Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
Delayed dermal sensitization study using the guinea pig maximization test described by B. Magnusson and A.M. Kligman (J. Invt. Derm. 1969, 52:268-276
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes.
Species:
guinea pig
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Porcellus Animal Breeding Limited, Heathfield, Surrey- Age at study initiation: no data- Weight at study initiation: 300-350 grams- Housing: caged individually- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: no dataENVIRONMENTAL CONDITIONS- Temperature (°C): 17 °C +/- 1 °C- Humidity (%): 50-70%- Air changes (per hr): no data- Photoperiod (hrs dark / hrs light): "controlled lighting conditions"IN-LIFE DATES: From: To: No data
Route:
intradermal and epicutaneous
Vehicle:
other: deionized water and Freunds complete adjuvant (DIFCO Labs)
Concentration / amount:
5%
Route:
epicutaneous, open
Vehicle:
other: deionized water and Freunds complete adjuvant (DIFCO Labs)
Concentration / amount:
5%
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: no dataMAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: one injection followed 7 days later by epicutaneous exposure - Exposure period: patch is left on for 14 days- Test groups: 10 animals- Control group: no data- Site: shoulder region- Frequency of applications: once by injection, once by epicutaneous exposure- Duration: 14 days for epicutaneous- Concentrations: 5% in injection; undiluted (neat) in epicutaneous exposureB. CHALLENGE EXPOSURE- No. of exposures: once- Day(s) of challenge: 21 days after injection and 14 days after epicutaneouls exposure- Exposure period: 24 hours- Test groups: 10 animals- Control group: no data- Site: 5 x 5 cm area on flank- Concentrations: undiluted (neat)- Evaluation (hr after challenge): 24 and 48OTHER:
Challenge controls:
no data
Positive control substance(s):
not specified
Positive control results:
no data
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted (neat)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none reported
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted (neat). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
No animals showed a challenge reaction at 24 or 48 hours. Sodium toluene sulfonate (40%) is not a sensitizer
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
: Post-study body weights of animals are not mentioned.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hacking and Churchill Ltd.- Age at study initiation: Young females- Weight at study initiation: 599-853 gm- Housing: Caged in groups of two by dose group in grid floor propylene cages.- Diet (e.g. ad libitum): Guinea Pig diet, standard with vitamin C, Special diets Srvices Ltd., Witham, ad libitum- Water (e.g. ad libitum): ad libitum (A certificate for quality of drinking water was issued by the Yorkshire Water Authority)- Acclimation period: at least 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18-26 deg C- Humidity (%): 40-64%- Air changes (per hr): Not available- Photoperiod (hrs dark / hrs light): 12/12 (artificial light, 06.00 to 18.00)IN-LIFE DATES: From: 1983-06-01 To: 1983-07-01
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
One group of 20 test animals was treated with 0.4 ml of undiluted test material for an exposure period of 6 hours weekly for 3 induction exposures. Both test (20) and control (10) animals were challenged with 0.4 ml of undiluted test material.
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
One group of 20 test animals was treated with 0.4 ml of undiluted test material for an exposure period of 6 hours weekly for 3 induction exposures. Both test (20) and control (10) animals were challenged with 0.4 ml of undiluted test material.
No. of animals per dose:
Induction: group of 20 test animal treated with 0.4 ml of undiluted sodium cumene sulphonate.Range Finding test: 2 test animals were taken, for each of the following concentration- undiluted test material, 50%, 25% and 10% (v/v).Primary challenge: 10 control animals previously untreated were treated with undiluted test material.
Details on study design:
RANGE FINDING TESTS: 2 test animals were taken, for each of the following concentration- undiluted test material, 50%, 25% and 10% (v/v).MAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 3- Exposure period: 6 hours- Test groups: 0.4 ml of undiluted sodium cumene sulphonate.- Control group: None- Site: Shaved left flank of each animal.- Frequency of applications: once a week for 3 weeks- Duration: 6 hours, test substance was applied to the lint pads and were held in place with an overlapping impermeable occlusive tape and secured by elastic adhesive bandage.- Concentrations: undiluted sodium cumene sulphonate.B. CHALLENGE EXPOSURE- No. of exposures: One 6 hour exposure - Day(s) of challenge: 2 weeks after the last induction exposure- Exposure period: 6 hours under occlusion- Test groups: 0.4 ml of undiluted sodium cumene sulphonate.- Control group: 0.4 ml of undiluted sodium cumene sulphonate.- Site: freshly clipped Right flank that has not been treated before. - Concentrations: undiluted sodium cumene sulphonate.- Evaluation (hr after challenge): 21 and 45 hours after challenge exposure OTHER: None
Challenge controls:
10 control animals (previously unexposed) treated with 0.4 ml of undiluted sodium cumene sulphonate.
Positive control substance(s):
no
Statistics:
Not applicable
Positive control results:
Not applicable
Key result
Reading:
1st reading
Hours after challenge:
21
Group:
test chemical
Dose level:
0.4 ml of undiluted sodium cumene sulphonate
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 21.0. Group: test group. Dose level: 0.4 ml of undiluted sodium cumene sulphonate. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No response.
Reading:
1st reading
Hours after challenge:
21
Group:
negative control
Dose level:
0.4 ml of undiluted sodium cumene sulphonate.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 21.0. Group: negative control. Dose level: 0.4 ml of undiluted sodium cumene sulphonate.. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No response.
Reading:
2nd reading
Hours after challenge:
45
Group:
test chemical
Dose level:
0.4 ml of undiluted sodium cumene sulphonate.
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 45.0. Group: test group. Dose level: 0.4 ml of undiluted sodium cumene sulphonate.. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No response.
Reading:
2nd reading
Hours after challenge:
45
Group:
negative control
Dose level:
0.4 ml of undiluted sodium cumene sulphonate.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 45.0. Group: negative control. Dose level: 0.4 ml of undiluted sodium cumene sulphonate.. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No response.

none

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Thus, undiluted sodium cumene sulphonate is not a skin sensitizer in guinea pigs.
Executive summary:

The sensitization potential of sodium cumene sulfonate was assessed in a study where one group of 20 test animals was treated with 0.4 ml of undiluted sodium cumene sulphonate for an exposure period of once weekly to 6 hours induction exposures for 3 weeks. After a 2 week rest period, both test (20) and control (10) animals were challenged with 0.4 ml of undiluted sodium cumene sulphonate.

On challenge with 0.4 ml of undiluted sodium cumene sulphonate, no reaction was observed in any of the test animals and conrtrol animals at both the 21 -hour and 45 -hour reading. No evidence for sensitization was observed in this study.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
: Post-study body weights of animals are not mentioned.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Redfern Animal Breeders, Frant, Tunbridge Wells- Age at study initiation: Not avaiable- Weight at study initiation: 274-321 gm- Housing: Caged in groups of two by sex in grid floor propylene cages.- Diet (e.g. ad libitum): Guinea Pig diet, standard with vitamin C, Special diets Srvices Ltd., Witham, ad libitum- Water (e.g. ad libitum): ad libitum (A certificate for quality of drinking water was issued by the Yorkshire Water Authority)- Acclimation period: at least 7 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18-23 deg C- Humidity (%): 40-60%- Air changes (per hr): Not available- Photoperiod (hrs dark / hrs light): 12/12 (artificial light)IN-LIFE DATES: From: 1984-02-01 To: 1984-03-01
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
One group of 20 test animals was treated with 0.5 ml of 50% sodium cumene sulphonate for an exposure period of 6 hours weekly for 3 induction exposures. Both test (20) and control (10) animals were challenged with 0.5 ml of sodium cumene sulphonate
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
One group of 20 test animals was treated with 0.5 ml of 50% sodium cumene sulphonate for an exposure period of 6 hours weekly for 3 induction exposures. Both test (20) and control (10) animals were challenged with 0.5 ml of sodium cumene sulphonate
No. of animals per dose:
Induction: group of 20 test animal treated with 0.5 ml of 50% sodium cumene sulphonateRange Finding test: 4 test animals were taken, for the following concentration- undiluted test material, 50%, 25% and 10% (v/v).Primary challenge: 10 control animals previously untreated were treated with 0.5 ml 50% sodium cumene sulphonate
Details on study design:
RANGE FINDING TESTS: 2 test animals were taken, for the following concentration- undiluted test material, 50%, 25% and 10% (v/v).MAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 3- Exposure period: 6 hours- Test groups: 0.5 ml of 50% sodium cumene sulphonate- Control group: None- Site: Shaved left flank of each animal.- Frequency of applications: once a week for 3 weeks- Duration: 6 hours, test substance was applied to the lint pads and were held in place with an overlapping impermeable occlusive tape and secured by elastic adhesive bandage.- Concentrations: 50% sodium cumene sulphonateB. CHALLENGE EXPOSURE- No. of exposures: One 6 hour exposure - Day(s) of challenge: 2 weeks after the last induction exposure- Exposure period: 6 hours under occlusion- Test groups: 0.5 ml of 50% sodium cumene sulphonate- Control group: 0.5 ml of 50% sodium cumene sulphonate- Site: Shaved and freshly clipped right flank that has not been treated before. - Concentrations: 50% sodium cumene sulphonate- Evaluation (hr after challenge): 21 and 45 hours after challenge exposure OTHER: None
Challenge controls:
10 control animals (previously unexposed) treated with 0.5 ml of 50% sodium cumene sulphonate
Positive control substance(s):
no
Statistics:
Not applicable
Positive control results:
Not applicable
Key result
Reading:
1st reading
Hours after challenge:
21
Group:
test chemical
Dose level:
0.5 ml of 50% sodium cumene sulphonate
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 21.0. Group: test group. Dose level: 0.5 ml of 50% sodium cumene sulphonate. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No response.
Reading:
1st reading
Hours after challenge:
21
Group:
negative control
Dose level:
0.5 ml of 50% sodium cumene sulphonate
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 21.0. Group: negative control. Dose level: 0.5 ml of 50% sodium cumene sulphonate. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No response.
Reading:
2nd reading
Hours after challenge:
45
Group:
test chemical
Dose level:
0.5 ml of 50% sodium cumene sulphonate
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 45.0. Group: test group. Dose level: 0.5 ml of 50% sodium cumene sulphonate. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No response.
Reading:
2nd reading
Hours after challenge:
45
Group:
negative control
Dose level:
0.5 ml of 50% sodium cumene sulphonate
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 45.0. Group: negative control. Dose level: 0.5 ml of 50% sodium cumene sulphonate. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No response.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Sodium cumene sulphonate is not a skin sensitizer in guinea pigs.
Executive summary:

The skin sensitization potential of sodium cumene sulfonate was investigated in a study where one group of 20 test animals was treated with 0.5 ml of 50% sodium cumene sulphonate for weekly 6 hour induction exposures for 3 weeks(once per week on 1st, 8th and 15th day). Both test (20) and control (10) animals were challenged (On 28th day) with 0.5 ml of 50% sodium cumene sulphonate.

On challenge with 0.5 ml of 50% sodium cumene sulphonate, no reaction was observed in any of the test animals and conrtrol animals at both the 21 -hour and 45 -hour reading. No evidence for sensitization was observed in this study.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes.
Species:
guinea pig
Strain:
other: Dunkin Hartley, Pirbright White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Harlan Winkelmann GmbH, Versuchstierzucht, Borchen, Germany- Age at study initiation: young adults, no further details mentioned- Weight at study initiation: 317 ± 21 g- Housing: conventional, Makrolon Type IV cages (maximum 5 animals per cage) - Diet (e.g. ad libitum): Ssniff G4 complete feed for guinea pigs ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany- Water (e.g. ad libitum): drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3- Humidity (%): 30 - 70- Air changes (per hr): 15 - Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 1995-03-06 To: 1995-03-09 (preliminary study) From: 1995-03-20 To: 1995-04-20 (main study)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
induction: 42.79 % (delivery form)challenge: 42.79 % (delivery form)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
induction: 42.79 % (delivery form)challenge: 42.79 % (delivery form)
No. of animals per dose:
test animals: 20 (main experiment), 3 (pilot study), 3 (determination of challenge concentration)control animals: 10
Details on study design:
RANGE FINDING TESTS: Determination of the non-irritant concentration of the test substance with occlusive epicutaneous applications for 6 hours of test substance 5%, 10%, 20% in deionized water and 42.79% (delivery form). Reading at 30 and 54 hours after application. Redetermination of the maximum non-irritant concentration for the challenge treatment in the 4th week with 3 additional guinea pigs which had not been treated up to this time. The concentrations and test conditions were the same as in the pilot study. This additional testing was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approx. the same weights as the 30 animals in the challenge phase.MAIN STUDYA. INDUCTION EXPOSURE- No. of exposures: 3- Exposure period: occlusive dermal applications for 6 hours, scoring at 30 hours after start of application- Test group: receiving test substance (0.3 cm³/patch)- Control group: receiving vehicle (0.3 cm³/patch)- Site: left flanks- Frequency of applications: induction on days 0, 7 and 14- Duration: 3 weeks- Concentrations: 42.79% (delivery form)B. CHALLENGE EXPOSURE- No. of exposures: 1- Day(s) of challenge: on day 28- Exposure period: occlusive dermal application for 6 hours- Test groups: receiving test substance solution and vehicle (0.3 cm³/patch each)- Control group: receiving test substance solution and vehicle (0.3 cm³/patch each)- Site: right flanks (front: vehicle, back: test substance solution)- Concentrations: 42.79% (delivery form)- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
same treatment as test group animals
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole
Positive control results:
The sensitivity of the used guinea pig strain was checked from 1994-11-07 to 1994-12-02. The test compound was used as an well-known standard allergen. The maximisations method was carried out for this test. A test goup of 10 and a control group of 5 animals were used to test the sensitivity. 48 and 72 hours after challenge treatment all skin reaction were recorded: Dermal irritation was found on the right flank of 9 of 10 test animals 48 and 72 hours after treatment with the allergen. Treatment of the test animals with the vehicle on the left flank likewise resulted in a slight or to distinct subcutaneous reaction after 48 and 72 hours in two animals.There were no signs of irritation at these times on the skin on the left (standard allergen) and right (vehicle) flanks of the control animals.It was necessary to pretreat the skin with 10% sodium dodecylsulphate in vaseline in order to cause slight to moderate cutaneous inflammation, because the highest allergen concentration which could be administered satisfactorily caused no dermal irritation.On the basis of these results (90% of test animals showed evidence of delayed contact hypersensitivity), the guinea pig strain was judged to be sensitive under the test conditions described. In the maximisation method, a figure of 30% or more is regarded as positive result.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
42.79%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical effects observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 42.79%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical effects observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
42.79%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical effects observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 42.79%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical effects observed.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
42.79%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical effects observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 42.79%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical effects observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
42.79%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical effects observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 42.79%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no clinical effects observed.

RESULTS OF PILOT STUDY

No irritant effects at any concentration of the test substance tested.

RESULTS OF TEST

- Sensitisation reaction: No sensitising effects observed.

- Clinical signs: No clinical effects observed. Body weight increase comparable to control.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The test substance sodium toluenesulphonate showed no sensitizing effect on guinea pig skin under the described test conditions.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are a total of 4 skin sensitization studies on the hydrotrope category substances.

All studies gave negative responses for sensitization.

The in vivo study data were obtained in studies performed before any in vitro sensitization tests tests had been validated and accepted for regulatory purposes.


Migrated from Short description of key information:
There are 4 skin sensitisation studies for the hydrotrope category substances. The 4 studies consistently support a conclusion that these substances are "not sensitising".

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
N/A

Justification for classification or non-classification

The available studies demonstrate that the hydrotrope category substances are not skin sensitizers. Therefore a classification is not justified.