6,6'-di-tert-butyl-4,4'-butylidenedi-m-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

14 January 1997 to 06 March 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with OECD & EU test guidelines in compliance with GLP and reported with a valid GLP certificate.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

125643-61-0

Cas Number:

125643-61-0

IUPAC Name:

125643-61-0

Constituent 2

Reference substance name:

NAUGALUBE 531

IUPAC Name:

NAUGALUBE 531

Test material form:

liquid: viscous

Details on test material:

Sponsor's identification: NAUGALUBE 531
Date received: 17 December 1996
Description: dark straw coloured viscous liquid
Storage conditions: ambient temperature (< 25°C), stored under artificial light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley CD (Crl:CD BR) strain rats supplied by Charles River (UK) Ltd., Margate, Kent, UK. were used. At the start of the main study the males weighed 230 to 251g, and the females 203 to 2298, and were eight to twelve weeks of age. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 20 to 21 °C and relative humidity of 46 to 55%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Range finding study: 1 male & 1 female
Main study: 5 males & 5 females

Control animals:

no

Details on study design:

Range-finding Study: A range-finding study was performed to establish a dosing regime as follows: IN TABLE FORM ATTACHED UNDER Any other information.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed

Main Study: Based on the results of the range-finding study a further group of animals was treated as follows: IN TABLE FORM - ATTACHED UNDER Any other information.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:

Range-finding Study: There were no deaths or clinical signs of toxicity.
Based on this information, a dose level of 2000 mg/l

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

TABLE 2: INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN THE MAIN STUDY

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	3-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-4 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	4-4 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = no signs of systemic toxicity

 

TABLE 3: INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT CHANGES IN THE MAIN STUDY

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	3-0 Male	230	301	348	71	47
	3-1 Male	251	300	3378	49	37
	3-2 Male	239	304	351	65	47
	3-3 Male	232	308	374	76	66
	3-4 Male	233	306	362	73	56
	4-0 Female	219	242	269	23	27
	4-1 Female	211	240	266	29	26
	4-2 Female	205	228	242	23	14
	4-3 Female	203	232	250	29	18
	4-4 Female	229	250	269	21	19

 

TABLE 4: INDIVIDUAL NECROPSY FINDINGS IN THE MAIN STUDY

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	3-0 Male	Killed Day 14	No abnormalities detected
	3-1 Male	Killed Day 14	No abnormalities detected
	3-2 Male	Killed Day 14	No abnormalities detected
	3-3 Male	Killed Day 14	No abnormalities detected
	3-4 Male	Killed Day 14	No abnormalities detected
	4-0 Female	Killed Day 14	No abnormalities detected
	4-1 Female	Killed Day 14	No abnormalities detected
	4-2 Female	Killed Day 14	No abnormalities detected
	4-3 Female	Killed Day 14	No abnormalities detected
	4-4 Female	Killed Day 14	No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material, NAUGALUBE 531, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

Astudy was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of CouncilDirective 67/548/EEC). The study was performed in compliance with the Principles of Good Laboratory Practice (GLP) and reported with a valid GLP certificate.

 

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 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

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

 

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

 

All animals showed an expected gain in bodyweight during the study.

 

No abnormalities were noted at necropsy.

 

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