Ethylene bis(3-mercaptopropionate)

Endpoint summary

Description of key information

Based on the categroy approach, GDMP is concidered to be neither skin nor eye irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Currently, do data on toxicokinetics/metabolism is available for this category. Based on structural features (e.g. sterical hindrance) it is however assumed, that ester cleavage would not be fast and complete, especially since the substances contain up to 6 ester functions, which are in addition sterically shielded. Therefore, it seems more reasonable to base the category hypothesis on structural similarity.
In addition, it is not clear yet, whether the strength of the effects vary in a predictable manner, or if no relevant variations occur. However, there are variations in structure (number of ester bonds and consequently number of free -SH groups) and physicochemical properties (especially water solubility and log Kow). It is assumed that these variations will also be reflected by variations in effect levels. Therefore, scenario 4 is the working hypothesis for the time being.
More data points within the category are needed to further strengthen the category hypothesis (refer to Data matrix toxicity endpoints (systemic effects)). The scenario selection will be re-evaluated after the studies are finished.
This currently selected scenario covers the category approach for which the read-across hypothesis is based on structural similarity. For the REACH information requirement under consideration, the property investigated in studies conducted with different source substances is used to predict the property that would be observed in a study with the target substance if it were to be conducted. Similar properties are observed for the different source substances; this may include absence of effects for every member of the category.
There are expected to be differences in strength of the effects forming a regular pattern. The prediction will be based on a worst-case approach. The read-across is a category approach based on the hypothesis that the substances in this category share structural similarities with common functional groups. This approach serves to use existing data on acute toxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
The hypothesis corresponds to Scenario 4 of the RAAF. The substances GDMP, TMPMP, PETMP, and Di-PETMP are esters of a common acid, 3-mercaptopropionic acid (3-MPA). The key functionality of the substances within this category is the presence of free SH-groups. It is hypothesised that the strength of effects correlates with the number of SH-groups. In addition, differences in bioavailability are expected to influence the strength of effects.
For details, please refer to the category document attached to Iuclid section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rabbit

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

Based on QSAR prediction and read-across from PETMP, GDMP is considered not irritating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Currently, do data on toxicokinetics/metabolism is available for this category. Based on structural features (e.g. sterical hindrance) it is however assumed, that ester cleavage would not be fast and complete, especially since the substances contain up to 6 ester functions, which are in addition sterically shielded. Therefore, it seems more reasonable to base the category hypothesis on structural similarity.
In addition, it is not clear yet, whether the strength of the effects vary in a predictable manner, or if no relevant variations occur. However, there are variations in structure (number of ester bonds and consequently number of free -SH groups) and physicochemical properties (especially water solubility and log Kow). It is assumed that these variations will also be reflected by variations in effect levels. Therefore, scenario 4 is the working hypothesis for the time being.
More data points within the category are needed to further strengthen the category hypothesis (refer to Data matrix toxicity endpoints (systemic effects)). The scenario selection will be re-evaluated after the studies are finished.
This currently selected scenario covers the category approach for which the read-across hypothesis is based on structural similarity. For the REACH information requirement under consideration, the property investigated in studies conducted with different source substances is used to predict the property that would be observed in a study with the target substance if it were to be conducted. Similar properties are observed for the different source substances; this may include absence of effects for every member of the category.
There are expected to be differences in strength of the effects forming a regular pattern. The prediction will be based on a worst-case approach. The read-across is a category approach based on the hypothesis that the substances in this category share structural similarities with common functional groups. This approach serves to use existing data on acute toxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
The hypothesis corresponds to Scenario 4 of the RAAF. The substances GDMP, TMPMP, PETMP, and Di-PETMP are esters of a common acid, 3-mercaptopropionic acid (3-MPA). The key functionality of the substances within this category is the presence of free SH-groups. It is hypothesised that the strength of effects correlates with the number of SH-groups. In addition, differences in bioavailability are expected to influence the strength of effects.
For details, please refer to the category document attached to Iuclid section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Number of animals or in vitro replicates:

1+2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Only very slight conjunctival reactions, including very slight chemosis (grade 1), very slight redness of the conjunctiva (grade 1) and clear discharge, were observed in all animals on day 1.
No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, redness of the conjunctiva, iris lesions and corneal opacity.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on read-across from PETMP, GDMP is considered not irritating to eyes

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Experimental data for skin and eye irritation are available for PETMP. The results are representative for the other category members due to the structural similarity. For more detailed information see section 13.2.

 

Skin irritation and corrosivity

PETMP was not irritating to skin in an in-vivo test in rabbits according to OECD 404.

 

The potential of the test item PETMP to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92/69/EEC, B.4, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

In the first instance, the test item was applied for periods of 3 minutes and 4 hours to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals. A single dose of 0.5 mL of the undiluted test item was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions. The mean values of the scores for erythema and oedema were calculated for each animal.

After a 3-minute exposure (one animal): A very slight erythema was noted, on day 4 only. No other cutaneous reactions were observed.

After a 4-hour exposure (three animals): No cutaneous reactions were noted.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.0 for erythema and oedema. Under the experimental conditions, the test item PETMP is non-irritant when applied topically to rabbits.

 

This result is expected to be representative for the other category members due to the structural similarity.

 

Eye irritation

PETMP was not irritating to eyes in an in-vivo test in rabbits according to OECD 405.

The potential of the test item PETMP to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th February 1987) and EC (92/69/EEC, B.5,31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

A single dose of 0.1 mL of the undiluted test item was instilled into the left conjunctival sac of three male New Zealand White rabbits. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Only very slight conjunctival reactions (very slight chemosis, very slight redness of the conjunctiva and clear discharge) were observed in all animals on day 1. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for chemosis, redness of the conjunctiva, iris lesions and corneal opacity. Under the experimental conditions, the test item PETMP is non-irritant when administered by ocular route to rabbits.

 

This result is expected to be representative for the other category members due to the structural similarity

Justification for classification or non-classification

Based on read-across from PETMP, GDMP is not irritating to skin or eyes.