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Administrative data

Description of key information

Acute toxicity oral: LD50 > 5000 mg/kg bodyweight (OECD 401)

Acute toxicity dermal: LD50 > 5000 mg/kg bodyweight (non-guideline)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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:
other: Guideline study (OECD 401)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
-
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., 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 148 - 154 g, and females 133 - 153 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 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
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: 500 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: dose level 5000, 2000 and 200 mg/kg
Main study: dose level 5000 mg/kg
No. of animals per sex per dose:
Range-finding study: 1 male, 1 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Range-finding study: deaths and overt signs of toxicity were recorded 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 body weight.
Main study: deaths and overt signs of toxicity were recorded 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 or at death.
- Necropsy of survivors performed:
Range-finding study: no necropsies were performed
Main study: yes, macroscopic observation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
Range-finding study: no deaths
Main study: 2 animals (1 male and 1 female) were killed in extremis one day after treatment
Clinical signs:
Range-finding study: clinical signs of toxicity noted were hunched posture, occasional body tremors, ataxia, lethargy and ptosis.
Main study: common signs of systemic toxicity noted were hunched posture, lethargy, ataxia, and occasional body tremors. Additional signs were laboured respiration, loss of right reflex and ptosis.
Body weight:
Main study: surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
Main study: Abnormalities noted at necropsy of animals killed in extremis during the study were abnormally red lungs, patchy pallor in the liver, dark kidneys, haemorrhage of the gastric mucosa and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals killed at the end of the study (day 14).

Keys to tables:

H = hunched posture

To = occasional body tremors

L = lethargy

A = ataxia

Pt = ptosis

Rr = loss of righting reflex

X = animal killed in extremis on day 1

0 = no signs of systemic toxicity

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

HToA

HToA

HLToPtA

H

0

0

0

0

2-0 female

0

HToA

HToA

HLToA

0

0

0

0

0

2000

1-1 male

0

HToA

HToA

LToPtA

H

0

0

0

0

2-1 female

0

HToA

HToA

HToPtA

0

0

0

0

0

200

1-2 male

0

H

H

H

0

0

0

0

0

2-2 female

0

H

H

H

0

0

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

5000

3-0 M

0

0

0

ToAL

LToRlRrPt

HL

0

0

0

0

0

0

0

0

0

0

0

0

3-1 M

0

0

0

ToAL

HLPtToRlRrX

 

 

 

 

 

 

 

 

 

 

 

 

 

3-2 M

0

0

0

ToAL

HTo

HL

0

0

0

0

0

0

0

0

0

0

0

0

3-3 M

0

0

0

ToAL

HToARl

HL

0

0

0

0

0

0

0

0

0

0

0

0

3-4 M

0

0

0

ToAL

HToA

HL

0

0

0

0

0

0

0

0

0

0

0

0

4-0 F

0

0

0

HLToA

HA

HL

0

0

0

0

0

0

0

0

0

0

0

0

4-1 F

0

0

0

HLToA

HA

HL

0

0

0

0

0

0

0

0

0

0

0

0

4-2 F

0

0

0

HLToA

ToPtHLA

HL

0

0

0

0

0

0

0

0

0

0

0

0

4-3 F

0

0

0

HLToA

HToA

HL

0

0

0

0

0

0

0

0

0

0

0

0

4-4 F

0

0

0

HLToA

HLRlRrToPtX

 

 

 

 

 

 

 

 

 

 

 

 

 

Individual bodyweights and weekly bodyweight increases in the main study

 Dose Level

 mg/kg

 Animal Number

& Sex

   Bodyweight (g) at Day

       Increment (g) During Week

0

7

14  

At

Death 

2

5000

 

 

 

 

 

 

 

 

 3 -0 Male

149

213

290

 

64

77

 3 -1 Male

152

- -

121

-

 3 -2 Male

148

210

289 

 

62

79 

 3 -3 Male

152

218

288 

 

66

70

 3 -4 Male

154

225

289 

 

71

64 

 4 -0 Female

145

167

197 

 

22

30

 4 -1 Female

153

195

221 

 

42

26 

 4 -2 Female

133

177 

228

 

44

51 

 4 -3 Female

145

178

210 

 

33

32 

4-4 Female

151

-

-

129

-

-

- = animal dead

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material, DTBH, in the Sprague-dawley strain rat was found to be greater than 5000 mg/kg bodyweight. No symbol and risk phrase are required according to EEC labelling regulations.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material, DTBH, 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 dose of test material, as a solution/suspension in arachis oil B.P. at a dose level of 5000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were killed for gross pathological examination.

Two animals (one male and one female) were killed in extremis one day after treatment. common signs of systemic toxicity noted were hunched posture, lethargy, ataxia and occasional body tremors with additional signs of laboured respiration, loss of righting reflex and ptosis. Surviving animals appeared normal three days after treatment.

Surviving animals showed expected gain in bodyweight during the study.

Abnormalities noted at necropsy of animals killed in extremis during study were abnormally red lungs, patchy pallor of the liver, dark kidneys, haemorrhage of the gastric mucosa and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals killed at the end of the study.

The acute oral median lethal dose (LD50) of the test material in the Sprague-dawley strain rat was found to be greater than 5000 mg/kg bodyweight. No symbol and risk phrase are required according to EEC labelling regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Reliable

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline available
Principles of method if other than guideline:
0.5 ml per kg 2,6-di-tert-butylphenol were applied to the skin of rabbits and direct contact maintained for 24h.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
0.5 ml per kg
No. of animals per sex per dose:
10 rabbits (sex unknown)
Control animals:
no
Details on study design:
New Zealand rabbits ranging from 1.7 to 2.7 kg in body weight were used in these experiments. In preparation for the application of either of the compounds upon the skin of these animals, the hair was clipped as closely as possible from all areas of the trunk extending from the hips to the shoulders. A rubber sleeve, applied around the trunk in such manner as to fit snugly at its anterior and posterior edges but loosely in the intermediate area, covered the shorn skin of each rabbit. A measured amount of the specified compound was introduced beneath the sleeve and distributed in contact with as large an area of the bare skin as the dose would cover. The rubber sleeve was then covered completely with adhesive tape, and the animal was returned to its cage. After 24 hours had passed the sleeve was removed, and the skin was wiped as clean as possible with a dry towel.
Each of 10 rabbits was subjected in the manner described above, to contact of the skin with 2,6-di-tertiary butyl phenol in the dosage of 0.5 ml per kilogram.

Preliminary study:
Each of 10 rabbits was subjected to contact of the skin with 2,6—di—tertiary butyl phenol in the dosage of 0.5 ml. per kilogram. These survived and exhibited no signs of illness and gained in weight at normal rates. Three animals developed a slight to moderate degree of erythema in the treated areas of the skin.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
> 0.5 mL/kg bw
Remarks on result:
other: No signs of illness observed.
Mortality:
None
Clinical signs:
Three animals developed a slight to moderate degree of erythema in the treated areas of the skin.
Body weight:
Normal weight gain
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Very low dermal toxicity and slightly irritating.
Executive summary:

Each of 10 rabbits was subjected to contact of the skin with 2,6-di-tertiary butyl phenol in the dosage of 0.5 ml. per kilogram. These survived and exhibited no signs of illness and gained in weight at normal rates. Three animals developed a slight to moderate degree of erythema in the treated areas of the skin.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted in 1959. It is not a guideline study and is non-GLP.
Qualifier:
no guideline available
Principles of method if other than guideline:
The test material prepared as a suspension in peanut oil was placed in contact with intact abdominal skin of rabbits for 6 hours
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Rats were exposed for 7h to varying amounts of test substance (AN-33) 3.2 to 10 ml per kg.
Duration of exposure:
7 hours
Doses:
3.2 to 10 ml per kg
No. of animals per sex per dose:
No data
Control animals:
no
Details on study design:
No details
Preliminary study:
The rats had no local injuries and showed no signs of systemic illness following dermal exposure.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
10 mL/kg bw
Based on:
other: technical containing 70-80% 2,6-di-tert-butylphenol
Mortality:
None
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
Not classified for dermal toxicity.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted in 1959. It is not a guideline study and is non-GLP.
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats were exposed to varying amounts of a 10% solution of test substance (AN-33) in peanut oil. The solution was applied to the rat's skin 5 days per week for 3 weeks.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
peanut oil
Details on dermal exposure:
Rats were exposed to varying amounts of a 10% solution of test substance (AN-33) in peanut oil:- 0.32, 0.47, 0.70 and 1.0 g AN-33 per kg bw. The solution was applied to the rat's skin 5 days per week for 3 weeks.
Duration of exposure:
5 days per week for 3 weeks
Doses:
0.32, 0.47, 0.70 and 1.0 g AN-33 per kg bw
No. of animals per sex per dose:
No data
Control animals:
no
Details on study design:
No details
Preliminary study:
The rat which received the highest dose, 1.0g per kg bw, showed some fluctuation in weekly body weight gain and retardation of growth. All other rats showed no signs of illness.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
1 000 mg/kg bw
Based on:
other: technical containing 70-80% 2,6-di-tert-butylphenol
Mortality:
None
Clinical signs:
No data
Body weight:
The highest dose rate (1.0g per kg bw) showed fluctuation in weekly body weight gain and retardation of growth
Gross pathology:
No data

Animal on the 1.0 g/kg bw dose showed some fluctuation in its weekly gains in body weight and retardation in growth; otherwise there were no signs of illness.

Interpretation of results:
GHS criteria not met
Conclusions:
Not classified for dermal toxicity.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
no guideline available
Principles of method if other than guideline:
One rat was tested at each concentration using either undiluted 2,6-di-tert-butylphenol or a 50% solution of 2,6-di-tert-butylphenol in peanut oil.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The rats were exposed to both undiluted 2,6-di-tert-butylphenol warmed to 37C and a 50% solution of 2,6-di-tert-butylphenol in peanut oil for 6 hours.
Duration of exposure:
6 hours
Doses:
10, 16, 24, 36 ml/kg (9.18, 14.7, 22.0, 33.0 g/kg)
No. of animals per sex per dose:
1 rat per dose
Control animals:
no
Details on study design:
No details
Preliminary study:
One rat was tested at each concentration using either undiluted 2,6-di-tert-butylphenol or a 50% solution of 2,6-di-tert-butylphenol in peanut oil.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
> 36 mL/kg bw
Remarks on result:
other: No signs of illness observed.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
> 33 000 mg/kg bw
Remarks on result:
other: No signs of illness
Mortality:
None
Clinical signs:
No data
Body weight:
Normal weight gain
Gross pathology:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
Not classified for dermal toxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Additional information

Oral toxicity:

DTBP was evaluated for its acute oral toxicity in the Sprague-Dawley strain rat. The acute oral median lethal dose (LD50) of the test material in the Sprague-dawley strain rat was found to be greater than 5000 mg/kg bodyweight. (OECD 401)

Test method:

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 dose of test material, as a solution/suspension in arachis oil B.P. at a dose level of 5000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were killed for gross pathological examination.

Two animals (one male and one female) were killed in extremis one day after treatment. Common signs of systemic toxicity noted were hunched posture, lethargy, ataxia and occasional body tremors with additional signs of laboured respiration, loss of righting reflex and ptosis. Surviving animals appeared normal three days after treatment.

Surviving animals showed expected gain in bodyweight during the study.

Abnormalities noted at necropsy of animals killed in extremis during study were abnormally red lungs, patchy pallor of the liver, dark kidneys, haemorrhage of the gastric mucosa and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals killed at the end of the study.

Dermal toxicity:

Several studies were performed dating from 1955 to 1959. These studies were non-guideline and non-GLP but demonstrate that 2,6-di-tertbutylphenol is not toxic by dermal exposure and should not therefore be classified. Two studies were performed using rats and two studies using rabbits. No effects due to local injury or systemic illness were observed up to 33 g/kg bw. A value of 5000 mg/kg bw will be used in the risk assessment.

Justification for classification or non-classification

Acute toxicity oral:

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute oral toxicity based on the available data.

 

Acute toxicity dermal:

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required for acute dermal toxicity based on the available data.