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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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 141 - 167 g, and females 139 - 151 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 exception 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): 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
Main Study: 5
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 female treated with 5000 mg/kg was found dead three days after treatment
Main study: no deaths
Clinical signs:
Main study: no signs of systemic toxicity were noted during the study
Body weight:
Main study: All animals showed expected gain in bodyweight during the study
Gross pathology:
Main study: 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

0

0

0

0

0

2-0 female

0

0

0

0

0

LA

X

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

Key:

L = lethargy

A = ataxia

X = animal dead

0 = no signs of systemic toxicity

Individual bodyweights and weekly bodyweight increases 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 141  198 250  57  52   
   3 -1 Male 167 216  275  49  59   
   3 -2 Male 152 224  293  72  69   
   3 -3 Male 144  214 267  70  53  
2000   3 -4 Male 143  206  272  63  66   
   4 -0 Female 151  192  220  41  28  
   4 -1 Female  142 188 214  46 26  
   4 -2 Female 140  178  206  38 28   
   4 -3 Female 139  172  199  33  27   
  4 - 4 female  139   185  212  46  27  

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, DTBP, 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, DTBP, 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 oral dose of test material, as a 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, DTBP, 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.