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

Acute Toxicity: oral

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

Test material information

Constituent 1

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:

2-oxepanone, polymer with 2,2'-oxybis[ethanol]

additive 1

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:

other: 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

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.