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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Rodent Hershberger assay
GLP compliance:
yes (incl. certificate)
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Uvinul MC 80 N
- Physical state: Liquid
- Analytical purity: 99.9 %
- Lot/batch No.: UV2-01.019
- Stability under test conditions: The stability of the test substance in corn oil over the administration period was
demonstrated
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany

- Age at study initiation: 56 ±1 days
- Weight at study initiation: mean weights per group 199.8-205.7 g
- Fasting period before study: no
- Housing:
Singly in type DK III stainless steel wire mesh cages supplied by
Becker & Co., Castrop-Rauxel, Germany (floor area about 800 cm2). Underneath the
cages, disposable waste trays were used.

- Diet : ground Kliba maintenance diet rat-mouse meal, ad libitum
- Water : ad libitum
- Acclimation period: 14d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 hours light from 06.00 a.m. - 06.00 p.m., 12 hours dark from 06.00 p.m. - 06.00 a.m.


IN-LIFE DATES: From: 23.04.2003 To: 28.05.2003

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Concentration in vehicle: 6; 20 g/100 ml
- Amount of vehicle (if gavage): 5 ml/kg bw/day
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
10 days
Frequency of treatment:
daily
Duration of test:
4 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 300, 1000 mg/kg bw/day
Basis:
nominal conc.
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Statistics:
Food consumption, body weight, body weight change, food efficiency: A comparison of each group with control group was performed using DUNNETT's test (two-sided)
Organ weight parameter: Non-parametric one-way analysis using KRUSKAL-WALLIS test (two-sided). lf the resulting p-value was equal or less than 0.05, a
pairwise comparison of dose groups with control groups using the WILCOXON test for the hypothesis of equal medians

Results and discussion

Any other information on results incl. tables

Mortality:

No animal died prematurely.

Clinical examinations/ Food-Water consumption / Body weight data / Food efficiency:

No substance-related findings were obtained.

Hormones:

In the serum of castrated male rats testosterone levels were significantly decreased and luteinizing hormone concentrations slightly increased compared to the values of castrated animals receiving 0.4 mg/kg bw/day of testosterone propionate as reference androgen. No significant difference in serum dihydrotestosterone concentrations was seen between both test groups. No effects on testosterone, dihydrotestosterone and luteinizing hormone concentrations were found in the serum of castrated males treated with 1,000 mg/kg bw/day of Uvinul MC 80 N and 0.4 mg/kg bw/day of testosterone propionate for 10 days when compared with the hormone levels of animals given testosterone propionate, only.

Pathology:

Absolute liver weight was significantly increased (1000 mg/kg bw / day).

Relative liver weights were significantly increased (300,1000 mg/kg bw / day)

Absolute and relative weights of the accessory sex organs were significantly reduced (vehicle untreated) compared to

testosterone proprionate animals Histologically, prostate, seminal vesicle and the bulbo-urethral gland were immature.

Absolute weight of the ventral prostate (fresh) was significantly decreased (1000 mg/kg bw / day).

Absolute weights of the ventral prostate (fixed) were dose-related significantly decreased in (300,1000 mg/kg bw / day).

The relative weights of these organs did not show significant differences, when compared to control group 1.

The terminal body weight was slightly but not significantly decreased 300 mg/kg bw / day

(-2.3%) and 1000 mg/kg bw / day (-5.5%).

The decreased weights of the ventral prostate are considered as consequence of the slightly reduced terminal body weight of these animals and do not represent an adverse compound-related effect.

Absolute and relative weights of the other accessory sex organs were not significantly reduced.

Histology of prostate, seminal vesicle and the bulbo-urethral gland was comparable to control.

Applicant's summary and conclusion