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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 March 1982 - 15 April 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study cannot be considered reliable without restrictions, as it does not include a formal claim of GLP compliance, nor was it conducted in accordance with official test guidelines (it should be noted that such guidelines, and official GLP guidelines were not available at the time when the study was conducted). The study does contain a statement of Quality Assurance, and is generally well documented; in addition, the methodology employed is largely consistent with modern methodology for the assessment of acute oral toxicity, and on this basis the study is considered reliable (with restrictions).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
not applicable
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
S-205
IUPAC Name:
S-205
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): S-205, 2-anilino-3-methyl-6-[(N-ethyl-N-iso-pentyl)amino]-spiro(phthalide-3,9-xanthene)
- Lot/batch No.: LS 8

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 101 - 133 g
- Fasting period before study: Yes (overnight before dosing, and for approximately 4 hours after dosing).
- Housing: Housed by group in metal cages with wire mesh floors
- Diet (e.g. ad libitum): Ad libitum (except prior to dosing, as described above)
- Acclimation period: 4 or 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 ± 1.5°C
- Humidity (%):55 - 67%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hours period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% Aqueous Methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40% (w/v)
- Amount of vehicle (if gavage): 40 mL/kg bodyweight.
Doses:
16.0 g/kg
A concurrent control group was dosed with untreated 1% Methylcellulose at 40 mL/kg bodyweight.
No. of animals per sex per dose:
Preliminary study; two males and two females.
Main study; five males and five females.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (6 days during the preliminary study).
- Frequency of observations and weighing: Animals were observed shortly after dosing, then at frequent intervals for the remainder of day 1. On subsequent days animals were observed at least twice daily. Individual bodyweights were recorded on days 1, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Preliminary study:
No deaths were seen during the preliminary study; the main study was subsequently run using the same dose level (16 g/kg bodyweight)
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed in any of the animals treated with S-205 in either the preliminary or main studies.
Clinical signs:
other: Signs of reaction to treatment (Table 3) observed shortly after dosing in all treated rats included pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling).
Gross pathology:
Autopsy findings were within normal limits.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral dose (LD50) to rats of S-205 was found to be greater than 16.0 g/kg bodyweight.