Buehler tests are available which show the substance is not sensitising to the skin of Guinea pigs. On the basis of these studies the C12 -14 amine oxide does not require classification as a skin sensitiser.