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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Although conducted before the OECD Guideline 401 came into effect, the procedures used on this study were comparable in terms of species used, number of animals, dose selection and observations made.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4-naphthoquinone
EC Number:
204-977-6
EC Name:
1,4-naphthoquinone
Cas Number:
130-15-4
Molecular formula:
C10H6O2
IUPAC Name:
1,4-naphthoquinone
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Laboratory Animal Agriculture Co-operative association.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Around 9 weeks
- Weight at study initiation: Males (260 to 300 g) and females (170 to 205 g).
- Fasting period before study: Witheld overnight prior to dosing
- Housing: No details
- Diet (e.g. ad libitum): Pelleted diet provided freely
- Water (e.g. ad libitum): tap water provided freely
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 25°C
- Humidity (%): 50 to 60%
- Air changes (per hr): Not detailed
- Photoperiod (hrs dark / hrs light): Not detailed

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) gum tragacanth water solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Varies depending on dosage
- Amount of vehicle (if gavage): 5 mL/kg

Doses:
130, 169 and 220 mg/kg
No. of animals per sex per dose:
5 males and 5 females per sex per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodweight was measured on the day of exposure and Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, and gross necropsy.
Statistics:
LD50 calculated using Litchfield-Wilcoxon analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
124 mg/kg bw
Based on:
test mat.
Mortality:
100% of animals that received 220 mg/kg were found dead by 1 day after dosing.
90% of animals that received 169 mg/kg were found dead by 1 day after dosing.
60% of animals that received 130 mg/kg were found dead by 1 day after dosing.
Clinical signs:
other: Staggered gait was observed 5 minutes after treatment with lethargy and lack of spontaneous movement observed by 10 minutes in all dose groups. These findings were observed until 1 hour after treatment. Around half of the animals that received 169 or 220
Gross pathology:
Congestion and erosion was observed at the fundus of the stomach in animals which died shortly after treatment.Oedema was observed in animals which died up to 4 hours after treatment. Thickening and hardening of the cardia of the stomach was noted in all surviving animals on Day 14. In addition adhesion of the cardia of the stomach, liver and spleen was noted in one animal in each group receiving 130 or 169 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
A reliable near guideline study is available which provides a LD50 value of 124 mg/kg bw after a single dose of the substance. The test substance was considered to be highly stimulative to the stomach and induced acute gastritis which was regarded as the cause of death alongside CNS depression. Some evidence of recovery was noted in animals that survived until the end of the observation period.