Mercaptoacetic acid

Endpoint summary

Description of key information

Mercaptoacetic acid was corrosive to the rabbit skin and in an EpiDerm Skin Model study performed according to Directive 2000/33/EC, B.27. It was also corrosive to the eyes in a study in rabbits compliant with the OECD guideline # 405. Respiratory tract irritation was observed in rats exposed to a high concentration of a vapour/aerosol mixture, but not when exposed to saturated vapour.

 

Skin Irritation

The skin irritation potential of mercaptoacetic acid has been investigated in the EpiDerm Corrosivity test and in rabbits.

The corrosive potential of mercaptoacetic acid (99% pure) was assessed using a human skin model, the EpiDerm Skin Model (Directive 2000/33/EC, B.27). Duplicate EpiDerm tissues were treated with 50 µl of mercaptoacetic acid and exposed for 3 minutes and 60 minutes. The tissues were incubated at 37°C in a humidified atmosphere of 5% CO2in air for the appropriate exposure times. Toxicity was determined by the conversion of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to formazan by viable cells in the test material treated tissues relative to the negative/solvent control-treated tissues. The study was validated by the inclusion of a positive control material, 8.0 N potassium hydroxide. The relative mean viability was 4.96% after 3 minutes exposure, and 6.60% after 60 minutes exposure. As the relative mean viability of the test material-treated tissues was <10% after 3 minutes exposure, mercaptoacetic acid is considered to be corrosive in vivo (Warren, 2002).

 

Mercaptoacetic acid was applied as a single occlusive patch test on the abdominal skin of rabbits. Skin reactions were observed and recorded at various time intervals up to 7 hours or until a chemical burn was observed. At the end of the exposure period, the skin area was washed with soap and water. Mercaptoacetic acid application resulted in necrosis within 5 minutes. This was accompanied by hyperemia and edema (Rampy, 1973).

 

Eye Irritation

The eye irritation potential of mercaptoacetic acid has been investigated in rabbits in a study compliant with the OECD guidelines# 405. 0.1 ml of neat mercaptoacetic acid was instilled into the eye of 1 rabbit, followed by grading at various times between 4 hours and 72 or 96 hours. Whitening of the conjunctiva due to corrosion prevented scoring for erythema, defaulting to a maximum score of 3 for erythema. The score given for corneal opacity also reached the maximum of 4, there is no indications of the evaluation of the reversibility in the publication (Jacobs et al., 1988). Therefore, neat mercaptoacetic acid is considered as corrosive to the eyes.

In a former study, 0.1 g of neat mercaptoacetic acid was instilled into the conjunctival sac of the right eye of one rabbit. After 30 seconds this eye was flushed for two minutes with a stream of flowing tap water. Mercaptoacetic acid was then instilled in the same way into the left eye, which was left unwashed. After instillation into the second eye, both eyes were examined for conjunctival irritation, corneal injury and internal effects (iritis) at intervals up to two weeks. Instillation of mercaptoacetic acid resulted in severe pain, severe conjuntival inflammation, dense corneal opacity and severe iritis. These effects were not improved at the end of 14 days after exposure. Washing immediately after exposure did not modify the response (Rampy, 1973).

 

Respiratory Tract Irritation

In the acute inhalation toxicity studies performed with mercaptoacetic acid (Pauluhn, 2004), signs of respiratory tract irritation were observed in rats exposed for 4 hours to high concentrations of aerosols (>0.284 mg/l). However no respiratory tract irritation was observed in rats exposed for 7 hours to saturated vapours generated at room temperature (nominal concentration 2.4 mg/l) or 125°C (31.4 mg/l) (Rampy, 1973).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: 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:

other: Directive 2000/33/EC, B.27

GLP compliance:

yes

Test system:

human skin model

Remarks:

EpiDerm Skin Model Kit Supplier: MatTek Corporation, Ashland, MA, USA. Batch 4006, Kit F, stored at approx. 4°C in the dark.

Source species:

human

Vehicle:

unchanged (no vehicle)

Details on test system:

The study was performed to assess the corrosivity potential of the test material using the EpiDerm Skin Model (MatTek, Ashland, MA, USA). The test is based on the assumption that corrosivity potential is related to toxicity to the EpiDerm tissue. The study was validated by the inclusion of a positive control material, 8.0 N Potassium Hydroxide and a negative control material, sterile distilled water. The study design complies with the requirements of method 27 ATP 2000/33/EC. The experimental design of the study consists of a test for Direct Reduction of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) by the test material, followed by the main study. For the main study, duplicate EpiDerm tissues were treated with 50 µl of test material and exposed for 3 minutes and 60 minutes. The tissues were incubated at 37°C in a humidified atmosphere of 5% C02 in air for the appropriate exposure times. Negative control-treated tissues (50 µl sterile, distilled water), and positive control-treated tissues (8.0 N Potassium Hydroxide), were also exposed for 3 minutes and 60 minutes. Duplicate EpiDerm tissues were used for the above. At the end of the exposure period each EpiDerm tissue was rinsed using Dulbecco's phosphate buffered saline (DPBS) and placed into a `holding plate', until all of the tissues had been treated and rinsed. They were then transferred to an MTT `loading plate', and incubated at 37°C for 3 hours in a humidified atmosphere of 5% CO2 in air. At the end of this time, each EpiDerm tissue was blotted dry and placed into an MTT `extraction plate' in order to extract all of the reduced MTT from the tissues. At the end of the extraction period, the extracted MTT solution was mixed for each EpiDerm tissue and 3 x 200 µl samples for each tissue were transferred to the appropriate wells of a 96 well plate. The absorbency at 540nm (OD540) of each well was measured with the Anthos 2001 microplate reader. Data are presented in the form of % viability (MTT conversion relative to negative controls) for each of the two exposure times.  The ability of the test material to directly reduce MTT in the direct MTT reduction test proved inconclusive. There was a possibility that if the test material could not be totally rinsed off the EpiDerm tissues, that any residual test material present on the tissue may directly reduce MTT and could have given rise to a false negative result. Therefore a corrective procedure using a "freeze killed" control EpiDerm tissue, also treated with the test material, was necessary to quantify this possibility.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

50 µl

Duration of treatment / exposure:

3 and 60 min

Number of replicates:

2

Amount / concentration applied:

undiluted

Irritation / corrosion parameter:

% tissue viability

Remarks:

Time point: 3 min.

Value:

4.96

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Corrosive

Other effects / acceptance of results:

The relative mean viability was 4.96% after 3 minutes exposure, and 6.60% after 60 minutes exposure. The relative mean viability of the test material-treated tissues was < 10% after 3 minutes exposure. The quality criteria required for acceptance of results in the test were satisfied.

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

Thioglycolic acid is considered to be corrosive in vivo.

Executive summary:

The corrosive potential of thioglycolic acid (99% pure) was assessed using a human skin model, the EpiDerm Skin Model (Directive 2000/33/EC, B.27). Duplicate EpiDerm tissues were treated with 50 µl of thioglycolic acid and exposed for 3 minutes and 60 minutes. The tissues were incubated at 37°C in a humidified atmosphere of 5% CO₂ in air for the appropriate exposure times. Toxicity was determined by the conversion of MTT to formazan by viable cells in the test material treated tissues relative to the negative/solvent control-treated tissues.The study was validated by the inclusion of a positive control material, 8.0 N Potassium hydroxide.The relative mean viability was 4.96% after 3 minutes exposure, and 6.60% after 60 minutes exposure. As the relative mean viability of the test material-treated tissues was <10% after 3 minutes exposure, thioglycolic acid is considered to be corrosive in vivo.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

5 minute(s)

Details on study design:

The abdominal skin of the rabbits was shaved with a straight razor and  barber soap. The animals were rested for several days to allow razor  abrasions to heal. For the exposure, the animals were placed in a stock,  abdomen side up. Test material was applied to several spots on the intact  skin and covered with a small cotton pad. The area was loosely covered  with a plastic cover to retard evaporation of liquids. Skin reactions  were observed and recorded at various time intervals up to 7 hours or  until a chemical burn was observed.  At the end of the exposure period,  the skin area was washed with soap and water. The skin reaction was  evaluated again the following day.

Remarks on result:

other: Corrosive within 5 min

Irritant / corrosive response data:

Application of thioglycolic acid in the single patch test resulted in necrosis within 5 minutes. This was accompanied by hyperaemia and oedema.  Thus, it is clear that a chemical burn can occur within minutes after  application.

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

Classification: corrosive (causes burns)

Executive summary:

Thioglycolic acid was applied as a single occlusive patch test on the abdominal skin of rabbits. Skin reactions were observed and recorded at various time intervals up to 7 hours or until a chemical burn was observed. At the end of the exposure period, the skin area was washed with soap and water. Thioglycolic acid application resulted in necrosis within 5 minutes. This was accompanied by hyperemia and edema.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentations

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

Cited as Directive 84/449/EEC, B.5

GLP compliance:

not specified

Species:

rabbit

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount applied: 0.1 ml

Observation period (in vivo):

up to 7 days

Number of animals or in vitro replicates:

6

Details on study design:

not rinsed

Irritation parameter:

cornea opacity score

Basis:

animal: all

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal: all

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal: all

Time point:

24/48/72 h

Remarks on result:

other: not reported

Irritation parameter:

chemosis score

Basis:

animal: all

Time point:

24/48/72 h

Remarks on result:

other: not reported

Whitening of the conjunctiva due to corrosion and prevented scoring for  erythema, defaulting to a maximum score of 3 for erythema. The score  given for corneal opacity also reached the maximum of 4.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

The eye irritation potential of thioglycolic acid has been investigated in rabbits in a study compliant with the OECD guidelines# 405. 0.1 ml of neat thioglycolic acid was instilled into the eyes of 1 rabbit, followed by grading at various times between 4 hours and 72 or 96 hours. Whitening of the conjunctiva due to corrosion prevented scoring for erythema, defaulting to a maximum score of 3 for erythema. The score given for corneal opacity also reached the maximum of 4, there is no indications of the evaluation of the reversibility in the publication. Therefore, neat thioglycolic acid is considered as corrosive to the eyes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount applied: 100 other: mg

Number of animals or in vitro replicates:

1

Remarks on result:

other: Corrosive

Instillation of thioglycolic acid into the eyes of a rabbit resulted in  severe pain, severe conjuntival inflammation, dense corneal opacity and  severe iritis. These effects were not improved at the end of 14 days  after exposure. Washing immediately after exposure did not modify the  response  (no more data available).

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

In a former study, 0.1 g of neat thioglycolic acid was instilled into the conjunctival sac of the right eye of one rabbit. After 30 seconds this eye was flushed for two minutes with a stream of flowing tap water. Thioglycolic acid was then instilled in the same way into the left eye, which was left unwashed. After instillation into the second eye, both eyes were examined for conjunctival irritation, corneal injury and internal effects (iritis) at intervals up to two weeks. Instillation of thioglycolic acid resulted in severe pain, severe conjuntival inflammation, dense corneal opacity and severe iritis. These effects were not improved at the end of 14 days after exposure. Washing immediately after exposure did not modify the response.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

REGULATION (EC) No 1272/2008:

* According to Annex VI Table 3.1 mercaptoacetic acid is classified:

- Skin Corr. 1B

SELF-CLASSIFICATION

According to the available acute toxicity data, and CLP criteria, mercaptoacetic acid should be classified:

- Skin Corr. 1A

- Eye Damage 1