2,5,7,10-tetraoxaundecane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

other: read accross

Adequacy of study:

key study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read accross following OECD guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

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

Principles of method if other than guideline:

Read Accross tools: the main tool recommended in the regulatory context is the OECD (Q)SAR Application Toolbox (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 and ACD/Pyschem Suite version 12.0 were used for the calculation of several physico chemical properties, i.e. density, surface tension, water solubility, LogPow, needed to compare the physico chemical properties of the source chemicals and the target ones.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethoxymethane

EC Number:

203-714-2

EC Name:

Dimethoxymethane

Cas Number:

109-87-5

Molecular formula:

C3H8O2

IUPAC Name:

dimethoxymethane

Constituent 2

Reference substance name:

1,3-dioxolane

EC Number:

211-463-5

EC Name:

1,3-dioxolane

Cas Number:

646-06-0

Molecular formula:

C3H6O2

IUPAC Name:

1,3-dioxolane

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

3 127.89 mg/m³ air

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: weighted mean mathematical formalism

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The read-across analysis was performed for the toxicity super endpoint, including five endpoints, i.e. acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, subchronic inhalation toxicity (90 days, rat) and prenatal developmental toxicity study, that were treated with the same reasoning in terms of mechanism action and for which the read-across follow a similar justification.

In the current study, methylal and dioxolane were selected by the commissioner as source chemicals or analogs, to predict the same endpoints for the target chemicals, i.e. ethylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal, propylal, butylal, however, in the case experimental toxicity data of ethylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal, propylal, butylal were already available from the commissioner for some of the toxicity endpoints, these data were also employed for the read-across predictions of the remaining target chemicals. Thus, depending on the availability of their experimental toxicity data, the five acetals (ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal) were employed as source chemicals or target chemicals.

A many-to-many read-across was performed since the endpoint information for many chemicals, methylal and dioxolane, was used to estimate the same toxicity endpoints for the target chemicals, i.e. ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane and 2-ethylhexylal, which were considered to be “similar” enough according to their structural, mechanistic and physicochemical/reactivity property profiles to justify the read-across approach. Figure 4 (see full report attached below) shows an example of a many-to-many read-across approach.

Applicant's summary and conclusion

Conclusions:

The subchronic inhalation toxicity of the target 2,5,7,10-Tetraoxaundecane provided by the weighted mean mathematical formalism is a NOAEC (13-week) = 3127.89 mg/m3

Executive summary:

The read-across analysis was performed for the toxicity super endpoint, including five endpoints, i.e. acute oral toxicity, acute dermal toxicity, acute inhalation toxicity, subchronic inhalation toxicity (90 days, rat) and prenatal developmental toxicity study, that were treated with the same reasoning in terms of mechanism action and for which the read-across follow a similar justification.

In the current study, methylal and dioxolane were selected by the commissioner as source chemicals or analogs, to predict the same endpoints for the target chemicals, i.e. ethylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal, propylal, butylal, however, in the case experimental toxicity data of ethylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal, propylal, butylal were already available from the commissioner for some of the toxicity endpoints, these data were also employed for the read-across predictions of the remaining target chemicals. Thus, depending on the availability of their experimental toxicity data, the five acetals (ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane, 2-ethylhexylal) were employed as source chemicals or target chemicals.

A many-to-many read-across was performed since the endpoint information for many chemicals, methylal and dioxolane, was used to estimate the same toxicity endpoints for the target chemicals, i.e. ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane and 2-ethylhexylal, which were considered to be “similar” enough according to their structural, mechanistic and physicochemical/reactivity property profiles to justify the read-across approach. Figure 4 (see full report attached below) shows an example of a many-to-many read-across approach.

Subchronic inhalation toxicity

Source chemicals: methylal and dioxolane

Target chemical(s): ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane and 2-ethylhexylal

Read-across predictions: NOAEC (13-week) = 3127.89 mg/m3

In the current read-across analysis, the available experimental toxicity data of methylal and dioxolane were used for the read-across prediction of the subchronic inhalation toxicity of the targets ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane and 2-ethylhexylal. 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 reports of the two source substances. For 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). Thus, the read-across prediction was performed employing the NOAEC values of 6300 mg/m3 for methylal and of 903 mg/m3 for dioxolane. 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. Tests are available for methylal and dioxolane and have been performed by different labs with different sensitivity to define an adverse effect which is the basis of the NOAEC. This difference of sensitivity could explain the disparity between NOAEC of methylal and dioxolane.

Since inhalation toxicity is strongly influenced by the vapor pressure, the experimental inhalation toxicity data of the source methylal was weighted less than the one of dioxolane, because of its much higher vapor pressure than the targets.

The subchronic inhalation toxicity of the targets ethylal, propylal, butylal, 2,5,7,10-tetraoxaundecane and 2-ethylhexylal would be predicted of NOAEC (13-week) = 903 mg/m3 in the worst case scenario. However, a more consistent prediction is considered the one provided by the weighted mean mathematical formalism which led to prediction of NOAEC (13-week) = 3127.89 mg/m3.