2,2'-oxydi(ethylamine)

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Following the read across strategy, this endpoint is covered by a key study performed with the structural analogue BDMAEE (N, N, N', N'-tetramethyl-2,2'-oxybis(ethylamine)). The justification for read across is attached in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

46.4 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

46.4 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

ca. 131.2 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations confirmed by measured values; non pH-adjusted.

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

215 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations confirmed by measured values; non pH-adjusted.

Validity criteria fulfilled:

yes

Conclusions:

No reliable data is available for th test substance. Data generated with the analogue source substance BDMAEE is used for endpoint coverage. The 96-hr LC50 in Danio rerio (Zebra fish) was determined to be 131.2 mg/L under the conditions of the study. The same is assumed to be correct for the test substance.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-05-11 - 1998-05-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

- Concentrations: All test concentrations were sampled and analysed.
- Sampling method: Water samples were taken from the middle of the test vessel using a beaker at study start, after 24 and 48 hours before water renewal and at study end.
- Sample storage conditions before analysis: refrigerator

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The test substance was applied directly to the test water. The mixture was homogenized using an ultra-turrax stirrer

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

TEST ORGANISM
- Common name: Zebra fish
- Source: Bio International B.V., AP Roermond, Netherlands
- Age at study initiation (mean and range, SD): about 7 months
- Length at study initiation (length definition, mean, range and SD): 2.8 cm (2.1 - 3.1 cm)
- Weight at study initiation (mean and range, SD): 0.22 g (0.14 - 0.28 g)
- Feeding during test: no, withdrawal of food 1 day before test start

ACCLIMATION
- Acclimation period: 14 days
- Acclimation conditions (same as test or not): flow-through tank, unchlorinated charcoal filtered tap water, aeration with oil free air. 16:8 hours light: dark
- Type and amount of food: TETRAMIN standard feed, TETRA-Werke, Melle, Germany; ad libitum, on workdays generally additionally live brine shrimp; daily
- Feeding frequency: daily
- Health during acclimation (any mortality observed): 0% during the last 7 days of acclimatization

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

total hardness: about 2.5 mM
acid capacity: about 5.5 mM

Test temperature:

22 to 23 °C

pH:

8.3 to 9.8

Dissolved oxygen:

6.5 to 8.7 mg O2/L

Nominal and measured concentrations:

nominal test concentrations: 46.4, 100, 215, 464, 1000 mg/L. Additionally a control and a pH-adjusted sample of 1000 mg/L were tested in parallel
mean analytically determined concentrations: 45, 95, 203, 438 and 932 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: all-glass aquaria, 30 cm x 22 cm x 24 cm, 10 L
- Aeration: slight
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate: 3.5 g/L


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: municipal water of the city of Frankenthal (not chlorinated and passed through a charcoal filter
- Total hardness: 2.5 mmol/L
- Acid capacity: 5.5 mmol/L
- pH: about 8.0 to 8.6
- Ca content: about 90 mg/L
- Mg content: about 10 mg/L
- Other: The test water is regularly assayed for chemical contaminants as well as for the presence of microbes.


OTHER TEST CONDITIONS
- Adjustment of pH: the highest test concentration (1000 mg/L) was tested in parallel after pH adjustment with 20% HCl.
- Photoperiod: 16 h light, 8 h dark


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Mortality and symptoms: after 1, 4, 24, 48, 72 and 96 h
- pH, dissolved oxygen and temperature: after 1, 24, 48, 72 and 96 h


TEST CONCENTRATIONS
- Test concentration: 0 (control), 215, 464, and 1000 mg/l
- Range finding study
- Results used to determine the conditions for the definitive study: LC50(96 h): 100-1000 mg/L

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

46.4 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations confirmed by measured values; non pH-adjusted.

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

46.4 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations were confirmed by chemical analysis; non pH-adjusted.

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

ca. 131.2 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations confirmed by measured values; non pH-adjusted.

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

215 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: nominal concentrations were confirmed by measured values; non pH-adjusted.

Details on results:

- Behavioural abnormalities: apathy, swimming near water surface and swimming near bottom were noted in the concentrations >= 100 mg/L
- Mortality of control: 0%
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: Undissolved test item was observed in the concentrations >= 464 mg/L at the bottom of the aquaria. The aqueous phase was cloudy. The analytically detected concentrations were within a range of ±20% of the nominal values.
- Effect concentrations exceeding solubility of substance in test medium: no (mixable up to 10 g/L)
- Other: The pH-adjustment in the additional 100 mg/L group did not decrease the mortality rate over 96 h. Although the fish in the not pH-adjusted test solutions died immediately after placement into the aquaria. The fish in the pH-adjusted test solutions died after 48 h.

Sublethal observations / clinical signs:

Cumulative mortality

Nominal conc. (mg/L)	Number of fish	Mortality (cumulated) after
		1h	4h	24h	48h	72h	96h
0	10	0	0	0	0	0	0
46.4	10	0	0	0	0	0	0
100	10	0	0	0	0	0	1
215	10	0	0	7	10	10	10
464	10	0	8	10	10	10	10
1000	10	10	10	10	10	10	10
1000*	10	0	0	0	10	10	10

*: pH-adjusted

Observed symptoms

(A: Apathy, a: slight to very slight apathy, C: swimming near water surface, D: swimming near bottom)

Nominal conc. (mg/L)	Number of fish	Symptoms after
		1h	4h	24h	48h	72h	96h
0	10
46.4	10
100	10					a10	A9
215	10	a10	a10	C3
464	10	A10 D6	C2
1000	10
1000*	10

* :pH-adjusted

pH values

Nominal conc. (mg/L)	pH values after
	1h	24h	48h	72h	96h
0	8.4	8.3	8.6	8.3	8.5
46.4	8.8	8.4	8.4	8.5	8.5
100	9.1	8.6	8.8	8.6	8.5
215	9.4	9.1	9.1
464	9.5	9.4
1000	9.8
1000*	8.4	8.3	8.5

*: pH-adjusted

Oxygen content

Nominal conc. (mg/L)	Oxygen content (mg/L) after
	1h	24h	48h	72h	96h
0	8.7	7.4	7.3	7.4	7.6
46.4	8.3	6.9	6.5	7.4	7.6
100	8.5	6.9	6.9	7.3	7.7
215	8.5	8.0	8.3
464	8.6	8.5
1000	8.6
1000*	8.7	7.9	7.8

*: pH-adjusted

Analytically detected concentrations (unfiltered samples)

Although undissolved particles of the test compound were visible in the aquaria only unfiltered samples were analyzed.

The samples taken after 24 and 48 hours were drawn before replacement of the test solutions.

Nominal conc. (mg/L)	Analytically detected conc. (unfiltered samples) after
	1 h		24 h		48 h		96 h		Mean
	(mg/L)	(%)	(mg/L)	(%)	(mg/L)	(%)	(mg/L)	(%)	(mg/L)	(%)
0	< 5		< 5		< 5		< 5		< 5
46.4	48	103.4	44	94.8	48	103.4	38	81.9	45	95.9
100	94	94.0	92	92.0	98	98.0	97	97.0	95	95.3
215	211	98.1	187	87.0	212	98.6			203	94.6
464	437	94.2	403	86.9					438	94.4
1000	983	98.3	881	88.1					932	93.2
1000*	998	99.8	905	90.5	978	97.8			960	96.0

*: pH-adjusted

Validity criteria fulfilled:

yes

Conclusions:

The 96-hr LC50 in Danio rerio (Zebra fish) was determined to be 131.2 mg/L under the conditions of this study.

Reference 3

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

QSAR prediction using the most recent version of ECOSAR (2009) - can be used as key information in a weight-of-evidence approach.

Qualifier:

according to guideline

Guideline:

other: ECOSAR v.1.00 (ECOWIN v.1.00)

Principles of method if other than guideline:

QSAR predictions were conducted using ECOSAR v.1.00 (2009) using the QSAR for aliphatic amines

Specific details on test material used for the study:

- 2,2'-oxydi(ethylamine)
- SMILES: NCCOCCN
- Molecular weight = 104.15 g/mol
- A log Kow of -1.89 was used (instead of direct estimation by KowWin)
- A water solubility was entered of 1E+006 mg/L

Test organisms (species):

other: Fish

Details on test organisms:

Fish (not specified)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

4 020.509 mg/L

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

other: Chronic value

Effect conc.:

49.811 mg/L

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

Validity of EC50 model:
1. Defined endpoint: 96-h LC50 for Fish.
2. Unambiguous algorithm: linear regression QSAR; Log 96-h LC50 (mmol/L) = -0.6016  (log Kow) + 0.4479
3. Applicability domain: APPLICATION: This SAR may be used to estimate toxicity for aliphatic amines. LIMITATIONS: For aliphatic amines with log Kow values greater than 7.0, a test duration of greater than 96 hours may be required for proper expression of toxicity.  Also, if the toxicity value obtained by the use of this equation exceeds the water solubility of the compound (measured or estimated), mortalities greater than 50% would not be expected in a saturated solution during an exposure period of 96 hours.
4. Statistical characteristics: The LC50 is in millimoles per liter (mM/L); N = 117 + 23; and the Coefficient of Determination (R2) = 0.7609. 

Validity of chronic value model:
1. Defined endpoint: chronic value for Fish.
2. Unambiguous algorithm: linear regression QSAR; Log ChV (mmol/L) = -0.5648 (log Kow) - 1.3894
3. Applicability domain: APPLICATION: APPLICATION: This SAR may be used to estimate toxicity for aliphatic amines. LIMITATIONS: If the log Kow value is greater than 8.0, or if the compound is solid and the ChV exceeds the water solubility by 10X, no effects at saturation are predicted.
4. Statistical characteristics: The ChV is in millimoles per liter (mM/L); N = 3; and the Coefficient of Determination (R2) = 0.9979

Adequacy of prediction: the substance falls within the applicability domains described above and therefore the predicted values can be considered reliable.

Validity criteria fulfilled:

not specified

Conclusions:

QSAR predictions were conducted using the latest version of US EPA's ECOSAR (v.1.00, 2009) using input values of -1.89 for log Kow and 1E+006 mg/L for water solubility in the QSAR for aliphatic amines. The model predicted a 96-h LC50 and a chronic value for Fish of 4020.509 mg/L and 49.811 mg/L, respectively. Because the substance falls within the applicability domain of the models these predicted values can be considered reliable.

Description of key information

Following the read-across strategy, it is considered appropriate to cover this endpoint by a key study performed with the structural analogue BDMAEE, yielding a 96 h LC50 value of 131.2 mg/L.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

131.2 mg/L

Additional information

The key study, originally performed by BASF (2000) uses Danio rerio as test species. The acute test performed according to OECD 203 results in an LC50 of 131.2 mg/l after 96 hours for the nominal concentrations of BDMAEE. The same is assumed for the test substance BAEE.