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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test results are not sufficient reported without details.

Data source

Reference
Reference Type:
publication
Title:
Preliminary reproduction toxicity sreening test of dicyclohexylamine by oral administration in rats.
Author:
Umemura T, Katahira K, Tamura K, Katsumata T
Year:
1999
Bibliographic source:
Ministry of Health and Welfare (MHW, Japan) Toxicity Testing Reports of Environmental Chemicals Vol.7, 355-365, 717-725.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified
Details on test material:
purity 99.98%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
corn oil
Details on exposure:
doses 0, 20, 40, 80 mg/kg bw/day dissolved in corn oil, exposure once daily
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
males: 49 days; females from 14 days before mating to day 3 of lactation
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 20, 40, 80 mg/kg bw/day dissolved in corn oil
Basis:
no data
No. of animals per sex per dose:
12 pre sex and group

Examinations

Parental animals: Observations and examinations:
clinical signs of toxicity, body weight, mortality, pathology of male organs, number of pairs mated, number of pairs copulated, number of pregnant females, days until copulation, copulation index (no. of pairs with successful copulation / no. of pairs mated) X 100
fertility index (no. of pregnant rats / no. of pairs with successful copulation) X 100
duration of gestation,
---gestation index
(no. of females with live pups / no. of pregnant females) X 100,
---implantation index
(no. of implantations / no. of corpora lutea) X 100,
Oestrous cyclicity (parental animals):
estrus cycle length
Sperm parameters (parental animals):
no data
Litter observations:
live birth index (no. of live pups on day 0 / no. of pups born) X 100,
---delivery index (no of pups born / no. of implantations) X 100,
---sex ratio (no of males /no of females),
---viability index (no of live pups on day 4 / no. of live pups on day 0) X 100,
body weight of pups on day 0 and day 4
Postmortem examinations (parental animals):
Organ weight (absolute and relative):
- male, right and left testes, right and left epididymides
Statistics:
Statistical analysis of offspring was carried out using the litter as the experimental unit. Bartlett's test of homogeneity of variance was used to determine if the groups had equivalent at the 5% level of significance. If variance was equivalent, the groups were compared by one-way analysis of variance. If significant differences were found, Dunnett's test was performed. If the groups did not have equivalent variances, the Kruskal-Wallis test was used to assess the overall effects. Whenever significant differences were noted, Dunnett-type test was performed. Mann-Whitney U-test or Fisher's exact test was also used.

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
effects observed, treatment-related
Reproductive function: sperm measures:
not specified
Reproductive performance:
effects observed, treatment-related

Details on results (P0)

CLINICAL OBSERVATIONS AND FREQUENCY:
Mortality of two pregnantfemales was observed on day 21 or 22 day of pregnancy at a dose of 80 mg/kg bw/day.
Poor maternal behaviour and nursing were observed in 7 dams at a dose of 80 mg/kg bw/day. Gestation index was
slightly but not statistically significantly reduced in females pregnancy at a dose of 80 mg/kg bw/day: 90 % (1 of 10 surviving dams without
live pups) versus 100 % in controls. Reproductive parameters of animals at a dose of 40 mg/kg bw/day or less were unaffected by treatment with
Dicyclohexylamine. Reduction of ovary weights from 70 mg/kg bw/day dose level group upwards.

---Food consumption (graphic):
80 mg-groups of both sexes: low food consumption

PATHOLOGY
---male terminal mean body weight
low-mid-high dose versus control:
529g-547g-507g (p<0.05) versus 543g
---ORGANS EXAMINED AT NECROPSY (reported organs):
--Organ weight (absolute and relative):
- male, right and left testes: absolute weights showed no differences to concurrent controls
relative weights: low, mid, high dose versus control
- right testes: 0.32 g%, 0.31 g%, 0.34 g%(p<0.01) versus 0.30 g%
--left testes: no significant difference to the concurrent control
both testes together: 0.64 g%, 0.62 g%, 0.68g%(p<0.05) versus 0.61 g%
right and left epididymis: no significant differences to concurrent control

OTHER EXAMINATIONS:
---REPRODUCTIVE PERFORMANCE:
no differences to the concurrent controls:
-----estrus cycle length, number of pairs mated, number of -----pairs copulated, number of pregnant females, days -----until copulation, copulation index, fertility index

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: no data
Remarks on result:
other: Generation: offsprings (migrated information)
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: no data
Dose descriptor:
NOAEL
Effect level:
80 mg/kg bw/day
Sex:
male
Basis for effect level:
other: no data
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day
Sex:
female
Basis for effect level:
other: no data

Results: F1 generation

General toxicity (F1)

Clinical signs:
effects observed, treatment-related
Mortality / viability:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

no differences to the concurrent controls:
---duration of gestation,
---implantation index
---delivery index
---sex ratio
findings which differ from controls:
low - mid - high dose versus control
---gestation index
100% - 100% - 90% versus 100%
1/10 surviving high dose dam without pups

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
40 mg/kg bw/day
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: no data

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL (offsprings): 40 mg/kg bw/day (male/female)
NOAEL (P): 40 mg/kg bw/day (male/female)
Executive summary:

Based on the Reproduction/Developmental toxicity screening test (OECD Guideline 421), NOAEL (offsprings): 40 mg/kg bw/day (male/female), NOAEL (P): 40 mg/kg bw/day (male/female)