Registration Dossier

Administrative data

Description of key information

C12-14 AO was not sensitising in three human patch test studies. It was also not sensitising to the skin of Guinea pigs in two Buehler tests.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
23 november 2011-10 February 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
In the main study the skin was coated with sodium lauryl sulfate (SLS) on the day before stage 2 induction in order to ensure the induction of local irritation.
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
In the main study the skin was coated with sodium lauryl sulfate (SLS) on the day before stage 2 induction in order to ensure the induction of local irritation.
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The decision to perform this study in preference to the LLNA was taken based on the surface active properties of the substance. The potential for surface active substances to demonstrate sensitizing properties has been shown to be more accurately predicted using the M&K procedure than the LLNA. Some surfactants have been shown to demonstrate false positive responses in the LLNA, for example sodium lauryl sulfate.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH, Stolzenseeweg 32 – 36, 88353 Kißlegg, Germany
- Age at study initiation: 42 days
- Weight at study initiation: 315-420 g (excluding positive control group); positive control group 332-364 g
- Housing: The animals were kept in pairs in MAKROLON cages (MZK 80/25)
- Diet: Commercial diet, ssniff® Ms-H V2233 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany) served as food. This food was offered ad libitum.
- Water: Tap water (in drinking bottles) was offered ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: 28-11-2011 - 10-02-2012
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Preliminary Study:
Induction Phase: Intracutaneous - 0.1 mL of 0.004, 0.04, 0.4, 2 or 4% C10 AO; Topical - 2 mL of 0.4, 2, 4, 10, 20, 30 or 40 % C10 AO (non-depilated and depilated skin) and in addition 2 mL of 0.004, 0.02, 0.04, 0.2% C10 AO (depilated skin)
Main Study:
Induction Phase: Stage 1 (intracutaneous) - 0,1 mL of 0.2% C10 AO; Stage 2 (topical) - 2 mL of 10% C10 AO
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
2 mL of 0.04% C10 AO
Adequacy of challenge:
not specified
No. of animals per dose:
Preliminary Study: 10 animals for topical and 2 animals for intracutaneous
Main study: 20 animals for C10 AO; 10 animals for vehicle control; Historical data used for positive controls
Details on study design:
RANGE FINDING TESTS: see below

MAIN STUDY
A. INDUCTION EXPOSURE
STAGE 1 - INTRACUTANEOUS
- No. of exposures:1
- Exposure period: Day 0
- Test groups: (1) FCA (diluted 1:1 with 0.9% NaCl); (2) 0.2% C10 AO; (3) 0.2% C10 AO in a 1:1 mixture with FCA/physiological saline
- Control group: -
- Site: Shoulder
- Frequency of applications: single application
- Duration: -
- Concentrations: see above

STAGE 2 - TOPICAL
- No. of exposures:1
- Exposure period: Day 7
- Test groups: 10% C10 AO
- Control group: -
- Site: Shoulder
- Frequency of applications: single application
- Duration: -
- Concentrations: see above

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hrs
- Test groups: 10% C10 AO
- Control group: tap water (vehicle control)
- Site: L flank (test substance) R flank (control)
- Concentrations:
- Evaluation: 24 and 48 hrs after challenge

OTHER: On Day 6 the exposed skin was coated with 0.5 mL sodium lauryl sulfate (10% in vaseline) in order to ensure the induction of local irritation.
Challenge controls:
Treated with 0.04% C10 AO solution
Positive control substance(s):
yes
Remarks:
alpha-hexyl cinnamic aldehyde
Positive control results:
Animals of the same strain treated with alpha-hexyl cinnamic aldehyde in sesame oil exhibited a sensitising reaction in all animals in form of a discrete or patchy erythema (grade 1).
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.04 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no animals with positive responses
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.04 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no animals with positive responses
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: vehicle control
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: vehicle control
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.01%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: historical background group from October/November 2011
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.01%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: historical background group from October/November 2011

Preliminary Study:

Six concentrations of C10 AO were tested by intracutaneous injection: 0.004, 0.04, 0.2, 0.4, 2 or 4% solutions in tap water: A concentration of 0.004% revealed a discrete or patchy erythema, concentrations of 0.04% or 0.2% revealed a moderate and confluent erythema 24 to 72 hours after administration, respectively. Concentrations of 0.4%, 2% or 4% revealed an intense erythema and swelling with necrosis 24 to 72 hours after administration.

Several concentrations of C10 AO were tested by topical application: 0.4, 2, 4, 10, 20, 30 and 40% solutions to the non-depilated and depilated skin and, in addition, 0.004, 0.02, 0.04 and 0.2% to the depilated skin.

Non-depilated skin

Concentrations of 0.4% to 10% revealed a moderate and confluent erythema 48 hours and a discrete or patchy erythema 72 hours after start of exposure. The animals that received the 20% + 30% or 40% concentrations (equivalent to 3,300 and 2,640 mg AO/kg respectively) died prematurely. The cause of death could not be determined in this study.

Depilated skin

No skin reactions were observed up to the concentration of 0.04%. The concentration of 0.2% revealed a discrete or patchy erythema, concentrations of 0.4% or 2% revealed a moderate and confluent erythema 24 to 72 hours after start of exposure, respectively. Concentrations of 4% or 10% revealed a moderate and confluent erythema with brownish-green spots on the skin 24 to 72 hours after start of exposure. The animals receiving the 20% + 30% or 40% concentration (equivalent to 3,300 and 2,640 mg AO/kg respectively) died prematurely.

As mentioned, it was not possible to determine the cause of death of the animals in this study. In a subsequent study performed according to OECD TG 402 (see section 7.2.3) the acute dermal toxicity to rats was determined to be >2000 mg AO/kg bw, with no deaths or signs of toxicity observed in the study.

Based on the results of the preliminary study, it was decided to use a 0.2% concentration in tap water for the 1st (intracutaneous) induction stage, a 10% concentration in tap water for the 2nd (topical) induction stage and a 0.04% solution in tap water for the challenge.

Main Study:

A 0.2% solution of C10 AO chosen for the first (intracutaneous) induction stage revealed a discrete or patchy erythema in all 20 animals 24 and 48 hours after administration. However, in the main study the skin was coated with sodium lauryl sulfate on the day before the second (topical) induction using 10 % C10 AO in order to ensure the induction of local irritation. This treatment resulted in a moderate and confluent erythema in all test group animals 48 or 72 hours after start of exposure. Challenge with 2 mL of a 0.04 % solution of C10 AO revealed no skin irritation in any animal.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the present test conditions N,N-dimethyldecylamine-N-oxide revealed no sensitising properties in guinea pigs in a test model according to MAGNUSSON and KLIGMAN.
Executive summary:

The skin sensitisation potential of C10 AO was assessed in a study performed according to OECD TG 406 (Magnusson and Kligman Maximisation Test) under GLP using male Dunkin-Hartley Guinea pigs.

A preliminary study was performed to determine the appropriate dose level of C10 AO to use in the main study following intracutaneous and topical administration. Six concentrations of C10 AO in aqueous solution were tested by intracutaneous injection using two animals. The first animal received doses (0.1 mL) of 0.4, 2 and 4 % C10 AO in aqueous solution. The second animal received doses (0.1 mL) of 0.004, 0.04 and 0.2 % C10 AO in aqueous solution. A concentration of 0.004% C10 AO revealed a discrete or patchy erythema, concentrations of 0.04% or 0.2% C10 AO revealed a moderate and confluent erythema 24 to 72 hours after administration, respectively. Concentrations of 0.4%, 2% or 4% C10 AO revealed an intense erythema and swelling with necrosis 24 to 72 hours after administration. A total of ten animals were used for topical administration. The test area of four animals was shaved, whilst for six animals the test area was shaved and then depilated. The animals were then treated occlusively with one or two concentrations of C10 AO solution (2 mL per application). The patches were removed after 24 hours (shaved and depilated) or 48 hours (shaved-only) and assessed immediately, 24 and 48 hours after removal (shaved and depilated) or immediately and 24 hours (shaved-only) after removal for erythema and oedema. The concentrations of C10 AO tested were 0.4, 2, 4, 10, 20, 30 and 40 % to the shaved-only and shaved and depilated skin and in addition 0.004, 0.02, 0.04 and 0.2% to the shaved and depilated skin. In the shaved-only animals concentrations of 0.4% to 10% revealed a moderate and confluent erythema 24 hours and a discrete or patchy erythema 48 hours after removal of the patches. The animals that received the 20% + 30% or 40% concentrations (equivalent to 3,300 and 2,640 mg/kg respectively) died prematurely. The cause of death could not be confirmed in this study. In the shaved and depilated animals no skin reactions were observed up to the concentration of 0.04%. The concentration of 0.2% revealed a discrete or patchy erythema, concentrations of 0.4% or 2% revealed a moderate and confluent erythema 24 to 72 hours after start of exposure, respectively. Concentrations of 4% or 10% revealed a moderate and confluent erythema with brownish-green spots on the skin 24 to 72 hours after start of exposure. The animals receiving the 20% + 30% or 40% concentration (equivalent to 3,300 and 2,640 mg/kg respectively) died prematurely. The cause of death could not be confirmed in this study. In a subsequent study performed according to OECD TG 402 (see section 7.2.3) the acute dermal toxicity to rats was determined to be >2000 mg AO/kg bw, with no deaths or signs of toxicity observed in the study. Based on the results of the preliminary study, it was decided to use a 0.2% concentration in tap water for the 1st (intracutaneous) induction stage, a 10% concentration in tap water for the 2nd (topical) induction stage and a 0.04% solution in tap water for the challenge in the main study. The main study was performed using 20 animals and a further 10 animals were used as vehicle (tap water) controls. For the intradermal induction the animals received three pairs of injections (0.1 mL each) into the shoulder region as follows: Freund’s complete adjuvant (diluted 1:1 with 0.9 % NaCl); 0.2 % C10 AO solution; 0.2 % C10 AO solution in a 1:1 mixture with FCA/0.9 % NaCl solution. On Day 6, prior to topical induction, the shoulder area was shaved again and the skin coated within sodium lauryl sulfate (0.5 mL, 10 % solution in vaseline) in order to ensure the induction of local irritation. Although this step is considered unnecessary based on the irritation seen in the preliminary study, it was standard practice in the laboratory that conducted the study. On Day 7 the animals were exposed topically under occlusive conditions to a 10 % C10 AO solution (2 mL) for 48 hours.The test animals and control animals were challenged with a 0.04% solution of C10 AO two weeks after the final induction. The test substance was applied to the shaved and depilated flank of the test animal and covered occlusively for 24 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.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1978-08-16 to 1978-10-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
- Pre and post study body weights of the animals are not given
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre-GLP
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: Singly in wire mesh cages suspended above the droppings
OR Animal under restrainer during treatment
- Diet (e.g. ad libitum): Purina Guinea Pig Chow, ad libitum
- Water (e.g. ad libitum): Animals were maintained on medicated water containing 4% of sulfaethoxypyridazine ( 6.25% S.E.Z., American Cyanamid ) for 4 days. Then they were furnished with non-medicated water ad libitum.
- 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): 12 hour light dark cycle


IN-LIFE DATES: From: 1978-08-16 To: 1978-10-10
Route:
epicutaneous, occlusive
Vehicle:
other: Challenge - Distilled water
Concentration / amount:
One group of 20 test animals was treated with 0.4 ml of undiluted P0434 (27.8% DDAO) for an exposure period of 6 hours weekly for 3 induction
exposures.
Both test (20) and control (10) animals were challenged with P0434 as a 10% v/v solution in distilled water.
Route:
epicutaneous, occlusive
Vehicle:
other: Challenge - Distilled water
Concentration / amount:
One group of 20 test animals was treated with 0.4 ml of undiluted P0434 (27.8% DDAO) for an exposure period of 6 hours weekly for 3 induction
exposures.
Both test (20) and control (10) animals were challenged with P0434 as a 10% v/v solution in distilled water.
No. of animals per dose:
Range Finding test: 4 test animals treated with each of the following concentration- 10%, 5%, 2% and 1% v/v solutions of P0434 in distilled water.
Induction: group of 20 test animal treated with 0.4 ml of undiluted P0434.
Primary challenge: 20 test animals and 10 control animals treated with P0434 as a 10% v/v solution in distilled water.
Details on study design:
RANGE FINDING TESTS: Four animals treated with Dodecyl amine oxide as 10%, 5%, 2% and 1% v/v solutions in distilled water
Exposure period: 6 hours


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 induction exposure
- Exposure period: 6 hours
- Test groups: 0.4 ml of undiluted Dodecyl amine oxide
- Control group: None
- Site: Upper left quadrant of the backs of test animals
- Frequency of applications: Once a week for 3 weeks
- Duration: 6 hours under occlusion
- Concentrations: Undiluted Dodecyl amine oxide

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: Dodecyl amine oxide as a 10% v/v solution in distilled water
- Control group: Dodecyl amine oxide as a 10% v/v solution in distilled water
- Site: Lower left quadrant of the backs of test and control animals
- Concentrations: Dodecyl amine oxide as a 10% v/v solution in distilled water
- Evaluation (hr after challenge): 24 and 48 hours after challenge exposure


OTHER: none
Challenge controls:
10 animals (previously unexposed) treated with a 10% v/v solution of P0434 in distilled water.
Positive control substance(s):
no
Positive control results:
No positive controls reported in the study.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Dodecyl amine oxide as a 10% v/v solution in distilled water
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
2 animals - grade 1
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Dodecyl amine oxide as a 10% v/v solution in distilled water. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: 2 animals - grade 1.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Dodecyl amine oxide as a 10% v/v solution in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no animals with positive responses
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Dodecyl amine oxide as a 10% v/v solution 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:
Dodecyl amine oxide as a 10% v/v solution in distilled water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no animals with positive responses
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Dodecyl amine oxide as a 10% v/v solution 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:
Dodecyl amine oxide as a 10% v/v solution in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no animals with positive responses
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Dodecyl amine oxide as a 10% v/v solution in distilled water. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no animals with positive responses.
Interpretation of results:
GHS criteria not met
Conclusions:
P0434 (27.8% Dodecyl dimethyl amine oxide) did not induce sensitization in the guinea pig model.
Executive summary:

One group of 20 test animals was treated with 0.4 ml of undiluted P0434 (27.8% active dodecyl dimethyl amine oxide) for an exposure period of 6 hours weekly for 3 induction exposures. Both test (20) and control (10) animals were challenged with a 10% v/v solution of P0434 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 irritation in nature. P0434 (27.8% Dodecyl dimethyl amine oxide) did not induce sensitization in the guinea pig model.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
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
Justification for non-LLNA method:
Study performed before LLNA was available.
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.
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
GHS criteria not met
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:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Two reliable animal studies are available for C12-14 AO. 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 three reliable human patch test studies available for C12-14 AO. 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. In the second 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 third 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.

In addition, supporting studies are available for the following category members:

C10 AO: Guinea pig maximisation test (OECD TG 406) – not sensitising [Haferkorn J (2012)]

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.

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, C12 -14 AO is not sensitising to the skin of Guinea pigs. On the basis of these studies the C12 -14 AO does not require classification as a skin sensitiser.