Registration Dossier

Administrative data

Description of key information

4,4`-sulphonyldiphenol is not classified as a sensitizer in a LLNA and in albino guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-03-03 to 2010-02-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted 24 Apri 2002
Deviations:
yes
Remarks:
Test conditions (the relative humidity in the animal room was between approximately 25 - 65 % for a few hours)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V.; Postbus 6174; 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks (beginning of treatment)
- Weight at study initiation: 17.7 - 21.8 g
- Housing: single; Makrolon Type II, with wire mesh top (EHRET GmbH, 79302 Emmendingen, Germany)
- Diet (e.g. ad libitum): Pelleted standard diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimatisation: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 20-65%
- Photoperiod (hrs dark / hrs light): Artificial light 6.00 a.m. - 6.00 p.m.
Vehicle:
methyl ethyl ketone
Concentration:
5, 10, and 25% (w/v)
No. of animals per dose:
5 females (nulliparous and non-pregnant) per dose
Details on study design:
RANGE FINDING TESTS: a pre-test was performed in two animals
- Compound solubility: 10% or 25% by topical application
- Irritation: no signs of local irritation as confirmed by the ear thickness and ear weight measurements

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: First, that exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
Positive control substance(s):
other: Alpha-Hexylcinnamaldehyde, tech. 85%
Statistics:
For all statistical calculations SigmaStat for Windows (Version 2.0) was used. A One-Way-Analysis-of-Variance was used as statistical method. In case of significant results of the One-Way-ANOVA, multiple comparisons were performed with the Dunnett test.
Positive control results:
- Mean DPM per group (5 animals): 5918.7+/- 2521.5
- Stimulation Indices: 6.49
Parameter:
SI
Value:
1.39
Test group / Remarks:
5 % DHDPS
Parameter:
SI
Value:
1.9
Test group / Remarks:
10 % DHDPS
Parameter:
SI
Value:
1.68
Test group / Remarks:
25 % DHDPS
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: - 5% DHDPS: Mean DPM per group 661.1 +/-240.0 - 10% DHDPS: Mean DPM per group 904.1 +/- 205.0 - 25% DHDPS: Mean DPM per group 799.3 +/- 560.4

- No deaths occurred during the study period.

- No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item 4,4`-sulphonyldiphenol was not a skin sensitiser under the test conditions of this study.
Executive summary:

The test item 4,4`-sulphonyldiphenol was tested in a Local Lymph Node Assay (LLNA) in mice according to OECD guideline 429 and EU method B.42. Three groups each of five female mice were treated with 5, 10 or 25% (w/v) test item concentration by topical application at the dorsum of each ear on three consecutive days. Two negative control groups were treated with the respective vehicle only (methyl ethyl ketone for the test item and acetone:olive oil (4+1) for the positive control item).

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. Signs of local irritation (e.g. reddening of the ear skin, ear swelling) were also not observed during the study period. A statistically significant increase in ear weights was not observed in any of the groups treated with different concentrations of the test item in comparison to the vehicle control group.

Here, Stimulation Indices (S.I.) of 1.39, 1.90 and 1.68 were determined with the test item at concentrations of 5, 10 and 25% (w/v) in methyl ethyl ketone, respectively. A statistically significant difference in DPM/animal was not observed in any of the groups treated with different concentrations of the test item in comparison to the vehicle control group. The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3. The S.I. of the positive control group was 6.49.

The test item 4,4`-sulphonyldiphenol did not show skin sensitizing potential in this assay under the conditions of this study.

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

In the key study, 4,4`-sulphonyldiphenol was tested in a Local Lymph Node Assay (LLNA) in mice according to OECD guideline 429 and EU method B.42. Three groups each of five female mice were treated with 5, 10 or 25% (w/v) test item concentration by topical application at the dorsum of each ear on three consecutive days. Two negative control groups were treated with the respective vehicle (methyl ethyl ketone for the test item and acetone:olive oil (4+1) for the positive control item). The highest test dose was chosen based on the max. solubility in the vehicle.

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed. Signs of local irritation (e.g. reddening of the ear skin, ear swelling) were also not observed during the study period. A statistically significant increase in ear weights was not observed in any of the groups treated with different concentrations of the test item in comparison to the vehicle control group. Here, Stimulation Indices (S.I.) of 1.39, 1.90 and 1.68 were determined with the test item at concentrations of 5, 10 and 25% (w/v) in methyl ethyl ketone, respectively. A statistically significant difference in DPM/animal was not observed in any of the groups treated with different concentrations of the test item in comparison to the vehicle control group. The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3. The S.I. of the positive control group was 6.49. 4,4`-sulphonyldiphenol did not show skin sensitizing potential.

In the supporting study (CIBA-Geigy, 1984), 4,4`-sulphonyldiphenol was tested in a sensitization test (maximisation test according to Magnusson and Kligman) in albino guinea pigs according to OECD guideline 406. The test was performed on 10 male and 10 female guinea pigs. The induction was a two-stage operation. First, intradermal adjuvant injections and epidermal closed patch exposure to the test compound (30 % in vaseline) in the neck region; second, closed patch exposure over the injection sites one week later. Two weeks after the epidermal induction application the animals were tested on the flank with 10 % 4,4`-sulphonyldiphenol in vaseline and the vehicle alone. According to the maximization grading 4,4`-sulphonyldiphenol showed a mild grade of skin-sensitizing (contact allergenic) potential in albino guinea pigs. This does not lead to a classification as skin sensitizer according to DSD and GHS.

In the further available study (Eastman-Kodak, 1973), the test compound was tested in 10 guinea pigs using a standardized skin sensitization test and found to be not a sensitizer. Due to minimal description of methods and results in this study (Reliability 4), no classification according to EU and GHS is possible.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results available, 4,4`-sulphonyldiphenol is not classified as a sensitzer according to Directive 67/548/EEC (DSD) and to Regulation (EC) No 1272/2008 (CLP) respectively.