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Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Dastib 845
IUPAC Name:
Dastib 845
Details on test material:
Lot No.: 040109-02

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Velaz Praha, Czech Republic
- Age at study initiation: (P) x wks; (F1) x wks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g
- Fasting period before study: no data
- Housing:all animals were kept in cages with the bedding in experimental animal house with the standard condition. The sanitation was made according to SOP. Temperature was 22±2°C, reelative humidity 45-65% (central monitoring and regulation), light 12/dark12,
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum):conventional laboratory diet
- Water (e.g. ad libitum):ad libidum
- Acclimation period: 6days, identical conditions to experiment conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±2°C
- Humidity (%):45-65%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

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

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food): conventional laboratory diet
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): substance is insoluble in water
- Amount of vehicle (if gavage): 0.5 mL/100g body weight
- Lot/batch no. (if required): 809182
- Purity:Ph.Eur. 5.0
Details on mating procedure:
Normally, 1:2 (male:female) ,ating were used in this study. P and F1 females were placed with the same P and F1 male until the pregnancy occurs or 21 days have elapsed. Every morning during the mating period all females were examined for the presence of sperms or vaginal plugs. The day 0 of pregnancy was defined as the day a vaginal plug or sperm are found. The pregnant female was keeping individually up to the weaning of pups. in case of pairing was unsuccessful, re-mating of females with the successful males of the same group was considered. For mating the F1 offspring the best representative pups of the litters control and all dose group were selected to produce F2 generation. Mating of siblings in animals F1 generation was no tolerable.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
P generation: acclimatisation: 7days
application/ males: 70 days before mating
application/ females: 14 days before mating, 21 days during mating , 22-24 days during birds, 21 days during weaning F1
F1 genaration:
application/ males: 70 days before mating
application/ females: 70 days before mating, 21 days during mating , 22-24 days during birds, 21 days during weaning F1
Frequency of treatment:
Dosing regime P0: daily (males)
Dosing regime P0: daily (females) Dosing regime F1: daily (males) Dosing regime F1: daily (females)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
25 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
125 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
250 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
control: 12 males / 24 females
dose 25 mg/kg: 12 males / 24 females
dose 125 mg/kg: 12 males / 24 females
dose 250 mg/kg: 12 males / 24 females
Control animals:
yes, concurrent vehicle

Examinations

Statistics:
The results obtained during the study were statistically evaluated by the statistical programme Statgraphics. For the identification homogeneity the groups were used the Bartletts test. In case of homogenity One-Way Analysis of variance with consecutive Multiple Rangers test was accomplished. In the case of non homogeneity Kruskal-Wallis One Way Analysis by Ranks was applied.
The relative weight of the observed organs was calculated from the formula:
R(%) = A (g) / Body weight (g) * 100

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
LOAEL
Effect level:
250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Dose descriptor:
LOAEL
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Dose descriptor:
NOAEL
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male

Results: F1 generation

Effect levels (F1)

open allclose all
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Considering results of this study following were made:
The test article Dastib 845 administered in dose 25 , 125 and 250 mg/kg
* did not cause treatment - related the deaths of P and F1 animals
* did not cause visible treatment-related the signs of intoxication
* did not cause treatment - related changes in the monitored parameters
* did not cause the pathological changes related to the effect of Dastib 845

The test article Dastib 845 administered in dose 250mg/kg
* caused the increase relative weight of liver in female P generation
* LOAEL is 250 mg/kg bw/day and NOAEL is 125 mg/kg bw/day for females P generation
* LOAEL and NOAEL is > 250 mg/kg bw/day for F1 generation and males P generation
Executive summary:

please, check attached background material Summary -test