Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In order to fulfil the standard information requirements set out in Annex IX, Section 8.7.1, of Regulation (EC) No 1907/2006, substance-tailored exposure-driven testing is conducted in accordance with Annex XI, Section 3.

Effects on developmental toxicity

Description of key information
Based on read-across from Propane-1,2-diyl diacetate (CAS 623-84-7):
(Pre-natal) development: NOAEL (rabbit) = 1058 mg/kg bw/day
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
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, 8.7, 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 (pre-natal) developmental toxicity of 1,3-Butylene diacetate (CAS 1117-31-3). In order to fulfil the standard information requirements set out in Annex VIII, 8.4, 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 (pre-natal) developmental 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 developmental 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

Developmental toxicity

RA CAS 623-84-7

Experimental result:

NOAEL: 1058 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 “--“.

Toxicity to reproduction – (pre-natal) developmental toxicity

CAS 623-84-7

A prenatal developmental toxicity study with Propane-1,2-diyl diacetate was conducted according to OECD 414 in compliance with GLP (Smiths van Prooije, 1989). Groups of 28 female New Zealand White rabbits per treatment group were dermally treated with undiluted Propane-1,2-diyl diacetate at doses of 0.3 and 1.0 mL/kg bw/day (high-dose corresponding to 1058 mg/kg bw/day) from Day 6-18 post mating. A concurrent negative control groups treated with distilled water only were included in the testing.

In the study, no maternal mortality occurred and no substance-related clinical signs of toxicity were observed. Mean maternal body weights and food intake were comparable in all groups. Mean weight gain during treatment was lower in the low-dose group when compared with controls. During the study, no dermal reactions were observed at the application sites of the treated rabbits that could be related to the dermal application of Propane-1,2-diyl diacetate. Furthermore, at scheduled necropsy no macroscopic changes related to treatment were noted in maternal animals. Mean absolute weights of the ovaries, gravid and empty uterus did not show significant differences between test groups and control. No compound-related differences were observed in gestation index, pre-and post-implantation loss, embryonic deaths, mean numbers of resorptions and total fetuses of the test groups in comparison to the control group.

Mean foetal and placental weight were slightly lower in the high-dose group, however without statistical significance. No macroscopically visible malformations were observed in foetuses that could be related to treatment. No statistically significant differences were observed in the incidence of skeletal malformations between the high-dose group and the controls, either for each observation separately or for the total incidence of skeletal malformations.

Therefore, due to the lack of adverse effects in this study, the NOAEL for maternal toxicity and developmental toxicity for rabbits was considered to be 1058 mg/kg bw/day (m,f).

Conclusion for developmental toxicity

A study investigating the developmental toxicity is available from the structurally related analogue substance Propane-1,2-diyl diacetate (CAS 623-84-7). The study from Propane-1,2-diyl diacetate did not show treatment-related effects up to the highest tested dose level. Thus, no hazard for developmental toxicity was identified and a NOAEL for developmental toxicity is considered to be the highest dose level (1058 mg/kg bw/day (m, f)).


Justification for selection of Effect on developmental toxicity: via dermal route:
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 source substances Propane-1,2-diyl diacetate (CAS 623-84-7) following an analogue approach, the available data on (pre-natal) developmental 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.

Data are lacking in regard to toxicity to reproduction (fertility) and effects via lactation.