Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 September to 8 October 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:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): CAPA 3050
- Substance type: Oligomer
- Physical state: Liquid
- Analytical purity: 100%
- Lot/batch No.: WCB000999
- Expiration date of the lot/batch: 23th August 2015
- Stability under test conditions: Stable for the duration of the study
- Storage condition of test material: Ambient

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female SPF-derived Hsd/Cpb:WU Wistar rats, obtained from Harlan/CPC, The Netherlands. Male rats wereighed 175-200 g, and females weighed 150-175 g, on arrival. The rats were acclimatised for 5 days.The rats were housed in Macrolon cages in groups of 2 or 3. Standard laboratory diet (RHM-TM, Hope Farms, The Netherlands) was provided ad libitum, except for ca. 18.5 hours prior to dosing until 6 hours after dosing. Water was available ad libitum. The animal room was maintained at a temperature of 21-22°C, and a relative humidity of 50-70%. Artifical light was provided for 12 hours per day, and radio sound was provided for 24 hours per day. There were approximately 16 air changes per hour.Individuals were identified by dye markings on the fur.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1.25% tragacanth solution in distilled water
Details on oral exposure:
CAPA 305 was suspended in a 1.25% tragacanth solution in distilled water. The final concentration was 0.2 g/ml. Aliquots of the suspension with a volume of 10 ml/kg body weight were taken, equivalent to 2000 mg/kg, and were administered by stomach tube to fasted rats.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five males and five females
Control animals:
no
Details on study design:
The rats were observed immediately after dosing, and at 1.5, 3, 6 and 26 hours after application and thereafter on each day for 14 days.The rats were weighed on the day before dosing, at the day of dosing prior to dose administration, and at 2, 7 and 14 days after dosing.At the end of the observation period, the rats were sacrificed by ether inhalation and gross necropsy was performed.
Statistics:
A statistical analysis was not required.

Results and discussion

Preliminary study:
A preliminary study was not reported.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality at the limit dose
Mortality:
No mortalities occurred during the 14 day observation period.
Clinical signs:
A slightly hunched posture and gait were observed in 4 out of 5 males and all females between 1.5 and 3 hours after dosing. Signs had completely disappeared by 26 hours after dosing.
Body weight:
Fasting on the day prior to dosing caused a small weight loss in all rats. There was a slight decrease of mean body weight-gain over the 14 day observation period in all rats. A reduced weight gain (males) or a small body weight loss (females) was noticed from day 2 to 7 after dosing. Normal body weight-gains for both males and females were observed during the second week of the observation period.
Gross pathology:
One male rat had a slightly swollen liver. One female showed a dilated uterus, and in another female the lungs were noted to have the appearance of emphysema. No other abnormalities were noted.
Other findings:
No other findings reported.

Any other information on results incl. tables

Dilation of the uterus is considered to be a normal physiological process within the oestrus cycle, and was not thought to be related to treatment. The authors suggested that the emphysema could be a consequence of a slight misdosing, or a compound-related effect.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The 14 -day acute oral LD50 of CAPA 305 in rats was found to be >2000 mg/kg bw
Executive summary:

The acute oral toxicity of CAPA 3050 was assessed in 5 male and 5 female Wistar rats. A single oral dose of 2000 mg/kg of CAPA 305, suspended in a 1.25% tragacanth solution in distilled water, was administered via gavage. There were no mortalities during the 14 -day observation period. The only clinical signs noted were abnormal gait and posture, all signs had disappeared within 26 hours of dosing. Reduced weight gain (males) or a small body weight loss was noticed from Day 2 to 7 after dosing; normal body weight gains were observed during the second week of the observation period. Autopsy of the rats at the end of the observation period did not reveal macroscopic abnormalities that were considered treatment-related, with the possible exception of lungs with the appearance of emphysema observed in 1 female rat. Acute oral LD50 of CAPA 305 in rats was therefore found to be > 2000 mg/kg bw under the conditions of this study.