Registration Dossier

Administrative data

Description of key information

The subchronic oral toxicity of 1,2,4-Benzenetricarboxylic acid, decyl octyl ester was investigated in a well-conducted study in Sprague Dawley rats after daily oral administration at dose levels of 50, 200 and 500 mg/kg/day for 13 weeks and recovery from any treatment-related effects during a recovery period of 4 weeks. Signs of treatment-related effects of the test item were observed in males and females dosed at 200 and 500 mg/kg/day. These effects included some changes in clinical pathology parameters and some post mortem findings. The liver was identified as the main target organ on the basis of the organ weight data and histopathological findings. However, these changes were mild and fully reversible. The morphological aspect of the hepatocytic hypertrophy was consistent with proliferation of endoplasmic reticulum. As such, the hepatic effects were not considered to be adverse.
No significant changes were observed in the animals dosed at 50 mg/kg/day. It can be concluded that the No Observed Adverse Effect Level (NOAEL) for this study was 500 mg/kg/day.
In a subacute 28-day oral toxicity study in rats some treatment-related effects were evident in males and to a minor extent in females at the high dose level of 1000 mg/kg/d. The adrenals were identified as the main target organs, based on the post-mortem examination. The observed effects were completely reversible over a 2-week recovery period in the high dose animals. Only mild effects were observed in the animals (essentially males) dosed at 300 mg/kg/d, therefore this dose is expected to be NOAEL. No effects were observed at the low dose level (NOEL = 100 mg/kg/d).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

The repeated dose toxicity of 1,2,4 -benzenetricarboxylic acid, mixed dodecyl and octyl triesters towards rats was not specifically determined, therefore results of the structurally related 1,2,4-Benzenetricarboxylic acid, decyl octyl ester are used. The subchronic oral toxicity of 1,2,4-Benzenetricarboxylic acid, decyl octyl ester was investigated in a well-conducted study in Sprague Dawley rats after daily oral administration at dose levels of 50, 200 and 500 mg/kg/day for 13 weeks and recovery from any treatment-related effects during a recovery period of 4 weeks. Signs of treatment-related effects of the test item were observed in males and females dosed at 200 and 500 mg/kg/day. These effects included some changes in clinical pathology parameters and some post mortem findings. The liver was identified as the main target organ on the basis of the organ weight data and histopathological findings. However, these changes were mild and fully reversible. The morphological aspect of the hepatocytic hypertrophy was consistent with proliferation of endoplasmic reticulum. As such, the hepatic effects were not considered to be adverse. No significant changes were observed in the animals dosed at 50 mg/kg/day. It can be concluded that the No Observed Adverse Effect Level (NOAEL) for this study was 500 mg/kg/day. In the study there were not seen any indications for reproductive effects, those investigated were spermatogenic staging, oestrus cycle, weights of ovaries and testes, including microscopic and macroscopic observations.In a subacute oral toxicity study in rats some treatment-related effects were evident in males and to a minor extent in females at the high dose level of 1000 mg/kg/d. The adrenals were identified as the main target organs, based on the post-mortem examination. The observed effects were completely reversible over a 2-week recovery period in the high dose animals. Only mild effects were observed in the animals (essentially males) dosed at 300 mg/kg/d, therefore this dose is expected to be NOAEL. No effects were observed at the low dose level (NOEL = 100 mg/kg/d). In the subacute 28 -day study, a dose of 500 mg/kg bw/d was not used but adverse effects were seen at 1000 mg/kg bw/d (LOAEL). Therefore for repeated dose toxicity, it can be concluded in summary that the NOAEL is 500 mg/kg bw/d.

Justification for classification or non-classification

The results of the repeated dose oral toxicity studies on the similar substance show that 1,2,4-Benzenetricarboxylic acid, mixed dodecyl and octyl triesters does not warrant classification according to EU regulations (Directive 67/548/EEC and Regulation (EC) No 1272/2008.