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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987 followed, reliability scoring based on OECD Guideline 423.
Deviations:
yes
Remarks:
-Source of test substance not reported; animals not observed at least once during the first 30 minutes; no individual data for signs and symptoms
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1984
Deviations:
yes
Remarks:
-Source of test substance not reported; animals not observed at least once during the first 30 minutes; no individual data for signs and symptoms
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): GRILONIT RV 1806.
- Physical state: Liquid.
- Analytical purity: Technical commercial quality (excluded from Statement of Compliance).
- Lot/batch No.: DC 2106.2.
- Stability under test conditions: Test article is stable for at least 1 year; test article in dilution is stable for at least 2 hours.

Test animals

Species:
rat
Strain:
other: KFM-Han. Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: 9 weeks (males); 11 weeks (females).
- Weight at study initiation: 198 to 238 g (males); 167 to 199 g (females).
- Fasting period before study: 12 to 18 hours.
- Housing: Groups of 5 in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 25/88 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland), available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: At least 1 week under laboratory conditions, after veterinary examination.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3.
- Humidity (%): 40 to 70.
- Air changes (per hr): 10 to 15.
- Photoperiod (hrs dark / hrs light): 12 / 12.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 4% solution of carboxymethylcellulose sodium salt purum in distilled water.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4% solution of carboxymethylcellulose sodium salt purum in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 20 mL./kg body weight


DOSAGE PREPARATION (if unusual): The test article was placed into a glass beaker on a tared Mettler PK 300 balance, and the vehicle, was added. A weight by volume dilution was prepared using a homogenizer.
Doses:
600, 2000, and 5000 mg/kg body weight.
No. of animals per sex per dose:
5 per sex per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality/Viability: 4 times during test Day 1, and daily during Days 2 to 15.
Body weights: Test Days 1 (pre-administration), 8, and 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The animals were checked for the symptoms such as general behavior, respiration, eye, nose, motility, body posture, motor susceptibility, skin, etc.
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95, and 99% confidence limits for the toxicity for each sex and the slope of the dose response line were estimated.

Results and discussion

Preliminary study:
Not applicable.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 163 mg/kg bw
95% CL:
646.7 - 1 757
Remarks on result:
other: None
Sex:
male
Dose descriptor:
LD50
Effect level:
1 118 mg/kg bw
95% CL:
165 - 2 345
Remarks on result:
other: None
Sex:
female
Dose descriptor:
LD50
Effect level:
1 293 mg/kg bw
95% CL:
427 - 2 341
Remarks on result:
other: None
Mortality:
600 mg/kg body weight group: In males, 1 death on Day 2; no death in females.
2000 mg/kg body weight group: In males, 2 deaths at Hour 2, 1 death at Hour 3, and 1 death on Day 2; In females, 2 deaths at Hour 2, 2 deaths at Hour 3, and 1 death on Day 2.
5000 mg/kg body weight group: In males, 1 death at Hour 1, 1 death at Hour 2, 1 death at Hour 3, and 2 deaths at Hour 5; In females, 4 deaths at Hour 1, 1 death at Hour 2.
Clinical signs:
The following symptoms were observed:
600 mg/kg body weight: sedation, dyspnea, hunched posture, ruffled fur.
2000 mg/kg body weight: sedation, dyspnea, ataxia, ventral body position, hunched posture, spasms (males), diarrhea (males), ruffled fur.
5000 mg/kg body weight: sedation, coma, dyspnea, latero-abdominal position, hunched posture, spasms (males), ruffled fur.
See Attached File 1 for further details on signs and symptoms.
Body weight:
See Attached File 2 for body weight changes.
Gross pathology:
The following macroscopic organ changes were observed:
1) 600 mg/kg body weight group:
-Dead and sacrificed: no pathologic changes
2) 2000 mg/kg body weight group:
-Dead: lungs - not collapsed; no pathologic changes
-Sacrificed: no pathologic changes
3) 5000 mg/kg body weight group:
-Dead: lungs - not collapsed; no pathologic changes
Other findings:
No other information reported.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Harmful if swallowed Criteria used for interpretation of results: other: CLP (EC 1272/2008)