2',3-bis[[3-[3,5-di-tert-butyl-4-hydroxyphenyl]propionyl]]propionohydrazide

Endpoint summary

Additional information

Toxicokinetic assessment

 

There were no studies available in which the toxicokinetic properties of the test substance were investigated.

 The test substance (molecular weight of 552.79 g/mol) is a white solid with a log P_ow of 4.8, a water solubility < 0.05 mg/L, and a vapor pressure of 1.3 E-10 Pa at 20°C (estimated).

 

Absorption

The low water solubility does not support ready dissolving in gastric fluids, suggesting a low absorption potential after oral ingestion. This is also supported by the available oral toxicity data obtained in rats. In an acute toxicity study, no mortality was reported up to the maximum dose level administered (7000 mg/kg bw) with the observation of commonly occurring clinical signs (dyspnoea, exophthalmus, diarrhea, ruffled fur and curved body position). No indications for systemic toxicity could be detected. In a 90-day repeated dose toxicity study no mortality and no relevant treatment-related findings were observed, indicating poor systemic distribution of the test substance.

In a guinea pig maximization and a guinea pig optimization assay, no indications of systemic availability after dermal application were detected. This is in line with the predictions made based on the physico-chemical parameters. According to ECHA guidance document Chapter R7c, molecules with a molecular size larger than 500 and with a log Pow greater than 4, skin penetration is expected to be low. In conclusion, a dermal uptake of the test substance is expected to be low.

Based on the low vapor pressure exposure to vapors can be excluded. Upon inhalation of dusty material, the particles have the potential to be inhaled (< 100 µm) and are supposed to reach alveolar region of the respiratory tract (ECHA GD 7c, 2008). Dust particles are expected to be poorly absorbed based on the low water solubility and removed by clearing mechanisms. The compound may be taken up by micellular solubilisation, a mechanism of importance for highly lipophilic compounds (log P > 4), particularly for those that are poorly soluble in water (1 mg/l or less) that would otherwise be poorly absorbed (ECHA GD 7c, 2008).

Metabolism

Using the OECD toolbox 3.0, the liver metabolism simulator predicted hydroxylation of the alkyl side chain and the aromatic ring. Furthermore, metabolites were proposed where the amide bond was hydrolyzed. Studies on genotoxicity (Ames-Test, micronucleus assay in-vivo) showed no increased mutagenicity or cytotoxicity in treatments with metabolic activation, indicating that the pigment is not converted into toxic or genotoxic metabolites.

 

Excretion

Some potential metabolites as well as the parent chemical have a molecular weight a little higher than 300 g/mol and were considered insoluble in water. Thus, they are expected to be excreted predominantly via the feces (ECHA GD 7c, 2008). Some potential metabolites have a molecular weight lower than 300 g/mol, and thus are expected to be excreted predominantly via the urine (ECHA GD 7c, 2008).