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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): TKA 40135 (CGI 819)
- Physical state: Pale yellow powder
- Lot/batch No.: 1031/2A
- Purity: 98.4 % (analytical certificate No. 960604/01)
- Expiration date of the lot/batch: November 1997
- Storage of test material: at 4°C in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd., Bicester, Oxon, England
- Age at study initiation: approximately four to seven weeks
- Weight at study initiation: approximately 103 to 121 g
- Fasting period before study: access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: in groups of up to five rats of the same sex in metal cages
- Diet (e.g. ad libitum): standard laboratory rodent diet (SDS LAD 1), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12hrs/12 hrs

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was formulated at a concentration of 20% w/v in distilled water and administered at a volume of 10 mL/kg bw.
The test substance was prepared on the day of dosing. As the test material was advised by the sponsor to be light sensitive, the test formulation was prepared under safelight and the formulation container kept wrapped with tin foil.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five animals per sex and group were used.
Control animals:
no
Details on study design:
MORTALITY AND CLINICAL SIGNS OF TOXICITY
The animals were checked at least twice daily for any mortalities. They were observed for clinical signs soon after dosing and at frequent
intervals for the remainder of day 1; on subsequent days animals were observed twice a day until ending of the observation period. The animals were observed for 14 days after dosing.

BODYWEIGHT
The bodyweight of each rat was recorded on days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

PATHOLOGY
The animals were sacrificed for the purpose of necropsy on day 15 by cervical dislocation. They were subjected to gross pathological examination.

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 mortalities were observed at the tested dose level of 2000 mg/kg bw.
Mortality:
All animals survived the single oral dosage with 2000 mg/kg bw of the test material.
Clinical signs:
Piloerection was observed in all rats within two minutes of dosing, persisting in all animals throughout day 2 of observation. There were no other clinical signs of toxicity. No more signs were seen from day 3 until the end of the observation period.
Body weight:
A slightly low bodyweight gain was recorded for one male on day 15. All remaining rats achieved satisfactory bodyweight gains throughout the study. For details, see tables below.
Gross pathology:
Necropsy was inconspicuous in all animals sacrificed on day 15.

Any other information on results incl. tables

Bodyweight changes:

Sex

Dose

Animal Number

Body weight (g) at

Day 1

Day 8

 Day 15

Males

2000 mg/kg bw

1

121

203

258

2

108

171

208

3

119

183

228

4

118

193

252

5

117

189

236

mean

117

188

236

Females

2000 mg/kg bw

6

104

142

162

7

118

170

200

8

104

148

176

9

103

146

168

10

118

172

195

mean

109

156

180

 

Body weight gains during the observation period:

Sex

Dose

Animal Number

Body weight gain (g) for

Week 1

Week 2

Males

2000 mg/kg bw

1

82

55

2

63

37

3

64

45

4

74

59

5

71

47

Females

2000 mg/kg bw

6

38

20

7

52

30

8

44

28

9

43

22

10

54

23

Applicant's summary and conclusion