Benzoic acid, 2,3,4,5-tetrachloro-6-cyano-, methyl ester, reaction products with 4-[2-(4-aminophenyl)diazenyl]-3-methylbenzenamine and methanol sodium salt (1:1)

Endpoint summary

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 760 Da) is an orange powder those water solubility (deionised water) is < 17 ug/l. The material decomposes at temperatures above 280 °C which excludes vaporisation of the test material. Examination of the particle size distribution revealed that most of the particles are 47.7 um or larger, only 10 % are 2.3 um or smaller. With regard to the molecular structure of the substance hydrolysis is not likely.

 

Absorption

In an acute oral, dermal and inhalation toxicity study, rats were administered to the test substance and structural analogues. No mortalities or clinical signs of toxicity were observed in doses of 6000 mg/kg bw, 2500 mg/kg bw and 1000 mg/m3, respectively, indicating primarily a very low level of oral, dermal and inhalation toxicity. The NOAEL in male and female rats in a subacute oral repeated dose study on a structural analogue is 1000 mg/kg bw.In regard to the poor water solubility and the absence of hydrolysable groups, the test substance cannot undergo pH-dependent hydrolysis in the stomach. 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.

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

The test substance has a comparably very low vapour pressure. This indicates that absorption of the substance via vapour inhalation is not relevant.

 

Metabolism

Single oral application of the test item to male and female rats did not provoke any effect. Oral administration of the analogue to Wistar rats at doses of 100, 300 and 1000 mg/kg/day, for 28 days (OECD 422) 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, and macroscopical/microscopical findings were of no toxicological relevance.

Based on the results of this study, 1000 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 the unlikely case of uptake, potential metabolism might involve hydroxylation of keto-groups and phase-II reaction, i.e. substitution of chlorine by GSH. 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 substitution of chlorine it isexpected 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.