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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: supportive evidence of corrosivity
Adequacy of study:
supporting study
Study period:
1997-05-15 to 1997-08-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
the doses differ from those of the current guideline
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, GERMANY
- Age at study initiation: 'young adults' (no further data given)
- Weight at study initiation: variation within 20% of mean (no further data given)
- Fasting period before study: 16 h
- Housing: 5 or fewer of the same sex/Makrolon type III cage
- Diet: ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: not clear

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.667 cm3/kg bw
Doses:
2000, 200, 25 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 3 males
200 mg/kg bw: 3 males and 3 females
25 mg/kg bw: 3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequent observations during treatment day, then daily until day 14. Body weights weekly.
- Necropsy of survivors performed: yes. Animals were killed on day 14 by CO2 inhalation and subjected to a macroscopic examination after opening the abdominal and thoracic cavities .
- Other examinations performed: clinical signs, body weight.
Statistics:
none

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD100
Effect level:
200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: death (or humane killing) of all animals of both sexes
Sex:
male/female
Dose descriptor:
LD0
Effect level:
25 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths in either sex
Mortality:
2000 mg/kg bw: 3/3 males died within 4h.
200 mg/kg bw: 1/3 male died on day 6. The remaining 2 males and 3 females were killed for humane reasons between days 6 and 8.
25 mg/kg bw: 0/3 males and 0/3 females died.
Clinical signs:
2000 mg/kg bw: severe clinical signs - abdominal position, heavy breathing, squatting, abnormal gait.
200 mg/kg bw: severe clinical signs of toxicity - squatting position, abnormal gait, sedation, salivation, piloerection, bodyweight loss and emaciation.
25 mg/kg bw: no evidence of systemic toxicity among males; females showed bodyweight loss and one was emaciated at day 14.
Body weight:
2000 mg/kg bw: no data as none survived past day 1
200 mg/kg bw: males - of the two animals surviving the first week, one showed severe loss of body weight. There were no further data - no males survived to the end of the 2nd week and no females survived to the end of the 1st week.
25 mg/kg bw: no clear treatment-related effect in males; in females 2/3 had moderate increase in body weight gain and 1/3 had body weight loss in week 2.
Gross pathology:
2000 mg/kg bw (3m): macroscopic examination showed severe inflammatory lesions particularly of the digestive system. In one male a fluid filled abdominal cavity and perforated gastric wall were observed. Severe necrosis of the liver and pancreas surfaces, congested spleen, and severe necrosis and haemorrhages of the mucosa were observed in all the animals.
200 mg/kg bw (3m, 3f): macroscopic examination showed severe lesions particularly of the digestive system. A severe fibrinous inflammation of the epithelial wall and gastritis were observed in one male. The other two males showed emaciated nutritional condition, bloody mouth and nose, perforation of the oesophagus and severe fibrinous inflammation of the adjacent tissues (lung), and not filled stomach and intestine. One female showed severe emaciation, perforation of the oesophagus and severe fibrinous inflammation of the adjacent tissues, not filled stomach and intestines, perforation of the gastric wall and ulcerative gastritis. In the other two females emaciation, inflammation of the oesophagus, not filled stimach and severe gastritis were observed.
25 mg/kg bw (3m, 3f): macroscopic examination showed mild lesions, predominantly of the stomach, in males, and severe lesions of the stomach and lung in one female, associated with emaciation. Multifocal thickening of the gastric wall was observed in all the male animals. Severe emaciation, bloody nose, severe reduction of the size of the tissues in the abdominal cavity, black-brown coloured liver with firm consistency, not filled stomach with yellowish mucus, haemorrhages in the small intestine and not filled caecum were observed in one female. No macroscopic abnormalities were noted in the rest of the females.

Other findings:
2000 + 200 mg/kg bw: Predominantly inflammatory lesions of the digestive system were noticed (perforation of the oesophagus or the stomach in association with severe fibrinous inflammation of the adjacent tissues)
25 mg/kg bw: Predominantly mild lesions in the stomach in males (multifocal thickening of the gastric wall). No macroscopic abnormalities in two females. One female showed severe lesions in the abdominal cavity.

Any other information on results incl. tables

Table 1: Number of animals dead or with evident toxicity

 Dose
(mg/kg bw)

Mortality (dead/total)

Time range of deaths or humane killing

Overt toxicity

Male

Female

Combined

Male

Female

2000

3/3

-

3/3

4 h

Abdominal position, heavy breathing, squatting, abnormal gait.

200

3/3

3/3

6/6

8 days

Squatting position, abnormal gait, sedation, salivation,piloerection,bodyweight loss and emaciation.

Severe signs of toxicity (presumably as for males at this dose)

25

0/3

0/3

0/6

-

No overt signs of toxicity

Reduced or absent body weight gains

 

Applicant's summary and conclusion