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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of the test substance were investigated. Based on the large molecular size, the absence of adverse findings in toxicity studies, and the presence of functional groups for metabolism, a potential for bioaccumulation is unlikely. Further details for this assessments are given below.

 

Chemistry

The test substance (molecular weight of 302 Da) is an orange powder those water solubility (deionised water) is < 0.098 mg/L. The material decomposes at temperatures above 230 °C which excludes vaporisation of the test material. Examination of the particle size distribution revealed that most of the particles are 82.2 µm or larger, only 10 % are 2.4 µm or smaller. With regard to the molecular structure of the substance hydrolysis is not likely.

 

Absorption

In an acute oral and inhalation toxicity study, rats were administered to the test substance. No mortalities or clinical signs of toxicity were observed in doses of > 6000 mg/kg bw and 2119 mg/m3 air, respectively, indicating primarily a very low level of oral and inhalation toxicity. The NOAEL in male and female rats in a subacute oral repeated dose study is 300 and 1000 mg/kg bw, respectively, due to an increase in absolute and relative liver weight. In an OECD 421 screening study the NOAEL for parental animals and F1 animals is considered to be 1000 mg/kg bw. Effects on organ weights were not observed. Orange-discolored feces during the treatment period as well as orange discoloration of the gastro-intestinal tract was observed indicating very limited absorption of the substance via the oral route.

An additional sub-acute study was performed to determine the bioavailability of the test substance after oral administration at limit dose. Clinical examination revealed

orange discolored feces in all animals from study day 1 onwards. Orange discoloration of contents in the glandular stomach, jejunum and cecum was also observed. Trace amounts of the applied substance could be detected in liver, spleen and kidney tissue of individual animals ranging from 0.94 - 15.3 ng/mg tissue. No test item could be detected in rat plasma samples. Thus, it could be concluded that the test item was bioavailable in the absence of signs of toxicity.

In regard to the poor water solubility and the absence of hydrolysable groups, the test substance cannot undergo pH-dependent hydrolysis in the stomach. As it does not bear resemblance to fatty acids, uptake via micelles with bile acids is unlikely.

Slight to marginal skin permeability can be assumed based on a model calculation (Fitzpatrick, et al., 2004).

 

Metabolism

Single oral application of the test item to male and female rats did not provoke any effect. Oral administration to Wistar rats at doses of 300, 1000 and 3000 mg/kg/day, for 28 days resulted in slightly increased liver weight. Based on the results of this study, 300 and 1000 mg/kg/day, respectively, were considered to be the no observed- adverse-effect-levels (NOAEL) for male and female animals. In the course of a reproduction / developmental toxicity screening study, no such effects were observed. The NOAEL for the F0 and F1 generation is considered to be 1000 mg/kg bw. No indication of chemical reactivity and only very limited absorption was observed in any study, including acute studies, irritation, sensitization and genotoxicity in vitro as well as the above described subacute and OECD 421 study.

In the case of uptake, potential metabolism might involve hydroxylation of keto and methyl -groups and enzymatic cleavage of azo bonds. The test substance is not expected to accumulate in the body.

  

Excretion 

The substance is expected to be excreted unchanged via the feces. In case of gastrointestinal uptake and metabolism through hydroxylation and phase-II metabolism it is expected that the test substance might be excreted predominantly via the urine. Overall, the test substance is not expected to accumulate in the body.

 

Used references: 

Fitzpatrick, D., et al. (2004). "Modelling skin permeability in risk assessment-the future." Chemosphere 55 (10): 1309-14.