Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 423), rat: LD50 cut-off >5000 mg/kg bw (RA from CAS 147256-33-5)
Inhalation (OECD 436), rat: LC50 >5.3 mg/L (air) (RA from CAS 68334-05-4)
Dermal: Data waiving

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity, common precursors and breakdown products of hydrolysis and consistent trends in the toxicological profile. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

There are only limited data available on acute toxicity of Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was 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 substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview on acute toxicity

CAS

Chemical name

Molecular weight [g/mol]

Acute toxicity Oral

Acute toxicity Inhalation

Acute toxicity Dermal

 

 

162353-70-0 (a)

Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol

 

 

610.99 - 1209.97

 

 

RA: CAS 147256-33-5

 

 

RA: CAS 68334 -05 -4

 

 

 Data waiving

 

147256-33-5 (b)

Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylol-propane

 

624.97 - 1762.80

 

Experimental result: LD50 cut-off value >5000 mg/kg bw (rat)

 

--

 

--

 

68334-05-4 (b)

Fatty acids, C18-unsaturated, dimers, 2-ethylhexyl esters

 

673.10

 

--

Experimental result: LC50 >5.3 mg/L (rat)

 

--

(a) The substance subject to registration is indicated in bold font.

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

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

No reliable data on acute toxicity are available with Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0). Therefore, read across from the structurally analogue substances Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) and Fatty acids, C18-unsaturated, dimers, 2-ethylhexyl esters (CAS 68334-05-4) was applied.

 

Acute oral toxicity

CAS 147256-33-5

Two acute toxicity studies are available with the read across substance Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5).

A reliable acute oral toxicity study with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) is available and was performed according to OECD TG 423 and in compliance with GLP (Harlan, 2012). In this study following the acute toxic class method three female fasted Wistar rats were administered a single dose of 2000 mg/kg bw of the test substance (CAS 147256-33-5) in a stepwise procedure via oral gavage. The animals were observed for 14 days after administration. No mortalities were observed during the study and no signs of systemic toxicity were noted during the observation period in any animal. All animals showed the expected gains in body weight and no abnormalities were observed at necropsy. The experimental acute oral LD50 value for females was considered to be greater than 2000 mg/kg bw. Thus, according to OECD TG 423, an oral LD50 cut-off value >5000 mg/kg bw was derived.

Another supporting study addressing acute oral toxicity with Fatty acids, C18-unsatd., dimers, mixed esters with oleic acid and trimethylolpropane (CAS 147256-33-5) is available and was performed according to EU Method B.1 and in compliance with GLP (Henkel, 1989). Groups of 5 Wistar rats of each sex were administered a single dose of 2000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after administration. No mortalities were observed during the study and no signs of systemic toxicity were noted during the observation period in any animal. Gross pathology revealed a filled bladder in two males and hydrometra in one female. However, these findings were considered not to be treatment-related. Based on the results of the study, the LD50 value was considered to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

CAS 68334-05-4

A reliable acute inhalation study was performed with Fatty acids, C18-unsaturated, dimers, 2-ethylhexyl esters (CAS 68334-05-4) according to OECD TG 436 and in compliance with GLP (Notox, 2010). In this study following the acute toxic class method three Crl:WI(Han) rats of each sex were exposed to an aerosol with an analytical concentration of 5.3 mg/L of the test substance for 4 hours in an nose-only inhalation exposure chamber. No mortalities or any abnormal clinical signs were reported during the exposure or within the 14 days observation period. Additionally body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study and no abnormalities were found at macroscopic post mortem examination of the animals. The acute inhalation LC50 value was calculated to be greater than 5.3 mg/L. Based on the results of the study and according to EU classification criteria, the test substance is not to be classified.

Based on the above study results and according to EU classification criteria, the test substance is not to be classified.


Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C18-unsatd., dimers, reaction products with fatty acids, C14-18 and C16-18-unsatd. and propylidynemethanol (CAS 162353-70-0), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

Categories Display