Di-sec-butylphenol, mixed isomers

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2/07/1992-28/07/1992

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:

1992

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:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Di-sec-butylphenol, mixed isomers

EC Number:

226-854-6

EC Name:

Di-sec-butylphenol, mixed isomers

Cas Number:

5510-99-6

Molecular formula:

C14H22O

IUPAC Name:

2,6-bis(butan-2-yl)phenol

Details on test material:

- Name of test material (as cited in study report): Phenol 2,6-bis(1-methylpropyl)
- Substance type: Di-alkylphenol
- Physical state: dark straw-coloured liquid
- Analytical purity: 98.7% GC
- Purity test date: 04/02/1992
- Lot/batch No.: 20204010
- Expiration date of the lot/batch:
- Storage condition of test material: room temperature

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 130 - 160 g, and females 121 - 138 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 excepction 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 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): 20-23°C
- Humidity (%): 54-75%. In occasions the relative humidity was outside the upper limit specified in the protocol (70%). This did not affect the purpose or integrity of the study.
- 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: 200, 20 mg/ml. main study: 20 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 to determine a dosing regime.

Doses:

Dose level Range-finding study: 2000, 200 mg/kg
Dose level Main study: 200 mg/kg

No. of animals per sex per dose:

Range-finding study: 1
Main study: 5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration:
Range-finding study: four 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 four 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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Mortality:

Range-finding study: animals treated with 2000mg/kg were found dead 4 hours after dosing
Main study: there were no deaths

Clinical signs:

other: Range-finding study: common signs of systemic toxicity noted were lethargy, loss of righting reflex, decreased and laboured respiration and ptosis with additional signs of ataxia, hunched posture and coma. Main study: common signs of systemic toxicity not

Gross pathology:

Main study: no abnormalities were noted at necropsy.

Any other information on results incl. tables

Keys to tables:

A = ataxia

Co = coma

H = hunched posture

L = lethargy

Pt = ptosis

Rd = decreased respiratory rate

Rl = laboured respiration

Rr = loss of righting reflex

X = animal dead

0 = no signs of systemic toxicity

Individual clinical observations and mortality data in the rage-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
2000	3-0 male	LRr RdPt	LRrPt RdRl	RlRd PtCo	X
	4-0 female	LRr RdPt	LRrPt RdRl	RdRl PtCo	X
200	3-1 male	0	0	0	H	H	0	0	0
	4-1 female	0	0	HA	HA	H	0	0	0

Individual clinical observations and mortality data in the main 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	6	7	8	9	10	11	12	13	14
200	5-0 M	0	0	HL	HL	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	5-1 M	0	0	L	L	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	5-2 M	0	0	L	L	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	5-3 M	0	0	HL	HL	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	5-4 M	0	0	L	HLA	HL	0	0	0	0	0	0	0	0	0	0	0	0	0
	6-0 F	0	0	HL	HLA	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	6-1 F	0	0	HL	HLA	HL	0	0	0	0	0	0	0	0	0	0	0	0	0
	6-2 F	0	0	HL	HLA	L	0	0	0	0	0	0	0	0	0	0	0	0	0
	6-3 F	0	0	HLA	HLA	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	6-4 F	0	0	HL	HLA	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Individual bodyweights and weekly bodyweight gain in the main study

Dose Level  mg/kg	Animal Number & Sex	Bodyweight (g) at Day			Bodyweight gain (g) During Week
		0	7	14	1	2
200	5 -0 Male	160	249	301	89	52
	5 -1 Male	145	239	295	94	56
	5 -2 Male	138	237	301	99	64
	5 -3 Male	130	205	255	75	50
	5 -4 Male	145	221	282	76	61
	6 -0 Female	128	197	229	69	32
	6 -1 Female	134	193	212	59	19
	6 -2 Female	138	192	218	54	26
	6 -3 Female	131	184	204	53	20
	6-4 Female	121	183	209	62	26

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information if swallowed Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material, phenol 2,6-bis(1-methylpropyl), in the Sprague-Dawley strain rat was found to be greater than 200 mg/kg bodyweight but less than 2000 mg/kg bodyweight. The symbol "Xn" and risk phrase R 22 "harmful if swallowed" are required according to EEC labelling regulations. As no significant toxicity occured at 200 mg/kg, an acute oral GHS cat. 4 is suggested (threshold 300 mg/kg bw).

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) 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 91/325/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 200 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

There were no deaths. Common signs of systemic toxicity noted were hunched posture and/or lethargy with additional signs of ataxia. Animals appeared normal one or two days after dosing.

All animals showed expected gain in body weight during the study.

No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material, phenol 2,6-bis(1-methylpropyl), in the Sprague-Dawley strain rat was found to be greater than 200 mg/kg bodyweight but less than 2000 mg/kg bodyweight. The symbol "Xn" and risk phrase R 22 "harmful if swallowed" are required according to EEC labelling regulations.