Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 MAR 2000 - 19 MAY 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
22 March 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Remarks:
HsdCpb:WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 6-8 weeks
- Weight at study initiation: mean 178 g (range from 157 to 200 g)
- Fasting period before study: Diet was withheld from about 17 hours before dosing up to 4 hours after treatment.
- Housing: The rats were housed in an air-conditioned room of about 10 m2 in the Institute of Toxicology. The rats were kept separately in Makrolon cages type III with a shelter, placed on mobile racks. They were kept generally on conventional softwood granulate as bedding. On day before treatment up to 24 hours after dosing, metal grids were placed above the softwood granulate. The cages and the metal grids had been machine-cleaned before the start of the experimental part. The bedding was changed two times a week.
- Diet (e.g. ad libitum): ad libitum, the diet (Altromin Standard Diät TPF®N 1324) is checked periodically according to the specifications of the manufacturer by an independent laboratory approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.
- Water (e.g. ad libitum): ad libitum, tap water from Makrolon drinking bottles
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 44-64
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 g/L
- Amount of vehicle (if gavage): 20 mL/kg
- Lot/batch no. (if required): ZDP 12/2000

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

DOSAGE PREPARATION (if unusual): The test material was freshly prepared prior to application. The test material was prepared with a vibrator and an Ultra-Turrax ®device.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after the administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
The body weight data were recorded with the PC-program „AKUDAT". The statistical evaluations of the body weight were carried out with the PC-program „TOX 511 A", 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 was calculated for each measurement and printed on tables.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
No signs of toxicity were detected in the 3 male and 3 female rats after treatment.
Body weight:
Body weight development of the treated rats was inconspicuous.
Gross pathology:
At necropsy, no organ alterations were seen.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations. According to the results of this study the LD50 value exceeds 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was determined in a limit test according to OECD 423 and following GLP. The test item 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 as vehicle. No signs of toxicity were detected in the 3 male and 3 female rats after treatment and no rat died. The gross pathological examination revealed no organ alterations. According to the results of this study the LD50 value exceeds 2000 mg/kg bw.