Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 January 1997 - 29 January 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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 401 (Acute Oral Toxicity)
Version / remarks:
February 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
other: HsdCpb:WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: about 7 and 8 weeks
- Weight at study initiation: 151 - 159 g (females), 178 - 189 f (males)
- Fasting period before study: Food was withheld from about 17 hours before dosing up to 4 hours after treatment.
- Housing: separately in Makrolon cages type III (floor area: 37.5 x 21cm = 787.5 cm2, height: 15 cm)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22
- Humidity (%): 31 to 66 (The relative atmospheric humidity in the animal room were transiently outside the target range of 45 to 75%. This minor and short deviations did not influence the integrity of the study.)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous Methocel K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 mg/mL


MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: All rats were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the inlife-phase. The behaviour and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The body weight data and the clinical findings were processed by means of a PC - pro gram, developed by the Institute of Toxicology of Merck KGaA, Darmstadt. The body weight development of each rat and group was determined. The group mean value and the difference to the initial value, expressed as percentage, were calculated for each measurement and printed out on tables.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All the rats survived the observation period.
Clinical signs:
No signs of intoxication occurred after treatment.
Body weight:
Body weight development of the treated rats was normal.
Gross pathology:
At necropsy, no organ alterations were seen.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item was determined to be greater than 2000 mg/kg bw in rats after oral administration.
Executive summary:

The test material was tested for acute toxicity in rats after oral administration of 2000 mg/kg body weight. Directly before the administration the test material was prepared with aqueous Methocel K4M Premium solution.

No signs of intoxication were detected after treatment and no rat died. Thus, the study was performed as limit test. The gross pathological examination revealed no organ alterations. For regulatory purposes, the median lethal dose (LD50), after an observation period of 15 days can be declared as > 2000 mg/kg.