2-methoxyethyl methacrylate

Endpoint summary

Description of key information

Skin irritation:
- not irritating in rabbits: OECD Guideline 404; GLP; RL1; undiluted test material applied to the intact skin of 3 animals for 4 hours; very slight to moderate cutaneous reactions (erythema grade 1 and 2) were observed for up to 72 hours (2/3 animals) or 4 d (1/3 animals); fully reversible within 4 - 5 days; read-across from ETMA

Eye irritation:
- not irritating in rabbits: OECD Guideline 405; GLP; undiluted test material applied to left eye of 3 animals without washing; slight redness (grade 1) of the conjunctiva in 2/3 animals after 1 hour, no ocular reactions 24, 48 and 72 hours after treatment; read-across from ETMA

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 from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: methacrylate esters
• the metabolism pathway leads to comparable products (methacrylic acid and short chain alcohol).

Therefore, read-across from the existing (eco)toxicity studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see crossreference “Justification for read-across”

3. ANALOGUE APPROACH JUSTIFICATION
see crossreference “Justification for read-across”

4. DATA MATRIX
see crossreference “Justification for read-across”

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

4 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 5 d

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to rabbit 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:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: methacrylate esters
• the metabolism pathway leads to comparable products (methacrylic acid and short chain alcohol).

Therefore, read-across from the existing (eco)toxicity studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see crossreference “Justification for read-across”

3. ANALOGUE APPROACH JUSTIFICATION
see crossreference “Justification for read-across”

4. DATA MATRIX
see crossreference “Justification for read-across”

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Observation period (in vivo):

72 h

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

No experimental data on MTMA are available for the assessment of skin and eye irritation. However, studies are available for the source substance ETMA. A detailed justification for read-across is attached to IUCLID section 13.

 

Hypothesis for the analogue approach

 

The read-across hypothesis relies on the close structural similarity between the source substance ETMA and the target substance MTMA, differing only by one CH₂-group. This read-across hypothesiscorresponds to scenario 2 -different compounds have qualitatively similar properties- of the read-across assessment framework i.e.properties of the target substance are predicted to be quantitatively equal to those of the source substance. Namely, the structurally similar source substance ETMApredicts the toxicological properties of the target substance MTMA.

 

Toxicological data are summarised in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

 

Therefore, read-across from the existing toxicity studies conducted with the source substance is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

A detailed justification for the proposed read-across approach is attached to Iuclid section 13.

 

Common assessment elements for analogue approaches:

AE A.1 Characterisation of source and target substances

 

There is close structural similarity between the source and the target substances and the identity and characterisation of these substances is unambiguous thereby giving a high level of confidence in the validity of the read across.

The target and source substances are highly pure mono-constituent substances. They do not contain impurities, which would be of toxicological concern.

 

The target substance MTMA is an ester of Methacrylic acid and 2-Methoxyethanol. It is produced by esterification of Methacrylic acid and 2-Methoxyethanol.

 

The source substance ETMA is an ester of Methacrylic acid and 2-Ethoxyethanol. It is produced by esterification of Methacrylic acid and 2-Ethoxyethanol. ETMA is different to MTMA in only one CH₂-group.

 

AE A.2 Link of structural similarities and structural differences with the proposed prediction

The read-across hypothesis relies on local effects mediated by electrophilic reactivity of the parent ester. Hydrolysis occurs at the site of this ester bond so is a detoxification process with respect to nucleophilic action

 

AE 2.2 Common underlying mechanism

Since carboxylesterases are widely distributed throughout the body and the half-life of the parent ester is very short the impact of parent compound (AE 1.4) is unlikely to be significant other than at the site of initial contact. Indeed, local hydrolysis at the site of contact is likely to be very rapid thereby minimising exposure to parent ester even at local targets. Since the source and target compounds are monoconstituents of high purity there are no impurities worthy of consideration.

 

AE A.3 Reliability and adequacy of the source study

All available studies have been conducted according to OECD guidelines and have been assigned a reliability of 1 as documented in the data matrix (see detailed justification for read-across attached to Iuclid section 13).

 

Overall, the study design of the respective source studies is adequate and reliable for the purpose of this read-across.The results of the selected key studies are adequate for classification and labelling and for risk assessment purposes.

 

Data availability

Skin irritation

In a primary dermal irritation study according to OECD guideline 404, 3 male New Zealand white rabbits were dermally exposed to 0.5 mL of ETMA for 4 h to ca. 6 cm² body surface area. Animals then were observed for 6 days. Irritation was scored by the method of Draize.

Very slight to moderate cutaneous reactions (erythema grade 1 and 2) were observed for up to 72 hours (2/3 animals) or 4 d (1/3 animals) after the removal of the dressing. From day 3 to 6, a dryness of the skin was observed at the treatment site in 1/3 animals. During the whole observation period, the animals were free of oedema. All effects were fully reversible within 4 or 5 days.

In this study, ETMA is not a dermal irritant.

 

Eye irritation

In a primary eye irritation study according to OECD guideline 405, 0.1 mL of ETMA was instilled into the conjunctival sac of 3 young adult New Zealand White rabbits without washing. The untreated right eye served as control. Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

Slight redness (grade 1) of the conjunctiva was noted in 2/3 animals after 1 hour. No ocular reactions were observed 24, 48 and 72 hours after treatment. 

In this study, ETMA is not irritating to the rabbit eye.

 

There are no data gaps in skin and eye irritation. Even though there is no information on irritation in humans, there is no reason to believe that the lack of irritation potential observed in experimental animals would not be relevant for human health.

Justification for classification or non-classification

Based on the available data, MTMA does not need to be classified for eye irritation or skin irritation according to regulation (EC) 1272/2008. Thus, no labelling is required.