Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Annex V method B7 Directive 84/449/EEC
Principles of method if other than guideline:
Duration of test : 28 days
Limit test : 150 mg/kg or mg/l per h/day
Species / Strain : Sprague-Dawley Rats
Route of administration : Oral - Method of administration : Gavage
Vehicle : 1% w/v aqueous Methylcellulose
Dosing regime : 7 days per week
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-butyl-4-chloro-4,5-dihydro-5-hydroxymethyl-1-[2'-(2-triphenylmethyl-1,2,3,4-2H-tetrazol-5-yl)-1,1'-biphenyl-4-methyl]-1H-imidazole
EC Number:
412-420-5
EC Name:
2-butyl-4-chloro-4,5-dihydro-5-hydroxymethyl-1-[2'-(2-triphenylmethyl-1,2,3,4-2H-tetrazol-5-yl)-1,1'-biphenyl-4-methyl]-1H-imidazole
Cas Number:
133909-99-6
Molecular formula:
C41H37ClN6O
IUPAC Name:
[2-butyl-4-chloro-1-({2'-[2-(triphenylmethyl)-2H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazol-5-yl]methanol

Results and discussion

Any other information on results incl. tables

CLINICAL OBSERVATIONS : No deaths occured. No signs of ill health or behavioural changes were noted. There is no notable difference in overall bodyweight gains between control and treated rats of both sexes. Food consumption for all treated rats was comparable to that of control animals.

LABORATORY FINDINGS : A statistically significant decrease in haemoglobin values for males at the 150 and 1000 mg/kg/day dose levels (i.e. P<0.05) was noted. Also, the thrombotest values for males at all 3 dose levels were reduced significantly (i.e. P<0.05 to P<0.01) compared to the controls.

Analysis of blood smears revealed the occurence of slight polychromasia and/or slight anisocytosis. However this finding is not uncommon among young laboratory rats and at the incidence seen in this study was not considered to be toxicologically important.

There were no notable differences in haematology for females treated compared to controls.

Elevated Alkaline phosphatase values occured at all dose levels for both sexes achieving significance (P<0.05) for high dose females.

Individual male animals exhibited raised Aspartate aminotransferase at all dose levels, achieving statistical significance for those at the 1000 mg/kg/day, while one female animal at 150 mg/kg/day also achieved an elevated AST level. A slight reduction in the glucose values for females at 15 and 150 mg/kg/day was noted compared to controls.

EFFECT IN ORGANS : Decreased adjusted kidney weights were recorded for males at 15, 150 and 1000 mg/kg/day achieving statistical significance compared to controls (P<0.05). Elevated weights for ovaries were noted and achieved statistical significance (P<0.05) at the 1000 mg/kg/day dose level. One male rat at 1000 mg/kg/day exhibited a slightly reduced liver weight (not statistically significant).

DOSE OR CONCENTRATION AT WHICH NO EFFECT WAS OBSERVED : 15 mg/kg/day

Applicant's summary and conclusion