2,4-di-tert-butylphenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01/02/1991-07/03/1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study (OECD 401)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4-di-tert-butylphenol

EC Number:

202-532-0

EC Name:

2,4-di-tert-butylphenol

Cas Number:

96-76-4

Molecular formula:

C14H22O

IUPAC Name:

2,4-di-tert-butylphenol

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Manston, Kent, U.K.
- Age at study initiation: approximately five to eight weeks old
- Weight at study initiation: At the start of the main study the males weighed 141 - 167 g, and females 139 - 151 g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: the animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): with the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, food ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): with the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, drinking water ad libitum
- Acclimation period: after minimum acclimatisation period of at least five days the animals selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 42-55%
- Air changes (per hr): approximately 15 changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: range-finding study: 500, 200, 20 mg/ml. main study: 200 mg/ml
- Dose volume 10 ml/kg. The volume administered to each animal was calculated according to its fasted bodyweight at time of dosing.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A range-finding study was performed using pre-selected dose levels to determine the highest of these dose levels that caused no deaths

Doses:

Range-finding Study: 200, 2000 and 5000 mg/kg
Main Study: 2000 mg/kg

No. of animals per sex per dose:

Range-finding Study: 3
Main Study: 5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration:
Range-finding study: five days
Main study: 14 days
- Frequency of observations and weighing:
Range-finding study: 1/2, 1, 2, and 4 hours after dosing and then daily for five days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes.
Main study: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (Day 0) and on Days 7 and 14
- Necropsy of survivors performed:
Range-finding study: no
Main study: yes, macroscopic observation

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Range-finding study: the female treated with 5000 mg/kg was found dead three days after treatment

Main study: no deaths

Clinical signs:

other: Main study: no signs of systemic toxicity were noted during the study

Gross pathology:

Main study: no abnormalities were noted at necropsy (killed day 14)

Any other information on results incl. tables

Individual clinical observations and mortality data in the range finding study

Dose level Mg/kg	Animal number & sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		1/2	1	2	4	1	2	3	4	5
5000	1-0 male	0	0	0	0	0	0	0	0	0
	2-0 female	0	0	0	0	0	LA	X
2000	1-1 male	0	0	0	0	0	0	0	0	0
	2-1 female	0	0	0	0	0	0	0	0	0
200	1-2 male	0	0	0	0	0	0	0	0	0
	2-2 female	0	0	0	0	0	0	0	0	0

Key:

L = lethargy

A = ataxia

X = animal dead

0 = no signs of systemic toxicity

Individual bodyweights and weekly bodyweight increases in the main study

Dose Level	Animal Number	Bodyweight (g) at Day			Increment (g) During Week
mg/kg	& Sex	0	7	14	1	2
2000	3 -0 Male	141	198	250	57	52
	3 -1 Male	167	216	275	49	59
	3 -2 Male	152	224	293	72	69
	3 -3 Male	144	214	267	70	53
2000	3 -4 Male	143	206	272	63	66
	4 -0 Female	151	192	220	41	28
	4 -1 Female	142	188	214	46	26
	4 -2 Female	140	178	206	38	28
	4 -3 Female	139	172	199	33	27
	4 - 4 female	139	185	212	46	27

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, DTBP, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material, DTBP, in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 401 "Acute Oral Toxicity" referenced as Method B1 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in arachis oil B.P. at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study.

All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material, DTBP, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrases are required according to EEC labeling regulations.