Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: oral, other
Remarks:
Sub-Acute Oral Toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar (RccHan: WIST) rat
Sex:
not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% w/v aqueous carboxy methyl cellulose (CMC)
Duration of treatment / exposure:
Treatment period: 28 days; Recovery period: 14 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
G1 (vehicle control)
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
G5 (vehicle control recovery)
Dose / conc.:
250 mg/kg bw/day (nominal)
Remarks:
G2 (low dose)
Dose / conc.:
500 mg/kg bw/day (nominal)
Remarks:
G3 (mid dose)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
G4 (high dose)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
G6 (high dose recovery)
No. of animals per sex per dose:
5 rats/sex/group
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No morbidity or abnormal clinical sign was observed in any group, throughout study period.
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in any group, throughout study period.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant change was observed in the mean body weight and mean body weight change in rats from treatment groups.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No significant change was observed in the mean food consumption in rats from treatment groups.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Description (incidence and severity):
Ophthalmological examination did not reveal any abnormality in any rat.
Haematological findings:
no effects observed
Description (incidence and severity):
Test item treatment did not lead to any adverse effect in clinical pathology (haematology, coagulation, clinical chemistry and urinalysis) parameters.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Test item treatment did not lead to any adverse effect in clinical pathology (haematology, coagulation, clinical chemistry and urinalysis) parameters.
Urinalysis findings:
no effects observed
Description (incidence and severity):
Test item treatment did not lead to any adverse effect in clinical pathology (haematology, coagulation, clinical chemistry and urinalysis) parameters.
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
No treatment related change was observed in neurobehavioural observations and functional observational battery performed in rats from treatment groups
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Test item treatment did not lead to any alteration on organ and relative organ weights.
Gross pathological findings:
no effects observed
Description (incidence and severity):
External and internal examination of terminally and recovery sacrificed rats of either sex across various groups (G1 to G6) did not reveal any abnormality.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
The microscopic examination did not reveal any significant alteration related to the test item treatment.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
male/female
Basis for effect level:
other: no effects observed

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
Sub-acute oral NOAEL in rats: > 1000 mg/kg bw/day.
Executive summary:

The objective of this study was to evaluate the potential toxicity of molybdenum disilicide in Wistar rats, following daily administration through oral gavage for 28 consicutive days. Results of this study provide information on any systemic adverse effect, target organ, and an estimation of the No Observed Adverse Effect Level (NOAEL) and/or No Observed Effect Level (NOEL).

Based on results of this study, it is concluded that molybdenum disilicide did not produce any toxicity or adverse effect up to the dose level of 1000 mg/kg b. wt./day after the 28 days repeated oral administration through gavage in Wistar rats. The NOAEL (No Observed Adverse Effect Level) for molybdenum disilicide, in both male and female rats, was found to be 1000 mg/kg b. wt./day, under conditions and procedures followed in this study.