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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
This strain has been used for non-clinical safety studies, recommended by regulatory agencies.
Sex:
male/female
Details on test animals and environmental conditions:
10 males and 13 females
Total 40 males and 52 females

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Males: Premating -two weeks, during the mating period, post mating – till total dosing period of 28 days.
Females: Premating - two weeks, during mating period (variable time to conception), duration of pregnancy and 13 days after delivery.
Doses / concentrationsopen allclose all
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CLINICAL SIGNS AND MORTALITY; FUNCTIONAL OBSERVATION BATTERY; BODY WEIGHT; FOOD CONSUMPTION; DURATION OF GESTATION AND LITTER EXAMINATION; HAEMATOLOGY AND CLINICAL CHEMISTRY
Sacrifice and pathology:
GROSS NECROPSY; ORGAN WEIGHTS; HISTOPATHOLOGY;

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
Slight lowering of body weight gain during premating period (for both males and females) and mating period (for males)
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
A solitary incidence of statistically significant decrease was noticed in absolute weight of epididymides in male rat (in G4 dose group) which was not considered to be a treatment related change due to lack of change in relative weight of epididymides, hence not considered to be of toxicological significance.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Few incidental findings were observed in lungs and mediastinal lymph nodes and these comprised of reddening and abscess in lungs and enlargement of mediastinal lymph nodes. As these findings were not dose dependent and present in animals from control group as well, were therefore considered to be unrelated to treatment.
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
ca. 500 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
body weight and weight gain

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion