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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24/09/1991- 8/10/1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
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

Constituent 1
Chemical structure
Reference substance name:
ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol
EC Number:
500-092-7
EC Name:
ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol
Cas Number:
36890-68-3
Molecular formula:
C6H10O2x.C4H8O3
IUPAC Name:
ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol
additive 1
Chemical structure
Reference substance name:
Glycerol
EC Number:
200-289-5
EC Name:
Glycerol
Cas Number:
56-81-5
Molecular formula:
C3H8O3
IUPAC Name:
glycerol
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
The test animals were obtained from Harlan/CPB, Zeist, Netherlands. Male rats weighed 175-200g and females weighed 150-175g at study initiation. The rats were housed in Macrolon cages with 2-3 animals per cage. Rats had free access to food except for a period of about 18 hours prior to dosing and 6 hours after dosing. Water was available ad libitum.

Environmental conditions included; Temperature: 21-22 °C, Humidity: 50-70%, Air changes: approximately 16 per hr, Photoperiod: artificial light from 7am till 7 pm and Radio-sound: 24 hours per day. At the end of the study, all rats were killed by ether inhalation

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: tragacanth
Details on oral exposure:
CAPA 304 was suspended in a 1.25% tragacanth solution in distilled water. The final concentration was 0.2 g/ml.
Doses:
Single dose of 2000 mg/kg
No. of animals per sex per dose:
5 animals/sex/ dose
Control animals:
no
Details on study design:
The duration of observation period following administration was 14 days. Rats were observed from 0-0.5 and at 1.5, 3 and 6 hours after application and thereafter on each day till the end of the experiment. Rats were weighed one day before dosing (day-1), at the day of dosing prior to dose administration (day 0) and at 2, 7 and 14 days after treatment. At the end of the study, all rats were killed by ether inhalation and an autopsy was performed which included the inspection of the external appearance, the cervical area, and the thoracic and abdominal cavities.
Statistics:
None required

Results and discussion

Preliminary study:
None performed
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities for the duration of the study
Clinical signs:
A slightly hunched posture and gait was observed in 4 out of 5 males and in all females between 30 and 90 minutes. No clinical signs were noticed 6 hours after dosing
Body weight:
Fasting on the day prior to dosing caused a small weight loss in all animals and there was a slight decrease in mean body weight gain between day 2 and 7 in female rats
Gross pathology:
With one exception of lungs with the appearance of emphysema observed in one female rat, no gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Any other information on results incl. tables

 

Table 1: Individual and mean body weights (g) of male and female rats given a single oral dose of CAPA 304

 

Sex

Dose (mg/kg)

Animal number

Day -1

Day 0

Day 2

Day 7

Day 14

Male

2000

1

199

184

206

228

254

2

199

184

206

210

223

3

197

186

217

242

280

4

189

185

207

196

219

5

187

187

215

235

268

Mean

196.2

185.2

210.2

222.2

248.8

Female

2000

1

165

155

169

161

172

2

151

143

156

151

161

3

171

158

173

179

188

4

157

146

159

154

161

5

165

151

169

179

191

Mean

161.8

150.6

165.2

164.8

174.6

 

 

 

Table 2 : Mean body weight gain (g) of groups of five male and female rats given a single oral dose of CAPA 304

 

Sex

Dose (mg/kg)

Day -1 to 2

Day 2 to 7

Day 7 to 14

Day -1 to 14

Male

2000

14.0

12.0

26.6

52.6

Female

2000

3.4

-0.4

9.8

12.8

 

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the conditions of this study, CAPA 304 was of low toxicity to rats. The LD50 values for male and female animals was greater than 2000 mg/kg/bw
Executive summary:

In this study ( method according to EEC – Directive 84-449, Annex V, Part B1 ) groups of 5 male and 5 female Wistar rats were given a single dose of CAPA 304 suspended in a 1.25% tragacanth solution in distilled water via a stomach tube (oral gavage). Animals were observed for 14 days following dosing, and all animal were examined macroscopically. Body weights were recorded one day before dosing (Day-1), at the day of dosing prior to dose administration (Day 0) and at 2, 7 and 14 days after treatment. No deaths were recorded for the duration of the study. Fasting on the day prior to dosing caused a small weight loss in all animals and there was a slight decrease in mean body weight gain between day 2 and 7 in female rats. With one exception of lungs with the appearance of emphysema observed in one female rat, no gross abnormalities were noted for any of the animals when necropsied. Clinical signs noticed only at the beginning of the study were; a slightly hunched posture and gait. The LD50 value for male and female animals was greater than 2000 mg/kg bw. Under the conditions of the study, CAPA 304 was of low toxicity in rats therefore classification according to Regulation (EC) No 1272/2008 is not required.

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