2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]-2-methylpropanenitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanenitrile

EC Number:

811-752-1

Cas Number:

169032-19-3

Molecular formula:

C32 H38 N2 O2

IUPAC Name:

2-(4-{1-hydroxy-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butyl}phenyl)-2-methylpropanenitrile

Method

Target gene:

Histidine
his G 46 (for strains TA100 and TA1535), his C 3076 (for strain TA1537), his D 3052 (for strain TA98), his G 428 (for strain TA102)

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

uvrB - (except for TA 102)
mutation in the rfa gene
pKM101 plasmid (for strains TA98, TA100 and TA102)
pAQ1 plasmid (for strain TA102)

Metabolic activation:

with and without

Metabolic activation system:

liver homogenate (S9) obtained from rats pretreated with Aroclor 1254

Test concentrations with justification for top dose:

Mutagenicity experiment (for all strains): 3, 10, 30, 100, 300, 1000 and 1750 µg/plate
First repeat of mutagenicity experiment due to severe bacterial toxicity for TA100 with and without metabolic activation; for TA 1535, TA1537, TA102 without metabolic activation: 0.3, 1, 3, 10, 30, 100 ans 300 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

sodium azide

mitomycin C

other: 6-Chloro-9-(3-[2-chloroethylamino]propylamino)-2-methoxyacridine]dihydrochloride (ICR191)

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 300 µg/plate with metabolic activation and from 100 µg/plate without metabolic activation

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 300 µg/plate with metabolic activation and from 100 µg/plate without metabolic activation

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 300 µg/plate with metabolic activation and from 100 µg/plate without metabolic activation

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 300 µg/plate with metabolic activation and from 100 µg/plate without metabolic activation

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

from 1000 µg/plate with metabolic activation and from 300 µg/plate without metabolic activation

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Under the experimental conditions of the study, Fexofenadin-Nitrile was found negative in the bacterial reverse mutation test conducted on Salmonella typhimurium strains TA100, TA1535, TA1537, TA98 and TA102 in the presence and absence of metabolic activation. The scoring of dose ranges applied was limited by significant bacterial toxicity.