Registration Dossier

Administrative data

Description of key information

WoE:
All available acute toxicity studies resulted in an LD50 > 2000 mg/kg bw.
Studies on acute oral toxicity were available for the following Read Across substances (CAS No.): 119-06-2 and 68442-70-6
The acute oral and dermal LD50 for rats was found to be greater than 2000 mg/kg bw.
While no reliable acute inhalation toxicity studies are available, the picture of all available data is consistent supporting also a low level of inhalation toxicity for 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters.

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), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute inhalation toxicity of 1,2 Benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). In order 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, 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 of acute toxicity

CAS

Chemical name

Acute toxicity Oral

Acute toxicity inhalation

Acute toxicity dermal

90193-76-3 (a)

1,2 Benzenedicarboxylic acid, di-C16-C18-alkyl esters

WoE:

RA: CAS 119-06-2

RA: CAS 68442-70-6

--

Experimental result:
LD50 >2000 mg/kg bw (rat)

119-06-2 (b)

Ditridecyl phthalate

Experimental result:
LD50 >2000 mg/kg bw (rat)

--

--

68442-70-6

1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters

Experimental result:
LD50 >5000 mg/kg bw (rat)

LD50 = 15,8000 mg/kg bw (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 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Acute oral toxicity

CAS 119-06-2

An acute oral toxicity study with ditridecyl phthalate (CAS No. 119-06-2) was performed in a GLP study according to OECD guideline 401 (Ohara, 1996). Male and female Crj: CD(SD) rats received the test substance at a limit dose of 2000 mg/kg bw via oral gavage. No substance related abnormal clinical signs or body weight changes were observed in the 14 days observation period. No deaths occurred during the study period. Therefore the LD50 under the given conditions was set to >2000mg/kg bw.

 

CAS 68442-70-6

Two studies on the oral acute toxicity of 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS 68442-70-6) performed are available, but only limited data is given on test conditions. In these studies, rats were exposed to the test substance at a limit dose of 5000 and 15,800 mg/kg bw, which did not result in any mortalities and clinical signs up to the end of the observation period (Gloxhuber, 1971 and Potokar 1981).

In summary, the oral LD50 of 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters was greater than 5000 mg/kg bw.

 

Acute inhalation toxicity

According to Annex VIII, Section 8.5.2, Column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. The solid test substance has a melting point of 40 - 47 °C and a very low vapour pressure (< 0.001 Pa at 20°C). Exposure to vapour can thus be precluded. Sieve analysis of particle size distribution showed that > 99.9% of particles were greater than 150 µm. The proportion of respirable dust is therefore negligible. With respect to the animal welfare, the conduct of an acute inhalation toxicity study would be scientifically unjustified.

 

Acute dermal toxicity

The acute dermal toxicity (limit test) of 1,2 Benzenedicarboxylic acid (CAS No. 90193-76-3) was investigated in male and female Wistar rats in a GLP study according to OECD guideline 402. Chromodacryorrhoea on the snout was noted in the majority of animals and piloerection and/or hunched posture were also noted for several animals. The animals had recovered from the symptoms between Days 2 and 3. No mortalities and no abnormalities at necropsy were observed in animals dosed with 2000 mg/kg body weight. The LD50 was found to be greater than 2000 mg/kg bw (Stitzinger, 2010).

 

Conclusions for acute toxicity

In summary, the acute oral toxicity studies with ditridecyl phthalate (CAS No. 119-06-2) and 1,2-Benzenedicarboxylic acid, mixed cetyl and stearyl esters (CAS 68442-70-6) showed LD50 values greater than 2000 mg/kg bw. Acute dermal toxicity data with 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3) showed no effects at the limit dose of 2000 mg/kg bw. As 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters are solids with calculated vapour pressures below 0.001 Pa at 20 °C and more than 99.9% of the particles are greater than 150 µm exposure via the inhalation route can be considered negligible under the identified use conditions and no further test are necessary.

 

Thus, the available data on 1,2 benzenedicarboxylic acid, di-C16-C18-alkyl esters (CAS 90193-76-3) and structural analogues indicate a very low level of acute toxicity and thus no hazard for acute oral and dermal toxicity was identified.


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substances and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
There is only one study available.

Justification for classification or non-classification

Based on substance-specific studies and read-across from structurally similar substances, the available data on the acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.