Trimethylsulfonium bromide

Endpoint summary

Description of key information

Skin:

The substance is not corrosive or irritating to skin.

Eye:

The substance is not irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 20 to 22, 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Version / remarks:

2019

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Lot number: 21MR1-2
Purity: 99%

Test system:

human skin model

Cell type:

non-transformed keratinocytes

Cell source:

other: reconstructed

Details on animal used as source of test system:

SOURCE ANIMAL
- Source: EpidermTM tissues from MatTek Corporation.

Justification for test system used:

The test systetm (non-transformed human-derived epidermal keratinocytes cultured to form a complex model of the human epidermis) was validated and approved by regulatory authorities for evaluation of skin irritation potential.

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpidermTM tissues

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37.2oC
- Temperature of post-treatment incubation (if applicable):

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: tissues were rinsed with sterile DPBS by filling and emptying the tissue insert at least 15 times to remove any residual test material.

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: in 96-well plate
- Wavelength: 570 nm

NUMBER OF REPLICATE TISSUES: 3 replicates in each group

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Fresh tissues / killed tissues
- Procedure used to prepare the killed tissues (if applicable):
- N. of replicates : 3
- Method of calculation used:

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be irritating to skin if the viability after 1 hour exposure is less than or equal to 50%.
- The test substance is considered to be non-irritating to skin if the viability after 1 hour exposure is greater than 50%.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg
- Concentration (if solution):

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 uL
- Concentration (if solution):

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 uL
- Concentration (if solution): 5%

Duration of treatment / exposure:

1 hour

Duration of post-treatment incubation (if applicable):

18 hours

Number of replicates:

3 replicates per group

Irritation / corrosion parameter:

% tissue viability

Value:

62.4

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

Positive and negative controls performed as expected and all validity criteria were met.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, TMSBr is considered a non-irritant.

Executive summary:

The in vitro Epiderm skin irritation test was performed using three-dimensional RHE tissue, according to OECD Guideline 439 under GLP.

Under the conditions of the study, TMSBr is considered a non-irritant.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 14 to 28 April 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Lot No.: 21MR1-2
Purity: 99%

Test system:

other: Reconstructed Human Epithelium

Cell type:

non-transformed keratinocytes

Details on animal used as source of test system:

SOURCE:
The in vitro EpidermTM skin corrosion test was performed using three-dimensional Reconstructed Human Epithelium obtained from MatTek Corporation (Ashland, MA).

Justification for test system used:

The test system (non-transformed human derived epidermal keratinocytes cultured to form a complex model of the human epidermis) has been validated and approved by regulatory authorities for evaluation of skin corrosion potential. The present test is based on the experience that corrosive chemicals are cytotoxic after a short term exposure to the stratum corneum of the epidermis, if cytotoxicity is immediately determined after chemical exposure.

Vehicle:

water

Details on test system:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 oC
- Temperature of post-treatment incubation (if applicable):

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 minutes, 1 hour

NUMBER OF REPLICATE TISSUES: two

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.

Control samples:

yes, concurrent vehicle

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg

VEHICLE
- Amount(s) applied (volume or weight with unit): 25 uL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 uL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 uL

Duration of treatment / exposure:

3 minutes, 1 hour

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 minutes exposure

Value:

84.3

Vehicle controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1 hour exposure

Value:

63.4

Vehicle controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

Tissue viability after exposure to TMSBr was 84.3% after 3 minutes and 63.4% after 1 hour. The substance is not expected to cause skin corrosion.

Executive summary:

The in vitro EpidermTM skin corrosion test was performed using three-dimensional Reconstructed Human Epithelium, to identify the skin corrosivity potential of TMSBr, according to OECD Guideline 431 under GLP.

Tissue viability after exposure to TMSBr was 84.3% after 3 minutes and 63.4% after 1 hour. The substance is not expected to cause skin corrosion.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Lot No.: 21MR1-2
Purity: 99%

Species:

other: Bovine cornea

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: Spear Products Inc., 520 Springfield street, coopersburg, PA 18036.
- Number of animals: 9 corneas
- Selection and preparation of corneas: Eyes were carefully examined for defects (opacity, scratches, pigmentation, etc) shortly after arrival to the facility. Any eyes with defects were omitted from the study and discarded. The tissue surrounding the eye ball was carefully pulled away, and the cornea was excised, leaving a rim of sclera approximately 2 to 3 mm wide. The isolated corneas were maintained in HBSS until all were dissected.

Vehicle:

water

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 uL
- Concentration (if solution): 20% w/v

Duration of treatment / exposure:

4 hours

Duration of post- treatment incubation (in vitro):

90 mins

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: washed at least 3 times with MEM containing phenol red until no color change occurred.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity:
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of [UV/VIS spectrophotometry / microtiter plate reader] (OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: the decision criteria as indicated in the TG was used.

Irritation parameter:

in vitro irritation score

Value:

-1

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

TMSBr meets the requirements of EPA category III and UN GHS no category for the BCOP test.
Proper conduct of the BCOP was confirmed via a positive response with imidazole and a negative response with 0.9% sterile NaCl.

Interpretation of results:

GHS criteria not met

Conclusions:

TMSBr is not irritating to eyes in the BCOP test.

Executive summary:

The Bovine corneal opacity & permeability assay was performed using isolated bovine cornea, according to OECD Guideline 437 under GLP.

TMSBr is not irritating to eyes in the BCOP test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

The in vitro EpidermTM skin corrosion test was performed using three-dimensional Reconstructed Human Epithelium, to identify the skin corrosivity potential of TMSBr, according to OECD Guideline 431 under GLP. Tissue viability after exposure to TMSBr was 84.3% after 3 minutes and 63.4% after 1 hour. The substance is not expected to cause skin corrosion.

The in vitro Epiderm skin irritation test was performed using three-dimensional RHE tissue, according to OECD Guideline 439 under GLP. Under the conditions of the study, TMSBr is considered a non-irritant.

 

Eye:

The Bovine corneal opacity & permeability assay was performed using isolated bovine cornea, according to OECD Guideline 437 under GLP. TMSBr is not irritating to eyes in the BCOP test.

Justification for classification or non-classification

Skin irritation / corrosion:

In vitro skin corrosion, OECD 431: not corrosive

In vitro skin irritation, OECD 439: not irritating

According to Regulation (EC) No 1272/2008, section 3.2, this substance should not be classified for this endpoint.

 

Eye irritation:

In vitro eye irritation, BCOP study, OECD 437: not irritating.

According to Regulation (EC) No 1272/2008, section 3.3, this substance should not be classified for this endpoint.