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Skin sensitisation

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Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01-Oct-1981 to 31-Dec-1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report that meets basic scientific principles; study not on the substance defined in section 1
Justification for type of information:
No skin sensitisation data are available on S261a. Studies on a structurally related material, benzyl butyl phthalate (BBP), provide some insight into the likely skin sensitisation potential of S261a.
Cross-referenceopen allclose all
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
01-Oct-1981 to 31-Dec-1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report that meets basic scientific principles; study not on the substance defined in section 1
Justification for type of information:
No skin sensitisation data are available on S261a. Studies on a structurally related material, benzyl butyl phthalate (BBP), provide some insight into the likely skin sensitisation potential of S261a.
Reason / purpose:
read-across source
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Intradermal induction with benzyl butyl phthalate in the presence of Freunds complete adjuvant, followed by epicutaneous challenge 14 days after induction and evaluation of erythema at the challenge sites
GLP compliance:
no
Type of study:
other: guinea pig skin sensitisation test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco Inc., Omaha, NE and St Louis, MO
- Age at study initiation: no data
- Weight at study initiation: 350-400 g
- Housing: 4/metal cage
- Diet (e.g. ad libitum): Purina guinea pig chow #5025, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: >=1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2
- Humidity (%): "ambient"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): dark 24 hours

IN-LIFE DATES: No data for guinea pig study (study VIII) specifically, but series of 10 studies took place From: 01-Oct-1981 To: 31-Dec-1982
Route:
intradermal
Vehicle:
other: acetone/corn oil
Concentration / amount:
Initiation: 1 mM [0.3 mg/ml]
Challenge: 3.6, 36 and 360 mM [1.1, 11 and 110 mg/ml]
Route:
epicutaneous, open
Vehicle:
other: acetone/corn oil
Concentration / amount:
Initiation: 1 mM [0.3 mg/ml]
Challenge: 3.6, 36 and 360 mM [1.1, 11 and 110 mg/ml]
No. of animals per dose:
4
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single administration to all 4 footpads of each animal
- Exposure period: single administration by injection
- Test groups: one group of 4 animals
- Control group: no vehicle control group; positive control group of 4 animals
- Site: footpad
- Frequency of applications: once
- Duration: single administration by injection, challenge 14 days later
- Concentrations: 1 mM [0.3 mg/ml]
- 11.2 µl BBP at 3.6 M added to 2 ml acetone (making a 20 mM solution), diluted 1:10 in 0.15 M NaCl (making a 2 mM solution), mixed 1:1 with Freunds Complete Adjuvant (making a 1 mM solution ); a 200 µl volume was administered to each animal, by injecting 50 µl into each footpad (total amount injected = 0.2 µmoles [~60 µg])

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after induction
- Exposure period: 18 hours, then washed
- Test groups: one group of 4 animals
- Control group: no vehicle control group; one positive control group of 4 animals
- Site: clipped abdominal skin
- Concentrations: 0, 3.6, 36 and 360 mM [0, 1.1, 11 and 110 mg/ml]
- 500 µl BBP at 3.6 M added to 4.5 ml acetone/corn oil (making a 360 mM solution), diluted 1:10 (making a 36 mM solution), or 1:100 (making a 3.6 mM solution ); a 50 µl volume of each concentration, and also vehicle only, was administered to each animal epicutaneously (no data on occlusion, so presumably open)
- Evaluation (hr after challenge): 24 hours after start of challenge exposure (i.e. 6 hours after end) and at 48 hours

OTHER:
- Rechallenge: ~5 weeks later, using highest concentration (360 mM) only, read at 48 hours
Challenge controls:
Each of the 4 test animals were administered 3 challenge concentrations of benzyl butyl phthalate and a vehicle control
Positive control substance(s):
yes
Remarks:
2,4-dinitrofluorobenzene, 0.2 µmol induction, 5 mM challenge
Positive control results:
At 24 hours, 1/4 positive control animals showed a moderate positive response, 2/4 showed a weak, but definitely positive, response and 1/4 showed an ambiguous response. At 48 hours, 3/4 had a strongly positive response and 1/4 a moderate response.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5 mM 2,4-DNFB
No. with + reactions:
3
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 5 mM 2,4-DNFB. No with. + reactions: 3.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5 mM 2,4-DNFB
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 5 mM 2,4-DNFB. No with. + reactions: 4.0. Total no. in groups: 4.0. Clinical observations: no data.

No positive skin reactions were seen at 24 or 48 hours after challenge in the groups of 4 animals treated with concentrations of 3.6 or 36 mM Santicizer 160.

Interpretation of results:
other: BBP not sensitising
Conclusions:
No skin sensitisation data are available for S261A. However, in a reliable study with the structurally-related material, benzyl butyl phthalate, no skin sensitisation was seen in guinea pigs after intradermal induction and epicutaneous challenge.
Executive summary:

No skin sensitisation data are available for S261A. However, in a skin sensitisation study with the structurally-related material, benzyl butyl phthalate (BBP), induction involved intradermal injection of a 200 µl volume of BBP (1 mM) with Freunds Complete Adjuvant into the four footpads (50 µl/footpad) of each of 4 guinea pigs. Fourteen days later, epicutaneous challenges with 50 µl volumes of three concentrations of BBP (3.6, 36 and 360 mM) and of the vehicle (acetone/corn oil) were applied to the shaved abdominal skin of each animal. The skin was washed after 18 hours and skin reactions were read 24 and 48 hours after the start of the challenge exposure. Approximately 5 weeks later, a rechallenge using the highest concentration was made and skin reactions read at 48 hours. Four guinea pigs were treated with a positive control substance, 2,4 -dinitrofluorobenzene, in the same way.

No skin sensitisation reactions were seen at any of the challenge sites in any of the BBP animals at either challenge or rechallenge. Clear positive responses were seen in the positive controls animals.

In a reliable study, no skin sensitisation was seen in guinea pigs after intradermal induction and epicutaneous challenge with benzyl butyl phthalate.

Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Intradermal induction with benzyl butyl phthalate in the presence of Freunds complete adjuvant, followed by epicutaneous challenge 14 days after induction and evaluation of erythema at the challenge sites
GLP compliance:
no
Type of study:
other: guinea pig skin sensitisation test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Santicizer 160 (benzyl butyl phthalate)
- Molecular formula (if other than submission substance): C19-H20-O4
- Molecular weight (if other than submission substance): 312.4
- Substance type: no data
- Physical state: clear, colourless, slightly viscous liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: DA-892AB (11/9/81)
- Expiration date of the lot/batch: no data
- Stability under test conditions: "there was no apparent change in the physical state of the test article throughout the duration of this study"
- Storage condition of test material: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco Inc., Omaha, NE and St Louis, MO
- Age at study initiation: no data
- Weight at study initiation: 350-400 g
- Housing: 4/metal cage
- Diet (e.g. ad libitum): Purina guinea pig chow #5025, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: >=1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2
- Humidity (%): "ambient"
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): dark 24 hours

IN-LIFE DATES: No data for guinea pig study (study VIII) specifically, but series of 10 studies took place From: 01-Oct-1981 To: 31-Dec-1982

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: acetone/corn oil
Concentration / amount:
Initiation: 1 mM [0.3 mg/ml]
Challenge: 3.6, 36 and 360 mM [1.1, 11 and 110 mg/ml]
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone/corn oil
Concentration / amount:
Initiation: 1 mM [0.3 mg/ml]
Challenge: 3.6, 36 and 360 mM [1.1, 11 and 110 mg/ml]
No. of animals per dose:
4
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single administration to all 4 footpads of each animal
- Exposure period: single administration by injection
- Test groups: one group of 4 animals
- Control group: no vehicle control group; positive control group of 4 animals
- Site: footpad
- Frequency of applications: once
- Duration: single administration by injection, challenge 14 days later
- Concentrations: 1 mM [0.3 mg/ml]
- 11.2 µl BBP at 3.6 M added to 2 ml acetone (making a 20 mM solution), diluted 1:10 in 0.15 M NaCl (making a 2 mM solution), mixed 1:1 with Freunds Complete Adjuvant (making a 1 mM solution ); a 200 µl volume was administered to each animal, by injecting 50 µl into each footpad (total amount injected = 0.2 µmoles [~60 µg])

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after induction
- Exposure period: 18 hours, then washed
- Test groups: one group of 4 animals
- Control group: no vehicle control group; one positive control group of 4 animals
- Site: clipped abdominal skin
- Concentrations: 0, 3.6, 36 and 360 mM [0, 1.1, 11 and 110 mg/ml]
- 500 µl BBP at 3.6 M added to 4.5 ml acetone/corn oil (making a 360 mM solution), diluted 1:10 (making a 36 mM solution), or 1:100 (making a 3.6 mM solution ); a 50 µl volume of each concentration, and also vehicle only, was administered to each animal epicutaneously (no data on occlusion, so presumably open)
- Evaluation (hr after challenge): 24 hours after start of challenge exposure (i.e. 6 hours after end) and at 48 hours

OTHER:
- Rechallenge: ~5 weeks later, using highest concentration (360 mM) only, read at 48 hours
Challenge controls:
Each of the 4 test animals were administered 3 challenge concentrations of benzyl butyl phthalate and a vehicle control
Positive control substance(s):
yes
Remarks:
2,4-dinitrofluorobenzene, 0.2 µmol induction, 5 mM challenge

Results and discussion

Positive control results:
At 24 hours, 1/4 positive control animals showed a moderate positive response, 2/4 showed a weak, but definitely positive, response and 1/4 showed an ambiguous response. At 48 hours, 3/4 had a strongly positive response and 1/4 a moderate response.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
360 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 360 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0 mM
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 mM. No with. + reactions: 0.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5 mM 2,4-DNFB
No. with + reactions:
3
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 5 mM 2,4-DNFB. No with. + reactions: 3.0. Total no. in groups: 4.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5 mM 2,4-DNFB
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 5 mM 2,4-DNFB. No with. + reactions: 4.0. Total no. in groups: 4.0. Clinical observations: no data.

Any other information on results incl. tables

No positive skin reactions were seen at 24 or 48 hours after challenge in the groups of 4 animals treated with concentrations of 3.6 or 36 mM Santicizer 160.

Applicant's summary and conclusion

Interpretation of results:
other: BBP not sensitising
Conclusions:
No skin sensitisation data are available for S261A. However, in a reliable study with the structurally-related material, benzyl butyl phthalate, no skin sensitisation was seen in guinea pigs after intradermal induction and epicutaneous challenge.
Executive summary:

No skin sensitisation data are available for S261A. However, in a skin sensitisation study with the structurally-related material, benzyl butyl phthalate (BBP), induction involved intradermal injection of a 200 µl volume of BBP (1 mM) with Freunds Complete Adjuvant into the four footpads (50 µl/footpad) of each of 4 guinea pigs. Fourteen days later, epicutaneous challenges with 50 µl volumes of three concentrations of BBP (3.6, 36 and 360 mM) and of the vehicle (acetone/corn oil) were applied to the shaved abdominal skin of each animal. The skin was washed after 18 hours and skin reactions were read 24 and 48 hours after the start of the challenge exposure. Approximately 5 weeks later, a rechallenge using the highest concentration was made and skin reactions read at 48 hours. Four guinea pigs were treated with a positive control substance, 2,4 -dinitrofluorobenzene, in the same way.

No skin sensitisation reactions were seen at any of the challenge sites in any of the BBP animals at either challenge or rechallenge. Clear positive responses were seen in the positive controls animals.

In a reliable study, no skin sensitisation was seen in guinea pigs after intradermal induction and epicutaneous challenge with benzyl butyl phthalate.