Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute oral LD50: 859 mg/kg bw  (Nissan Chemical Industries, 1994)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, similar to guideline study, available as unpublished report, adequate for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan SLC. Inc., 3371-8, Koto-cho, Hamamatsu-shi, Shizuoka-ken 431-11, Japan
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: males 163 – 195 g, females 121 – 138 g
- Fasting period before study: 16 hours
- Housing: five rats per cage, in wire mesh cages (21.5 x 27.5 x 19.5 cm) suspended from stainless steel and aluminium racks (745 x 50 x 182 cm) made by Tokyo Giken service Co., Ltd. (Wakamatsu-cho 2-8-16, Fuchu-shi, Tokyo, Japan).
- Diet: ad libitum, a commercial rat and mouse diet MF (Oriental Yeast Co., Ltd., Kodenma-cho 10-11, Nihonbashi, Chuo-ku, Tokyo)
- Water: ad libitum, tap water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 50 - 60
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 1 mL/100 g bw
Doses:
518, 622, 746, 896, 1075 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following administration, each animal was observed at every hour during the first 8 hours and at least twice daily and as often as practicable thereafter. The body weight of each animal was determined shortly before the administration, and 7 and 14 days after dosing. All of the dead animals were weighed and then necropsied.
- Necropsy of survivors performed: yes
Statistics:
The LD50 values were calculated by the method of Litchfield and Wilcoxon (1949).
Sex:
male
Dose descriptor:
LD50
Effect level:
969 mg/kg bw
Based on:
test mat.
95% CL:
777 - 1 210
Sex:
female
Dose descriptor:
LD50
Effect level:
859 mg/kg bw
Based on:
test mat.
95% CL:
742 - 993
Mortality:
- No mortality was observed in animals exposed to 518 or 622 mg/kg bw.
- 1 male and 1 female rat died exposed to 746 mg/kg bw, at 2 and 3 days after dosing, respectively.
- 2 male and 3 female rats died exposed to 896 mg/kg bw, within 2 and 3 days after dosing, respectively.
- All animals died exposed to 1075 mg/kg bw, the males within 3 days and the females within 2 days after dosing.
Clinical signs:
- Decrease in spontaneous motor activity, prone position, miosis, lacrimation and ptosis were observed in both sexes exposed to 518 mg/kg bw. In the male group chromodacryorrhea was additionally observed. The surviving male and female rats recovered from these toxic signs within 8 to 24 hours after dosing.
- Decrease in spontaneous motor activity, prone position, miosis, lacrimation and ptosis were observed in both sexes exposed to 622 mg/kg bw. Additionally lateral position and chromodacryorrhea in female group were observed. The surviving male and female rats recovered from these toxic signs till 8 to 24 hours after dosing.
- Decrease in spontaneous motor activity, lateral position, prone position, subnormal temperature, miosis, lacrimation, chromodacryorrhea and ptosis were observed in both sexes exposed to 746 mg/kg bw. Nasal discharge was additionally observed in the female group. The surviving male and female rats recovered from these toxic signs within 8 to 24 hours and 4 days after dosing, respectively.
- Decrease in spontaneous motor activity, lateral position, prone position, subnormal temperature, miosis, salivation, lacrimation, chromodacryorrhea and ptosis were observed in both sexes exposed to 896 mg/kg bw. Further, the toxic signs of nasal discharge in male group and of tarry stool in female group were observed. The surviving male and female rats recovered from these toxic signs within 3 days and 6 days after dosing, respectively.
- Decrease in spontaneous motor activity, prone position, subnormal temperature, miosis, salivation and ptosis were observed in both sexes exposed to 1075 mg/kg bw. Further, the toxic signs of edema in male group and of lateral position and nasal discharge in female group were observed.
Body weight:
All of the surviving animals showed an increase in body weight both 1 and 2 weeks after dosing.

Mean body weight (g) males:
- 518 mg/kg bw: 178, 242 and 308 at day 0, 7 and 14, respectively.
- 622 mg/kg bw: 176, 236 and 294 at day 0, 7 and 14, respectively.
- 746 mg/kg bw: 175, 236 and 294 at day 0, 7 and 14, respectively.
- 896 mg/kg bw: 173, 231 and 302 at day 0, 7 and 14, respectively.
- 1075 mg/kg bw: 176 at day 0.

Mean body weight (g) females:
- 518 mg/kg bw: 129, 162 and 186 at day 0, 7 and 14, respectively.
- 622 mg/kg bw: 129, 163 and 190 at day 0, 7 and 14, respectively.
- 746 mg/kg bw: 130, 157 and 187 at day 0, 7 and 14, respectively.
- 896 mg/kg bw: 130, 148 and 193 at day 0, 7 and 14, respectively.
- 1075 mg/kg bw: 129 at day 0.
Gross pathology:
- Necropsy of animals that died: Expansion of stomach, existence of black-brownish content in the gastric lumen, black zone in the glandular stomach, existence of black-brownish content in the small intestine, enlargement (bilateral) of the kidney, retention of dark-red urine in the urinary bladder and the existence of black-brownish content in the cecum were observed in both sexes. Moreover, the change to red in color of the small intestine and the red zone in the cecum in male rats and of dilated lumen in the small intestine in female rats were observed and only two male rats in 1075 mg/kg bw were observed edema in cervical subcutaneous tissue.
- Necropsy of surviving animals: No abnormalities observed.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
859 mg/kg bw
Quality of whole database:
GLP compliant, similar to guideline study, available as unpublished report, adequate for assessment

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

An acute oral toxicity test was performed similar to OECD 401 and in compliance with GLP. Five Sprague-Dawley rats per sex/dose were exposed to 518, 622, 746, 896, and 1075 mg/kg bw test substance by oral gavage. Following administation the animals were observed for 14 -days for mortality and clinical signs. After 14 days the animals were macroscopically examined. Substance related clinical signs were observed in all dose groups. No mortality was observed in animals exposed to 518 or 622 mg/kg bw. After dosing 746, 896, and 1075 mg/kg bw 2, 5, and 10 animals died, respectively. No abnormalities were observed after necropsy of the surviving animals. The necropsy of the animals that died showed expansion of stomach, existence of black-brownish content in the gastric lumen, black zone in the glandular stomach, existence of black-brownish content in the small intestine, enlargement (bilateral) of the kidney, retention of dark-red urine in the urinary bladder and the existence of black-brownish content in the cecum in both sexes. Under the conditions of this test, the acute oral LD50 was determined to be 859 mg/kg bw in females and 969 mg/kg bw in males.


Justification for selection of acute toxicity – oral endpoint
Only study available

Justification for classification or non-classification

Based on the available information for acute oral toxicity the substance is classified as Acute Tox. 4 (H302) in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.

Categories Display