4-tert-butylphenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1/02/91 - 6/03/91

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 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)

Remarks:

GLP compliance statement 19/03/91

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylphenol

EC Number:

202-679-0

EC Name:

4-tert-butylphenol

Cas Number:

98-54-4

Molecular formula:

C10H14O

IUPAC Name:

4-tert-butylphenol

Details on test material:

- Name of test material (as cited in study report): para-tertiary butylphenol, UCAR Butylphenol 4T-Flake (para tert-Butyl Phenol), PTBP.
- Physical state: White flakes.
- Analytical purity: Not reported.
- Lot/batch No.: Charge No. 496500; BRRC Sample No. 48-186.
- Expiration date of the lot/batch: Not reported.
- Stability under test conditions: Not reported.
- Storage condition of test material: Not reported.

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 weighd 135 - 145 g, and females 130 - 146 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 excepction of an overnight fast immediately before dosing and for approximately two hours after dosing, drinking wtare 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 male, 3 female
Main Study: 5 male, 5 female

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 male treated with 5000 mg/kg was found dead two days after treatment.
Main Study: There were no deaths.

Clinical signs:

other: Main Study: no signs of systematic toxicity

Gross pathology:

Main Study: all animals 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	HLPtSsA	X
	2-0 female	0	0	0	0	0	0	0	0	0
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

Keys:

H = hunched posture

L = lethargy

Pt = ptosis

Ss = red/brown stains around snout

A = ataxia

X = death

0 = no signs of systemic toxicity

Individual bodyweights and weekly bodyweight increase 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	135	182	236	47	54
	3 -1 Male	145	210	270	65	60
	3 -2 Male	136	190	248	54	58
	3 -3 Male	137	194	257	57	63
2000	3 -4 Male	140	208	276	68	68
	4 -0 Female	139	171	195	32	24
	4 -1 Female	146	182	220	36	38
	4 -2 Female	130	139	192	9	53
	4 -3 Female	138	175	192	37	17
	4 - 4 female	137	175	204	38	29

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material, BUP, 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.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material, BUP, 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 adpated 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 solution/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, BUP, 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.