Potassium salicylate

Endpoint summary

Description of key information

Various studies were summarized to ascertain the degree of dermal sensitization caused by Sodium Salicylate in living organisms.The studies are based on in vivo experiments in humans, mice along with for Sodium salicylate and its structurally similar read across chemicals,Methyl salicylate [CAS: 119-36-8]; Salicylic Acid[ CAS: 69-72-7]. Based on the available data for Sodium salicylate as well as structurally similar read across chemicals and applying the weight of evidence approach, Potassium salicylate can be considered to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Type of information:

not specified

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The allergenic potential of Sodium Salicylate was determined in a number of studies using up to 31 patients, 19 males and 12 females, with a history of aspirin intolerance

GLP compliance:

not specified

Type of study:

other: Intradermal Skin test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Sodium salicylate - Molecular Formula: C7H6O3.Na- Molecular Weight: 160.105 g/mol- Smiles Notation: - InChI: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1- Substance Type: Organic- Physical State: Solid

Species:

other: humans

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

Age: aged between 6 and 64 years

Reading:

1st reading

Hours after challenge:

20

Group:

test chemical

Dose level:

0.02 ml of 0.1% of sodium salicylate

No. with + reactions:

1

Total no. in group:

31

Clinical observations:

Sodium salicylate is not skin sensitizing

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

There was one positive reaction to Sodium Salicylate in the skin test was observed out of 31 pateints.Hence, Sodium Salicylate can be considered to be not sensitizing to skin.

Executive summary:

The allergenic potential of Sodium Salicylate was determined in a number of studies using up to 31 patients. 19 males and 12 females, with a history of aspirin intolerance were used for the assay. 31 patients were given an intradermal injection of 0.02 ml of 0.1% Sodium Salicylate; the results were scored 20 min after dosing. There was one positive reaction to Sodium Salicylate in the skin test was observed out of 31 patients. Hence, Sodium Salicylate can be considered to be not sensitizing to skin.

Reference 2

Endpoint:

skin sensitisation, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: Patch test

Principles of method if other than guideline:

Patch test were conducted on a patient with allergic contact dermatitis to sunscreen

GLP compliance:

not specified

Remarks:

Study data from handbook or collection of data

Type of study:

patch test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Sodium salicylate - Molecular Formula: C7H6O3.Na- Molecular Weight: 160.105 g/mol- Smiles Notation: c1(c(cccc1)O)C(=O)[O-].[Na+]- InChI: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1- Substance Type: Organic- Physical State: Solid

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2% in petrolatum

No. with + reactions:

0

Total no. in group:

1

Clinical observations:

no signs of sensitization observed

Remarks on result:

no indication of skin sensitisation

Table: Patch test results

Test compound	CAS	Test concentration	Function	Day 3 reading**	Day 7 reading**
Sodium salicylate	54-21-7	2% in petrolatum	Denaturant and preservative	-	-

**-readings are for the patient in the case report

 

Interpretation of results:

other: not sensitizing

Conclusions:

No dermal reactions were observed on day 3 and day 7 of observation when the patient was tested with 2% sodium salicylate in petrolatum.Hence, sodium salicylate can be considered to be not sensitizing to skin.

Executive summary:

Patch test were conducted on a patient with allergic contact dermatitis to sunscreen.

A 48 year old woman with a 12 year history of rosacea was advised to use sunscreen. A sample of Anthelios dermo-pediatrics SPF-50+ was given to the patient. Half year later, the patient developed facial dermatitis. She was tested with the European baseline series using panels 1,2, and 3 of the Thin Layer Rapid Use Epicutaneous Test [T.R.U.E Test] supplemented petrolatum-based allergens in Finn chambers on Scanpor tape and with her own topical products including the Anthelios dermo-pediatrics SPF-50+ lotion. The tests were occluded for 2 days and read according to the ICDRG[International Contact Dermatitis Research Group]scoring scale on day 3 and day 7.

The patient was subsequently patch test with individual components of the Anthelios dermo-pediatrics SPF-50+ lotion as provided by the manufacturer.

No dermal reactions were observed on day 3 and day 7 of observation when the patient was tested with 2% sodium salicylate in petrolatum.

Hence, sodium salicylate can be considered to be not sensitizing to skin.

Reference 3

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journal.

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The skin sensitizing potential of the test chemical Methyl salicylate (CAS no: 119-36-8) was assessed by using the Mouse Local Lymphnode Assay.

GLP compliance:

not specified

Remarks:

Study data from handbook or collection of data

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

- Name of test material (as cited in study report): Methyl salicylate- Molecular formula : C8H8O3- Molecular weight: 152.15 g/mol- Substance type: Organic- Physical state: liquid-Smiles: c1(c(cccc1)O)C(OC)=O- InChI:1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS Source: No data. Age at study initiation: 7-12 weeks. ENVIRONMENTAL CONDITIONS: No data

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

1%, 2.5%, 5%, 10% or 20% (25µl)

No. of animals per dose:

5 female mice/dose

Details on study design:

Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute. An SI was calculated for each chemical group as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer , if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3)

Statistics:

The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value. Refer Table 1 and 2 for more information

Parameter:

EC3

Value:

> 20

Remarks on result:

other: The calculated EC3 value for methyl salicylate was >20.0%

Parameter:

SI

Value:

ca. 1

Test group / Remarks:

1 %

Parameter:

SI

Value:

ca. 1.1

Test group / Remarks:

2.5 %

Parameter:

SI

Value:

ca. 1.6

Test group / Remarks:

5 %

Parameter:

SI

Value:

ca. 1.4

Test group / Remarks:

10 %

Parameter:

SI

Value:

ca. 0.9

Test group / Remarks:

20 %

Cellular proliferation data / Observations:

The calculated EC3 value for methyl salicylate was >20.0%

Table 1:Classification of relative skin sensitization potency by local lymphnode assay (LLNA) EC3 values
EC3 values (%)	Potency classification
≥10 to ≤100	Weak
≥1 to <10	Moderate
≥0.1 to <1	Strong
<0.1	Extreme

CAS

Vehicle

LLNA%

LLNA%

LLNA%

LLNA%

LLNA%

LLNA SI

LLNA SI

LLNA SI

LLNA SI

LLNA SI

LLNA EC3

Relative Potency

122-40-7

AOO

1.0

2.5

5.0

10.0

20.0

1.0

1.1

1.6

1.4

0.9

NC

Nonsensitizer

Where AOO – Acetic acid in olive oil ; SI - Stimulation Index; NC-Not Calculated

Interpretation of results:

other: not sensitizing

Conclusions:

The relative potency index of Methyl salicylate (CAS no: 119-36-8) was estimated to be >20.0%. Based on the relative potency index Methyl salicylate (CAS no: 119-36-8) was considered to be not sensitizing in the Mouse Local Lymphnode Assay.

Executive summary:

The skin sensitizing potential of the test chemical Methyl salicylate (CAS no: 119-36-8) was assessed by using the Mouse Local Lymphnode Assay.

 

The LLNA was conducted on groups of five female CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl of 1%, 2.5%, 5%, 10% or 20% in acetone/olive oil (4:1). Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute.

An SI was calculated for each chemical group as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer , if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3).The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.

 

For each concentration of methyl salicylate, a stimulation index (SI) relative to the concurrent vehicle-treated control was calculated. The calculated EC3 value for methyl salicylate was >20.0%. Thus based on the relative potency index Methyl salicylate (CAS no: 119-36-8) was considered to be not sensitizing in theMouse Local Lymphnode Assay.

Reference 4

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The skin sensitizing potential of salicylic acid was assessed by using the Mouse Local Lymphnode Assay.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

- Name of test material (as cited in study report): salicylic acid- Molecular formula: C7H6O3- Molecular weight: 138.12 g/mol- Substance type: organic - Physical state: liquid -Smiles: c1(c(cccc1)O)C(=O)O-InChI: 1S/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS Source: No data Age at study initiation: 7-12 weeks ENVIRONMENTAL CONDITIONS: No data

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

5, 10, 25 %

No. of animals per dose:

no data available

Details on study design:

no data available

Positive control substance(s):

not specified

Statistics:

no data available

Positive control results:

no data available

Parameter:

EC3

Value:

0

Test group / Remarks:

test group

Remarks on result:

other: not sensitizing

Parameter:

SI

Value:

ca. 0.8

Test group / Remarks:

5 %

Parameter:

SI

Value:

ca. 1.5

Test group / Remarks:

10 %

Parameter:

SI

Value:

ca. 2.5

Test group / Remarks:

25 %

Cellular proliferation data / Observations:

The relative potency index of salicyclic acid was not calculates since the SI were less than 3

Table 2: Results of the LLNA study

CAS

Vehicle

LLNA%

LLNA%

LLNA%

LLNA%

LLNA%

LLNA SI

LLNA SI

LLNA SI

LLNA SI

LLNA SI

LLNA EC3

Relative Potency

69-72-7

AOO

5

10

25

-

-

0.8

1.5

2.5

0

0

NC

Non sensitizer

Where AOO – Acetic acid in olive oil(4:1) ; SI - Stimulation Index; NC – Not calculated

 

Interpretation of results:

GHS criteria not met

Conclusions:

The relative potency index of salicyclic acid was not calculated since the SI were less than 3.Based on the relative potency, salicylic acid was considered to be not sensitizing to mice skin.

Executive summary:

The skin sensitizing potential of Salicylic acid was assessed by using the Mouse Local Lymphnode Assay. The study was conducted as per OECD 429 Guidelines.

The LLNA was conducted on groups of CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute. An SI was calculated for each chemical group as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group.

A substance was classified skin sensitizer, if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3) The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.

The relative potency index of salicylic acid was not calculated since the SI were less than 3.

Based on the relative potency, salicylic acid was considered to be not sensitizing to mice skin.

Reference 5

Endpoint:

skin sensitisation, other

Remarks:

in vivo (LLNA/non-LLNA)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature survey, Based on structural similarity, the result can be used for read across, classification and risk assessment of potassium salisylate.

Justification for type of information:

Based on structural similarity, the results from Sodium salicylate can be used for read across, classification and risk assessment of potassium salisylate.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reading:

1st reading

Hours after challenge:

20

Group:

test chemical

Dose level:

0.02 ml of 0.1 % of sodium salicylate

No. with + reactions:

1

Total no. in group:

31

Clinical observations:

Sodium salicylate is not skin sensitizing

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2% in petrolatum

No. with + reactions:

0

Total no. in group:

1

Clinical observations:

no signs of sensitization observed

Remarks on result:

no indication of skin sensitisation

Parameter:

EC3

Value:

> 20

Remarks on result:

other: The calculated EC3 value for methyl salicylate was >20 %

Parameter:

EC3

Value:

0

Test group / Remarks:

test group

Remarks on result:

other: not sensitizing

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Various studies were summarized to ascertain the degree of dermal sensitization caused by Sodium Salicylate in living organisms.The studies are based on in vivo experiments in humans, mice along with for Sodium salicylate and its structurally similar read across chemicals,Methyl salicylate [CAS: 119-36-8]; Salicylic Acid[ CAS: 69-72-7]. Based on the available data for Sodium salicylate as well as structurally similar read across chemicals and applying the weight of evidence approach and concidering thr CLP classification criteria, Potassium salicylate can be considered to be not sensitizing to skin.