Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Jun. 1978 to Mar. 6, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
-comparable to OECD guideline; but very high vehicle volumes; synergistic effects between vehicle and test item possible
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar-AF/HAN-EMD-SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: 89 to 134 g (mean weight 108 g)
- Fasting period before study: Not reported
- Housing: Group housed in model III makrolon cages (in pairs or in groups of 3)
- Diet (e.g. ad libitum): Altromin Standard Diet TPF No. 1324, batch 1151 dated 01.06.78 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 27 ± 7
- Humidity (%): 52 ± 20
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5 and 10% solutions
- Amount of vehicle (if gavage): Not reported
- Justification for choice of vehicle: Not reported

MAXIMUM DOSE VOLUME APPLIED: 3.2 mL/100 g body weight

DOSAGE PREPARATION (if unusual): The test material was produced by making up to 5 or 10 g of the substance to 100 mL with peanut oil of DAB7-quality.

Doses:
0, 1250, 1400, 1600, 1800, 2000, 2500, and 3200 mg/kg body weight
No. of animals per sex per dose:
5/sex/dose group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All of the animals were weighed at regular intervals. They were weighed prior to administration of the substance and also at 1, 5, 7, 12, and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The behavior and general condition of all of the rats were observed closely during the 5-6 hours after the treatment and were then checked daily. With the exception of animals which died within 24 hours of the treatment, rats that died after this period were dissected and examined pathologico-anatomically. In the cases where dead animals had been savagely mutilated by other rats, the dissection was not carried out. All of the animals which survived were sacrificed, dissected and examined pathologico-anatomically at the end of the trial.
Statistics:
All statistical calculations were made using a modified test according to DUNNETT, C.W. (1955, 1964), and significant differences between the dose groups and the control group were expressed as a + in the case of p ≤ 0.05 and as ++ in the case of p ≤ 0.01. The calculations were made in the Scientific Data Processing Department of E. Merck, Darmstadt.

Results and discussion

Preliminary study:
No data.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 694 mg/kg bw
95% CL:
1 583 - 1 811
Mortality:
Mortality observations are provided in a table attached (Attached background material).
Clinical signs:
After oral administration of the substance, there were signs of toxicity about 5 minutes after the intubation.
Body weight:
Body weight measurements were not discussed by the author but mean and individual body weight measurements were provided in tables.
Gross pathology:
Animals which died:
Of the rats treated orally, the animals which died showed fatty liver infiltration and dilation of the bladder (starting at 1800 mg/kg) as well as mucous content of the intestine (starting at 2000 mg/kg).
Animals which were sacrificed:
The body organs were examined microscopically in all of the rats that were treated. There were no abnormal histopathological findings.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was found to be harmful by oral gavage.
LD50 (oral, rats) = 1694 mg/kg bw.
Executive summary:

In this guideline (OECD 401), the acute oral LD50 of the test material (EC 231 -272 -0) to rats was determined to be 1694 mg/kg bw. The test material was administered via gavage at doses of 1500, 2000, 2500, 3000, and 3500 mg/kg bw. The result of the test was sufficient to trigger classification and labelling of the test material for acute toxicity 4 (300 < ATE ≤ 2000) under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).