Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data migrated from NONS with permission to refer granted by ECHA.

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 92/69/EEC
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
No information on test material available. Endpoint study information provided by ECHA from migrated NONS data and specific information not included.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 days per week
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
75 mg/kg bw/day (nominal)
Dose / conc.:
225 mg/kg bw/day (nominal)
Dose / conc.:
750 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 male and female animals at each dose group
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Decreased faeces were observed in all rats that received 750 mg/kg/day and sialorrhea was observed in all treatment groups.
Mortality:
mortality observed, treatment-related
Description (incidence):
In animals that received 750 mg/kg/day 1 male was found dead on Day 3 and 1 male was sacrificed as moribund on Day 11.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
In males that received 750 mg/kg/day, mean bodyweights were significantly lower than in controls.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
effects observed, treatment-related
Description (incidence and severity):
Food consumption for males that received 750 mg/kg/day was reduced on Days 4 and 7.
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Alkaline phosphatase (ALP) and ALAT concentrations were increase in males that received 750 mg/kg/day. A slight, statistically significant increase in ALAT was also observed in males that received 225 mg/kg/day. The slight increases in ALAT and ALP could be related to the changes observed in the pancreas of animals that received 750 mg/kg/day.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
In males that received 750 mg/kg/day, there were increases in relative adrenal, testes, kidney and liver weights and decreased absolute spleen, kidney and thymus weights. Liver weights were also increased in females that received 750 mg/kg/day. No associated gross or microscopic findings were observed in these organs.
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
Mild exocrine cell necrosis of the pancreas was observed in animals that received 750 mg/kgbw.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
225 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
not specified
Basis for effect level:
histopathology: non-neoplastic
Dose descriptor:
NOEL
Effect level:
< 75 mg/kg bw/day (nominal)
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: Lack of toxicologically significant effects

Target system / organ toxicity

Critical effects observed:
yes
Lowest effective dose / conc.:
750 mg/kg bw/day (nominal)
System:
other: Pancreas
Organ:
pancreas
Treatment related:
yes
Dose response relationship:
no
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
Based on information provided by ECHA, the results of a 28 day repeated dose study include a NOAEL of 225 mg/kg/day based on effects observed in the pancreas of high dose animals.