Registration Dossier

Administrative data

Description of key information

Oral LD50 (rat) (males/females) > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From August 5th to December 25th, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted according to internationally accepted testing guidelines.
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan, Inc. (Hino Breeding Center, Shiga, Japan).
- Age at study initiation: six-week old.
- Weight at study initiation: 221 -239 g for males; 164 - 183 g for females.
- Fasting period before study: fasting period about 20 hours before the dosing and 4 hours after the dosing.
- Housing: two or three animals of the same sex were placed in a suspended aluminium cage with wire-mesh floor (floor 22.4 cm x 41.9 cm, height 20.0 cm; YAMATO Scientific Co., Ltd., Tokyo, Japan). The cage and tray were changed at least once and twice weekly, respectively.
- Diet: rats were fed laboratory animal chows (CRF-1 sterilized by 60Co at 30 kGy, pellet type, Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum.
- Water: tap water passed through a filter apparatus, ad libitum except for the 4 hours after dosing.
- Acclimation period: quarantine and acclimatization period of 11 days.

ENVIRONMENTAL CONDITIONS
- Temperature:24 ± 2 °C
- Humidity: 55 ± 15 %
- Air changes: more than 10 times per hour.
- Photoperiod: 12 hours light/dark cycle by fluorescent lighting system.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Dosing volume: 10.0 ml/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: observation of clinical signs and mortality was carried out at 10 and 30 minutes, 1, 2 and 4 hours after administration and once daily for 2 weeks thereafter. Each animal was weighed on Days 0, 7 and 14 during the observation period.
- Necropsy of survivors performed: yes. At the end of observation period, all animals were exsanguinated from the abdominal aorta under pentobarbital anaesthesia, and were necropsied for gross pathological examination.
Statistics:
Analysis of variance in one way classifications was performed for mean body weight and mean body weight gain. With regard to the parameters in which a significant difference was found at the 5 % level, the least significant difference (LSD) method was used as a test for significant difference compared with the control group.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No dead animals were found in any groups.
Clinical signs:
Fecal excretion of blue substance was observed in males and females at 2000 mg/kg. This clinical sign appeared 4 hours after dosing and disappeared within 3 days.
Body weight:
In 2000 mg/kg males, the mean body weight gain on day 0 to day 7 was lower than that of control. This change was recovered by 14 days after administration. There was no difference in the mean body weight or mean body weight gain between the treated group and control group at any measurement point in females.
Gross pathology:
Retention of white substance in the urinary bladder was found in both control and treated groups. There was no treatment-related finding in the gross pathological examination.
Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation (EC 1272/2008) Criteria used for interpretation of results: EU
Conclusions:
LD50 (rat) (males/females) > 2000 mg/kg bw
Executive summary:

Acute oral toxicity of the test substance was examined in rats at the dosage of 2000 mg/kg in both sexes. The test material was suspended in distilled water at the concentration of 200 mg/ml, and orally administrated at 10.0 ml/kg body weight. None of the animals employed in the experiment died. Fecal excretion of blue substance was observed in both sexes at 2000 mg/kg. The mean body weight gain on day 0 to day 7 at 2000 mg/kg males V was lower than that of control. No treatment-related findings were observed by gross pathological examination.

Conclusion

LD50 (rat) (males/females) > 2000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 2000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

There are no experimental data for dermal and inhalation acute toxicity, however, based on the physicochemical properties and based on the acute oral toxicity study outcomes, no adverse effects are expected for both these exposure routes.

In conclusion, the test substance is non classified for oral acute toxicity, according to the CLP Regulation (EC 1272/2008).