Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Link to relevant study record(s)

Description of key 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 at the test item and structural analogues, and the presence of functional groups for metabolism, a potential for bioaccumulation is unlikely.

A full toxicokinetk assessment is attached (Information panel --> Attachments) and can be found in Additional Information below.

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 at the test item and structural analogues, 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 919.7 g/mol) is a yellow powder those water solubility (deionised water) is 1.7 mg/l. The log Pow is - 0.59 and the material decpmposes at temperatures above 310 °C. Examination of the particle size distribution revealed variability within a wide range according to manufacturing conditions; 50 - 100% of the material has a particle size below 10 µm or 4 µm, respectively. In regard to the molecular structure of the substance hydrolysis appears to be unlikely.

Absorption

In an acute oral and dermal toxicity study, rats were administered to the test substance or an structural analogue. No mortalities or clinical signs of toxicity were observed at dose levels of 10.000 and 2000 mg/kg bw, respectively, indicating primarily a very low level of oral and dermal toxicity. The NOAEL in male and female rats in a subacute oral repeated dose study on an analogue substance (OECD guideline 422) is 1110 mg/kg bw. Due to the high molecular weight (> 500 g/mol) gastrointestinal absorption is very limited. As it does not bear resemblance to fatty acids, uptake via micelles with bile acids is unlikely. It is presumed that the complex dissolves in an acidic environment (pH < 3; e.g. stomach) into the cation (calcium) and the organic compound. The divalent metal ion Ca2+is of low toxicity so that the hazard profile is determined by the organic anion. At environmentally relevant pH values (pH 4 to pH 9) the substances are not expected to hydrolyze.

Skin penetration can be excluded based on model calculation (Fitzpatrick, et al., 2004).

The test substance decomposes at temperatures above 300 °C. This indicates that absorption of the substance via vapour inhalation is not relevant.

 

Metabolism

Single oral application of the analogue substance to male and female rats did not provoke any effect up to 14 days post observation period. Oral administration of the analogue to Wistar rats at doses of 110, 330 and 1110 mg/kg/day, for 28 days, resulted in no test item-related effects and no differences in food consumption or body weight development. The hematology, clinical biochemistry and urinalysis parameters did not show test item-related differences when compared with those of the controls. Organ weights of test item-treated animals were unaffected. Macroscopically yellow discoloration of the content of the digestive tract in numerous animals was observed. In single treated animals and single organs of the digestive tract these yellow pigments could also be observed histopathologically. Beside the discoloration no signs of toxicity in the respective tissues were noted. Based on the results of this study, 1110 mg/kg/day was considered to be the no observed- adverse-effect-level (NOAEL).

No indication of uptake or chemical reactivity was observed in any study, including acute studies, irritation, sensitization and genotoxicity in vitro as well as the above described subacute study.

In case of uptake, a potential metabolism might involve hydroxylation of keto- and methyl-groups. Furthermore, cleavage of the azobond by gastrointestinal bacterial enzymes may lead to formation of aromatic amines. Reduction of the nitro-group by bacterial or hepatic enzymes to hydroxylamin and aromatic amines is also possible. Though, corresponding clinical signs, e.g. met-Hb formation or anemia, were not observed. Regarding phase II metabolism, substitution of the chlorine by glutathion seems conceivable. The test substance is not expected to accumulate in the body.

  

Excretion 

As mentioned above, the substance is expected to be excreted unchanged via the feces. In case of gastrointestinal uptake and metabolism through hydroxylation, azobond reduction and phase-II substitution of chlorine 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.