Registration Dossier

Diss Factsheets

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:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1987)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
FAT 92376/A
IUPAC Name:
FAT 92376/A
Details on test material:
- Name of test material (as cited in study report): FAT 92376/A
- Physical state: solid, white crystals
- Analytical purity: 98%
- Lot/batch No.: 10.26
- Storage condition of test material: room temperature
- Other:
Date of reanalysis: Dec 1996
Test material received: 11 Feb 1993

Test animals

Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: "young", no further data available
- Weight at study initiation: 174 - 211 g
- Fasting period before study: Before administration of dose animals were fasted overnight
- Housing: 5 per cage in Makrolon Type 4 cages
- Diet: NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % (w/v) hydroxypropyl-methylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
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: 14 days
- Frequency of observations and weighing:
Mortality: twice daily (am and pm) at week days; once (am) at weekends
Weighing: immediately before administration and on day 7 and 14
Signs and symptoms: daily
- Necropsy of survivors performed: yes
The animals were submitted to a gross necropsy at the end of the observation period.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
No mortalities occured in this study.
Clinical signs:
2000 mg/kg bw, males: piloerection was observed directly after administration until 5 days after administration (moderate at 3 and 5 h, slight at other time points). Hunched posture was observed in all animals until day 2 and dyspnea was observed until 1 day after administration.

2000 mg/kg bw, females: piloerection was observed directly after administration until 3 days after administration (moderate at 3 and 5 h, slight at other time points). Hunched posture was observed in all animals until day 2 and dyspnea was observed until 1 day after administration.
Body weight:
see table 1 ("Any other information on results incl. tables")
Gross pathology:
At necropsy, no deviations from normal morphology were found in all animals.

Any other information on results incl. tables

Table 1: Individual body weights of male and female rats at day 0, 7, and 14:

Animal number

Body weights (g)

 

 

 

Day 0

Day 7

Day 14

Males

 

 

 

1

201

271

303

2

211

269

320

3

202

271

296

4

210

260

286

5

209

265

301

Mean

207

267

301

SD

4.7

7.9

12.4

 

 

 

 

Females

 

 

 

1

174

206

218

2

176

210

223

3

198

216

218

4

191

227

251

5

192

209

238

Mean

186

214

230

SD

10.6

8.3

14.5

 

 

 

 

Applicant's summary and conclusion