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Diss Factsheets

Ecotoxicological information

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
02 September 1999 -11 November 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method C.2 (Acute Toxicity for Daphnia)
Deviations:
no
Qualifier:
according to guideline
Guideline:
ISO 6341 (Water quality - Determination of the Inhibition of the Mobility of Daphnia magna Straus (Cladocera, Crustacea))
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
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: 98.6%
- Lot/batch No.: 992301
- Expiration date of the lot/batch: 01 July 2001
- Stability under storage conditions: Stable
- Storage condition of test material: In refrigerator in the dark
- Stability in water: Not indicated

Sampling and analysis

Analytical monitoring:
yes
Details on sampling:
During the final test samples were taken from 2.2, 22 and 220 mg/l for analysis. Also samples were taken from the control.

Frequency: at t=0h and t=48h.
Volume: 10 ml from the approximate centre of the test vessel.
Storage: The samples were stored in a freezer until analysis.
sample pre-treatment:All samples were stored in a deep freeze. On the day of analysis, the frozen samples were defrosted at room temperature. The entire volume of each sample (10 ml) was transferred quantitatively into a 20 ml volumetric flask usingacetonitrile. The flasks were filled up to the mark with acetonitrile. If necessary, the solutions were further diluted with 50/50 (v/v) acetonitrile/ISO-medium to obtain concentrations within the calibration range.

Test solutions

Vehicle:
no
Details on test solutions:
STI571 Y5A is a brown solid with a purity of 98.6% and completely soluble in test medium at the concentrations tested. Preparation of test solutions started with a stock solution at 100 mg/l for the range-finding test, and a stock solution of 250 mg/l for the final test. No special treatment other than careful mixing was necessary to dissolve the test substance in the test medium. The lower concentrations were prepared by subsequent dilutions of the stock solutions in test medium. The final test solutions ranged from clear and colourless to clear yellow.

Test organisms

Test organisms (species):
Daphnia magna
Details on test organisms:
TEST ORGANISM
- Common name: Daphnia magna (Crustacea, Cladocera) (Straus, 1820)
- Source: In-house laboratory culture with a known history.
- Age at study initiation: < 24 hours
- Method of breeding: With newborn daphnids, i.e. less than 3 days old, by placing about 250 of them into 10 litres of medium in an all-glass culture vessel.
- Feeding during test: No

Study design

Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
48 h

Test conditions

Hardness:
250 mg/l expressed as CaCO3
Test temperature:
between 20.3 and 21.6°C
pH:
Between 8.0 and 8.2
Dissolved oxygen:
Between 8.8 and 9.3 mg/l
'
Nominal and measured concentrations:
Nominal concentrations:0-2.2, 22 and 220 mg/l
Measured concentrations:Analysis of the samples taken at the start (t=0) of the final test showed measured concentrations of 1.91 mg/l (87%), 22.1 mg/l (100%) and 179 mg/l (81%) at the nominal concentrations of 2.2, 22 and 220 mg/l, respectively. After 48 hours of exposure the test substance concentrations measured remained constant at nominal 2.2 and 22 mg/l and increased to 211 mg/l at nominal 220 mg/l. Hence, the average exposure concentration at 220 mg/l was 194 mg/l, being the geometric mean of the concentrations measured at the start and the end of the test
Details on test conditions:
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: glass, 100 ml, normal headspace, 80 ml
- Aeration: no
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 2
- No. of vessels per control (replicates): 2
TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: ISO-medium: the following chemicals (analytical grade) are dissolved in freshly prepared ultra-pure water (tap water purified by reverse osmosis (milli-RO) and subsequently passed over activated carbon and ion-exchange cartridges:
Milli-Q water; Millipore Corp., Bedford, Mass., USA) (mg/l):
CaCl2.2H2O : 293.8
MgSO4.7H2O : 123.3
NaHCO3 : 64.8
KCl : 5.8
The hardness: 250 mg/l expressed as CaCO3 and the pH: 8.0 ± 0.2 after aeration.
- Culture medium different from test medium: yes, for culturing M7 medium is used
OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16 hours photoperiod daily
EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : EC50 t=48 h
TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2.2
- Test concentrations:: 0 , 2.2, 4.6, 10, 22, 46, 220 mg/l
Reference substance (positive control):
yes
Remarks:
potassium dichromate:

Results and discussion

Effect concentrations
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
> 194 mg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mobility
Details on results:
Behavioural abnormalities: no
- Immobility of control: no immobility was observed.
- Other adverse effects control: no
Results with reference substance (positive control):
The 24h-EC50 was estimated to be 1.2 mg/l.
(regression line: log10(conc.)=2.76+(probit-2.58)/7.69).

The 48h-EC50 was 0.60 mg/l with 95% fiducial limits of 0.52 – 0.76 mg/

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
Under the conditions of the present study STI571 Y5A induced not more than 25% immobility of daphnids up to and including a highest tested concentration of 220 mg/l, corresponding with an average measured concentration of 194 mg/l. Hence, the 48h-EC50 was above 194 mg/l.