2-Propen-1-one, 3-(dimethylamino)-1-(3-pyridinyl)-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

07 June 2000 - 21 June 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

434-770-8

EC Name:

-

Cas Number:

55314-16-4

Molecular formula:

C10 H12 N2 O1

IUPAC Name:

3-(dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one

Details on test material:

- Name of test material (as cited in study report): STI571 Y5A
- Substance type: Brown solid
- Physical state: solid
- Analytical purity: >95%
- Lot/batch No.: 0093800007
- Expiration date of the lot/batch: 08 May 2001 (allocated by NOTOX, 1 year after receipt of the test substance)
- Storage condition of test material: In refrigerator in the dark.
- Purity: Not indicated by sponsor; treated as 100% pure
- Stability under storage conditions: Not indicated
- Stability in vehicle: Not indicated

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8 weeks old). Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: not applicable
- Housing: Individually housed in labelled polycarbonate cages containing purified sawdust as bedding material.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: 07 June 2000 To: 21 June 2000

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Remarks:

(Milli-U)

Details on dermal exposure:

TEST SITE
- Area of exposure: The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- % coverage: test site covered for 100%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using tap water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight.
- Concentration (if solution): 10 ml/kg
- Constant volume or concentration used: no
- For solids, paste formed: no

Dose volume: 10 ml/kg

The vehicle was selected based on a pretest performed at NOTOX.

The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality/viability: twice daily
body weights: days 1 (pre-administration), 8 and 15
clinical signs: once daily
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs indicative of systemic toxicity were noted in any of the animals. Yellow staining of the treated skin-area, flank and/or chest caused by the test substance was seen in all animals during the observation period. Focal erythema of the tr

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of STI571 Y5A in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), STI571 Y5A does not have to be classified and has no obligatory labelling requirement for dermal toxicity.