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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From 18 August 1998 to 11 September 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Dicerium trisulphide
EC Number:
234-603-7
EC Name:
Dicerium trisulphide
Cas Number:
12014-93-6
Molecular formula:
Ce2S3
IUPAC Name:
Dicerium trisulphide
Test material form:
solid: particulate/powder
Remarks:
powder
Details on test material:
- Name of test material (as cited in study report): Cerium sulphide

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd, Bicester, Oxon, England
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 0.222-0.273 kg
- Fasting period before study: overnight
- Housing: Rats were allocated without conscious bias to cages within the treatment group and housed in groups of five rats of the same sex in metal cages with wire mesh floors in Building Rl4 Room 7
- Diet (ad libitum): standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet). The batch of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organisms.
Access to diet was prevented for 4 hours after dosing.
- Water (ad libitum): Results of routine physical and chemical examination of drinking water, as conducted by the supplier, are made available to the testing laboratory as quarterly summaries.
Access to water was prevented for 4 hours after dosing.
- Acclimation period: 8 days

Each animal was identified by cage number and ear punching. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initiais of the Study Director and Home Office licensee.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23.5
- Humidity (%): 41-61
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):12/12 (0700-1900 hours)

A permanent daily recordings of the environmental condition parameters was made and archived with other Department raw data.

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
PRELIMINARY STUDY:
In the absence of precise toxicological information, a group of two rats (one male and one female) was dosed at 2000 mg/kg bodyweight.

VEHICLE
- Concentration in vehicle: 50% w/v
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no data
-Lot/ batch (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not applicable
Doses:
Males and females: 5000 mg/kg bw
No. of animals per sex per dose:
Males: 5 per dose
Females: 5 per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15, or at death. Individual weekly bodyweight changes and group mean body weights were calculated.
Cages of rats were checked at least twice daily for any mortalities.
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15- morning only). The nature and severity of the clinical signs and time were recorded at each observation. All surviving animals were observed for 14 days after dosing.
All surviving animals were killed on Day 15 by carbon dioxide.
- Necropsy of survivors performed: yes. All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities.The macroscopic appearance of all examined orgnas was recorded.
- Other examinations performed: no further examinations
Statistics:
Not applicable

Results and discussion

Preliminary study:
The dose of the main study was selected based on results of a preliminary study. As no precise toxicological information was available, a group of two rats (one male and one female) was dosed at 2000 mg/kg body weight.
There were no deaths. Clinical signs were confined to piloerection and hunched posture with waddling/unsteady gait also seen in the female. Bodyweight gain was considered satisfactory. No macroscopic abnormalities were recorded at the terminal necropsy on Day 8.
Based on these results, 5000 mg/kg was selected as a suitable dose leve for the main study
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Only one animal died. However, this death was due to intubation error during dosing, and was not considered to be related to the toxicity of the test material.
Mortality:
One male died within approximately 9 minutes of dosing. Macroscopic examination of this animal revealed congestive changes (characterised by dark tissue) in the bram, heart, liver and spleen. ln addition, congestion with red fluid contents was seen in the lungs and thoracic cavity, with red fluid contents also seen in the stomach. These findings were considered to indicate the death of this animal was due to intubation error during dosing, rather than to be related to the toxicity of the test material.
Clinical signs:
other: Piloerection was observed in all surviving rats soon after dosing. This sign persisted and was accompanied in surviving animals later during the study by hunched posture, waddling/unsteady gait, abnormal faeces and ungroomed appearance. ln addition, dark
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.
Other findings:
No other findings were reported.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of Dicerium trisulphide is greater than 5000 mg/kg bw in male and female rats.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.
Executive summary:

This study was performed to assess the acute oral toxicity of Dicerium trisulphide to the rat. 

Methods

The method followed was that described in:

- EPA Health Effects Testing Guidelines, Subpart B - General Toxicity Testing § 798.1175 Acute oral toxicity, September 27, 1985 (described in Federal Register VoL 50, No. 188) and subsequent revisions. Subpart B provides detailed information relating to data requirements of 40 CFR Part

798 and supports the Toxic Substances Control Act (TSCA).

- EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animais 81-1 (Revised Edition November 1984).  Subdivision F provides detailed information relating to data requirements of 40 CFR Part 158 and supports the Federal Insecticide, Fungicide

and Rodenticide Act (FIFRA).

- Japanese Ministry of Agriculture, Forestry and Fisheries, Requirements for Safety Evaluation of Agricultural Chemicals and Testing Guidelines for Toxicology Studies, Acute Oral Toxicity Study, 59 NohSan No. 4200, Agricultural Production Bureau, January 28, 1985.

 

A group of ten fasted rats (five males and five females) received a single oral gavage dose of the test substance, formulated in corn oil and administered at a dose level of 5000 mg/kg body weight. This dosage was selected on the basis of results from a preliminary investigation. All surviving animals were killed and examined macroscopically on Day 15, the end of the observation period.

 

Results

One male died within approximately 9 minutes of dosing. Macroscopic examination of this animal revealed congestive changes in sorne tissues and congestion and red fluid contents in the lungs. Necropsy findings were considered to indicate the death of this animal was a result of intubation error during dosing and not related to the toxicity of the test material.

 

Clinical signs of reaction to treatment included piloerection, hunched posture, waddling/unsteady gait, abnormal faeces, ungroomed appearance and dark colouring to eyes, seen in both males and females. In addition, lethargy, abnormal respiration, pallid extremities, walking on toes, increased sensitivity to touch, thin appearance and prostration were seen in females only, with protruding eyes noted in one male only. Recovery of surviving rats was complete in all animals by Day 8.

 

All animals were considered to have achieved satisfactory bodyweight gains throughout the study. No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Conclusion

The acute median lethal oral dose (LD50) to rats of Dicerium trisulphide was demonstrated to be greater than 5000 mg/kg bodyweight.