Sodium benzothiazol-2-yl sulphide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and OECD Guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
[Describe why the read-across can be performed (e.g. common functional group(s), common precursor(s)/breakdown product(s) or common mechanism(s) of action]

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIX

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

basic toxicokinetics

Type of information:

other: read across approach

Adequacy of study:

supporting study

Reliability:

other: data matrix read across approach

Rationale for reliability incl. deficiencies:

other: data matrix read across approach, target chemical SMBT, source chemical MBT

Principles of method if other than guideline:

other: data matrix read across approach

SMBT is a sodium salt of MBT (mass content SMBT: MBT 88%, sodium: 12%). SMBT is a strong base (pH 10, as discussed in chapter 1.3) and is classified as corrosive (R34/category 1C). The corrosive character of SMBT is the predominant local effect and determines the local DNEL. According to ECHA Guidance Document Part E: Risk Characterisation, substances with R-phrases R34 (causes burs), R41 (risk of serious damage to the eyes), which relate to corrosive or severe irritant effects to the eye or irritant effects to the eyes are allocated to the moderate hazard category.

Read across approach (systemic effects)

There are no toxicokinetic data, no valid repeated dose study data and reproduction toxicity data available for SMBT. A read-across approach with systemic toxicity data from MBT (benzothiazole-2 -thiol) was performed. In addition, the second component the sodium ion Na+ is briefly discussed.

The available systemic mammalian toxicity data from SMBT were compared with data from MBT (see table data matrix). Similarities in mammalian systemic toxicity were noted in SMBT and MBT treated animals. The oral and dermal toxicity of SMBT and MBT is very low, indicated by oral LD50 values > 2000 mg/kg bw and dermal LD50 values >7940 mg/kg bw. No mutagenic potential or even a weak response was indicated for SMBT and MBt in bacteria.

Data Matrix, analogue approach

	Target Chemical (SMBT)	Source Chemical (MBT)
CAS #	2492-26-4	149-30-4
Chemical Name	sodium benzothiazol-2-yl sulphide	benzothiazole-2-thiol
Structure
Physico-Chemical Data
Physical state at 20°C and 101.3 kPa	liquid (aqueous solution)	solid (crystalline)
Appearance	Colour: yellowish-brown	colour: yellow
Molecular weight range	189.2331 g/mol	167.2513 g/mol
Relative density	1.26 kg/l (20°C) was reported by Lanxess 50% solution and 1.14 kg/l (20°C) for 30% solution	1.42 g/cm³ at 20°C. (Lide 2002)
Water solubility	liquid (aqueous solution)	118 mg/l at 25°C and pH 7. (Monsanto 1980)
Mammalian Toxicity
Dermal irritation/corrosion	corrosive	not irritating rabbit (Monsanto Co. 1975)
Eye irritation	corrosive	not irritating rabbit (New Zealand White) (Monsanto Co. 1975)
Dermal sensitization	corrosive	moderate skin sensitizing Guinea pig maximisation test (Bayer AG 1999)
Mutagenicity (bacteria)	Ames assay: negative (Monsanto Co. 1976, Goodyear 1979)Ames assay: weak positive (NTP 1984)	Ames assay: negative (CMA 1984)
Mutagenicity in vivo assays	no data	Genotoxicity: negative micronucleus assay (CMA 1984)
Acute toxicity (oral)	LD50: 2100 mg/kg bw (Bayer AG 1978)	LD50: 3800 mg/kg bw rat (Monsanto Co.1975)
Acute toxicity (inhalation)	no valid data available	no data available
Acute toxicity (dermal)	LD50:> 7940 mg/kg bw (Monsanto Co. 1974)	LD50: > 7940 mg/kg bw (Monsanto Co.1975)

Sodium

Sodium is the quantitative main cation of the extracellular room. In combination with other electrolytes as chloride and potassium, the sodium ion is involved in several essential functions in the human body. The main function is the maintenance of the extracellular volumes, the regulation of the osmotic pressure, the regulation of the acid-base homeostasis, production of gastric acid, activation of enzymes and the trans-membrane potential (e.g. transmitting signals in neurons and muscle cells). The recommended daily intake is in the range of 575 to 3500 mg Na⁺/day (SCF 2003).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Read-across from supporting substance (structural analogue or surrogate). Additional, the test substance is classified as corrosive to skin; according to REACH regulation Annex VII, chapter 8.3. skin sensitization, column 2, in vivo testing does not need to be conducted.

Test material

Test material information

Constituent 1

Reference substance name:

Benzothiazole-2-thiol

EC Number:

205-736-8

EC Name:

Benzothiazole-2-thiol

Cas Number:

149-30-4

Molecular formula:

C7H5NS2

IUPAC Name:

1,3-benzothiazole-2-thiol

Details on test material:

2-mercaptobenzothiazole, batch no. 01631-077 (supplied by Aldrich Chemie)

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: HSD Poc:DH strain

Sex:

female

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Induction 2

Concentration / amount:

intradermal induction: 5 % (= 20 mg test item/animal) topical induction: 25 % (= 125 mg test item/animal), challenge: 12 % (= 60 mg test item/animal)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Challenge 2

Concentration / amount:

intradermal induction: 5 % (= 20 mg test item/animal) topical induction: 25 % (= 125 mg test item/animal), challenge: 12 % (= 60 mg test item/animal)

No. of animals per dose:

treatment group: 10, neagitve control: 5

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

12 %

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

Appearance and behavior of the test item group were not different from control group

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 12 %. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: Appearance and behavior of the test item group were not different from control group.

Results 2

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

12 %

No. with + reactions:

6

Total no. in group:

10

Clinical observations:

Appearance and behavior of the test item group were not different from control group

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 12 %. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Appearance and behavior of the test item group were not different from control group.

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

no effects

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: no effects.

Results 4

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

At the end of the study , the mean body weight of the treatment group animals was slightly higher than that of the control group animals.

The total number of animals with skin reactions was 70 % in the test substance group and 20 % in the control group.