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: The study was carried out in compliance with the OECD Guideline for Testing of Chemicals No. 423 "Acute Oral Toxicity", 1996, and Directive 96/54/EEC, Part B.1 tris "Acute Toxicity - Oral Acute Toxic Class Method, 1996, with no deviations reported.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Swiss Federal Department of the Interior
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Triol
- Physical state: white solid
- Analytical purity: 99.5 % (LC), 99.8 % (DSC)
- Lot/batch No.: 6262/ZTN/03/N/08/001/003
- Expiration date of the lot/batch: 1 December 2000
- Stability under test conditions: not specified in polyethylene glycol
- Storage condition of test material: in refridgerator at 4 +/- 3 °C, protected from sunlight
- Other:

Test animals

Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Biotechnology & Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 227.3-229.5 g (males), 156-167.7 g (females)
- Fasting period before study: overnight prior to treatment
- Housing: groups of three in Makrolon type-4 cages with standard softwood bedding (Lignocel, Schill AG, Muttenz, Switzerland)
- Diet (e.g. ad libitum): pelleted standard Kliba 3433 (batch 43/99) (Provimi Kliba AG, Kaiseraugst, Switzerland) ad libitum
- Water (e.g. ad libitum): community tap water from Füllinsdorf ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg


Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
three males, three females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality/viability: ten minutes (females), one, two, three and five hours after treatment on test day 1, and twice daily during days 2-15; bodyweight: test day one (before treatment), 8 and 15; clinical signs: five times (females) and four times (males) on day one, once daily during days 2-15
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the study.
Clinical signs:
Dyspnea and weak activity were noted in one female within ten minutes and one hour after treatment. Slight ruffled fur and weak activity were observed in all female animals two hours after article administration. Slight ruffled fur was noted in all mal animals from 2 to 5 hours after treatment.
Body weight:
The bodyeight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Any other information on results incl. tables

Table 1: Bodyweights of the individual animals during the test (g).

Bodyweights in g

Sex/Dose

Animal no.

Day 1

Day 8

Day 15

Females

2000 mg/kg bw

1

156.0

173.9

189.3

2

161.5

180.2

193.5

3

167.7

195.5

210.8

Males

2000 mg/kg bw

4

229.4

261.2

283.9

5

227.3

276.0

300.2

6

229.5

264.8

300.7

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The median lethal dose of Triol after single oral administration to rats of both sexes, observed over a period of 14 days is: LD50 > 2000 mg/kg bodyweight.
Executive summary:

The acute oral toxicity of Triol to the rat was tested with the acute toxic class method according to the OECD Guideline No. 423 and Directive 96/54/EEC B.1 tris. Two groups, each using thre male or three female HanIbm: WIST (SPF) rats, were treated with Triol at 2000 mg/kg bodyweight by a single dose via oral gavage. The test article was suspended in polyethylene glycol (PEG 300) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg. The animals were examined for clinical signs four to five times during day 1 and once daily during test days 2 -15. Mortality/viability was recorded together with clinical signs at the same time intervals on test day 1 and then twice daily on test days 2 -15. Bodyweights were recorded on day 1 before administration and days 8 and 15. All animals were subjected to necropsy and examined macroscopically.

No deaths occurred during the study. Dyspnea and weak activity were noted in one female animal (no. 1) within ten minutes and one hour after treatment. Slight ruffled fur and weak activity were observed in all female animals two hours after test article administration. Slight ruffled fur was noted in all male animals from 2 to 5 hours after treatment.

The bodyweight of the animals was within the range commonly recorded for animals of this strain and age.

No macroscopic findings were observed at necropsy.

The median lethal dose of Triol after single oral administration to rats of both sexes, observed over a period of 14 days, is: LD50 > 2000 mg/kg bodyweight.