Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From December 18, 1990 to January 18, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Acid Violet 048
IUPAC Name:
Acid Violet 048

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: at the start of the main study, rats were approximately five to eight weeks old.
- Weight at study initiation: at the start of the main study, males 170 - 200 g and females 143 - 157 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 up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet: Rat and Mouse Expanded Diet No. l (Special Diet Services Limited) was allowed throughout the study.
- Water: free access to mains drinking water.
- Acclimation period: a minimum period of at Ieast five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 21 °C. On occasions the temperature was below the Iower Iimit specified in the protocol (19 °C). This did not affect the purpose or integrity of the study.
- Humidity: 42 - 62 %
- Air changes : approximately 15 changes per hour.
- Photoperiod: 12 hours continuous Iight and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in distilled water.
The composition and stability of the test material and the stability of the preparations were not determined.
- Dose volume: 10 ml/kg
- Concentration: 200 mg/ml
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Details on study design:
MAIN EXPERIMENT
- Duration of observation period following administration: 14 days
- Frequency of observations: deaths and overt signs of toxicity were recorded 1/2, 1, 2 and 4 hours after dosing and then daily for 14 days.
- Frequency of weighing: individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14 or at death.
- Necropsy of survivors performed: yes; at the end of the study the animals were killed by cervical dislocation. The abdominal and thoracic cavities were opened for examination of all major organs. The macroscopic appearance of any abnormal organs was recorded. No tissues were retained.

DOSE RANGE-FINDING
- Dose levels: 5000, 2000 and 200 mg/kg bw.
- No of animals per dose: 1 male and 1 female.
- Observations: 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 treatment volumes. No necropsies were performed.

Results and discussion

Effect levels
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:
MAIN EXPERIMENT
One female was found dead approximately six hours after dosing.

DOSE RANGE-FINDING
One male treated with 5000 mg/kg was found dead one day after treatment.
Clinical signs:
MAIN EXPERIMENT
Isolated incidents of toxicity noted during the study were hunched posture and lethargy.
Purple-coloured staining of the fur was commonly noted during the study.

DOSE RANGE-FINDING
Signs of toxicity noted were hunched posture, lethargy and ptosis. Purple-coloured staining of the fur was also noted.
Body weight:
MAIN EXPERIMENT
Surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
MAIN EXPERIMENT
Abnormalities noted at necropsy of the female that died during the study were abnormally red lungs, dark liver and dark kidneys.
No abnormalities were noted at necropsy of animals killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation (EC) No 1272/2008
Conclusions:
LD50 (male and female) > 2000 mg/kg bw
Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed the recommendations of 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).

Based on the results of the dose range finding experiment, 5 males and 5 females were treated at a dosage level of 2000 mg/kg bw. The substance was administered as a single dose by gavage. After administration of the compound, the animals were observed for 14 days; at the end of the observation period, surviving animals were killed and an autopsy performed.

One female was found dead approximately six hours after dosing; abnormalities noted at necropsy of the female that died during the study were abnormally red lungs, dark liver and dark kidneys.

Isolated incidents of toxicity noted during the study were hunched posture and lethargy. Purple-coloured staining of the fur was commonly noted during the study. Surviving animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy of animals killed at the end of the study.

Conlcusion

LD50 (male and female) > 2000 mg/kg bw