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Description of key information

Final report of test performed according to OECD 408 and GLP will be available on 28 February 2020. Preliminary test is available and provided.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read accross following OECD guidelines
Qualifier:
according to
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
Principles of method if other than guideline:
In the read-across technique, the endpoint information for one chemical is used to predict the same endpoint
for another chemical, which is considered “similar” in some way (usually based on structural similarity). The
chemical being used to make an estimate is commonly referred to as a source chemical, or analogue
whereas a chemical for which the endpoint is being estimated is referred to as a target chemical. In the
current study, the endpoint information of Methylal, selected by the commissioner as source chemical or
analogue, was used to predict the same endpoints for the target substances Ethylal and Butylal, which were
considered to be similar to Methylal on the basis of structural and mechanistic similarity. The read-across
study was performed according to the guidance document on the grouping of chemicals (including readacross
and chemical categories)1. According to the guideline, the regulatory acceptance of a read-across
analysis requires the analysis to be supported by a detailed documentation to be provided according to the
defined read-across reporting formats2,3. The main elements of the read-across reporting format are the
following:
a) Hypothesis for the analogue approach. Description of the molecular structure a chemical must
have to be suitable as a source chemical. All functional groups need to be identified. Provide the
hypothesis for why the read-across can be performed. If there is a mechanistic reasoning to the readacross,
describe the foreseen mode of action for source and target chemicals.
b) Source chemical(s). Description the source chemical(s) as comprehensively as possible. Provide
CAS numbers, names and chemical structures of the source chemical(s).
c) Analogue approach justification. Based on available data, including basic physicochemical
properties, it has to be summarised how these results verify that the read-across is justified. The data
should also show that functional groups not common to source and target chemicals do not affect the
anticipated toxicity.
d) Data matrix. A matrix of data (endpoints vs. target and source chemical(s)) has to be provided.
GLP compliance:
no
Limit test:
no
Dose descriptor:
NOAEC
Effect level:
6 300 mg/m³ air
Based on:
test mat.
Sex:
not specified
Critical effects observed:
not specified

Please refer to attached full study report for details of analogue approach (structural similarity, mechanistic reasonning, toxicity profiling), of source chemical, justification of the approach (undelying rationale, comparison of physchem and molecular properties) and data matrix.

Conclusions:
Source chemical: Methylal
Target chemicals: Ethylal, Butylal
Read-across predictions: NOAEC (13-week) = 6300 mg/m3
Executive summary:

Source chemical: Methylal

Target chemicals: Ethylal, Butylal

Read-across predictions: NOAEC (13-week) = 6300 mg/m3

Experimental data for subchronic inhalation toxicity are available for the source compound Methylal based on

a OECD 413 study conducted in rat under 90-days exposure period (GLP study). The available data refer to

two different measurements, the NOEL, which is the no observed effect level, and the NOAEC, which is the

no observed adverse effect concentration. The commissioner analysed in more details the study report of the

source substance Methylal. No NOAEC is defined in the report but a NOAEC value could be defined at 6300

mg/m3 as a worst case value (=NOEL value). It has to be taken into account that the determination of the

NOAEC is highly toxicological evaluation-dependent, since the determination of an adverse effect is not as

theoretical as the determination of an LC50 in an acute toxicity test.

In the current read-across analysis, the available experimental toxicity data of Methylal (i.e., NOAEC value

of 6300 mg/m3) was used for the read-across prediction of the sub-chronic inhalation toxicity of the target

compounds Ethylal and Butylal. However, since inhalation toxicity is strongly influenced by the vapor

pressure, the experimental inhalation toxicity data of the source Methylal is expected to be higher than the

inhalation toxicity of Ethylal Butylal because of their lower volatility with respect to the source Methylal.

Therefore, it was concluded that for the target compounds Ethylal and Butylal the read-across approach

provided a conservative sub-chronic inhalation toxicity prediction of NOAEC = 6300 mg/m3.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
6 300 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Endpoint derived by read-across (Klimisch code 2) from an OECD TG 413 (GLP) study with methylal (Hofmann, 1994). RSS of the source test report is provided. RSS of the source subtance is provided.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

DNEL have been derived from the NOAEC of 6300 mg/m3 coming from the read-across (90 day inhalation study with methylal_Hofman, 1994).

It is important to note that no alert has been found among the mechanistic profilers relevant for repeated dose toxicity in the read-across report with source methylal and target butylal, supporting the similarity of toxicokinetic behavious of both compounds (Pavan, 2016).

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

Selected as only subchronic study available.

Justification for classification or non-classification

No study available