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Description of key information

Oral (OECD TG 401), rat: LD50 > 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:
19 Aug 2010 - 02 Sep 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Sprague-Dawley (Crl:CD(SD)), SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Orientbio INC., Korea
- Age at study initiation: 6 weeks old (m/f)
- Weight at study initiation: 160.9-181.0 g (males) and 122.3- 138.3 g (females)
- Fasting period before study: overnight, approximately 16 hours prior to dosing
- Housing: stainless wire mesh cages, 260W x 350D x 210H (mm). 1 animal per cage during the study
- Diet: pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C). The diet was placed in feeders and provided ad libitum
- Water: public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum via a polycarbonate bottle (500 mL) in an quarantine room and by an automatic watering system in the animal room
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS- Temperature (°C): 20.2-23.0
- Humidity (%): 39.4-57.0
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12-07-2010 To: 02-09-2010
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): a small amount of water was added to the weighed test substance and mixed using a vortex mixer until dissolved. Additional vehicle was gradually added to yield the desired concentration ( 100, 150, and 200 mg/mL).
- Lot/batch no. : GBA0001

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
1000, 1500 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to dosing (day 0), 30 min after dosing, 1 h, 2 h, 4 h, 6h and then once daily thereafter for 14 days (days 1 to 14)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights and histopathology (in the case of gross findings)
Statistics:
Statistical analysis was performed using SAS Program (version 9.1.3, SAS Institute Inc., U.S.A). Body weights were analysed utilising Bartlett's test for homogeneity (significance level: 0.05). One-way analysis of variance (ANOVA) was employed on homogenous data; then, if significant, Dunnett's test was applied for multiple comparisons (significance level: 0.05 and 0.01, two-tailed). Kruskal-Wallis test was employed for heterogeneous data; then if significant, Steel test was applied for multiple comparisons (significance level: 0.05 and 0.01, two-tailed).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Glaucosuria in one male and one female, hematuria and/or decrease of fecal volume in two females were evident on day 1 in the animals dosed with 1000 mg kg bw of the test substance, but these signs returned to normal on day 2 after dosing.
Hematuria and/or glaucosuria were also evident in two males and four females on day 1 in the 1500 and 2000 mg/kg bw dose groups, respectively. These signs in males in the 1500 mg/kg bw dose group returned to normal on day 1 after dosing. Furthermore, males in the 2000 mg/kg bw dose groups and females in the 1500 mg/kg bw and 2000 mg/kg bw dose groups returned to normal on day 2 after dosing.
Abnormal gait and/or decreased respiration in all animals and prone position, decrease in locomotor activty and/or loss of locomotor activity in two males and two females were evident on the day of dosing in the 1500 and 2000 mg/kg bw dose groups.
Body weight:
Slight decreases in body weight were evident in two females in the 1000 mg/kg bw dose group on day 1 after dosing, but they returned to normal on day 3. Overall, no statistically significant effect on body weight was noted between the control and dosed groups.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

Acute toxicity: oral

The test substance was investigated for acute oral toxicity according to OECD TG 401 and in compliance with GLP (Moon, 2010). The test substance was administered by stomach intubation to Sprague-Dawley rats (5/sex/dose), at doses of 1000, 1500 and 2000 mg/kg bw. No mortality occurred during the 14-day obervation period. The predominant clinical sings seen in animals dosed with 1500 and 2000 mg/kg bw of the test substance, respectively, were glaucosuria, hematuria, abnormal gait, decreased respiration, prone position and loss or decrease in locomotor activity, but these signs were fully reversed by day 2 after dosing. Glaucosuria in one male and one female, hematuria and/or decrease of fecal volume in two females were evident on day 1 in the animals dosed with 1000 mg/kg bw of the test substance, but these signs returned to normal on day 2 after dosing.

Slight decreases in body weight were evident in two females in the 1000 mg/kg bw dose group on day 1 after dosing, but they returned to normal on day 3. However, no statistically significant effect on body weight was noted between the control and dose groups. No test substance related effects were evident in necropsy findings in any of the dose groups. Therefore, based on the results of this study, the LD50 value for both males and females was found to be > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

There is only one study available

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance do not meet the criteria for classification according to Regulation 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

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