Diethoxymethane

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation, other

Remarks:

other: in silico (Read Accross calculation)

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: read-across from guidelines studies

Justification for type of information:

HYPOTHESIS FOR THE ANALOGUE APPROACH , SOURCE AND TARGET CHEMICAL(S), ANALOGUE APPROACH JUSTIFICATION and DATA MATRIX are provided in the attached report

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: OECD Joint meeting of the chemicals committee and the working party on chemical, pesticides and biotechnology, Guidance on grouping of chemicals, ENV/JM/MONO(2007)28

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Guidance document for using the OECD (Q)SAR Application Toolbox to develop chemical categories according to the OECD Guidance on Grouping of Chemicals, ENV/JM/MONO(2009)5

Principles of method if other than guideline:

In the current study, the skin sensitization information of the methylal, propylal, butylal, dioxolane, 2-ethylhexylal and 2,5,7,10-Tetraoxaundecane (TOU) selected by the commissioner as source chemicals or analogs, were used to predict the same endpoint for the target chemical, i.e. ethylal, which was considered to be similar to the source chemicals on the basis of structural similarity. The read-across study was performed according to the guidance document on the grouping of chemicals (including read-across and chemical categories) (OECD Joint meeting of the chemicals committee and the working party on chemical, pesticides and biotechnology, Guidance on grouping of chemicals, ENV/JM/MONO(2007)28).

GLP compliance:

no

Type of study:

other: Read Accross calculation

Remarks on result:

other: Negative based on not sensitizing potential of source chemicals methylal, propylal, butylal and 2-ethylhexylal (in OECD 406 test)

Remarks on result:

other: Negative based on not sensitizing potential of source chemicals dioxolane and TOU (in OECD 429 nad 442b tests, respectively).

A many-to-one read-across was performed since the endpoint information for many chemicals, methylal, propylal, butylal, dioxolane, 2-ethylhexylal and 2,5,7,10-tetraoxaundecane, was used to estimate the same endpoint for the target chemical ethylal, which was considered to be “similar” enough according to their structures and their physicochemical property profiles to justify the read-across approach. Figure 5 shows (cfr attached report) the many-to-one read-across approach.

Interpretation of results:

not sensitising

Conclusions:

The suggested source chemicals, i.e. methylal, propylal, butylal, dioxolane, 2-ethylhexylal and 2,5,7,10-tetraoxaundecane were considered sufficient similar in relation to skin sensitization to the target chemical ethylal, to apply the read-across approach. Their structural similarity is also supported by a close similarity in terms of reactivity properties relevant for skin sensitization and in terms of physicochemical properties with the only exception of 2-ethylhexylal that was shown to have some physicochemical differences form the other acetals, and therefore from the target ethylal, and for this reason its experimental data was weighted less than the other available data in the read-across prediction. The read-across analysis led to the conclusion that the target chemical ethylal is NOT SENSITIZER for skin. This outcome is further supported by the outcomes of the skin sensitization profilers applied on all the acetal under investigation.

Executive summary:

The suggested source chemicals , i.e. methylal, propylal, butylal, dioxolane, 2-ethylhexylal and 2,5,7,10 -tetraoxaundecane, can be considered sufficient similar in relation to skin sensitization to the target chemical

ethylal, to apply the read-across approach. Their structural similarity is also supported by a close similarity in terms of reactivity properties relevant for skin sensitization and in terms of physicochemical properties,

although it was noted that 2-ethylhexylal shows some relevant physicochemical differences form the other acetals. Thus, it was concluded that the acetals are sufficiently similar to justify the experimental test results of the source chemicals to be read-across to target chemical, although the 2-ethylhexylal test result needed to be weighted less than the other in the read-across due to its lower similarity to the target ethylal.

For the source chemicals two major animal test data were available as provided by the commissioner: the Guinea Pig Maximisation Test (GPMT) of Magnusson and Kligman (i.e. TG 406) and the Local Lymph

Node Assay (LLNA; TG 429). The original Test Guideline (TG) for the determination of skin sensitization in the mouse, the Local Lymph Node Assay (LLNA; TG 429) was adopted in 2002. This is the second TG to be designed for assessing skin sensitization potential of chemicals in animals. The other, the Guinea Pig Maximisation Test (GPMT) of Magnusson and Kligman (i.e. TG 406) utilises guinea pig tests. The LLNA provides advantages over TG 406 with regard to animal welfare.

The 2-ethylhexylal skin sensitization data was weighted less than the other data, because of the lower physicochemical property similarity of 2-ethylhexylal with respect to the target ethylal.

Data processing is needed when data from more than one source chemical are to be used to make a prediction for a target chemical. There are many mathematical formalism used to combine the data, the most common ones for ordinal data like the skin sensitization data, are the following:

 Maximum/minimum function: this returns the maximum or minimum value of the set of data. It is defined as the “worst or best scenario assessment”.

 Mode: this returns the most frequently occurring value in the set of data.

 Median: this returns the value half away from through the order data set, above and below which there are an equal number of data values. It is considered generally a good descriptive measure of the data which works well for data with outliers.

In the current read-across analysis, irrespectively to the mathematical formalism employed, the target chemical ethylal is predicted NOT SENSITIZER for skin, since all the available data for the source chemicals are in agreement being all of them not sensitizers. This outcome is further supported by the outcomes of the skin sensitization profilers applied on all the acetal under investigation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:

The read-across analysis led to the conclusion that the target chemical ethylal is NOT SENSITIZER for skin. This outcome is further supported by the outcomes of the skin sensitization profilers applied on all the acetal under investigation.

This result is confirmed by an experimental study

Justification for selection of skin sensitisation endpoint:

The suggested source chemicals, i.e. methylal, propylal, butylal, dioxolane, 2-ethylhexylal and 2,5,7,10-tetraoxaundecane were considered sufficient similar in relation to skin sensitization to the target chemical ethylal, to apply the read-across approach. Their structural similarity is also supported by a close similarity in terms of reactivity properties relevant for skin sensitization and in terms of physicochemical properties with the only exception of 2-ethylhexylal that was shown to have some physicochemical differences form the other acetals, and therefore from the target ethylal, and for this reason its experimental data was weighted less than the other available data in the read-across prediction.