SUMILIZER GP

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 Jun - 29 Oct 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

adopted in 1992

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

adopted in 2008

Deviations:

yes

Remarks:

environmental conditions for the animal housing: temperature was 24 ± 2 °C instead of 22 ± 3 °C

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-450-4

EC Name:

-

Cas Number:

203255-81-6

Molecular formula:

C42H61O4P

IUPAC Name:

6-(3-(3-tert-Butyl-4-hydroxy-5-methylphenyl)propoxy)-2,4,8,1 0-tetra-tert-butyldibenz(d,f)(1,3,2)dioxaphosphepin

Test animals

Species:

rat

Strain:

other: Crj:CD (SD) IGS

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc., Hino Breeding Center, Shiga, Japan
- Age at study initiation: 6 weeks
- Weight at study initiation: 202 - 227 g (males) and 156 - 174 g (females)
- Fasting period before study: 20 h before dosing and 4 h after dosing
- Housing: 2 - 3 animals of the same sex were placed in a suspended aluminium cage with wire-mesh floor (22.4 cm x 41.9 cm x 20.0 cm height)
- Diet: CRF-1 laboratory animal chows, sterilized by G0Co at 30 kGy, pellet type (Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 9 days
- Microbiological status when known : SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): more than 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 % aqueous solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Observation of clinical signs and mortality was carried out at 10 and 30 min, 1, 2 and 4 h after administration and once daily for 2 weeks thereafter.
- Frequency of weighing: Each animal was weighed on Days 0, 7 and 14 during the observation period.
- Necropsy of survivors performed: Yes, at the end of observation period, all animals were exsanguinated from the abdominal aorta under pentobarbital anesthesia, and were necropsied for gross pathological examination.

Statistics:

Analysis of variance in one way classifications was performed for mean body weight and mean body weight gain. With regard to the parameters in which a significant difference was found at the 5% level, the least significant difference (LSD) method was used as a test for significant difference compared with the control group.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Retention of white substance in the urinary bladder was observed in 2/5 males of the control group and in 1/5 males at 2000 mg/kg bw. Retention of fluid in the uterine horn were found in 2/5 females at 2000 mg/kg bw. The findings were considered to be not treatment-related.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified