Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data source is the English summary of a Japanese study report

Data source

Reference
Reference Type:
other: study report summary
Title:
Unnamed
Year:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
not specified
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate
EC Number:
278-575-4
EC Name:
Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate
Cas Number:
76918-62-2
Molecular formula:
C18H13N3O3.Na
Details on test material:
- Name of test material (as cited in study report): Naphtolone sodium salt

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age at study initiation: 5 weeks

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days treatment, 14 days recovery (control and high dose group)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
200 mg/kg/bw
Basis:
actual ingested
Remarks:
Doses / Concentrations:
40 mg/kg/bw
Basis:
actual ingested
No. of animals per sex per dose:
6 males and 6 females
Control animals:
yes
Details on study design:
A 28-day repeated oral dose toxicity study of Nathtolone sodium salt followed by a 14-day recovery study was performed in groups of six male and six female Crj:CD(SD) rats at 5 weeks of age. The high dose was set at 1,000 mg/kg, and altogether 3 doses including 200 and 40 mg/kg were employed. Recovery groups were also set for the 1,000 mg/kg and vehicle control groups.

Examinations

Observations and examinations performed and frequency:
mortality, clinical signs, body weights and food intakes during dosing period, hematological examinations, urinalyses, organ weights, necropsy and histopathological examinations at termination of the dosing period
Sacrifice and pathology:
yes

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
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):
bilirubin was increased in females of the 1,000 mg/kg
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOEL
Effect level:
200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Total bilirubin was increased in females of the 1,000 mg/kg group

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOEL: 200 mg/kg/day

Executive summary:

A 28-day repeated oral dose toxicity study of Naphtolone sodium salt followed by a 14-day recovery study was performed in groups of six male and six female Crj:CD(SD) rats at 5 weeks of age. The high dose was set at 1,000 mg/kg, and altogether 3 doses including 200 and 40 mg/kg were employed. Recovery groups were also set for the 1,000 mg/kg and vehicle control groups.

No death occurred in all examinations.

No abnormality was noted in clinical signs, body weights and food intakes during dosing period, in hematological examinations, urinalyses, organ weights, necropsy and histopathological examinations at termination of dosing period.

Concerning the blood chemical examinations, there was a dose-relationship. Total bilirubin was increased in females of the 1,000 mg/kg group at termination of dosing period.

No abnormalities were noted in the recovery group.

Based on these results, the NOEL of Naphtolone sodium salt in rats under the present study conditions was estimated to be 200 mg/kg/day.