Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 Apr - 02 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No information on purity was given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
No information on purity was given.
GLP compliance:
no
Remarks:
Basic documentation of quality assurance of experimental procedures and study report available, but not comparable to nowadays GLP provisions
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Remarks:
BOR: WISW (SPF TNO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 199.4 - 247.0 g (males), 150.0 - 187.2 g (females)
- Fasting period before study: food was withdrawn 16 h prior to and approx. 4 h after dosing.
- Housing: in groups of maximum 5 in Makrolon cages (Typ III), sawdust was used as bedding material
- Diet: Ssniff-R Alleindiät für Ratten (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 85
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
A range-finding study was carried out to establish a dosing regimen for the main study.

VEHICLE
- Concentration in vehicle: 25%

MAXIMUM DOSE VOLUME APPLIED: approx. 4 mL/kg bw
Doses:
Range-finding study: 1.0 and 2.5 mL/kg bw (corresponding to 1020 and 2550 mg/kg bw based on density of 1.02 g/cm³); 500 and 750 mg/kg bw
Main study: 250, 500, 750 and 1000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 2 females
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
Range-finding study:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed 20 min and 1, 2, 3, 6, 24 and 48 h after administration and subsequently once daily for 14 days.

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 20 min and 1, 2, 3, 6, 24 and 48 h after administration and subsequently once daily for 14 days. Individual body weights were determined on Days 0 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit Analysis according to Finney (1971) was used to calculate the orale LD50 values.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
620.42 mg/kg bw
Based on:
test mat.
Mortality:
Range-finding study: All animals died at approx. 1020 and 2550 mg/kg bw within 24 h after administration. No mortality occurred at 500 and 750 mg/kg bw.

Main study: At 250 mg/kg bw no mortality occurred during the study period. At 500 mg/kg bw three animals died within 3 days after administration. At 750 mg/kg bw five animals died within 6 days after administration. At 1000 mg/kg bw all animals died within 3 days after administration.
Clinical signs:
Main study: The test substance induced apathy, posture anomalies, ataxia, decreased excitability, piloerection, ptosis and dark red coloured urine. The symptoms occurred in surviving animals approx. 20 min post administration and continued with first increasing then decreasing intensity until 48 hours post administration. The surviving animals recovered completely whereas animals which died before study termination showed the symptoms with constant intensity until exitus.
Body weight:
At the end of the observation period all surviving animals showed the expected body weight gain.
Gross pathology:
Gross pathological examination of dead animals revealed partially severe gastrointestinal haemorrhages and one urinary bladder filled with bloody urin.
Post mortem examination of rats surviving until scheduled sacrifice on Day 14 revealed no abnormalities.

Any other information on results incl. tables

Table 1. Results of the acute toxicity study.

Group

Dose level (mg/kg bw)

Mortality

24 h

48 h

7 days

6/14 days

m

f

m

f

m

f

m

f

I

250

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

II

500

0/5

0/5

0/5

1/5

1/5

2/5

1/5

2/5

III

750

0/5

3/5

0/5

3/5

1/5

3/5

1/5

4/5

IV

1000

2/5

4/5

3/5

5/5

5/5

5/5

5/5

5/5

Applicant's summary and conclusion

Interpretation of results:
other: Acute Tox. Cat. 4 according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value of 620.42 mg/kg bw in male and female rats was calculated according to the method of Finney.