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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Mar-May 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across to cetrimonium bromide from data on cetrimonium chloride (with data reliability value of 1). Read-across justifications are provided in the endpoint summary.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from standard test according to OECD 406 GPMT are considered suffiecient.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
intradermal
Vehicle:
water
Concentration / amount:
Induction: intradermal injections of 0.125% of the test substance,
Challenge: topical application of 0.5% of the test substance on 8 cm²
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: intradermal injections of 0.125% of the test substance,
Challenge: topical application of 0.5% of the test substance on 8 cm²
No. of animals per dose:
Preliminary study: 9 males and 10 females
Main study: 10 animals/sex in the treatment group and
5 animals/sex in the two control groups
Details on study design:
The preliminary study showed that topical application of a 1% of the test substance led to
erythema formation, while no alterations were observed in the areas treated with the test
substance diluted to 0.5%, 0.3% or 0.1%. Therefore 0.5% was chosen as the challenge
concentration. With regard to the intradermal injections, the lowest concentration tested in
the preliminary study (0.125%) induced clear erythema formation and was chosen as
induction concentration.
In the main study, the test group consisted of 10 male and 10 female Guinea pigs and the
two negative control groups of 5 male and 5 female Guinea pigs. Induction commenced
(day 0) with pairs of three intradermal injections, of a) FCA, b) test substance (0.125%) in
saline, and c) test substance (0.125%) in a 1: 1 mixture of FCA and saline. A 2 x 4 cm
shaven area on the supracapular region of each animal, on either side of the mid-dorsal line
was treated. The control group received injections of the respective vehicles without test
substance. One week later, the induction process was completed with a single topical
application of the test substance (3% in distilled water) on a 2 x 4 cm filter paper patch
onto the test area. The patch was covered by an occlusive bandage for 48 hours. The
control groups received only the vehicle without test substance. After removal of the
patches, the skin area was washed with warm water. On day 21, the previously shaven left
side of treated animals and the first control group animals was treated topically with 0.5 ml
test substance (0.5%) in distilled water; 0.5 ml vehicle alone was applied to the right side.
The sites were covered by an occlusive bandage for 24 hours. After patch removal, the zone
was washed with warm water. On day 28, a second challenge was carried out identically to
the first one. The test substance was applied to the right side of the treated animals and the
second control group animals. Each animal was observed at least twice a day for clinical
signs.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
Mild erythema (grade 1)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 3.0. Total no. in groups: 20.0. Clinical observations: Mild erythema (grade 1).
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
na
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
Mild erythema (grade 1) on vehicle-treated side
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: na. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: Mild erythema (grade 1) on vehicle-treated side.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
na
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
Mild erythema (grade 1) on the vehicle-treated side
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: na. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: Mild erythema (grade 1) on the vehicle-treated side.
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group treated with test substance
Dose level:
0.5%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Mild erythema (grade 1)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group treated with test substance. Dose level: 0.5%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: Mild erythema (grade 1).
Reading:
1st reading
Hours after challenge:
24
Group:
other: control group treated with test substance
Dose level:
na
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Mild erythema (grade 1) on vehicle-treated-side
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: other: control group treated with test substance. Dose level: na. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: Mild erythema (grade 1) on vehicle-treated-side.
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
Mild erythema (grade 1)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: Mild erythema (grade 1).
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
na
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Mild erythema (grade 1) on the vehicle-treated side
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: na. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: Mild erythema (grade 1) on the vehicle-treated side.
Reading:
2nd reading
Hours after challenge:
24
Group:
other: control group treated with test substance
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Mild erythema (grade 1)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: other: control group treated with test substance. Dose level: 0.5%. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: Mild erythema (grade 1).
Reading:
2nd reading
Hours after challenge:
24
Group:
other: control group treated with test substance
Dose level:
na
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
Mild erythema (grade 1) on vehicle-treated-side
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 24.0. Group: other: control group treated with test substance. Dose level: na. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: Mild erythema (grade 1) on vehicle-treated-side.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Both test and control groups
Dose level:
0.5%
No. with + reactions:
0
Total no. in group:
30
Clinical observations:
No skin reactions were observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: Both test and control groups. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 30.0. Clinical observations: No skin reactions were observed.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the observations in the study it is concluded that the test substance - 24-26% cetrimonium chloride in water produced no skin sensitisation under conditions of the study. The observed skin reactions occurred at similar incidence and severity in the animals of both the treatment and control groups and similar reactions were found in vehicle-treated animals of both groups.
Executive summary:

The SCCS opinion document refers to a study with cetrimonium chloride: 24-26% cetrimonium chloride in water. Skin sensitisation was studied for 24 -26% cetrimonium chloride in water following the OECD TG 406, Magnusson Kligman Maximisation test. Based on the observations in the study it is concluded that the test substance 24-26% cetrimonium chloride in water produced no skin sensitisation under conditions of the study. The observed skin reactions occurred at similar incidence and severity in the animals of both the treatment and control groups and similar reactions were found in vehicle-treated animals of both groups.

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

No indication of sensitising properties. SCCS conclude in their opinion (SCCS/1246/09): "..it must be recognised that quaternary ammonium compounds are not known to be sensitising, but merely corrosive. There are some rare clinical reports, but considering the many years of use of these compounds, they are considered to be of minor importance. Therefore there is no reason to consider cetrimonium chloride, steartrimonium chloride or behentrimonium chloride as skin sensitisers.

Overall, based on read-across from data on cetrimonium chloride and the OECD Toolbox prediction on cetrimonium bromide this indicates that there is no concern for sensitisation of cetrimonium bromide.

Migrated from Short description of key information:

SCCS evaluated this OECD 406 study to be negative. SCCS also found a Buehler test on cetrimonium chloride negative.

Supporting read across based on grouping approach using the OECD QSAR Toolbox predicted that the substance is not a skin sensitizer.

Justification for selection of skin sensitisation endpoint:

OECD 406 (GPMT)  on cetrimoium chloride relevant for read-across to cetrimonium bromide

Justification for classification or non-classification

The substance is not considered to be a skin sensitizer according to read-across from data on cetrimonium chloride and according to the OECD QSAR Toolbox prediction.