Propanoic acid, 2-[4-[4,6-bis([1,1'-biphenyl]-4-yl)-1,3,5-triazin-2-yl]-3-hydroxyphenoxy]-, isooctyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-Oct-2002 to 13-Nov-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD test guideline 423)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adoted on 22th March 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

444-090-3

EC Name:

-

Cas Number:

204848-45-3

Molecular formula:

C44 H43 N3 O4

IUPAC Name:

Propanoic acid, 2-[4-[4,6-bis([1,1'-biphenyl]-4-yl)-1,3,5-triazin-2-yl]-3-hydroxyphenoxy]-, isooctyl ester

Test animals

Species:

rat

Strain:

other: Crl;CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Manston Road, Margate, Kent, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 95-123 g
- Fasting period before study: overnight prior to dosing until 4 hours after dosing
- Housing:
Rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of three rats of the same sex in metal cages with wire mesh floors
- Diet:
A standard laboratory rodent diet (Special Diet Services RMl(E) SQC expanded pellet) was provided ad libitum. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 40-70%
- Photoperiod: 12 hours dark/ 12 hours light

IN-LIFE DATES: From: 24-Oct-2002 to: 11-Nov-2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1 % (w/v) aqueous methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 1% (w/v) in water at a dose volume of 10 mL/kg bodyweight

Doses:

One single dose of 2000 mg/kg bw

No. of animals per sex per dose:

6 animals (3 males and 3 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days. The day of dosing was designated Day 1.
- Frequency of observations and weighing:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing. The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes. All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Statistics:

Individual weekly bodyweight changes and group mean bodyweights were calculated.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral gavage dose to a group of six rats (three males and three females) at a dose level of 2000 mg/kg.

Clinical signs:

Clinical signs of reaction to treatment were confined to piloerection observed in all females on Day 2, resolving completely by Day 3. No clinical signs were observed in the males during the study.

Body weight:

All animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

No abnormalities were revealed at the macroscopic examination.

Other findings:

No other findings were noted.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal oral dose of the test substance to rats was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

A GLP-compliant acute oral toxicity study according to OECD TG 423 was performed to determine the acute lethal dose of the test substance after oral administration. A group of three fasted male and female rats respectively received a single oral gavage dose of the test substance, formulated in 1 % w/v aqueous methylcellulose, at a dose level of 2000 mg/kg bodyweight. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. There were no deaths throughout the duration of the study. Clinical signs of reaction to treatment were confined to piloerection observed in all females on Day 2, resolving completely by Day 3. No clinical signs were observed in the males during the study. All animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. As result, the acute lethal oral dose of the test substance was demonstrated to be greater than 2000 mg/kg bodyweight in rats.