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Description of key information

No acute toxicity data for the submission substance is available. However adequate and reliable data for structural anologues (i.e. C8TM and C8C10TM, for read-across justification please see read-across report in section 13) are reported here. Oral LD50 values of > 2000 and > 3000 mg/kg bw in rats have been reported for C8TM and C8C10TM, respectively (key study and supporting study). A dermal LD50 value for rats in a reliable study using C8C10TM as test material was > 2000 mg/kg bw . No data on acute toxicity after inhalation exposure is available. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 150 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred; LD50 level corrected for molecular weight
Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study performed according to OECD guideline 401 (limit test) and GLP, the (LD50) of the 1,2,4-benzenetricarboxylic acid, trioctyl ester (C8TM) was >2000 mg/kg bodyweight in male and female rats.
Executive summary:

The study used as source investigated acute oral toxicity (RL2, according to OECD TG 401, GLP conform study) for the test material 1,2,4 -benzenetricarboxylic acid, trioctyl ester (C8TM)

In this limit test 5 male and 5 female Sprague-Dawley rats were exposed to the limit dose of 2000 mg/kg bodyweight and a control group received only vehicle (corn oil). No mortality, relevant clinical signs or differences in body weight development between control and treatment group were observed. Based on the results obtained, the LD50 was judged to be > 2000 mg/kg bodyweight in male/female rats (corresponding to > 2150 mg submission substance/kg bw) .Results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross-reference “assessment report”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 150 mg/kg bw
Quality of whole database:
Three studies performed with structural analogues with high reliability show comparable results. The quality of the database is high.
Low LD50 reported from adequate GLP study of high reliability (Klimisch score 1), which was performed with a structural anologue of the submission substance.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
No study needed as data requirements are met having the high reliability studies performed with structural analogues on acute oral and dermal toxicity.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint specific justification please see read-across report in section 13 or find a link in cross-reference “assessment report”.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 150 mg/kg bw
Remarks on result:
other: LD50 level corrected for molecular weight
Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was investigated following dermal administration of a single dose to the rat at 2000 mg/kg. The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg.
Executive summary:

The study used as source investigated the acute toxicity of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters following dermal administration of a single dose to the rat at 2000 mg/kg according to OECD guideline 402 (5 male and 5 female animals for 24 hours). Within the 14 days observation period no mortality occurred and no other abnormalities were found. These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg (corresponding to > 2150 mg submission substance/kg bw) . Results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13 or find a link in cross-reference “assessment report”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
GLP study of high reliability (Klimisch score 1, only one study available), which was performed with a structural anologue of the submission substance. The quality of the data is high.

Additional information

No acute toxicity data for the submission substance is available. However adequate and reliable data for structural anologues (i.e. C8TM and C8C10TM, for read-across justification please see read-across report in section 13) are reported below.

The test material 1,2,4-benzenetricarboxylic acid, trioctyl ester (C8TM) was tested for acute oral toxicity (according to OECD TG 401, GLP conform). In this limit test 5 male and 5 female Sprague-Dawley rats were exposed to the limit dose of 2000 mg/kg bodyweight. Acontrol group received only vehicle (corn oil). Animals were checked for mortality, clinical signs and body weight changes during the 14 days observation period. At the end of the study animals were sacrificed and necropsy was performed. No mortality, relevant clinical signs or differnec in between body weight development between control and treatment group were observed. Based on the results obtained, the LD50 was judged to be > 2000 mg/kg bodyweight in male/female rats (corresponding to > 2150 mg submission substance/kg bw; MoHLW, 2001, RL1).

These findings are supported by two other studies using 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters (C8C10TM) as test material.

A study was performed to assess the acute oral toxicity of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters to the rat. A group of 10 rats (5 male and 5 female) was given a single oral application of the test substance at a dose level of 3000 mg/kg bodyweight. The undiluted liquid test substance was administered by gavage using a stomach tube with an application volume at 3.06 cm³/kg bodyweight.

There were no deaths and no signs of systemic reaction to treatment. All animals achieved satisfactory bodyweight gains throughout the study.

The rats were killed and examind macroscopically on day 14, the end of the observation period. The macroscopical examination revealed no abnormalities.

The dosis letalis media (LD50 oral) to male and female rats of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was found to be > 3000 mg/kg (corresponding to > 2800 up to > 3250 mg subsmission substance/kg bw; Sasol_Mürmann, 1989, RL2).

The test substance "WITAMOL 218 Nr. 770928" was evaluated for the LD50 oral to male rats as single intragastric application. The test substance was administered undiluted in the following dose levels: 10.0, 13.3, 17.8, 23.7 and 31.6 mL/kg bodyweight. 10 animals per dose level were treated with test substance with an exception in the 10.0 mL/kg dose level, where only 5 animals were used. The observation of clinical signs and recording of mortality were carried out up to 14 days after application. Gross necropsy was conducted at animals found dead and at termination of the observation period in all dose groups. Body weight gains were inconsistent throughout the study. In the first week after application the body weights of the 23.7- and 31.6 mL/kg-group were equal, while the mean body weights of the animals of the 17.8 mL/kg-group were reduced. In all dose groups animals showed signs of toxicity. Mainly reduced spontaneous activity, soft faeces and reduced quantity of faeces were recorded. From day 12 on the majority of the surviving animals were free of symptoms. Gross necropsy revealed no observalble abnormalities. In the study performed the LD50 to male rats of "WITAMOL 218 Nr. 770928" was found to be 24.9 mL/kg bodyweight with a 95% confidence limit of 21.5 - 28.8 (24.9 mL/kg bw correspond to 24.2 g/kg bw and when corrected for molecular weight these are corresponding to 22.5 to 26 g submission substance/kg bw; Sasol_Billmeyer, 1978, RL2).

The acute dermal toxicity of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters (C8C10TM) was investigated following dermal administration of a single dose to the rat at 2000 mg/kg according to OECD guideline 402, adopted on 24 February 1987 and Test method B.3 "Acute Toxicity (dermal)" described in Council Regulation (EC) No. 440/2008.

A single dose of 2000 mg/kg was administered to a group o 5 male and 5 female animals for 24 hours under semiocclusive conditions. After 14 days all animals were killed and subjected to necropsy examination. No mortality occurred following dosing and no signs of toxicity were observed. The body weight changes observed during the study were within the expected range for this species and age of animals. No significant abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg.

The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg (corresponding to > 2150 mg submission substance/kg bw; Sasol_Salvador, 2009, RL1).

No acute toxicity studies via inhalation exposure are available for the submission substance or any of the structural analogues.

Justification for classification or non-classification

According to criteria in Regulation (EC) No.1272/2008 the substance does not have to be classified for acute oral or dermal toxicity, based on the observed LD50 values from structural analogues (acute oral and dermal toxicity: LD50 > 2000 mg/kg bw rats). No inhalation toxicity studies are available, however toxicity is expected to be low.

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