Reaction mass of methyl acetate and methanol

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

fish life cycle toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 2

Endpoint:

long-term toxicity to fish, other

Remarks:

acute-to-chronic ratios (ACRs)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Principles of method if other than guideline:

Review of acute-to-chronic ratios based on an extensive data set of 456 aquatic invertebrate and fish.

GLP compliance:

no

Remarks on result:

other: Median ACR for chemicals classified as nonpolar narcotics: 9.9

Details on results:

Median ACR for chemicals classified to act as nonpolar narcotics: 9.9

Validity criteria fulfilled:

not applicable

Conclusions:

In a study on the variability of acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action, the median ACR for chemicals classified as nonpolar narcotics was determined to be 9.9.

Reference 3

Endpoint:

long-term toxicity to fish, other

Remarks:

acute-to-chronic ratios (ACRs)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Principles of method if other than guideline:

Study on the variability of acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action.

GLP compliance:

no

Remarks on result:

other: Average ACR for nonpolar narcotics: 2.58 +/- 1.57

Details on results:

Average ACR for nonpolar narcotics: 2.58 +/- 1.57

Validity criteria fulfilled:

not applicable

Conclusions:

In a study on the variability of acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action, the median ACR for chemicals classified as nonpolar narcotics was determined to be 2.58 +/- 1.57. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class.

Reference 4

Endpoint:

fish early-life stage toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to IUCLID section 13 for Read Across Justification.

Reason / purpose for cross-reference:

read-across source

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

14 536 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Remarks on result:

other: 95% CL: 12798-16590

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

9 164 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Remarks on result:

other: 95% CL: 7900-10586

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

10 270 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Remarks on result:

other: 95% CL: 9322-11376

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

39 505 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

9 638 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2 and 10 each

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

5 609 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Reference 5

Endpoint:

long-term toxicity to fish, other

Remarks:

acute-to-chronic ratios (ACRs)

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to IUCLID section 13 for Read Across Justification.

Reason / purpose for cross-reference:

read-across source

Remarks on result:

other: Median ACR for chemicals classified as nonpolar narcotics: 9.9

Reference 6

Endpoint:

long-term toxicity to fish, other

Remarks:

acute-to-chronic ratios (ACRs)

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to IUCLID section 13 for Read Across Justification.

Reason / purpose for cross-reference:

read-across source

Remarks on result:

other: Average ACR for nonpolar narcotics: 2.58 +/- 1.57

Reference 7

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Early lifestage bioassay. An in vitro fertilization method was used to study the effects on Medaka embryos reared either from 0.5 h or 6.5 h post-fertilization for 200 h.

GLP compliance:

not specified

Analytical monitoring:

yes

Details on sampling:

Concentrations: nominal values of 0.30, 0.50, and 2.00% v/v were measured through time (from 0 - 168 h) in 20 mL vials containing 2 mL of the respective nominal concentrations

Vehicle:

no

Test organisms (species):

Oryzias latipes

Details on test organisms:

TEST ORGANISM
- Common name: Medaka
- Strain: orange-red strain
- Source: laboratory by first author
- Age at study initiation: 0.5 (embryo stage 2) and 6.5 h (embryo stage 10) post-fertilization

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

200 h

Post exposure observation period:

72 h

Hardness:

no data

Test temperature:

25 ± 1°C

pH:

no data

Dissolved oxygen:

no data

Nominal and measured concentrations:

474, 1027, 1975, 3950, 7900, 11850, 15800 mg/L (nominal) (re-calculated from % v/v data provided)

Details on test conditions:

TEST SYSTEM
- Test vessel: vials containing 2 mL test solution
- Renewal rate of test solution: without renewal
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 5
- No. of vessels per control (replicates): 5
- No. of vessels per negative control (replicates): 5
- all experiments were run twice

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Rearing medium (RM)

OTHER TEST CONDITIONS
- Photoperiod: 16 h light, 8 h dark

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
daily: mortality (absence of heartbeat and blood stagnation), hatching failure (unable to hatch by day 21 after fertilization), any deviation from normal development

Reference substance (positive control):

no

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

14 536 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Remarks on result:

other: 95% CL: 12798-16590

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

9 164 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Remarks on result:

other: 95% CL: 7900-10586

Duration:

200 h

Dose descriptor:

EC50

Effect conc.:

10 270 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Remarks on result:

other: 95% CL: 9322-11376

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

39 505 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Duration:

200 h

Dose descriptor:

LOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

7 900 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

15 800 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Key result

Duration:

200 h

Dose descriptor:

NOEC

Effect conc.:

11 850 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 10

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 2

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

9 638 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Larva swim bladder inflation for stage 2 and 10 each

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

5 609 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 2

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

other: % Embryo-cardiovascular for stage 10

Duration:

200 h

Dose descriptor:

other: MATC

Effect conc.:

13 667 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

number hatched

Remarks:

for stage 10

Details on results:

Based on anatomical abnormalities no differences between both time windows (stage 2 and 10) were observed at concentrations of methanol ≤ 1975 mg/L. Only hatching success (EC50 14536 mg/L) points to the earlier window of exposure as significantly more sensitive.

Reported statistics and error estimates:

In an effort to normalize the distributions and to stabilize the variances, proportional data were transformed using the arcsine square root and continuous data were log-transformed. Differences from the controls and between treatments were identified with Dunnet’s procedure and Tukey–Kramer’s analysis (P < 0.05), respectively. When data were not normally distributed, the Wilcoxon’s sign-rank test was applied (P < 0.05). The designated known control vial used in each assay as temporal reference for normal development was excluded from statistical analysis. For the analytical studies, differences between sample concentrations were identified with one-way ANOVA and the Wilcoxon’s sign-rank test (P < 0.05). These tests were done using JMP statistical software (SAS, Cary, NC).

All effect concentrations given under results and discussions were re-calculated from % v/v data provided in publication.

Validity criteria fulfilled:

not applicable

Conclusions:

In a 200-hours early lifeestage test (non-guideline) with Medaka fish the 200-hour NOEC based on % embryo with cardiovascular effects for stage 2 and 10 as well as based on the the hatching success for stage 10 were determined to be 15800 mg/L (meas. not specified). The 200-hour NOEC for hatching success in stage 2 was found to be 7900 mg/L (meas., not specified), the 200-hour NOEC based on % Larva swim bladder inflation for stage 2 was 11850 mg/L (meas., not specified).

Executive summary:

The chronic effects of the test item to embryos of Medaka fish (Oryzias latipes) of the orange-red strain were investigated in a static early lifestage bioassay (non-guideline). Embryos (5 animals per vessel, 5 replicates per treatment) were exposed over 200 hours to nominal test item concentrations of 0 (negative control), 474, 1027, 1975, 3950, 7900, 11850, 15800 mg/L (re-calculated from % v/v data provided). All experiments were run twice and the post exposure period was about 72 hours. Based on anatomical abnormalities no differences between both time windows (stage 2 and 10) were observed at concentrations of methanol ≤ 1975 mg/L. Only the hatching success (EC50 14536 mg/L) points to the earlier window of exposure as significantly more sensitive. As a result, the NOEC (200 h) based on % embryo with cardiovascular effects for stage 2 and 10 as well as the hatching success for stage 10, respectively, were determined to be 15800 mg/L (meas. not specified). The 200-hour NOEC for hatching success in stage 2 was found to be 7900 mg/L (meas., not specified), the 200-hour NOEC based on % Larva swim bladder inflation for stage 2 was 11850 mg/L (meas., not specified).

Description of key information

In compliance with section 1 of Annex XI to Regulation (EC) 1907/2006 (REACH) the study on long-term toxicity to fish was waived because the chemical safety assessment of the registration substance did not reveal the need to investigate further effects on fish. However, based on a read-across approach to the structural analogue Methanol (CAS 67 -56 -1) a NOEC of 7900 mg/L was derived.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

7 900 mg/L

Additional information

According to section 1 of Annex XI to Regulation (EC) 1907/2006 (REACH) testing of long-term toxicity to fish shall be proposed by the registrant if the chemical safety assessment indicates the need to investigate further effects on fish. The registration substance is neither classified for environmental hazards according to Regulation (EC) 1272/2008 (CLP), nor is it identified as PBT or vPvB substance, nor are there any further indications that the substance may be hazardous to the environment. This conclusion is supported by assessments for the structural analogues Methanol (CAS 67-56-1) and Methyl acetate (CAS 79-20-9) provided in its public ECHA REACH dossiers demonstrating that long-term toxicity to fish is not to be expected. Therefore, generating additional data is scientifically not justified.

Nevertheless, supporting information available for the structural analogue Methanol is presented below.

Supporting information

In an in vitro early lifestage bioassay by Gonzales-Doncel et al. (2008) embryos of Oryzias latipes (5 organisms per test vessel, 5 replicates per concentration and control) were exposed for 200 hours to a static regime with nominal test item concentrations of 474, 1027, 1975, 3950, 7900, 11850, 15800 mg Methanol/L. The following effect parameters were recorded daily: mortality (absence of heartbeat and blood stagnation), hatching failure (unable to hatch by day 21 after fertilization), any deviation from normal development. Based on anatomical abnormalities no differences between stage 2 and 10 were observed at concentrations of Methanol ≤ 1975 mg/L. Only hatching success (EC50 14536 mg/L) points to the earlier window of exposure as significantly more sensitive. In result, NOECs determined for the test item ranged between 7900 - 15800 mg/L.

Roex et al. (2000) and Raimondo et al. (2007) investigated the variability in acute-to-chronic ratios (ACRs) based on an extensive data set on acute aquatic toxicity of various chemicals. As a result, Roex et al. (2000) derived an average ACR for nonpolar narcotics of 2.58 +/- 1.57. According to Raimondo et al. (2007) the median ACR for chemicals classified as nonpolar narcotics is 9.9, which is in the same order of magnitude as the ACR determined by Roex et al. (2000).

Toxicity of Methanol to early-life stages of fish has been investigated by Chromcova et. al. (2012) and Zeljenkova et.al. (2004) (for details please refer to IUCLID scetion 6.1.1). In a semi-static Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages Test according to OECD Guideline 212 the 96 h NOEC (morphology) of the test item was determined to be 0.5 % v/v which corresponds to 3.95 g/L (Chromcova et al., 2012). To compare the acute toxicity data in adult zebrafish (Danio rerio) to fish eggs a test according to the OECD guidelines 203 and 210, respectively, was performed (Zeljenkova et al., 2006). In result, the 96-hour LC50 (adult fish) was 22300 mg/L and the 96-hour LC50 (fish embryo) was 290 mg/L.

Conclusion

In accordance with section 1 of Annex XI to Regulation (EC) 1907/2006 (REACH) the study on long-term toxicity to fish was waived because the chemical safety assessment of the registration substance did not reveal the need to investigate further effects on fish. This conclusion is supported by information on long-term toxicity available for the source substance Methanol. By applying a worst case approach and based on the most relevant and reliable information (Gonzales-Doncel et al., 2008) the NOEC for long-term toxicity to fish was determined to be 7900 mg/L.