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Toxicological information

Acute Toxicity: oral

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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:
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:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): Phenol, 2,6-bis(1,1-dimethylethyl)
- Substance type: di-alkylphenol
- Physical state: white crystalline solid
- Analytical purity: 99.26% (GC)
- Purity test date: 03/10/1990
- Lot/batch No.: 2,6-AP/308
- Storage condition of test material: in original container at room temperature in the dark
Specific details on test material used for the study:
-

Test animals

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

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: 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

Results and discussion

Effect levels
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).

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.