Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

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
Type:
Constituent
Test material form:
other: solid, not further specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium
- Age at study initiation: 9-10 weeks
- Weight at study initiation: males 326-352 g, females 206-238 g
- Fasting period before study: yes, feed was withheld twice; once overnight before first dosing until approximately 3-3.5 hours after administration and a second time 10-11 hours overnight before the second dosing until approximately 4 hours after administration of the test substance. Between the two fasting periods there was a 3-hour feeding period.
- Housing: Individually in polycarbonate cages; Bedding material (purified sawdust, Woody Clean, was recceived from the Broekman Institute, Someren, The Netherlands).
- Diet (e.g. ad libitum): Standard laboratory animal diet (RMH-B, pellet diameter 10 mm), which was obtained from Hope Farms, Woerden, The Netherlands, ad libitum.
- Water (e.g. ad libitum): Tap water, ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 50-95
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 160 mg/mL
- Amount of vehicle (if gavage): 7.5 mL
- Justification for choice of vehicle: very low water solubility of test substance

MAXIMUM DOSE VOLUME APPLIED: 2 times 7.5 mL/kg within 24 hours

DOSAGE PREPARATION (if unusual):
The test substance was heated to melting point (approximately 60 °C) and suspended in corn oil (maydis oleum, ACF, Maarssen, The Netherlands). Prior to dosing the suspension was heated to approximately 65 °C and was transferred to a glass syringe; subsequently the syringe was cooled under running cold tap-water and the suspension was administered using a stainless steel cannula.
Doses:
2400 mg/kg bw (twice 1200 mg/kg bw : maximum dose feasible for oral administraion)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cage side observations on the day of dosing (approx. once every 2 hours) and daily thereafter. With exception of weekends and holidays a mortality check was performed at the end of the day. Individual body weights (with group means and standard deviation) were measured weekly.
- Necropsy of survivors performed: yes, at the end of the study (Day 14) all surviving animals were sacrificed by CO2-asphyxiation and subjected to autopsy.
- Other examinations performed: clinical signs, body weight
Statistics:
Body weight group means with standard deviations.

Results and discussion

Preliminary study:
In order to establish an appropriate dose range six groups of Wistar rats, each comprising 1 male and 1 female, were dosed with an oral dose of the test substance at 2400, 1800, 1000, 560, 320 and 180 mg/kg bw, respectively. No mortalities occurred and no signs of systemic toxicity were observed during the 7-day observation period.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 400 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 400 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity were observed during the 14-day observation period with exception of Day 1 when lethargy was frequently observed. There was no evident sex-related effect.
Body weight:
Weekly group mean body weight gain was normal. There was no evident sex-related effect.
Gross pathology:
There were no test substance-related gross abnormalitites.

Applicant's summary and conclusion