Registration Dossier

Administrative data

Description of key information

Skin sensitisation, guinea pig (OECD 406): sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
in vivo (LLNA and non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Refer to analogue justification document provided in IUCLID section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%, challenge: 12.5% and 25%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
first study; source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%, challenge: 25% and 50%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
second study; source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 25%, challenge: 12.5%
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 25%, challenge: 25%
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 1%, challenge: 25%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 1%, challenge: 50%
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%, challenge: 12.5%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
first study; source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%, challenge: 25%
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
first study; source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%, challenge: 25% and 50%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
second study; source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 25%, challenge: 12.5%
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 25%, challenge: 25%
No. with + reactions:
13
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 1%, challenge: 25%
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
no indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 1%, challenge: 50%
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
source, CAS 59-50-7, key rel.2, Bomhard & Löser 1980
Parameter:
SI
Value:
0.99
Test group / Remarks:
1%
Remarks on result:
other: source, CAS 59-50-7, key rel.2, Vohr 2000
Parameter:
SI
Value:
0.71
Test group / Remarks:
10%
Remarks on result:
other: source, CAS 59-50-7, key rel.2, Vohr 2000
Parameter:
SI
Value:
1.28
Test group / Remarks:
50%
Remarks on result:
other: source, CAS 59-50-7, key rel.2, Vohr 2000
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
CLP: Skin Sens. 1B, H317

The available data on the source substance (CAS 59-50-7) revealed a skin sensitising potential resulting in a classification as Skin Sens. 1B, H317 according to the Regulation (EC) No 1272/2008. Applying the read-across approach, the target substance (CAS 15733-22-9) is expected to have a similar skin sensitising potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

There are no data available on the skin sensitisation effects of sodium p-chloro-m-cresolate (CAS 15733-22-9). The assessment was therefore based on studies conducted with the analogue substance p-chloro-m-cresol (CAS 59-50-7) as part of a read across approach, which is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 59-50-7

A study for skin sensitisation in guinea pigs was conducted with the source substance p-chloro-m-cresol using the Magnusson-Kligman method similar to the OECD Guideline 406 (1992; Bomhard & Löser, 1980). Groups of 15 Pirbright White guinea pigs each were used in two parts of the study. In the first study, male animals received intradermal induction treatments consisting of three pairs of injections. The first pair of injections was of Freund's complete adjuvant (FCA) 50% diluted in water, the second pair was of 25% of the test substance in the vehicle, and the third pair of injections was of 25% of the test substance with FCA. The control group received three pairs of injections that were the same as the test group except for the absence of the test material. One week following intradermal induction an epicutaneous induction under occlusive conditions for 48 h was performed. In the test group, 25% of the test substance in vehicle was applied, while for the control group only vehicle was applied. Three weeks after the intradermal induction the animals were challenged with 25% (right flank) or 12.5% (left flank) of the test substance in vehicle under occlusive conditions for 24 h. In the second study, female animals received were induced and challenged in the same way compared to the male animals of the first study with different test substance concentrations: For the intradermal and the topical induction 1% of the test substance was applied while 25% (left flank) and 50% (right flank) were used for topical challenge. Skin reactions were evaluated at 24 and 48 h after patch removal. The Magnusson-Kligman scoring system was used to rate the skin reactions. In the first study (25% induction concentration) a skin reaction was observed in 1/15 animals (6%) after challenging with 12.5% of the test substance at 24 h and in 3/15 animals (20%) at 48 h. The application of a challenging concentration of 25% led to sensitising effects in 7/15 males (47%) at 24 and in 13/15 animals (87%) at 48 h. In the second study (1% induction concentration) no reactions were observed after challenging with 25% the test substance at 24 and 48 h while skin reactions were noted after topical challenge with 50% test substance (4/15 females at 24 h and 2/15 females at 48 h; 27 and 13%, respectively). Thus, under the conditions of this study, the test substance is classified as Skin Sensitiser Category 1B according to Regulation (EC) No 1272/2008.

In addition a modified local lymph node assay (LLNA) was performed in NMRI mice to determine the sensitising potential and the irritating potential of the source substance p-chloro-m-cresol (Vohr, 2000). The test was done similar to the OECD Guideline 429 (2010) and in compliance with GLP with the following modifications: Instead of radioactive labelling cell counts were measured. Therefore animals were sacrificed one day after the last application instead of three days after the last application. In addition, a measurement of the ear swelling after treatment was included in the test. No pre-screen test was performed. The test substance was formulated at concentrations of 1, 10 and 50% in DAE 433 (mixture of dimethylacetamide (40%), acetone (30%) and ethanol (30%)) as vehicle. Groups of 6 female NMRI mice received 25 µL of these formulations applied epicutaneously onto the dorsal part of both ears on three consecutive days. After the third application animals were sacrificed and the auricular lymph nodes were transferred into sterile physiological saline. After preparation the weight and cell counts were determined and the stimulation index was calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated ones. In addition, on day 0 and 3 the ear swelling was measured using a spring-loaded micrometer and the mean ear swelling was determined. After sacrifice the ear weights were determined and the ratio ear swelling / ear weight was calculated. For the determination an 8 mm in diameter ear punch was weighed. The NMRI mice showed a slight increase compared to vehicle treated animals regarding the cell counts and the weight of the draining lymph nodes in the highest dose group. Thus, under the conditions of the study the test substance has a weak sensitising potential in mice after dermal application. An irritating potential at the same doses measured by ear swelling or ear weights could not be determined. The results are not considered sufficient for a proper assessment of the compound with respect to classification and labelling according to Regulation (EC) No 1272/2008.

A further study for skin sensitisation in female guinea pigs was conducted with the source substance p-chloro-m-cresol using the open epicutaneous method (Bomhard & Löser, 1981). Groups of 7 Pirbright White guinea pigs each were topically induced with 1, 3, 10 or 30% of the test substance formulated in Lutrol as vehicle (0.1 mL per application site; Bomhard & Löser, 1981). Seven animals received the vehicle only and served as control group. The test substance was applied 5 days a week for 4 weeks during the induction phase. Skin reactions were examined 24 h after every application. The first challenge started 4 weeks after beginning of the induction phase. The test substance was applied at concentrations of 3, 10, 30 and 100% in vehicle and skin reactions were noted 24 and 48 h after application. Six weeks after start of the induction phase a second challenge phase was conducted in the same way as the first challenge. Application sites remained uncovered after both induction and challenge dosing. In a preliminary test skin irritation was examined on 4 female guinea pigs after single topical applications at test substance concentrations of 12.5, 25, 50 and 100%. The application site remained uncovered and were examined every 24 h. Confluent erythema was observed on the treated skin of animals pertaining to the highest dose group (100%) only. During the induction phase of the main test only 1/7 animal of the test group treated with 30% of the test substance showed isolated sporadic erythema. Skin reactions were observed in the majority of animals of the control and all test groups at 100% test substance concentration during the challenge and the rechallenge at 24 and 48 h after application. The noted skin reactions were limited to sporadic and spotty erythema. 1/7 animal of the test group induced with 3% and challenged with 30% of the test substance exhibited sporadic and spotty erythema at 24 and 48 h after rechallenge application.Thus, under the conditions of this study, the test substance is not sensitising to female guinea pigs.

Overall conclusion for skin sensitisation:

The available data on the source substance show skin sensitising effects. Therefore, the target substance sodium p-chloro-m-cresolate (CAS 15733-22-9) is expected to have a similar skin sensitising potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No 1907/2006, information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to sodium p-chloro-m-cresolate, data will be generated from data of the reference source substance to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

                                                                   

The available data on skin sensitisation meet the criteria for classification according to Regulation (EC) 1272/2008. The source and the target substance are classified as Skin Sensitiser Category 1B, H317: May cause an allergic skin reaction.

According to Annex VI of Regulation (EC) 1272/2008 the source substance is classified as Skin Sensitiser Category 1, H317: May cause an allergic skin reaction.

According to the Opinion of the Committee for Risk Assessment (RAC), adopted 10 March 2016, the source substance is classified as Skin Sensitiser Category 1B, H317: May cause an allergic skin reaction.