Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 99.56%

Test animals

Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 weeks
- Weight at study initiation: 141-112 g for the males and 133 - 118 g for the females
- Housing: 2 rats for each cage were housed in suspended metal cages with stainless steel mesh at the front and floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-20 times/hour,
- Photoperiod (hrs dark / hrs light): illumination: 150-300 Lux, 12 hours of light and 12 hours of dark

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF TEST SUBSTANCE FORMULATION: For the treated groups, the test substance was mixed with a part of the basal diet in a beaker, and the mixture was put into the rest of basal diet for further mixing by mixer for 20 minutes, then put into stainless steel barrel with lid.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Duration of test:
13 weeks
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
500, 2500 and 12500 mg/kg
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
Males: 44.3, 218.8, 947.0 mg/kg; Females: 48.1, 246.9, 1133.2 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
16/sex at 0 and 12500 mg/kg (for which 6/sex served as recovery animals)
10/sex at 500 and 2500 mg/kg
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure recovery period in satellite groups: 2 weeks
Statistics:
Mean organ weights and organ weight to bodyweight ratio were analyzed by Bartlett's for homogeneity of variance. The data with homogeneity pattern of variance (p>0.05) were compared using One-way Analysis of Variance (ANOVA); The data with heterogeneous pattern of variance (p≤0.05) were compared using the Kruskal-Wallis test. If result of Analysis of Variance test was significant differences (p≤0.05) between each treated group and control group, and using Dunnett's test; otherwise, end test. If result of the Kruskal-Wallis test was significant differences (p≤0.05), then using Dunnett's no parameter test, or else end test.

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Remarks:
for reproductive organ effects
Effect level:
12 500 mg/kg diet
Sex:
male/female
Basis for effect level:
other: This NOEL corresponds to 947.0 and 1133.2 mg/kg bw/day for males and females, respectively. No effects were observed in reproductive organs at the highest dose tested.

Observed effects

No effects were observed in reproductive organs of male or female rats in a 90-day feeding study.

Applicant's summary and conclusion

Conclusions:
No effects were observed in reproductive organs of male or female rats in a 13-week feeding study.
Executive summary:

Male and female Sprague-Dawley rats were fed diets containing 0, 500, 2500, 12500 mg/kg diet for 13 weeks, with an additional recovery observation period for animals at 0 and 12500 mg/kg/bw. All rats were examined for gross and microscopic pathological changes and select organs were weighed at the end of the 13-week treatment period and the recovery period. No effects were observed in reproductive organs of male and female rats in this 13-week feeding study at the highest dose tested, 12500 mg/kg diet (947.0 and 1132.0 mg/kg bw/day for males and females, respectively).