Sodium benzoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

See Read Across Justification document in Section 13.2 of IUCLID

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

read-across: supporting information

Cross-reference 2

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

See Read Across Justification document in Section 13.2 of IUCLID

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

The lead author, G.F. Gerberick, is cited in the current OECD 429 guideline, and was involved in the establishment of the guideline. Therefore, this paper represents work done toward the development of the guideline.

GLP compliance:

not specified

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: Jackson Labs (Bar Harbor, ME) or NCI (Fredrick, MD)
- Age at study initiation: 6 - 9 weeks
- Weight at study initiation:
- Housing: in compliance with standards set by US Animal Welfare act
- Diet (e.g. ad libitum): in compliance with standards set by US Animal Welfare act
- Water (e.g. ad libitum): in compliance with standards set by US Animal Welfare act
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): in compliance with standards set by US Animal Welfare act
- Humidity (%): in compliance with standards set by US Animal Welfare act
- Air changes (per hr): in compliance with standards set by US Animal Welfare act
- Photoperiod (hrs dark / hrs light):

Vehicle:

other: acetone

Concentration:

5% , 10% and 20%

No. of animals per dose:

5 female animals

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of the test method: local lymph node assay
- Criteria used to consider a positive response: DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group. The SI is the ratio of the DPM/group compared to DPM/vehicle group. If the results indicate a SI > 2 (but SI < 30), the test substance may be regarded as a weak to moderate skin sensitiser; if the results indicate a SI > 30, the test substance may be regarded as a strong skin sensitiser, based on the article.

TREATMENT PREPARATION AND ADMINISTRATION:
Groups of five experimental animals were treated with the test substance concentrations of 5%, 10% and 20% on four consecutive days, by open application on both ears (total 25 microliter/ear). Five vehicle control animals were similarly treated, but with vehicle alone (acetone). Eighteen to 24 hours after the last exposure, all animals were injected with 3H-methyl thymidine in phosphate-buffered saline into the tail vein and after five hours the test animals were euthanized and the bilateral auricular lymph nodes were excised. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed.

Positive control substance(s):

not specified

Statistics:

None stated

Positive control results:

No information provided

Parameter:

SI

Value:

1

Test group / Remarks:

vehicle control

Parameter:

SI

Value:

0.8

Test group / Remarks:

test substance concentration: 5%

Parameter:

SI

Value:

0.9

Test group / Remarks:

test substance concentration: 10%

Parameter:

SI

Value:

0.8

Test group / Remarks:

test substance concentration: 20%

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

The mean DPM/animal value for the vehicle control group was 5.42E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 5% was 4.20E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 10% was 5.00E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 20% was 4.27E-02 DPM.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The SI values calculated for the test substance concentrations 5%, 10% and 20% were 0.8, 0.9 and 0.8 respectively.
There was no indication that the test substance could elicit an SI >=2 when tested on higher concentrations.
Therefore the test substance does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact.

Executive summary:

This LLNA test was conducted according to a modification of a method described by kimber et al., 1989. Five CBA mice per dose were used.

The SI values calculated for the test substance concentrations 5%, 10% and 20% were 0.8, 0.9 and 0.8 respectively. There was no indication that the test substance could elicit an SI >=2 when tested on higher concentrations. Therefore the test substance does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

The lead author, G.F. Gerberick, is cited in the current OECD 429 guideline, and was involved in the establishment of the guideline. Therefore, this paper represents work done toward the development of the guideline.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid

EC Number:

200-618-2

EC Name:

Benzoic acid

Cas Number:

65-85-0

Molecular formula:

C7H6O2

IUPAC Name:

Benzoic acid

Details on test material:

No data given

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Jackson Labs (Bar Harbor, ME) or NCI (Fredrick, MD)
- Age at study initiation: 6 - 9 weeks
- Weight at study initiation:
- Housing: in compliance with standards set by US Animal Welfare act
- Diet (e.g. ad libitum): in compliance with standards set by US Animal Welfare act
- Water (e.g. ad libitum): in compliance with standards set by US Animal Welfare act
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): in compliance with standards set by US Animal Welfare act
- Humidity (%): in compliance with standards set by US Animal Welfare act
- Air changes (per hr): in compliance with standards set by US Animal Welfare act
- Photoperiod (hrs dark / hrs light):

Study design: in vivo (LLNA)

Vehicle:

other: acetone

Concentration:

5% , 10% and 20%

No. of animals per dose:

5 female animals

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of the test method: local lymph node assay
- Criteria used to consider a positive response: DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group. The SI is the ratio of the DPM/group compared to DPM/vehicle group. If the results indicate a SI > 2 (but SI < 30), the test substance may be regarded as a weak to moderate skin sensitiser; if the results indicate a SI > 30, the test substance may be regarded as a strong skin sensitiser, based on the article.

TREATMENT PREPARATION AND ADMINISTRATION:
Groups of five experimental animals were treated with the test substance concentrations of 5%, 10% and 20% on four consecutive days, by open application on both ears (total 25 microliter/ear). Five vehicle control animals were similarly treated, but with vehicle alone (acetone). Eighteen to 24 hours after the last exposure, all animals were injected with 3H-methyl thymidine in phosphate-buffered saline into the tail vein and after five hours the test animals were euthanized and the bilateral auricular lymph nodes were excised. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed.

Positive control substance(s):

not specified

Statistics:

None stated

Results and discussion

Positive control results:

No information provided

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1

Test group / Remarks:

vehicle control

Results 2

Parameter:

SI

Value:

0.8

Test group / Remarks:

test substance concentration: 5%

Results 3

Parameter:

SI

Value:

0.9

Test group / Remarks:

test substance concentration: 10%

Results 4

Parameter:

SI

Value:

0.8

Test group / Remarks:

test substance concentration: 20%

Results 5

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

The mean DPM/animal value for the vehicle control group was 5.42E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 5% was 4.20E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 10% was 5.00E-02 DPM. The mean DPM/animal value for the experimental group treated with test substance concentrations 20% was 4.27E-02 DPM.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The SI values calculated for the test substance concentrations 5%, 10% and 20% were 0.8, 0.9 and 0.8 respectively.
There was no indication that the test substance could elicit an SI >=2 when tested on higher concentrations.
Therefore the test substance does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact.

Executive summary:

This LLNA test was conducted according to a modification of a method described by kimber et al., 1989. Five CBA mice per dose were used.

The SI values calculated for the test substance concentrations 5%, 10% and 20% were 0.8, 0.9 and 0.8 respectively. There was no indication that the test substance could elicit an SI >=2 when tested on higher concentrations. Therefore the test substance does not have to be classified and has no obligatory labeling requirement for sensitization by skin contact.