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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:
1991-05-08 to 1991-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Test material form:
solid: particulate/powder
Details on test material:
Direct Red 83:1

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Male and female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the main study the males weighed 136 -155 g, and the females 135-148 g, and were approximately five to eight weeks old. After a minimum acclimatization period of at least five days the animals were 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.
HUSBANDRY:
The animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet N0. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
The animal room was maintained at a temperature of 21 - 24 °C and relative humidity of 36 - 62%.
The rate of air exchange was approx. 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE (arachis oil)
Single oral dose as suspension in arachis oil
- Amount of vehicle (if gavage): NA
- Justification for choice of vehicle: solubility of test material
Doses:
Range finding-Study
A range-finding study was performed to establish a dosing regima as follows:

Dose level mg/L Concentration mg/L Dose volume mL/Kg Number of Rats
2000 200 10 1(male) 1(female)


Main-study

Based on the results of the range-finding study a further group of animals was treated as follows:

Dose level mg/L Concentration mg/L Dose volume mL/K Number of Rats
2000 200 10 5 (male) 5(female)

No. of animals per sex per dose:
5 males (136 – 155 g) 2000mg/L single dose
5 females (135 – 148 g) 2000mg/L single dose
Approx. 5 – 8 weeks old
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were dose once only by gavage using a metal cannula attached to graduated syringe.
Deaths and other sign of toxicity were recorded 1, 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 day 7 and 14

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and histopathology.
Statistics:
DATA EVALUATION:
Data evaluation included the relationship if any, between the animals’ exposure of the test material and the incidence of severity of all abnormalities including behavioral and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained and estimate according to the acute oral median dose (LD50) of the test material was made.

 

Results and discussion

Preliminary study:
RANGE FINDING STUDY
A range finding study was performed to establish a dosing regime as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of Rates
2000 200 10 1 Male 1 Female

Death and overt signs of toxicity were recorded 1/2, 1, 2 and 4 hours after dosing and the daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths,
No abnormalities at necropsy
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
The animals showed expected gain in bodyweight during the study

Any other information on results incl. tables

No deaths

No signs of systemic toxicity

All animals showed expected gain in bodyweight

No abnormalities at necropsy

 

TableI: 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)

2000

1-0 Male

0

0

0

0

0

0

0

0

0

2-0 Female

0

0

0

0

0

0

0

0

0

 

0= no signs of systemic toxicity were noted during the study.

 

 

TableII: 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)

 

 

 

 

 

 

 

 

 

 

 

 

2000

3-0 Male

1/2

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

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 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4-4 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0= no signs of systemic toxicity were noted during the study.

 

TableIII: INDIVIDUAL NECROPSY FINDINGS IN THE MAIN STUDY

 

Dose level (mg/kg)

 

Animal Number & Sex

 

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:
GHS criteria not met
Conclusions:
The acute oral lethal median dose (LD50) of Direct Red 83:1 in the Sprague-Dawley strain Rat was found to be greater than 2000 mg/kg bodyweight
-no symbol and risk phrase are required according to CLP labelling regulations

Executive summary:

A study was performed to assess the acute oral toxicity of Direct Red 83:1 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 Directives 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basic 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 10 fasted animals (five males and five females) was given a single oral dose of Direct Red 83:1, 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 then 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 in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg body weight.

No symbol and risk phrase are required according to EEC labelling regulations.

 

 

 

.

Results Synopsis and test report:

Species

Strain

Origin

Sex of animals dosed

Tabulation of response data by dose level

LD50 Value

Findings

Sprague Dawley rats

 

HSD: Sprague Dawley SD

Charles River (U.K.) Ltd., Manston, Kent. U.K.

Male and female

No animals died during the test.

>2000 mg/kg body weight

The animals killed at the end of the observation period showed no macroscopically visible changes.