Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04-18 april 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
a minor deviation (relative humidity recorded in the animal room was sometimes outside of range specified in the protocol), not considered to have compromised the validity or integrity od the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories (69210 L'Arbresle, France)
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: 166 ± 5 g (males) and 142 ± 12 g (females)
- Fasting period before study: yes, an overnight period af approximately 18 hours before dosing (but free access to water)
- Housing: in polycarbonate cages
- Diet (e.g. ad libitum): free access to A04C pelleted diet (UAR, Villemoisson Epinay sur orge, France)
- Water (e.g. ad libitum): filtered water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2°c
- Humidity (%):30 to 70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methylcellulose
Details on oral exposure:
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 5 ml glass syringe (0.05 ml graduations).
The volume adminitered to each animal was adjusted according to body weight determined on the day of treatment (Volume administered: 10 ml/kg).
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males + 5 females per group
Control animals:
no
Details on study design:
- Clinical signs: examined frequently during the hours following administration of the test substance and then at least once a day until the end of experiment
- Mortality: recorded at least twice a day
- Body weight: measured just before administration then on days 8 and 15. The body weight gain of the treated animals was compared to that of CIT control animals with similar initial body weight.
- Necropsy:
. macroscopic examination of the main organs: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities.
. microscopic examination: no
Statistics:
no data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: only one female died
Mortality:
1 female died on day 1, with 30 minutes following treatment. No clinical signs were observed prior to death.
Clinical signs:
No clinical signs occurred in treated animal.
Body weight:
The bodyweight gain of the surviving animals was similar to that of CIT historical control animals (see tables).
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Any other information on results incl. tables

Table 1: Individual and mean body weight and weekly body weight change (g)

Dose (mg/kg)

Volume (mL/kg)

Sex

Animals

Days

 

1

(1)

8

(1)

15

2000

10

male

01

168

72

240

54

294

02

167

72

239

57

296

03

157

81

238

60

298

04

167

79

246

58

304

05

171

95

266

71

337

M

166

80

246

60

306

SD

5

9

12

7

18

2000

10

female

06

134

33

167

31

198

07

144

41

185

29

214

08

140

-

-

-

-

09

160

52

212

47

259

10

130

35

165

19

184

M

142

40

182

32

214

SD

12

9

22

12

33

(1): body weight gain

M= mean; SD = standard deviation

-: animal found dead during the study

 

Table 2: Mean body weight of control rats (g)

Dose (mg/kg)

Volume (mL/kg)

Sex

days

 

1

8

15

0

10

male

M

178

253

300

SD

12

19

24

n

35

35

35

0

10

female

M

141

184

208

SD

10

14

18

n

35

35

35

M= mean; SD = standard deviation; n = number of animals

 

Table 3: Mean body weight change of control rats (g)

Dose (mg/kg)

Volume (mL/kg)

Sex

days

 

1 to 8

8 to 15

0

10

male

M

75

47

SD

12

11

n

35

35

0

10

female

M

43

23

SD

10

6

n

35

35

M= mean; SD = standard deviation; n = number of animals

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under these experimental conditions, the oral LD50 of CDBC is higher than 2000 mg/kg bw in rat.
Executive summary:

The acute oral toxicity of the test substance CDBC was evaluated in rats according to OECD (401) and EC guidelines, and in compliance of GLP. The test substance was administered by oral route (gavage) to one group of ten fasted rats (5 males and 5 females). The test substance was prepared in 0.5 % methylcellulose and was administered to the animals at the dose of 2000 mg/kg, under a volume of 10 ml/kg. Clinical signs, mortality and bodyweight gain were checked for a period of up to 14 days following the single administration of the test substance. All animals were subjected to necropsy.

one female died on day 1, within 30 minutes following treatment. No clinical signs were observed prior to death. No clinical signs and no deaths occurred in the other treatment animals. The body weight gain of the surviving animals was similar to that of historical control animals. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the oral LD50 of CDBC is higher than 2000 mg/kg bw in rat.