Registration Dossier

Administrative data

Description of key information

Based on read-across from Propane-1,2-diyl diacetate (CAS 623-84-7):
Dermal: NOAEL (rat, m/f) > 1000 mg/kg bw/day (subacute)

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

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) as the source and target substances are both esters of similar di-functional alcohols with the carboxylic acid acetic acid (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s) as the source and target substances are both esters of similar di-functional alcohols with the carboxylic acid acetic acid (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no data available on the repeated dose toxicity of 1,3-Butylene diacetate (CAS 1117-31-3). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Propane-1,2-diyl diacetate (CAS 623-84-7) is selected as reference substance for assessment of repeated dose toxicity.

The read-across is based on the structural similarity between the source and target substances which are all esters of similar di-functional alcohols with the carboxylic acid acetic acid. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of Repeated dose toxicity

CAS#

1117-31-3 (a)

623-84-7 (b)

Chemical name

1,3-Butylene diacetate

Propane-1,2-diyl diacetate

Molecular weight

174.20 g/mol

160.17 g/mol

Repeated dose toxicity, dermal route

RA CAS 623-84-7

Experimental result:

NOAEL > 1000 mg/kg bw/day (m,f)

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

Subacute toxicity: dermal

CAS 623-84-7

Propane-1,2-diyl diacetate was tested in a subacute toxicity study via the dermal route according to OECD guideline 410 in compliance with GLP (Debets, 1987). Propane-1,2-diyl diacetate was dermally administered to groups of 6 Sprague-Dawley rats per sex and at doses of 100, 300 and 1000 mg/kg bw/day, 5 days/week for 4 weeks. A concurrent negative control group receiving the vehicle propylene glycol only was included in the testing.

In the study, no test substance related mortality occurred and no signs of systemic toxicity were observed. In addition, no effects on body weight gain, food consumption, organ weights, organ to body weight ratios, haematology and clinical chemistry data were observed and gross and microscopic pathology revealed no test substance related changes. Local eschar formation was temporarily observed on the treatment sides of several animals among all groups. The authors conclude that the combination of shaving and the way of bandaging was responsible for the local effects and therefore the local effects were not test substance-related.

Thus, the resulting NOAEL for repeated dose toxicity is greater than the limit dose 1000 mg/kg/day (m/f).

Subchronic toxicity

In order to fulfil the standard information requirements set out in Annex IX, Section 8.6, of Regulation (EC) No 1907/2006, substance-tailored exposure-driven testing is conducted in accordance with Annex XI, Section 3.

Conclusion for repeated dose toxicity

Subacute dermal exposure to the structurally related analogue substance Propane-1,2-diyl diacetate (CAS 623-84-7) showed no adverse systemic effects resulting in a NOAEL of > 1000 mg/kg bw/day.

Based on the read-across data, no hazard was identified for (subacute) repeated dose toxicity by the dermal route.


Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from the analogue source substance Propane-1,2-diyl diacetate (CAS 623-84-7) following an analogue approach, the available data on repeated dose toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.