Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 18 to February 28, 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Necropsy of animals was not conducted. However, this deviation was not considered to have affected the scientific validity and interpretation of the results. No GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

(Necropsy of animals was not conducted. However, this deviation was not considered to have affected the scientific validity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4,6-tri-tert-butylphenol; 2,6-di-tert-butylphenol

EC Number:

907-745-9

Molecular formula:

Not applicable - Multiconstituent substance

IUPAC Name:

2,4,6-tri-tert-butylphenol; 2,6-di-tert-butylphenol

Details on test material:

- Physical state: Clear pale yellow liquid on receipt, but solidified on storage at 0-5 ºC.
- Storage condition of test material: On its arrival the test substance was stored in the dark at ambient temperature. Following receipt of further information, the storage conditions were changed on 13th September 1990 to in the dark at between 0-5 ºC.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Ltd.
- Age at study initiation: 9-11 weeks
- Weight at study initiation: males: 190-269 g; females: 128-161 g
- Fasting period before study: fasted overnight
- Housing: Single sex groups of up to three rats in cages with stainless steel wire-mesh walls, floors and tops (33 cm x 22 cm x 16 cm). Paper-lined trays for excreta were placed beneath each cage and changes three times weekly.
- Diet (e.g. ad libitum): Pelleted diet (LAD1, Special Diet Services Ltd.), ad libitum.
- Water (e.g. ad libitum): from the public supply, ad libitum.
- Acclimation period: The animals were quarantined for a minimum of four days in a non-barrier animal room with access restricted to essential personnel. At least five days before dosing the animals were rehoused.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 ºC
- Humidity (%): 30-70%
- Air changes (per hr): not documented.
- Photoperiod (hrs dark / hrs light): 12 hour day and 12 hour night


IN-LIFE DATES: From February 18 to February 28, 1991

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Animals were fasted overnight, weighed and given a single dose of the undiluted test material by gavage, using a ball pointed cannula and syringe.

Doses:

Animals were dosed at 1000, 1710, 2924 and 5000 mg/kg. The undiluted test material was administered at dose volumes of 1.06, 1.82, 3.11 and 5.32 ml/kg.

No. of animals per sex per dose:

Five animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A detailed clinical examination was made six times on the day of dosing and twice daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and changes in bodyweight calculated.
- Necropsy performed: no

Statistics:

The 14 day LD50, 95% confidence interval and the dose-mortality slope were calculated using a method based on probit analysis (Finney, 1977).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 976 mg/kg bw

Based on:

test mat.

95% CL:

2 667 - 3 551

Mortality:

Mortalities occurred on Days 2, 3 and 4 among rats dosed at 2924 and 5000 mg/kg. No rat survived treatment at the highest of these dose-levels.

Clinical signs:

other: The principal clinical signs observed among rats dosed with the test substance were piloerection, lachrymation, hunched posture, abasia/ataxia and/or prostration, diarrhoea, yellow staining of the anogenital fur and an unkempt appearance. There were addit

Any other information on results incl. tables

Table 7.2.1:      Summary of Acute Oral Toxicity

Males			Females
Dose	Mortality	Time of death	Dose	Mortality	Time of death
1000 mg/kg	0/5	--	1000 mg/kg	0/5	--
1710 mg/kg	0/5	--	1710 mg/kg	0/5	--
2924 mg/kg	1/5	Day 4	2924 mg/kg	3/5	Day 2
5000 mg/kg	5/5	Days 2-3	5000 mg/kg	5/5	Days 2 -3

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 for the test substance is 2976 mg/kg.

Executive summary:

Groups of five rats per sex were dosed at 1000, 1710, 2924 and 5000 mg/kg. A detailed clinical examination was made six times on the day of dosing and twice daily thereafter for the remainder of the 14 day observation period. The initial (Day 1), Day 8 and Day 15 bodyweights were recorded and changes in bodyweight calculated. Animals surviving to the end of the study were killed by carbon dioxide asphyxiation. Mortalities occurred on Days 2, 3 and 4 among rats dosed at 2924 and 5000 mg/kg. No rat survived treatment at the highest of these dose-levels. The acute oral LD50 for the test substance is 2976 mg/kg.