Ammonium 2-mercaptopropionate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 06, 1999 to December 08, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits supplied by David Percival Ltd, Maston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.58 to 2.87 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, UK) was allowed throughout the study.

The temperature and relative humidity were controlled to remain within target ranges of 17 to 23 °C and 30 to 70 % respectively. Occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

Test performance:
On the day before the test each rabbit was dipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test substance was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

Observations:
Four hours after application the corset and patches were removed from each animal and any residual test substance removed by gentle swabbing with cotton wool soaked in 74 % Industrial Methylated Spirits.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.
Any other skin reactions, if present, were also recorded. Additional observations were made on days 7 and 14 to assess the reversibility of skin reactions.

Interpretation of results:
Calculation of primary irritation index and grading of the irritancy potential using the Draize scheme:
The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test substance. The test substance was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity":
Primary irritation index:
0 (Non-irritant)
> 0 to 2 (Mild irritant)
> 2 to 5 (Moderate irritant)
> 5 to 8 (Severe irritant)

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

of three

Time point:

14 d

Score:

4.2

Reversibility:

not fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 d

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

- Well-defined erythema was noted at all treated skin sites 1-hour after patch removal and at the 24, 48 and 72-hour observations. Very slight erythema was noted at two treated skin sites at the 7-day observation.
- Moderate oedema was noted at one treated skin site with slight oedema at two treated skin sites 1-hour after patch removal and at the 24-hour observation. Slight oedema was noted at all treated skin sites at the 48 and 72-hour observations. Very slight oedema was noted at two treated skin sites at the 7-day observation.
- Scattered areas of blanching of the skin were noted at all treated skin sites with scattered haemorrhage of the dermal capillaries also noted at two treated skin sites 1-hour after patch removal.
- Light brown discolouration of the epidermis was noted at all treated skin sites at the 24-hour observation. Light brown discolouration of the epidermis, loss of skin flexibility and/or loss of skin elasticity were noted at all treated skin sites at 48 and 72-hour observations. Crust formation was noted at all treated skin sites at the 7-day observation. Reduced regrowth of fur was noted at all treated skin sites with glossy skin also noted at one treated skin site at the 14-day observation.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the study conditions, the test substance produced a primary irritation index of 4.2.

Executive summary:

A study was conducted to determine the irritancy potential of the test substance to the skin of the New Zealand White rabbit according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. A single 4 h, semi-occluded application of the test substance to the intact skin of three rabbits produced well-defined erythema and slight to moderate oedema. Blanching of the skin, haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, loss of skin flexibility, crust formation, reduced regrowth of fur and glossy skin were also noted. Under the study conditions, the test substance produced a primary irritation index of 4.2 (Sanders, 2000).

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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

Study period:

From October 28, 1999 and November 16, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Directive 92/69/EEC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits, supplied by David Percival Ltd, Moston, UK, were used. At the start of the study the animals weighed 2.64 to 2.80 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinkinng water and food (ST AN RAB SQC Rabbit Diet, Special Diets Services Ltd, UK) was allowed throughout the study.

The temperature and relative humidity were controlled to remain target ranges of 17 to 23 °C and 30 to 70 % respectively. Occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

15 days

Observation period (in vivo):

15 days

Number of animals or in vitro replicates:

3

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Animals showing evidence of ocular lesions were rejected and replaced.

One rabbit was initially treated. A volume of 0.1 mL of the test substance was instilled into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eye ball. The upper and lower eye lids were held together for about one second immediately after installation, to prevent loss of the test substance, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test substance, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. In order to minimise pain on instillation of the test substance, one drop of local anaesthetic (Amethocaine hydrochloride, Chauvin Pharmaceutials, UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).

Any other ocular effects were also noted. Examination of the eye was facilitated by the use the light source from a standard ophthalmoscope.
Additional observations were made on Days 7 and 14 or 15 to assess the reversibility of the ocular effects.

Due to a technical error, the Day 14 observation on the initial animal was performed one day late, on Day 15. This deviation from the Standard Test Method was considered not to effect the purpose or integrity of the study.

Classification according to a modified version of the Kay and Calandra system:
The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of opacity). For each tissue the sore was calculated as follows:
Score for conjunctivae: (A + B + C) x 2
Score for iris: D x 5
Score for cornea: (E x F) x 5
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962 13 281-289 was used to classify the ocular irritancy potential of the test substance. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit.
The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test substance. If any rabbit shows irreversible ocular damage the test substance will be classified as corrosive to eye.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Remarks:

of 3

Time point:

other: 15 d

Score:

39.3

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 15 d

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

- Dulling of the normal lustre of the cornea was noted in two treated eyes 1-hour after treatment. Diffuse corneal opacity was noted in all treated eyes at the 24-hour observation. Translucent corneal opacity was noted in one treated eye with diffuse corneal opacity in two treated eyes at the 48-hour observation. Translucent corneal opacity was noted in one treated eye with diffuse corneal opacity in one other treated eye at the 72-hour observation. Diffuse corneal opacity was noted in two treated eyes at the 7-day observation.
- lridial inflammation was noted in one treated eye 1-hour after treatment, in all treated eyes at the 48-hour observations, in two treated eyes at the 72-hour observations and persisted in one treated eye at the 7-day observation.
- Moderate conjunctiva irritation was noted all treated eyes 1-hour after treatment and at the 24-hour observation. Severe conjuntival irritation was noted in two treated eyes with moderate conjunctiva irritation in the remaining treated eye at the 48-hour observation. Severe conjunctival irritation persisted in one treated eye with moderate conjunctiva irritation in two treated eyes at the 72-hour observation. Minimal conjunctival irritation was noted in all treated eyes at the 7-day observation.
- Vascularisation, with a generalised ingrowth of vessels for approximately 2 - 3 mm, was noted in one treated eye at the 7-day observation.
- Two treated eyes appeared normal at the 14-day observation and the remaining treated eye appeared normal at the 15-day observation.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the study conditions, the test substance produced a maximum group mean score of 39.3.

Executive summary:

A study was conducted to determine the irritancy potential of the test substance to the eye of the New Zealand White rabbit according to OECD Guideline 405 and of Commission Directive 92/69/EEC, in compliance with GLP. A single instillation of the test substance to the non-irrigated eye of 3 rabbits produced diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctiva irritation. Dulling of the normal lustre of the cornea and vascularisation, with a generalised ingrowth of vessels for approximately 2 – 3 mm, was also noted. Two treated eyes appeared normal at the 14 d observation and the remaining treated eye appeared normal at the 15 d observation. Under the study conditions, the test substance produced a maximum group mean score of 39.3 (Sanders, 2000).

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study was conducted to determine the irritancy potential of the test substance to the skin of the New Zealand White rabbit according to OECD Guideline 404 and EU Method B.4, in compliance with GLP. A single 4 h, semi-occluded application of the test substance to the intact skin of three rabbits produced well-defined erythema and slight to moderate oedema. Blanching of the skin, haemorrhage of the dermal capillaries, light brown discolouration of the epidermis, loss of skin elasticity, loss of skin flexibility, crust formation, reduced regrowth of fur and glossy skin were also noted. Under the study conditions, the test substance produced a primary irritation index of 4.2 (Sanders, 2000).

 

Eye irritation

A study was conducted to determine the irritancy potential of the test substance to the eye of the New Zealand White rabbit according to OECD Guideline 405 and of Commission Directive 92/69/EEC, in compliance with GLP. A single instillation of the test substance to the non-irrigated eye of 3 rabbits produced diffuse to translucent corneal opacity, iridial inflammation and moderate to severe conjunctiva irritation. Dulling of the normal lustre of the cornea and vascularisation, with a generalised ingrowth of vessels for approximately 2 – 3 mm, was also noted. Two treated eyes appeared normal at the 14 d observation and the remaining treated eye appeared normal at the 15 d observation. Under the study conditions, the test substance produced a maximum group mean score of 39.3 (Sanders, 2000).

Justification for classification or non-classification

Skin irritation

The test substance produced a primary irritation index of 4.2 to the skin of the New Zealand White rabbit in the study according to OECD Guideline 404, therefore it warrants a classification as Skin Irrit. 2 – H315 (Causes skin irritation) according to EU CLP (EC 1272/2008) criteria.

Eye irritation

The eye irritation of the test substance was evaluated in OECD 405 Guideline study. The test substance produced following positive responses in 3 tested animals: (a) corneal opacity ≥ 1 and/or (b) iritis ≥ 1, and/or (c) conjunctival redness ≥ 2 and/or (d) conjunctival (chemosis) ≥ 2 calculated as the mean scores following grading at 24, 48 and 72 hours. Effects were fully reversible within 21 days. The test substance warrants a classification as Eye Irrit. 2 – H319 (Causes serious eye irritation) according to EU CLP (EC 1272/2008) criteria.