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Administrative data

Description of key information

Due to its corrosive properties, the skin sensitisation potential of not neutralized mercaptoacetic acid has not been investigated in vivo. The allergic contact dermatitis potential of mercaptoacetic acid was estimated in guinea pig and human with the three QSAR models (CASE Ultra, Leadscope, SciQSAR) of the Danish QSAR data base. All results were positive.

Mercaptoacetic acid salts are considered as skin sensitisers and toxicity of the mercaptoacetate salts is attributed to the mercaptoacetate anion. The sensitising potential of ammonium and sodium salts of mercaptoacetic acid was investigated in a local lymph node assay in mice performed following the OECD Guideline 429. Both substances were found to be sensitising to the skin with an EC3 value of 0.65% and ca. 6%, respectively.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
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: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 16-20 g
- Housing: in groups in macrolon cage
- Diet (ad libitum): Altromin 1324 maintenace diet for rats and mice
- Water (ad libitum): municipal drinking water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
other: T52-003:modified acetone/aqua/olive oil
Concentration:
20 %, 8% and 0.5 %
No. of animals per dose:
5
Details on study design:
The test item was assayed at three concentrations of 20 %, 8% and 0.5 %  respectively.  The main vehicle was modified acetone/aqua/olive oil (AAOO) to achieve  maximum solubility of the test item. Each female mouse was treated by  topical application with the selected solution to entire dorsal surface  of each once daily over three consecutive days. Five days after the first topical application treatment all mice were  injected intravenous with 3H-methyl thymidine.  Approximately 5 hours after 3H-methyl thymidine injection all mice were  sacrificed and the draining auricular lymph nodes were excised, in order  to prepare single cell suspension of the lymph node cells. The 3 H-methyl thymidine-incorporation was measured in a SS counter and  expressed as the number of disintegrations per minute (DPM).  Determination of radioactivity was performed individually for each animal. The proliferation response of lymph node cells was calculated as the  ratio of 3H-methyl thymidine incorporation into lymph node cells of test  group animals relative to that recorded for control group animals. A  stimulation index, ratio of test substance/vehicle control, was  calculated for each concentration. Additionally the EC3 value was determinated.
Positive control substance(s):
other: 1% p-phenylenediamine
Statistics:
None
Positive control results:
The test control ratio for the positive control (1 % p-phenylenediamine)  was 5.3.
Key result
Parameter:
EC3
Value:
0.65
Parameter:
SI
Value:
2.7
Test group / Remarks:
0.5%
Parameter:
SI
Value:
17
Test group / Remarks:
8%
Parameter:
SI
Test group / Remarks:
20%
Remarks on result:
other: Evaluation was not possible as all animals died after the third application, indicating systemic effects at his concentration.
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Ammonium thioglycolate up from a concentration of 0.65 % caused reactions identified as sensitization, as the stimulation index was equal to or greater than 3.0.
Executive summary:

The skin sensitization potential of ammonium thioglycolate (71% solution) was investigated in local lymph node assays performed according to the OECD guideline # 429. There were 5 CBA/Ca/Ola/Hsd female mice in each of the dose and control groups, respectively. The mice received 25 µl of topical solution consisting of 0, 0.5, 8.0, or 20.0% (a.i., w/v) of ammonium thioglycolate on the dorsal surface of each ear lobe once daily for three consecutive days. p-Phenylenediamine was used as positive controls and showed satisfactory sensitisation response. Five days after the first application of solution, all mice received radiolabelled thymidine (3HTdR) by i.v. injection in thet ail vein. All mice were killed five hours after the3HTdR injection. The lymph nodes of the mice were removed and studied for proliferation with3HTdR. The values were then used to calculate the stimulation index (SI) as reported in table 21. It was concluded that both ammonium thioglycolate and sodium thioglycolate were sensitising in mice.

The stimulation indexes were  2.7 and 17.0 at concentrations of 0.5 % and 8%, respectively. Evaluation for the 20 % concentration was not possible as all animals died after the third application, indicating systemic effects at his concentration. The EC3 value (derived by linear interpolation) was at 0.65 %.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May to July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/Ca/Ola/Hsd
Sex:
female
Details on test animals and environmental conditions:
ANIMALS:
- Source: Harlan Interfauna UK Limited, Blackthorne, Bicester, Oxon, UK
- Number used: 4 per group
- Age: young adults, 9-10 weeks old
- Diet: RM1, supplied by Special Diets Services Limited, Witham, Essex, UK  ad libitum
- Water: ad libitum
- Acclimatization: at least 5 days

CONDITIONS:
- Temperature: 22+/-3°C
- Humidity: 30-70 %
- Air changes: min 15/hour
- Light-Dark cycle: 12/12
Vehicle:
propylene glycol
Concentration:
0.25, 0.5 and 1.0 % w/v
No. of animals per dose:
4
Details on study design:
Groups of four female mice were used for this study.  Approximately 25µl of a 0.25%, 0.5% or 1% (w/v) preparation of the test  substance in propylene glycol was applied, using a variable volume  micropipette, to the dorsal surface of each ear. The procedure was  repeated daily for 3 consecutive days. Subsequently, a further three  groups of female mice were similarly dosed with 2.5%, 5% or 10 % (w/v)  preparations of the test substance in propylene glycol. On each occasion,  a concurrent control group was similarly treated using propylene glycol  alone. Three days after the third application, all the animals were injected,  via the tail vein, with approximately 250 µl of phosphate buffered saline  (PBS) containing approximately 20 µCi of a 2.0 Ci/mmol specific activity  3H-methyl thymidine. Approximately 5 hours later, the animals were  humanely killed and the draining auricular lymph node were removed from  each animal and pooled for each group. Animals were checked at least once daily for signs of systemic toxicity.  Body weight was recorded prior to dosing on day 1 and on day 6.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
None
Positive control results:
The application of hexylcinnamaldehyde at concentrations of 2.5 %, 5 % or  10 % (w/v) in acetone resulted in an increase in isotope incorporation  which was greater than 3-fold at all three concentrations. Therefore,  hexylcinnamaldehyde was shown to be a skin sensitizer, confirming the  validity of the protocol used for the study.
Key result
Parameter:
EC3
Value:
ca. 6
Remarks on result:
other: There were no signs of dermal irritation at the application site and no  signs of systemic toxicity
Parameter:
SI
Value:
2.05
Test group / Remarks:
0.5%
Parameter:
SI
Value:
1.16
Test group / Remarks:
0.25%
Parameter:
SI
Value:
0.92
Test group / Remarks:
1.0%
Parameter:
SI
Value:
1.17
Test group / Remarks:
2.5%
Parameter:
SI
Value:
2.32
Test group / Remarks:
5.0%
Parameter:
SI
Value:
6.7
Test group / Remarks:
10%

SKIN SENSITISATION POTENTIAL OF SODIUM THIOGLYCOLATE 98%. PURE

Concentration of

Number of

Disintegations

dpm per

Test:control ratio

test substance

(% w/v)

lymph nodes

assayed

per minute

(dpm)

lymph node

xl0-2

(stimulation index)

0 (vehicle only)

8

1910

2.39

N/A

0.25

8

2213

2.77

1.16

0.5

8

3909

4.89

2.05

1

8

1756

2.20

0.92

0 (vehicle only)

8

4362

5.45

N/A

2.5

8

5102

6.38

1.17

5

8

10102

12.63

2.32

10

8

29199

36.50

6.70

SKIN SENSITISATION POTENTIAL OF THE POSITIVE CONTROL SUBSTANCE (HEXYLCINNAMALDEHYDE)

Concentration of

Number of

Disintegations

dpm per

Test:control ratio

Hexylcinnamaldehyde (% w/v)

(% w/v)

lymph nodes

assayed

per minute

(dpm)

lymph node

xl0-2

(stimulation index)

0 (vehicle only)

8

2570

3.31

N/A

2.5

8

16088

20.11

6.26

5

8

15659

19.57

6.10

10

8

15611

19.51

6.08

N/A : not applicable


Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The application of sodium thioglycolate 98% at concentrations up to 10 %(w/v) in propylene glycol resulted in an increase in isotope incorporation which was greater than 3-fold at the 10 % (w/v) concentration. Consequently, the test substance was shown to be a potential skin sensitizer.
Executive summary:

The skin sensitization potential of sodium thioglycolate (98% pure) was investigated in local lymph node assays performed according to the OECD guideline # 429. There were 4 CBA/Ca/Ola/Hsd female mice in each of the dose and control groups, respectively. The mice received 25 µl of topical solution consisting of 0, 0.25, 0.5, 1.0, 2.5, 5.0, or 10% (w/v) of sodium thioglycolate on the dorsal surface of each ear lobe once daily for three consecutive days. Hexylcinnamaldehyde were used as positive controls and showed satisfactory sensitisation response. Five days after the first application of solution, all mice received radiolabelled thymidine (3HTdR) by i.v. injection in the tail vein. All mice were killed five hours after the3HTdR injection. The lymph nodes of the mice were removed and studied for proliferation with 3HTdR. The stimulation index (SI) was 6.7 at 10% (EC3 ca. 6%). It was concluded that sodium thioglycolate was sensitising in mice.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The skin sensitization potential of ammonium mercaptoacetate (71% solution; Albrecht, 2001) and sodium mercaptoacetate (98% pure; Johnson, 2003) was investigated in local lymph node assays performed according to the OECD guideline # 429. There were 5 or 4 CBA/Ca/Ola/Hsd female mice in each of the dose and control groups, respectively. The mice received 25 µl of topical solution consisting of 0, 0.5, 8.0, or 20.0% (w/v) of ammonium mercaptoacetate or 0, 0.25, 0.5, 1.0, 2.5, 5.0, or 10% (w/v) of sodium mercaptoacetate on the dorsal surface of each ear lobe once daily for three consecutive days. p-Phenylenediamine and hexylcinnamaldehyde were used respectively as positive controls and showed satisfactory sensitisation response. Five days after the first application of solution, all mice received radiolabelled thymidine (3HTdR) by i.v. injection in the tail vein. All mice were killed five hours after the3HTdR injection. The lymph nodes of the mice were removed and studied for proliferation with 3HTdR. The values were then used to calculate the stimulation index (SI) and EC3. It was concluded that both ammonium mercaptoacetate and sodium mercaptoacetate were sensitising in mice.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to CLP criteria, mercaptoacetic acid is considered as a skin sensitizer of category 1. The available data on the sodium and ammonium salts did not allow to discriminate between categories 1A and 1B.