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

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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).

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

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.

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.

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)

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

16 000 mg/kg bw

Quality of whole database:

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).

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

05 to 19 February 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study undertaken at GLP accredited laboratory to internationally accepted guidelines. The restriction is due to the use of the read across approach: the test was performed not with S-205 but with Black 400, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile .

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Seven to 10 weeks.
- Weight at study initiation: 205 to 231 g
- Fasting period before study: no
- Housing: Metal cages with mesh floors.
- Diet: standard laboratory rodent diet, Labsure LAD 1, ad libitum.
- Water: ad libitum
- Acclimation period: At least 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22°C
- Humidity (%): 46%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.

Type of coverage:

occlusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: 50mm x 50mm of clipped dorso-lumbar region
- % coverage: 10%
- Type of wrap if used: Gauze held in place with impermeable dressing

REMOVAL OF TEST SUBSTANCE
- Washing: Washed with warm water and blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2mg/kg bw
- Concentration (if solution): 80% w/v paste in distilled water
- Constant volume: yes, 2.5 ml/kg bw
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

2.0 g / kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No macroscopic abnormalities were found during the autopsy procedure.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal dermal dose to rats of ODB-2 was found to be: greater than 2.0 g / kg bodyweight.

Executive summary:

S-205 and ODB-2 (Black 400), which is tested for its dermal toxicity, are both colour precursor for heat sensitive record sheets. These substances have been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile. Due to the fact that S-205 and ODB-2 have nearly the same chemical structure. The same mode of interaction with bio-macromolecules, living cells and tissue and metabolic pathway is expected. Therefore, a read-across from S-205 to data obtained with ODB-2 is scientifically justified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study undertaken at GLP accredited laboratory to internationally accepted guidelines. The restriction is due to the use of the read across approach: the test was performed not with S-205 but with Black 400, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile.

Additional information

Justification for selection of acute toxicity – oral endpoint
The only oral study available.

Justification for selection of acute toxicity – dermal endpoint
The only study available.

Justification for classification or non-classification

The substance exceeds the classification levels at dermal and oral exposures. S-205 will therefore not be classified as toxic.