N-[3-(trimethoxysilyl)propyl]butylamine

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Please refer to the analogue approach justification provided in section 13.

Reason / purpose for cross-reference:

read-across source

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Conclusions:

A 48-h EC50 >100 mg/l in Daphnia magna was determined in a guideline test and in accordance with GLP. The result is taken to be reliable.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 28 to July 06 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 0 and Nominal 100 mg/L

- Sampling method: Duplicate samples were taken from the freshly prepared test medium of the single test concentration and the control just before the start of the test. Additional duplicate samples were taken from the the test medium and control at the test and and after 48 hours. For this, the contents of the two test test beakers of the single test concentration and the control were combined.
The silicon concentrations were measured in the duplicate test medium samples from the start and the end of the test.

- Sample storage conditions before analysis: All samples were deep frozen (at about -20 °C) immediately after sampling.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: Test medium prepared by dissolving 32 mg test item completely in 300 ml test water by intense stirring for 5 minutes at room temperature.
The pH of the test medium was 9.5 and was adjusted to pH 8.0 with a concentrated hydrochloric acid solution and sodium hydrochloride solution. The test medium was prepared just before introduction of the daphnids.

- Eluate:
- Differential loading:

- Controls: Test water with the addition of the test item


- Evidence of undissolved material (e.g. precipitate, surface film, etc): Not stated

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna

- Strain: Straus

- Source: Originally from the University of Sheffield/UK in 1992 defined from supplier as clone 5

- Age at study initiation (mean and range, SD): 6-24 hours old

- Weight at study initiation (mean and range, SD): Not stated
- Length at study initiation (length definition, mean, range and SD): Not stated
- Valve height at study initiation, for shell deposition study (mean and range, SD): Not stated
- Peripheral shell growth removed prior to test initiation: Not stated

- Method of breeding:

- Feeding during test: None

ACCLIMATION
- Acclimation period: Conditions prior to test are same as test conditions

- Acclimation conditions (same as test or not): Yes

- Type and amount of food: Not stated
- Feeding frequency: Not stated
- Health during acclimation (any mortality observed): Not stated

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Hardness:

2.5 mmol/L test water

Test temperature:

21-22 °C

pH:

7.8 - 8

Dissolved oxygen:

8.0 - 8.3 mg/L

Nominal and measured concentrations:

Nominal: 0 and 100 mg/L
Measured: 126 and 115 mg/L at start and end of test respectively

Details on test conditions:

TEST SYSTEM
- Test vessel: 100 ml glass beaker

- Type (delete if not applicable): open / closed: Covered with glass plates

- Material, size, fill volume: Glass, 100 ml, 60 ml

- Aeration: None

- Type of flow-through (e.g. peristaltic or proportional diluter): Static

- Renewal rate of test solution (frequency/flow rate): No renewal

- No. of organisms per vessel: 10

- No. of vessels per concentration (replicates): 2

- No. of vessels per control (replicates): 2

- Biomass loading rate: Lower than one daphnia per 2 ml of test solution

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Reconstituted water. Analytical grade salts were dissolved in deionized water

- Total organic carbon:
- Particulate matter:
- Metals:
- Pesticides:
- Chlorine:

- Alkalinity: 0.8 mmol/L

- Ca/mg ratio: 4:1

- Conductivity:

- Culture medium different from test medium: No

- Intervals of water quality measurement: 0 and 48 hours

OTHER TEST CONDITIONS
- Adjustment of pH: Yes

- Photoperiod: A 16 hour light to 8-hour darkness photoperiod with a 30 minute transition period.

- Light intensity: 200 - 1200 lux

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Mortality or Immobility at 24 and 48 hours

TEST CONCENTRATIONS
- Spacing factor for test concentrations: Limit test

- Justification for using less concentrations than requested by guideline: Based on the results of the range finding test, no mortalities or sub-lethal effects were obseved at maximum concentration, from the OECD/EC Test Guidelines, of 100mg/L

- Range finding study: Yes

- Test concentrations: Not stated

- Results used to determine the conditions for the definitive study: No mortalities observed up to 100 mg/l at the end of the study

Reference substance (positive control):

no

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Behavioural abnormalities:
- Observations on body length and weight:
- Other biological observations:

- Mortality of control:No mortality

- Other adverse effects control:
- Abnormal responses:
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values:

- Effect concentrations exceeding solubility of substance in test medium:No

Table 1: Influence of Y-15167 on the mobility of Daphnia magna

Nominal test item concentration (mg/L)	Number of Daphnids tested	Immobilized Daphnids after 24 hours		Immobilized Daphnids after 24 hours
		No.	%	No.	%
Control	20	0	0	0	0
100	20	0	0	0	0

Table 2: Dissolved oxygen concentrations, pH values and temperature in the test medium and the control

Nominal test item concentration (mg/L)	Start (0 hours)			End (48 hours)
	pH	Oxygen (mg/L)	Temperature (°C)	pH	Oxygen (mg/L)	Temperature (°C)
Control	7.8	8.3	22	7.8	8.2	21
100	9.5*/8.0	8.3	22	7.8	8.0	21

* before/after pH adjustment

Validity criteria fulfilled:

yes

Remarks:

Immobilisation in controls and maintenance of steady test conditions (including test substance concentration >80% of nominal) were all fulfilled.

Conclusions:

A 48-h EC50 >100 mg/l in Daphnia magna was determined in a guideline test and in accordance with GLP. The result is taken to be reliable.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

15-17 Aug 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Analytical monitoring:

yes

Vehicle:

yes

Details on test solutions:

- Method: A primary stock solution was prepared by solving the test substance in THF. Secondary stock solutions were prepared by diluting the primary stock solution with THF. For preparation of the required test concentrations the secondary stock solutions were diluted with well water. The test solutions were stirred overnight to allow hydrolysis.
- Chemical name of vehicle: tetrahydrofuran (THF)
- Concentration of vehicle in test medium (stock solution and final test solution(s) including control(s)): 0.10 mL/L
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no visible undissolved test substance following preparation

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Source: bred at testing facility
- Age at study initiation: < 24 h

ACCLIMATION
- Type and amount of food: green algae (Ankistrodesmus falcatus), suspension of YCT (yeast, cereal leaves and flaked fish food); the amoumt of food increased with the age of Daphnids
- Feeding frequency: daily

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

170 mg/L (as CaCO3)

Test temperature:

20 - 21 °C

pH:

8.2- 8.6

Dissolved oxygen:

5.7 - 8.9 mg/L

Nominal and measured concentrations:

Nominal test substance concentrations:
1.6, 3.1, 6.3, 13 and 25 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: glass beakers (250 mL)
- Material, size, fill volume: glass, 200 mL fill volume
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4
- No. of vessels per vehicle control (replicates): 4

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: fortified and filtered well water
- Total organic carbon: 0.29 mg/L
- Alkalinity: as CaCO3: 90 mg/L
- Conductivity: 680 µS/cm
- Culture medium different from test medium: no
- Intervals of water quality measurement: after 0, 24 and 48 hours

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16:8 h day-night regime
- Light intensity: 750 - 860 lux

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mobility after 24 and 48 hours of exposure

TEST CONCENTRATIONS
- Test concentrations: 0.0010, 0.010, 0.10 and 1.0 mg/L, a control and a solvent (THF) control.
- Results used to determine the conditions for the definitive study: no immobilisation observed at any of the tested concentrations

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

13 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

> 25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Behavioural abnormalities: Several Daphnids were observed to be lethargic at a concentration of 25 mg/L
- Mortality of control: none
The average measured TOC concentrations in solvent control and treatment solutions ranged from 19.03 to 24.94 mg C/L. A concentration gradient was not observed. The comparable TOC content in all treatments and the solvent control indicates that the measured organic carbon originated from the solubiliser THF. The concentration of the hydrolysis products of the test substance could not be determined.

Results with reference substance (positive control):

EC50 (24 h): 1.9 mg/L
The reference test was conducted from 27 - 28 Feb 2012.

Reported statistics and error estimates:

The LC50 was calculated using the computer program CETISTM (Ives, 2011)

Cumulative Immobilisation (%) after 24 and 48 hours (mean of all replicates)

Nominal Concentration (mg/L)	Cumulative Percent Immobilization (%)^a
	24 h	48 h
Control	0	0
Solvent Control	0	0
1.6	0	0
3.1	5(a)	5(a)
6.3	0	0
13	0	0
25	0	0

(a)

ASTM (2002) recognizes the limitations of acute toxicity testing, i.e., response less than or equal to 10% is allowable in a control population and is considered within the expected range of naturally occurring variability. Therefore, the immobilization (5%) observed in the 3.1 mg/L treatment level is not considered an adverse response from exposure to the test substance. 

ASTM, 2002. Standard practice for conducting acute toxicity tests with fishes, macroinvertebrates and amphibians. Standard E729-88a. American Society for Testing and Materials, 100 Barr Harbor Drive, West Conshohocken, Pennsylvania.

Validity criteria fulfilled:

yes

Conclusions:

The study with Daphnia magna as the test organism resulted in an EC50 (48 h) of > 25 mg/L. Tetrahydrofuran was used as a vehicle. The study was conducted accordint to OECD guideline and GLP standards.

Description of key information

EC50 (48 h) > 100 mg/L (OECD 202, D. magna, read across from CAS No. 227085-51-0), equivalent to > 81 mg/L when expressed in terms of the silanol hydrolysis product of the source substance, N-ethyl-3-trihydroxysilyl-2-methylpropanamine

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

> 81 mg/L

Additional information

A 48-hour EC50 value of > 25 mg/L and NOEC of ≥ 25 mg/L have been determined for the effects of the test substance on mobility of Daphnia magna. The results are expressed relative to nominal concentrations of the test substance. The corresponding mean measured concentration of the substance in the treated test medium over the course of the test could not be determinate. No effects could be detected up to the highest tested concentration but the maximum concentration used (25 mg/L) was well below the predicted solubility of the substance (13000 mg/L) and so does not provide an accurate representation of the likely toxicity of the substance.

Therefore it was considered appropriate to read across from the structurally analogous substance N-ethyl-3-trimethoxysilyl-2-methylpropanamine (CAS No. 227085-51-0). A limit test was conducted at a test concentration of 100 mg/l (OECD 202).

No effects were observed at this concentration to Daphnia magna. As the substance is subject to rapid hydrolysis, it is therefore likely that the test organisms were also exposed to hydrolysis products retained in the test media.

The results may be expressed in terms of concentration of the silanol hydrolysis product,N-ethyl-3-trihydroxysilyl-2-methylpropanamine, by applying a molecular weight correction: (MW of silanol (source) = 179.29 / MW of parent (source) = 221.37) * 100 = 81 mg/L.