Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from November 28th, 1988 to December 12th, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guidelines for testing of chemicals (no 401)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
A 500g sample of the test substance was received from the sponsor on September 19, 1988. It was a white powder, designated AF-366"

Test animals

Species:
rat
Strain:
other: Wistar outbred (Bor:WISW)
Sex:
male/female
Details on test animals and environmental conditions:
Test animals
Mult, about 16 weeks old, albino rats were used. They ware Wistar outbred
rats (Bor:WISW) obtained from a colony, maintained under SPF—conditions at
the Breeding Centre for Laboratory Animals, F. Winkelmann GmbH, Borchen,
F.R. Gerinany. The body weights of the males varied from 308 to 354 g, those
of the females from 182 to 202 g. The animals ware kept under the
environmental conditions of the Institute’s animal house for about 13 weeks
prior to the test.
Housing and maintenance
The rats ware housed in groups of f ive, males and females separated, in
stainless steel cages with wire—screen bottom and front, in a room
ventilated with about 10 air changes per hour and maintained at 20—24°C.
Relative humidity was regulated between 40 and 70 per cent, lighting was
artificial by fluorescent tubes, time switch—controlled at a sequence of
12 hours light, 12 hours dark. Tap water was freely available at all times
by means of an automatic watering system. The rats had free access to the
Institute’s cereal—based, open—formula diet for rats and mice,
except in the overnight period before dosing tili 4 hours after dosing,
when food was withheld. The diet is analyzed regularly for nutrients and
contaminants. Tap water is analyzed regularly for
contaminants.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): 20 mL/kg bw
- Justification for choice of vehicle: maize oil was selected as it was shown to be an appropriate vehicle in a pre-test study

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
one single dose of 20.0 ml per kg body weight
This dose level is equal to 5000mg test substance per kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no

Results and discussion

Preliminary study:
A preliminary study was carried out to find an appropriate vehicle and the
general level of acute toxicity of the test substance.
After these preliminary observations, the substance was given by gavage as
a 25% (w/v) suspension in maize oil, in one single dose of 20.0 ml per kg
body to 5 males and 5 females. This dose level is equal to 5000 mg test
substance per kg body weight. 1f a dose level of 5000 mg/kg or more does
not cause compound—related mortality, then a full study with various dose
levels is not required (OECD—Guidelines for Testing of Chemicals).
The rats were observed frequently for signs of intoxication, during the
first 4 hours after treatment and thereafter, at least once daily
throughout an observation period of 14 days. The individual body weights of
the rats were recorded on day 0, 3, 7 and 14. At the end of the observation
period, the rats were killed and examined grossly.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured and all rats looked quite heathly throughout the remaining part of the 14-day observation period
Clinical signs:
Except signs of sluggishness and piloerection during the first few hours after treatment no signs of intoxication were observed
Body weight:
The individual body weights of the rats on day 3, 7 and 14 did not reflect treatment-related growth changes.
Gross pathology:
Macroscopic examination of the rats at the termination of the study
revealed a mottled surface of one of the kidneys in one male and one
female. No other treatment—related gross alterations were found.
At necropsy, 1/5 males and 1/5 females had a mottled surface of one kidney, which is not considered to be substance-related. No other gross abnormalities were observed.

Any other information on results incl. tables

Table 1: Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

5000

0/5/5

1-24 h 

-

0

Females

5000

0/5/5

1-24 h 

-

0

Overall LD50 > 5000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with systemic clinical signs         

 third number = number of animals used                               

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the mortality figures, the oral LD50 of “AF—366” was found to exceed
5000 mg per kg body weight, both for male and for female rats. Therefore,
the test substance can be classified as unharmful (EC—directive 83/467/EEC,
Official Journal of the European Communities, L 257, September 16, 1983).
Not classified.