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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 October 1998 to 11 November 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-isopropyl-9H-thioxanthen-9-one
EC Number:
226-827-9
EC Name:
2-isopropyl-9H-thioxanthen-9-one
Cas Number:
5495-84-1
Molecular formula:
C16H14OS
IUPAC Name:
2-isopropyl-9H-thioxanthen-9-one
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: yellow powder

Test animals

Species:
rat
Strain:
other: Crl:Han Wist(Glx:BRL)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Five to seven weeks old
- Weight at study initiation: 113 to 128 g (males) and 107 to 126 g (females)
- Fasting period before study: Overnight fasting prior to dosing which continued until approximately three hours after dosing
- Housing: Up to five rats of the same sex were accommodated in suspended stainless steel mesh cages (with minimum internal dimensions of 55 x 34 x 20 cm). The cages were suspended over cardboard lined trays for collection of excreta. The liners were replaced at least twice weekly.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 40 to 80 % RH
- Air changes: At least 14 air changes per hour
- Photoperiod: The rooms were illuminated by fluorescent strip-lights for twelve hours daily.


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle: 20 mL/kg
- Lot/batch no.: T71685
- Purity: 1 % Methyl cellulose

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg
Doses:
2 000 mg/kg
No. of animals per sex per dose:
Preliminary study: Two females at 2 000 mg/kg
Main study: Five animals per sex at 2 000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical signs: Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study, (the minimum schedule being at least once within half an hour of dosing and four times within the first four hours following administration, twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period). Individual records of clinical signs were maintained for each treated rat.
- Body weights: Rats were weighed on Day -1 ( day before dosing), on Day 1 and Day 8 and on Day 15 of the main study.
- All rats were killed by intraperitoneal injection of sodium pentobarbitone on Day 15. After exsanguination a full macroscopic necropsy was performed and any lesions recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosa} surfaces of the stomach, small and large intestines.

Results and discussion

Preliminary study:
A preliminary group of two female fasted rats was subjected to a single oral dose of the test material at 2000 mg/kg. There was no death and no overt clinical signs following treatment. Necropsy on Day 8 revealed no macroscopic changes.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died following a single oral administration of the test material at 2 000 mg/kg.
Clinical signs:
No clinical signs of reaction to treatment were seen during the observation period.
Body weight:
All rats gained weight during the first and second weeks of the observation period.
Gross pathology:
No macroscopic changes were observed at necropsy on Day 15.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the oral LD50 value was established to exceed 2 000 mg/kg body weight.
Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1 under GLP conditions.

The test material was formulated in 1 % methyl cellulose at the limit dose of 2 000 mg/kg. The test formulation was kept stirring during dosing.

A preliminary group of two female fasted rats was subjected to a single oral dose of the test material at 2 000 mg/kg. There was no death and no overt clinical signs following treatment. Necropsy on Day 8 revealed no macroscopic changes. Five male and five females were then subjected to the same limit dose and observed for a period of 14 days.

No animal died following a single oral administration of the test material at 2 000 mg/kg. No clinical signs of reaction to treatment were seen during the observation period. All rats gained weight during the first and second weeks of the observation period and no macroscopic changes were observed at necropsy on Day 15.

Under the conditions of this study, the oral LD50 value was established to exceed 2 000 mg/kg body weight.