Registration Dossier

Administrative data

Description of key information

To induce skin sensitisation, the target substance must be bioavailable in the skin (i.e. it must penetrate the stratum corneum of the skin), therefore skin penetration is a prerequisite for the induction of skin sensitisation (step 1 in the Adverse Outcome Pathway for skin sensitisation, OECD 2012). However, nanomaterials usually do not penetrate the skin, recently summarized e.g. in a publication written by the ECETOC Nano Task Force (Landsiedel et al., 2017). In line with that, in vivo skin sensitisation studies with other carbon-based NM do not indicate a skin sensitisation potential of carbon-based NM: multiwalled carbon nanotubes (MWCNT) were found negative in guinea pigs (OECD TG 406, Ema et al., 2011 and Murthy et al., 2011 - see cross-reference for supporting information); singlewalled carbon nanotubes (SWCNT) were also negative in guinea pigs (OECD TG 406, Ema et a., 2011).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reason / purpose:
data waiving: supporting information
Reason / purpose:
data waiving: supporting information
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: Literature data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
OECD Guidelines for Testing of Chemicals, Number 406 "Skin Sensitization", adopted by the Council on July 17,1992 (reported Paris, April 29,1993).
Deviations:
no
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
no details given
Specific details on test material used for the study:
MWCNT1: 5-8 microns in length with 3-8 nm inside diameter and outside diameter of 140 ± 30 nm; Product No. 659258 purchased from Sigma-Aldrich, USA.
The multi-walled carbon nanotubes used in the study were produced by catalytic chemical vapor deposition (CCVD). MWCNT1 were composed of 99.9 % carbon with small amount (<0.1% Fe) of iron. The manufacturer specification for nanomaterial characterization was confirmed by the following techniques. MWCNT1 characteristics were assessed in the as-synthesized form prior to use for experiments or after dispersion in the vehicle (distilled water) for dosing. Solution characteristics were measured with dynamic light scattering (DLS).
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 300 - 400 g
- Housing: individually in standard stainless steel cages and sterilized paddy husk as bedding. Bedding material was changed daily, whereas water bottles were changed on alternate days
- Diet (e.g. ad libitum): ad libitum standard rabbit pellet food (supplier: M/s. Amrut Laboratory Animal Feed, Pune). The diet was supplemented with ascorbic acid.
- Water (e.g. ad libitum): ad libitum supply of UV treated water
The food and water was routinely analyzed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ±20 %
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle
Route:
epicutaneous, occlusive
Vehicle:
not specified
Remarks:
purified
Concentration / amount:
400 mg
Day(s)/duration:
induction (day 1), same treatment was repeated on day 7 and 14
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
200 mg
Day(s)/duration:
challenge on day 28, observation 30 and 54 h after challenge exposure
Adequacy of challenge:
not specified
No. of animals per dose:
20 (test group)
10 (control group)
Details on study design:
- Exposure period: day 0, day 7, day 14
- Test groups: 20 animals
- Control group: 10 animals
- Site: One flank of each animal was closely clipped free of hair, without any abrasion, 24 hours before the induction exposure
- Frequency of applications: 3 times
- Duration: 6h
- Concentrations: 400 mg

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Test groups: 20 animals
- Control group: 10 animals
- Site: posterior flank of both treatment and control groups
- Concentrations: 200 mg
- Evaluation (hr after challenge): 30h and 54 h after application challenge
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
30
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None of the animals treated with MWCNT1 showed any dermal reactions
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
54
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None of the animals treated with MWCNT1 showed any dermal reactions
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
None of the animals treated with MWCNT1 exhibited any dermal reactions. Hence MWCNT1 could be considered as non sensitizer.
Executive summary:

In order to assess the cutaneous allergenic potential of MWCNT1, the Buehler-Test was performed in 30 (20 test and 10 control) male Dunkin Hartley guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6.

The test substance at a dose of 400 mg was applied to all the animals of treatment group for a period of 6 h. The same treatment was repeated on days 7 and 14. Similarly, the animals in control group were treated with distilled water. On day 28 the nanomaterial was applied on a cotton pad at a dose of 200 mg to both treatment and control groups for 6 h.

The skin reactions were observed and scored at 30 h and 54 h after application.

None of the animals treated with MWCNT1 did exhibited any dermal reactions. Hence MWCNT1 could be considered as non sensitizer.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: Literature data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
OECD Guidelines for Testing of Chemicals, Number 406 "Skin Sensitization", adopted by the Council on July 17,1992 (reported Paris, April 29,1993).
Deviations:
no
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
no details given
Specific details on test material used for the study:
MWCNT 2: 1-10 microns in length with 2-6 nm inside diameter and outside diameter of 10-15 nm; Product No. 677248, purchased from Sigma-Aldrich, USA.
The multi-walled carbon nanotubes2 used in the study were produced by catalytic chemical vapor deposition (CCVD). The MWCNT2 were composed of 99.9 % carbon with small amount (<0.1% Fe) of iron. The manufacturer specification for nanomaterial characterization was confirmed by the following techniques. MWCNT2 characteristics were assessed in the as-synthesized form prior to use for experiments or after dispersion in the vehicle (distilled water) for dosing. Solution characteristics were measured with dynamic light scattering (DLS).
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 300 - 400 g
- Housing: individually in standard stainless steel cages and sterilized paddy husk as bedding. Bedding material was changed daily, whereas water bottles were changed on alternate days
- Diet (e.g. ad libitum): ad libitum standard rabbit pellet food (supplier: M/s. Amrut Laboratory Animal Feed, Pune). The diet was supplemented with ascorbic acid.
- Water (e.g. ad libitum): ad libitum supply of UV treated water
The food and water was routinely analyzed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ±20 %
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle
Route:
epicutaneous, occlusive
Vehicle:
not specified
Remarks:
purified
Concentration / amount:
400 mg
Day(s)/duration:
induction (day 1), same treatment was repeated on day 7 and 14
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
200 mg
Day(s)/duration:
challenge on day 28, observation 30 and 54 h after challenge exposure
Adequacy of challenge:
not specified
No. of animals per dose:
20 (test group)
10 (control group)
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures:
- Exposure period: day 0, day 7, day 14
- Test groups: 20 animals
- Control group: 10 animals
- Site: One flank of each animal was closely clipped free of hair, without any abrasion, 24 hours before the induction exposure
- Frequency of applications: 3 times
- Duration: 6h
- Concentrations: 400 mg

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Test groups: 20 animals
- Control group: 10 animals
- Site: posterior flank of both treatment and control groups
- Concentrations: 200 mg
- Evaluation (hr after challenge): 30h and 54 h after application challenge
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
30
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None of the animals treated with MWCNT2 showed any dermal reactions
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
54
Group:
test group
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None of the animals treated with MWCNT2 showed any dermal reactions
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
None of the animals treated with MWCNT2 exhibited any dermal reactions. Hence MWCNT2 could be considered as non sensitizer.
Executive summary:

In order to assess the cutaneous allergenic potential of MWCNT2, the Buehler-Test was performed in 30 (20 test and 10 control) male Dunkin Hartley guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6.

The test substance at a dose of 400 mg were applied to all the animals of treatment group for a period of 6 h. The same treatment was repeated on days 7 and 14. Similarly, the animals in control group were treated with distilled water. On day 28 the nanomaterial was applied on a cotton pad at a dose of 200 mg to both treatment and control groups for 6 h.

The skin reactions were observed and scored at 30 h and 54 h after application.

None of the animals treated with MWCNT2 did exhibited any dermal reactions. Hence MWCNT2 could be considered as non sensitizer.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information, it is concluded that the substance does not need to be classified according to Regulation (EC) No 1272/2008.