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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
other: Reproduction/Embryotoxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
multigenertation but only one dose applied. The evaluation also of this study is restricted because of the inadequate documentation. Furthermore, the study design does not allow the evaluation of parental toxicity and only a single (very high) dose was applied, which leads to further limitation in evaluating the findings.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Long term toxicity and reproduction study (including a teratogenicity study) with cyclamate, saccharin and cyclohexylamine
Author:
Kroes R, Peters PWJ, Berkvens JM, Verschuuren HG, de Vries Th, van Esch GJ
Year:
1977
Bibliographic source:
Toxicology 8, 285-300 (1977)
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report date:
1975

Materials and methods

Principles of method if other than guideline:
Method: multigeneration study : The P-generation started with 50 males and 50 females After an acclimisation period of 5 weeks 20 females were housed with 10 males to produce F1-generation, similar procedure to produce F2-, F3-, F4-, F5- and F6-generation.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
27817-50-1
Cas Number:
27817-50-1
IUPAC Name:
27817-50-1
Details on test material:
IUCLID4 Test substance: other TS: cyclohexylamine sulfate

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: (P) +/- 14 g
- Housing:
except for matimg males were housed individually,
pregnant females individually,
otherwise females in groups of 5
- Diet ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
-

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: mixed in diet
Details on exposure:
Mice were fed diets containing 0.5 % cyclohexylamine sulfate up to and including f6 generation
Details on mating procedure:
during mating period 2 females and 1 males were housed together
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: multigeneration experiment up to and including F6-generation
Frequency of treatment:
daily in diet
Details on study schedule:
20 females were housed with 10 males for the same group (2 females and 1 male in one cage) to produce a F1a generation. The F1a generation was killed after weaning because th litters were too small to produce further generations. Therefote 30 females were mated with 15 males of the same group which produced the F1 a generation.
Further generations were bred in a straight line. ´The breeding results were sufficient to use the a-litters for further reproduction. Therefore 20 females and 10 males of every new generation were aselectively chosen from all litters in each group
Doses / concentrations
Remarks:
Doses / Concentrations:
0.5 % in diet = ca. 600 mg/kg/day
Basis:

Control animals:
yes
Details on study design:
20 females were housed with 10 males for the same group (2 females and 1 male in one cage) to produce a F1a generation. The F1a generation was killed after weaning because th litters were too small to produce further generations. Therefote 30 females were mated with 15 males of the same group which produced the F1 a generation.
Positive control:
no

Examinations

Parental animals: Observations and examinations:
pregnancy rate, live born fetuses, sex ratio
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
From the litters of the F2, F3 and F4 generation the number of implantation sitesm the number of living feuses , the number of resorptions verus the total number of implantations, the mean fetal weights was calculated
Postmortem examinations (offspring):
post natal survival day 5, day 20 and the respective pup weight
Statistics:
student's t-test, Chi-square test, Wilcoxon test
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Cyclohexylamine showed an embryotoxic action as there was a significant difference between the test group in all generations and the controls including decreased number of live born fetuses, increased postnatal mortality and decrease in body weight. The number of implantations was significantly decreased

Effect levels (P0)

Dose descriptor:
dose level:
Effect level:
ca. 0.5 other: % in diet
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: no data
Remarks on result:
other: Generation: mean over all generations (migrated information)

Results: F1 generation

Details on results (F1)

Cyclohexylamine showed an embryotoxic action as there was a significant difference between the test group in all generations and the controls including decreased number of live born fetuses, increased postnatal mortality and decrease in body weight. The number of implantations was significantly decreased

Effect levels (F1)

Remarks on result:
other: See details on results section

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
Significant decrease in the number of implantation sites
and in the number of liveborn fetuses, increased perinatal
mortality and a significant reduction in weight gain of the
offspring were observed; no teratogenic effects were found.
The cyclohexylamine group shows a tendency to a delayed
ossification.
Breeding generations: growth retardation in the CHA group,
which was more pronounced in the first generations and
especially seen in the females. The growth inhibition was
already present at weaning.

Applicant's summary and conclusion