Bumetrizole

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Agonistic effects of diverse xenobiotics on the constitutive androstane receptor as detected in a recombinant yeast-cell assay

Author:

Kamata R, Nakajima D, Shiraishi F

Year:

2018

Bibliographic source:

Toxicology in vitro 46 (2018) 335-349

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The agonistic effect of each compound on the constitutive androstane receptor (CAR) was evaluated with a reporter gene assay using yeast cells (Saccharomyces cervisiae Y190) carrying the beta-galactosidase reporter gene.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bumetrizole

EC Number:

223-445-4

EC Name:

Bumetrizole

Cas Number:

3896-11-5

Molecular formula:

C17 H18 Cl N3 O

IUPAC Name:

2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol

Test material form:

solid

Results and discussion

Any other information on results incl. tables

The test substance did not induce an active response in this assay.

Applicant's summary and conclusion

Conclusions:

The test substance did not show any agonistic effects in this in vitro assay on the human CAR.

Executive summary:

The constitutive androstane receptor (CAR) is a nuclear receptor and transcription factor regulating proteins involved in xenobiotic metabolism. Agonist activation of the CAR can trigger metabolic activation and toxification as well as detoxification and clearance; accordingly, xenobiotic substances acting as CAR ligands may pose a threat to human and animal health. The authors used yeast cells transduced with the human CAR and the response pathway to measure the CAR-agonistic activities of 549 synthetic or natural compounds: 216 of the tested compounds exhibited CAR-agonistic effects. The ten most potent compounds were 4-tert-octylphenol (4tOP; reference substance), 4-nonylphenol, diethylstilbestrol, benzyl nbutyl phthalate, 2-(4-hydroxyphenyl)-2,4,4-trimethylchroman, o,p′-DDT, methoxychlor, di-n-propyl phthalate, hexestrol, and octachlorostyrene. The activities of these nine non-reference compounds exceeded 10% of the 4tOP activity. Analysis of para-monoalkyl phenols suggests that branching of the alkyl group and chlorination at the ortho position raises potency. This study provides critical information for identifying the potential of CARmediated toxic hazards and for understanding the relevant mechanism. The test substance did not show any agonistic effects in this in vitro assay on the human CAR.