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Description of key information

An acute oral toxicity study in rats, conducted according to OECD Test Guideline 401, has been carried out using ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol. No data are available for acute dermal and inhalation toxicity. An acute dermal toxicity study is not required since the substance has been shown not to be acutely toxic by the oral route when dosed at the limit dose 2000 mg/kg bw. An acute inhalation toxicity study is not required due to the physicochemical properties of the substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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

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
Preliminary study:
None performed
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.

 

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

 

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study, 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 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,

ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol

was of low toxicity in rats therefore classification according to Regulation (EC) No 1272/2008 is not required.

Justification for classification or non-classification

ε- Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol was of low toxicity in rats in an acute oral toxicity study, therefore classification according to Regulation (EC) No 1272/2008 is not required. The acute dermal toxicity of the substance is expected to be low and testing via the inhalation route is not required on account of the physicochemical properties of the substance.