2-Oxepanone, polymer with 1,6-hexanediol

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)

Remarks:

The study on a similar substance serves as data source for the endpoint study record "TARGET - Short-term toxicity to fish - Capa 2043" and the justification for read-across is provided there.

Adequacy of study:

key study

Study period:

20 July 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Confirmatory analysis is inadequate for test solutions

Justification for type of information:

Study serves as data source; read-across justification is found in Target record.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

no

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

A sample of 1 ml was taken from the old and new test solutions of the highest four concentrations on each day of the study. These samples were qualitatively analyzed by HPLC. As Capa-203 consists of a mixture of components the chromatogram measured at 218 nm shows a number of peaks.

As no samples of the pure components (i.e. analytical standards) of Capa-203 were available no quantitative conclusions could be drawn.
The chromatogram of freshly prepared and 24 hours old solutions were only compared qualitatively.

From each freshly prepared clear saturated solution (stock solution) a sample of 50 ml was taken for determination of the total organic carbon content (TOC). These determinations were done by Centrilab, Soest, The Netherlands. To avoid precipitation the solutions were diluted 1:1 with ISO-water before shipment.

Vehicle:

no

Details on test solutions:

The test was conducted using semi-static conditions (media renewal every 24 hours).

In order to simulate an accidental spill a saturated solution of Capa-203 was made by adding 6.5 g Capa-203 to 6.5 L of ISO-water under stirring by an ultra-turrax to provide a nominal stock solution at 1 g/L. Stirring was continued for 10 minutes which resulted in a turbid emulsion.

A clear solution was obtained by filtration through a nylon membrane filter (Gelman, Nylaflo, 0.45 pm) under vacuum. Dilutions were made by making up 1500, 750, 375,187 and 95 mL of the saturated solution to 3 L with ISO-water.

A control with ISO-water was included in the test.

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

The zebra fish used on the study originated from a commercial supplier, Ruinemans, Montfoort, The Netherlands. The batch of fish were received on the 20 May 1992 and held in a plastic container 40 x 60 x40 cm containing ca. 80L of reconstituted ISO-water which was continuously filtered and aerated. The aquaria were kept in a room at 21 ± 1˚C.

The fish were fed troutfeed and Daphnia (waterfleas).

Stock fish held at 21 ± 1˚C test conducted at ca. 23˚C.

The fish used in the final test were 2.3 - 2.9 cm long and had a mean weight of 0.25 g per fish.

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Post exposure observation period:

Not applicable

Hardness:

Hardness of ISO reconstituted water ca. 250 mg/L.

Test temperature:

The temperature of the test solutions varied between 22.0 and 23.8 °C.

pH:

The pH of the test solutions ranged from 7.3 to 8.0 during the test, except in one aquarium with dead fishes where the pH was 6.6.

Dissolved oxygen:

The dissolved oxygen concentration was between 5.3 and 9.5 mg/L.
In the aquarium with dead fishes (140 mg/L) the O2 concentration dropped to 1.8 mg/L.

Salinity:

Not applicable

Nominal and measured concentrations:

Nominal concentrations: 0, 19, 38 , 75, 150, 300 and 600 mg/L.
Measured concentrations: 0, 18, 35, 70, 140, 289 and 560 mg/L (Based on TOC analysis of initial saturated solution and calculation).
As % nominal: NA, 95, 92, 93, 93, 96 and 93%

Details on test conditions:

The initial saturated stock was prepared to simulate and accidental spill

Test media reconstituted ISO water:
Deionised water
CaCl2.2H2O - 294 mg/L
MgSO4. 7H2O - 123 mg/L
NaHCO3 - 64 mg/L
KCl - 5.8 mg/L
pH 7.8

Test solutions were aerated during the test and the light regime was 16 h light and 8 h dark.

Reference substance (positive control):

yes

Remarks:

Potassium bichromate

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

72 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Remarks on result:

other: 35 and 140 mg/L

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

140 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

35 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

<= 18 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

behaviour

Details on results:

All fishes exposed to 280 and 560 mg Capa-203/L were dead within 3 hours, and were removed from the aquaria. All fishes exposed to 140 mg/L died within 24 hours, but stayed in the aquarium during this whole period which influenced the pH and O2 concentration of the test solution.
40% mortality occurred after 96 hours when zebra fishes were exposed to 70 mg Capa-203/L. At lower concentrations no mortality was observed.
As the mortality in the controls is below 10%, the study meets the criterion.

Sub-lethal observations were identified at all test concentrations during the test, the sub lethal effects were uncontrolled and hypoactivity.

Results with reference substance (positive control):

Once a year an acute toxicity test with Brachydanio rerio and the reference substance, potassium bichromate, is conducted. The most recent test (as of the date when the current study was performed) was conducted in April 1992. The 96 h EC50 found in this reference test was 142 mg/L (study number C.REF.51.006b).

Reported statistics and error estimates:

The percentage mortality was plotted against the test concentration using a probit analysis model. From the results it was concluded that the 96 h-LC50 was 72 mg/L, with confidence limits of 35 and 140 mg/L.

Sublethal observations / clinical signs:

Fish mortality and sub-lethal observation during the study are presented below.

Calculated test concentrations (mg/L)	Number of surviving zebra fish per test vessel						% mortality
	0 h	3 h	24 h	48 h	72 h	96 h
0 (control)	10	10	10	10	10	10	0
18	10	10	10	10^4)	10^4)	10^5)	0
35	10	10	10	10^3)	10^3)	10^6)	0
70	10	10^1)	7	6^3)	6^3)	6^3)	40
140	10	1^2)	0	0	0	0	100
280	10	0	0	0	0	0	100
560	10	0	0	0	0	0	100

1) one fish showed uncontrolled movement

2) one fish showed hypo activity

3) all fishes showed uncontrolled movement and hypo activity

4) 5 fishes showed uncontrolled movement and hypo activity

5) 2 fishes showed uncontrolled movement and hypo activity

6) 4 fishes showed uncontrolled movement and 10 fishes showed hypo activity

Validity criteria fulfilled:

yes

Conclusions:

Zebra fish were exposed to Capa-203 at calculated concentrations of 18, 35, 70, 140, 280 and 560 mg/L in a semi-static 96 -hour acute toxicity test according to OECD 203 guidelines. The test design included an untreated control comprising of ISO dilution water only.
The 96-hour LC50 determined was 72 mg Capa-203/L (based calculated concentrations).

Executive summary:

Zebra fish were exposed to Capa-203 at calculated concentrations of 18, 35, 70, 140, 280 and 560 mg/L in a semi-static 96 -hour acute toxicity test according to OECD 203 guidelines. The test design included an untreated control comprising of ISO dilution water only.

The 96-hour LC50 determined was 72 mg Capa-203/L (based calculated concentrations).

This test was conducted in accordance with the 1984 version of the OECD 203 guideline. The current guideline of 1994 states that there must be evidence that the concentration of the substance being tested has been satisfactorily maintained and preferably it should be at least 80% of the nominal concentration throughout the test. This reported study was conducted prior to the issue of the 1994 OECD 203 document and therefore samples of test media have not been determines using an appropriate analytical method.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

key study

Study period:

20 July 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Confirmatory analysis is inadequate for test solutions

Justification for type of information:

It is considered appropriate to address the short-term toxicity to fish data requirement for 2-oxepanone, polymer with 1,6-hexanediol by applying read-across from available experimental study data on 2-oxepanone, polymer with 1,4-butanediol. The source and target substances are low molecular weight polyester diols terminated by primary hydroxyl groups and are structurally similar in that they both contain 6-hydroxyhexanoic acid repeating units. The linking unit is 1,4-butanediol in 2-oxepanone, polymer with 1,4-butanediol and 1,6-hexanediol in 2-oxepanone, polymer with 1,6-hexanediol. The diols differ by two carbons in the aliphatic chain and are therefore sufficiently structurally similar to support a read-across approach. The source and target substances share similar physico-chemical properties in that both are liquids at room temperature and have similar water solubility and log Pow values. The substances are therefore sufficiently similar in terms of basic physico-chemical properties to support a read-across approach. A read-across justification document is attached in section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

72 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Remarks on result:

other: 35 and 140 mg/L

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

140 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

35 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

<= 18 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Total organic carbon

Basis for effect:

behaviour

Details on results:

All fishes exposed to 280 and 560 mg Capa-203/L were dead within 3 hours, and were removed from the aquaria. All fishes exposed to 140 mg/L died within 24 hours, but stayed in the aquarium during this whole period which influenced the pH and O2 concentration of the test solution.

40% mortality occurred after 96 hours when zebra fishes were exposed to 70 mg Capa-203/L. At lower concentrations no mortality was observed.
As the mortality in the controls is below 10%, the study meets the criterion.

Sub-lethal observations were identified at all test concentrations during the test, the sub lethal effects were uncontrolled and hypoactivity.

Results with reference substance (positive control):

Once a year an acute toxicity test with Brachydanio rerio and the reference substance, potassium bichromate, is conducted. The most recent test (as of the date when the current study was performed) was conducted in April 1992. The 96 h EC50 found in this reference test was 142 mg/L (study number C.REF.51.006b).

Reported statistics and error estimates:

The percentage mortality was plotted against the test concentration using a probit analysis model. From the results it was concluded that the 96 h-LC50 was 72 mg/L, with confidence limits of 35 and 140 mg/L.

Sublethal observations / clinical signs:

Fish mortality and sub-lethal observation during the study are presented below.

Calculated test concentrations (mg/L)	Number of surviving zebra fish per test vessel						% mortality
	0 h	3 h	24 h	48 h	72 h	96 h
0 (control)	10	10	10	10	10	10	0
18	10	10	10	10^4)	10^4)	10^5)	0
35	10	10	10	10^3)	10^3)	10^6)	0
70	10	10^1)	7	6^3)	6^3)	6^3)	40
140	10	1^2)	0	0	0	0	100
280	10	0	0	0	0	0	100
560	10	0	0	0	0	0	100

1) one fish showed uncontrolled movement

2) one fish showed hypo activity

3) all fishes showed uncontrolled movement and hypo activity

4) 5 fishes showed uncontrolled movement and hypo activity

5) 2 fishes showed uncontrolled movement and hypo activity

6) 4 fishes showed uncontrolled movement and 10 fishes showed hypo activity

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of the target substance 2-oxepanone, polymer with 1,6-hexanediol to Zebra fish is estimated to be a 96 h LC50 = 72 mg/L, based on read-across from a reliable study testing Capa-203 (2-oxepanone, polymer with 1,4-butanediol).

Executive summary:

Zebra fish were exposed to Capa-203 (2-oxepanone, polymer with 1,4-butanediol) at calculated concentrations of 18, 35, 70, 140, 280 and 560 mg/L in a semi-static 96 -hour acute toxicity test according to OECD 203 guidelines. The test design included an untreated control comprising of ISO dilution water only. The 96-hour LC50 determined was 72 mg Capa-203/L (based calculated concentrations). This test was conducted in accordance with the 1984 version of the OECD 203 guideline. The current guideline of 1994 states that there must be evidence that the concentration of the substance being tested has been satisfactorily maintained and preferably it should be at least 80% of the nominal concentration throughout the test.This reported study was conducted prior to the issue of the 1994 OECD 203 document and therefore samples of test media have not been determines using an appropriate analytical method.

The basic physico-chemical properties and chemical structural of the source substance Capa-203 and the target substance Capa-2047A (2-oxepanone, polymer with 1,6-hexanediol) are considered to be sufficiently similar to support a read-across approach. Therefore, the target substance Capa-2047A is also concluded to have a 96-h LC50 value of 72 mg/L.      

Description of key information

The acute toxicity of the target substance 2-oxepanone, polymer with 1,6-hexanediol to Zebra fish is estimated to be a 96 h LC50 = 72 mg/L, based on read-across from a reliable study testing Capa-203 (2-oxepanone, polymer with 1,4-butanediol).

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

72 mg/L

Additional information

Zebra fish were exposed to the read-across substance Capa-203 (2-oxepanone, polymer with 1,4-butanediol) at calculated concentrations of 18, 35, 70, 140, 280 and 560 mg/L in a semi-static 96 -hour acute toxicity test according to OECD 203 guidelines. The test design included an untreated control comprising of ISO dilution water only. The 96-hour LC50 determined was 72 mg Capa-203/L (based calculated concentrations). This test was conducted in accordance with the 1984 version of the OECD 203 guideline. The current guideline of 1994 states that there must be evidence that the concentration of the substance being tested has been satisfactorily maintained, and preferably it should be at least 80% of the nominal concentration throughout the test. This reported study was conducted prior to the issue of the 1994 OECD 203 document and therefore samples of test media have not been determines using an appropriate analytical method.

The basic physico-chemical properties and chemical structural of the source substance Capa-203 and the target substance Capa-2047A (2-oxepanone, polymer with 1,6-hexanediol) are considered to be sufficiently similar to support a read-across approach. Therefore, the target substance Capa-2047A is also concluded to have a 96-h LC50 value of 72 mg/L.