2-methoxyethyl methacrylate

Endpoint summary

Description of key information

Guinea pig maximisation test: Not sensitising (OECD guideline 406/EU method B.6; GLP), induction: intradermal/epicutaneous; pretreatment with 10% SDS to provoke local skin irritation prior to epicutaneous induction; challenge: topical); read-across from ETMA

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

5

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100%

No. with + reactions:

0

Total no. in group:

5

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.5% left flank, 0.1% right flank

No. with + reactions:

5

Total no. in group:

5

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.5% left flank, 0.1% right flank

No. with + reactions:

5

Total no. in group:

5

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not a dermal sensitiser in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No data on the sensitising potential are available for MTMA. However, reliable, relevant and adequate data are available for the closely related 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

In a dermal sensitisation study according to OECD guideline 406, adopted 17 July 1992, and EU method B.6, 31 July 1992, with ETMA (99.94% a.i.), 10 young adult female Dunkin-Hartley guinea pigs were tested using the method of Magnusson & Kligman (Guinea Pig Maximisation Test).

Test concentrations were selected based on pretest results: 10% in paraffin oil was the minimal irritant concentration which did not provoke necrosis or ulceration by intradermal route. 100% was used for topical induction as well as for challenge. As the test substance was not irritating, the skin was preteated with 10% SDS in Vaseline to provoke local skin irritation prior to epicutaneous induction.

At the end of the induction period, on day 10, after removal of the dressing, signs of irritation were observed at the intradermal injection sites in control and treated groups.

No cutaneous reactions were observed 24 and 48 hours after removal of the dressing of the challenge cutaneous application of the test substance.

The positive control substance Dinitro-2,4-chlorobenzene induced positive skin sensitisation reactions in 100% of the guinea-pigs at a concentration of 0.5%.

The test material produced a response in 10% of animals. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 30% of the test animals of an adjuvant type guinea pig test method for skin sensitisation is considered as positive.

ETMA is not a dermal sensitiser in this study.

 

There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be filled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account. For skin sensitisation, there is no reason to believe that results obtained in guinea pigs would not be applicable to humans.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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