Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From october, 1986 to december, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
CI Reactive Red 231

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
These were specific pathogen free (SPF) Wistar-derived albino rats (Alpk:AP strain) supplied by the Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, UK. At the beginning of each study the rats weighed 269-342g for males and 186-245g for females.
Five male and five female rats per dose level were used for this study. Each animal was selected at random and given a number, unique within the study, using an ear-punch. Each animal was weighed and then fasted overnight for a period of up to 24 hours prior to dosing.

The rats were housed in suspended cages (370mm length x 320mm width x 200mm height). The floor and the back of each cage were made of 12mm square stainless steel mesh. The sides were made of solid stainless steel and the front was made of polycarbonate (MAKROLON). A maximum of five rats was housed in each cage in the oral toxicity study. In the dermal toxicity study the animals were housed individually, two per cage in experimental cages which were divided into two equal compartments by placing a solid metal partition within each cage and one animal was held in each compartment. The sexes were kept separately.
The animals were allowed free access to food (Porton Combined Diet, Special
Diets Services Ltd: Appendix 3) and given access to unlimited water via an automatic system.
The room in which the rats were held was designed to maintain a temperature of between 15°C and 24°C and a relative humidity of 50±10%. Temperature and relative humidity were recorded constantly using a thermohygrograph.
The air-exchange system was designed to give 20-30 air-changes per hour and the light pattern was controlled by a time switch to give alternate periods of 12 hours of artificial light and 12 hours of darkness.
The rats were acclimatised to the animal laboratory for a minimum of six days prior to each study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 mg, 100 mg and 200 mg/ml in deionised water
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: good water solubility


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw
Doses:
500, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were observed for signs of systemic toxicity once between 30 and 120 minutes after dosing and again between 4 and 7 hours after dosing. Subsequent observations were made once daily up to Day 15. The animals were weighed on the day before dosing (Day-1), the day of dosing (Day 1) and on Day 3, Day 8 and Day 15. The surviving animals dosed with 2000mg/kg were also weighed on Day 4. One female dosed with 500mg/kg was not weighed on Day 3.
At the end of the study, all of the animals were humanely killed by inhalation of excessive levels of halothane BP (FLUOTHANE, Imperial Chemical Industries PLC, Pharmaceuticals Division) and were examined by necropsy for any macroscopic abnormalities.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No test substance related mortatlity, one female animal died but it is concluded that it is not due to test susbtance.
Clinical signs:
No sign of toxicity
Body weight:
No test substance related effects
Gross pathology:
No test substance related effects

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the oral LD50 in rats was >2000 mg/kg bw.
Executive summary:

A study was performed to assess the acute oral toxicity of the test substance in rats according to a procedure similar to the acute toxic classic method, in compliance with GLP. Three dose levels of 500, 1000 and 2000 mg test sample/kg bw were tested in the acute oral toxicity study. The dose levels were administered as nominal 50 mg, 100 mg and 200 mg test sample/ml suspensions in deionised water, to groups of five male and five female rats. A standard volume of 10 ml/kg bw was dosed to each animal. The rats were observed for fourteen days after dosing.

There were no mortalities or test substance related adverse effects. One female died after dosing on Day 4 but it was concluded that the mortality was not caused by the test substance. Under the study conditions, the oral LD50 in rats was >2000 mg/kg bw (Oliver, 1986).