N-cyclohexylcyclohexanamine 2-[1-[[[(1R)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanyl]methyl]cyclopropyl]acetate

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; original reference in Japanese, compilation of data from English summary and tables

Data source

Reference

Title:

No information

Author:

Ohara N, Takashima H, Tanaka A, Katoh H, Seki T, Kojima K,|Inada H, Anjo T, Azegami J, Yoshimura S, Saegus K (1998).|Twenty-eight-day repeat oral dose toxicity test of|dicyclohexylamine in rats. Ministry of health and Welfare|(MHW, Japan) Toxicity Testing Reports of Environmental|Chemicals Vol. 6, 101-104, 105-116, 637-642.

Materials and methods

Principles of method if other than guideline:

Type: other: Sub-acute toxicity study
Method: other: Guidelines for 28 day Repeat Dose Toxicity Test of Chemicals (Japan)

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Dicyclohexylamine

EC Number:

202-980-7

EC Name:

Dicyclohexylamine

Cas Number:

101-83-7

IUPAC Name:

N-cyclohexylcyclohexanamine

Test material form:

liquid

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

28 days

Frequency of treatment:

one daíly

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 70, 200 mg/kg bw dissolved in corn oil
Basis:

Control animals:

yes, concurrent vehicle

Details on study design:

Duration of test: 42 days (28 days treatment + 14 days recovery)

Results and discussion

Observed effects

see freetext RS

Any other information on results incl. tables

RS-Freetext:
-Clinical signs: Salivation, convulsion observed in male and
female rats from 70 mg/kg bw/day onwards which disappeared
during recovery period.

200 mg-groups, male and females:
--Mortality:  8/13; reason of death unknown, 1/18 with
myocardial degeneration
--Body weight gain(as graphic): significantly decreased,
continued (but not significant) until the end of the
recovery period:
FINAL BODY WEIGHTS, m/f: control versus high dose: 
end of treatment time: 355g/232g versus 285g/184g  
end of recovery period: 399.9g/266g versus 333g/236g
--Food consumption(graphic): significantly reduced but had
recovered by the end of the test

GROSS AND HISTOPATHOLOGY
--ORGAN WEIGHTS (significant changes):
-----adrenal gland
absolute//relative(mg//mg/g), high dose versus control
---male: 62.5//0.220 versus 47.3//0.134
---female: 88.2//0.478 versus 61.0//0.263
-----ovaries
absolute//relative(mg//mg/g), mid, high dose versus control
---female: 79.6(p<0.05)//0.357, 59,9//0.352 versus
98.2//0.425
--HISTOPATHOLOGY
no relevant changes in comparison to the concurrent controls
reported