2'-anilino-6'-[ethyl(3-methylbutyl)amino]-3'-methylspiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one

Acute Toxicity: oral

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

Test material information

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.