Registration Dossier

Administrative data

Description of key information

not sensitising (HRIPT)

Not sensitising (GPMT; similar to OECD TG 406; intradermal induction: test substance 0.1 % v/v in water for injection, cutaneous induction: test substance 10% v/v in distilled water, challenge: 2.5 % or 1% v/v of the test substance in distilled water; cutaneous reactions were considered as irritative response; read-across from DHTDMAC)

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

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: quaternary ammonium and saturated or unsaturated alkyl chains with comparable length (corresponding to scenario 2 of the read-across assessment framework)

The read-across hypothesis is based on structural similarity of target and source substances. Based on available experimental data, including key physicochemical properties and data from acute toxicity, irritation, sensitization (human) and genotoxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all substances.

Therefore, read-across from the existing ecotoxicity, environmental fate and toxicity studies conducted with the source substances is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A justification for read-across is attached to IUCLID section 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See justification for read-across attached to IUCLID section 13.

3. ANALOGUE APPROACH JUSTIFICATION
See justification for read-across attached to IUCLID section 13.

4. DATA MATRIX
See justification for read-across attached to IUCLID section 13.
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across source
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted similar to guideline is available, which is reliable with restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.
Species:
guinea pig
Strain:
Dunkin-Hartley
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
4 and 3 animals with erythema grade 1 and 2 respectively.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 7.0. Total no. in groups: 15.0. Clinical observations: 4 and 3 animals with erythema grade 1 and 2 respectively..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
1 and 3 animals with erythema grade 1 and 2 respectively. One animal with erythema grade 2 showed also oedema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 1 and 3 animals with erythema grade 1 and 2 respectively. One animal with erythema grade 2 showed also oedema grade 1..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
1 and 2 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: 1 and 2 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
6 and 4 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 10.0. Total no. in groups: 15.0. Clinical observations: 6 and 4 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
4 and 3 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other).
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 7.0. Total no. in groups: 15.0. Clinical observations: 4 and 3 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other)..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
5
Total no. in group:
15
Clinical observations:
3 and 2 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other).
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 5.0. Total no. in groups: 15.0. Clinical observations: 3 and 2 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other)..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
1 animal with erythema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 1.0. Total no. in groups: 15.0. Clinical observations: 1 animal with erythema grade 1..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 15.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 15.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
2 and 1 animals with erythema grade 1 and 2 respectively.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: 2 and 1 animals with erythema grade 1 and 2 respectively..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
2 animals with erythema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 2.0. Total no. in groups: 15.0. Clinical observations: 2 animals with erythema grade 1..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
2 and 1 animals with erythema grade 1 and 2 respectively.
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
1 animal with erythema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2 and 1 animals with erythema grade 1 and 2 respectively.. No with. + reactions: 1.0. Total no. in groups: 15.0. Clinical observations: 1 animal with erythema grade 2..
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study and according to the criteria laid down in CLP (Reg 1272/2008/EC), the substance does not induce delayed contact hypersensitivity and is not classified.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

As the substance is classified as skin corrosion (Category 1), no testing of skin sensitisation is required. However, for the assessment of sensitisation potential of Di-C12-18 alkyldimethyl ammonium chloride two studies with volunteers (HRIPT) are available. Additional supporting data are available for the source substance DHTDMAC. A justification for read-across is attached to IUCLID section 13.

 

Di-C12-18 alkyldimethyl ammonium chloride (0.3% aqueous solution) was not sensitising in a human repeat insult patch test on 15 subjects. The test item found to be highly irritating when applied as received (3%), but was non-irritating after diluting 1:10 with distilled water (3% for the first two applications, 0.3% in distilled water for subsequent applications). There was no evidence of sensitisation of any panelist.

 

Di-C12-18 alkyldimethyl ammonium chloride (1% in isopropanol) was not sensitising in a human repeat insult patch test on 12 subjects.

 

Further supporting data are available for the source substance DHTDMAC:

A human repeat insult patch test was performed with a 75% aqueous dilution of DHTDMAC according to the method based on that of Shelanski and Shelanski. A total of 84 volunteers took part in the test. The panel included 77 women and 7 men ageing from 18 to 61 years and more. 73 panellists completed the full test.

A patch loaded with 0.5 ml of 2% v/v test material in distilled water was applied down the dorsal surface of the upper arm of each subject. Subjects were instructed to keep the patches dry and to remove and discard them after 24 hours. Patches were applied on Monday, Wednesday and Friday of the first 3 weeks, called the "induction" or "insult" period. Patches were re-applied to the same site unless reaction to a substance or adhesive necessitated relocation, in which case an adjacent location was chosen.

The test sites were scored before application of each subsequent patch and on the fourth Monday after the final insult patch.14 days after the final insult patch, challenge patches were applied to both arms of each subject. Scoring were done 48 and 96 hours after patch removal.

The potential of the substance to induce delayed contact hypersensitivity was assessed in guinea pigs using DHTDMAC (78% active in isopropanol/water). The study was performed according to a method equivalent to the OECD guideline 406 and a statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was provided.

The induction phase was realized both by intradermal route on day 1 (Test substance 0.1 % v/v in water for injection) and by cutaneous route on day 8 (Test substance 10% v/v in distilled water) in 2 groups of guinea pigs: 15 males for control group and 15 males for treated group. The challenge phase was realized on day 22 by cutaneous application of the test substance at 2.5% and 1% v/v in distilled water on two sites on the left flank. The cutaneous reactions were scored 24, 48 and 72 hours after the challenge phase.

After the challenge application with 2.5 % v/v of the test substance in distilled water, erythema grade 1 or 2 were observed in 7, 4 and 3 controls animals at the 24, 48 and 72-hours readings respectively. 1 control animal showed also oedema. In the treated group, the incidence and severitiy of the cutaneous reactions were quite similar: 10, 7 and 5 treated animals showed erythema grade 1 or 2 at the 24, 48 and 72-hours readings. 2 treated animals showed oedema.

After the challenge application with 1% v/v of the test substance, an erythema (grade 1 or 2) was observed in 3, 2 and 1 out the 15 animals of the treated group at the 24, 48 and 72-hour readings respectively. In the control group, 1animal showed an erythema grade 1at the 24 -hour reading.

The persistent cutaneous reactions observed in 3/15 animals of the treated group after the challenge application may be attributable to delayed contact hypersensitivity but as the cutaneous reactions were more confined to the 24 hour examination, they were more consistent with irritation than delayed contact hypersensitivity.

Therefore, the cutaneous reactions observed in 3/15 animals (20%) of the treated groups were considered as irritative response and the substance was not considered as a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account.

Justification for classification or non-classification

Based on the available data Di-C12-18 alkyldimethyl ammonium chloride does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 with respect to sensitisation.