4-methylmorpholine

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across GLP study performed according to OECD Guideline 211. An English summary is available from the Japanese authorities and an extensive summary is present in the OECD HPV program files.

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-ethylmorpholine
- Molecular formula (if other than submission substance): C6H13NO
- Molecular weight (if other than submission substance): 115.18
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state:
- Analytical purity: 99.9%
- Lot/batch No.: SEG4563
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Analytical monitoring:

yes

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Strain/clone: crustacea
- Justification for species other than prescribed by test guideline:
- Source:
- Age of parental stock (mean and range, SD): < 24 hours old
- Feeding during test: no
- Food type:
- Amount:
- Frequency:

ACCLIMATION
- Acclimation period: 4 weeks
- Acclimation conditions (same as test or not):
- Type and amount of food: Chlorella vulgaris
- Feeding frequency: 0.2 mg carbon/day/individual
- Health during acclimation (any mortality observed): mortality was less than 5% for 2 weeks before testing

QUARANTINE (wild caught)
- Duration:
- Health/mortality:

METHOD FOR PREPARATION AND COLLECTION OF EARLY INSTARS OR OTHER LIFE STAGES:

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

21 d

Hardness:

250 - 270 mg/L

Test temperature:

20 ± 1 °C

pH:

7.5 - 8.8

Dissolved oxygen:

7.5 - 8.9 mg/L

Nominal and measured concentrations:

Nominal Concentrations: control and 100 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 80 mL test solution in a 100 mL glass beaker covered water surface with teflon sheet and capped.
- Type (delete if not applicable): open / closed
- Material, size, headspace, fill volume:
- Aeration: none
- Type of flow-through (e.g. peristaltic or proportional diluter):
- Renewal rate of test solution (frequency/flow rate):
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates):
- No. of vessels per vehicle control (replicates):
- Biomass loading rate:

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water:
- Total organic carbon:
- Particulate matter:
- Metals:
- Pesticides:
- Chlorine:
- Alkalinity:
- Ca/mg ratio:
- Conductivity:
- Salinity:
- Culture medium different from test medium:
- Intervals of water quality measurement:

OTHER TEST CONDITIONS
- Adjustment of pH: pH on the concentration, 100mg/L (7.5 - 8.4) were higher than pH on the control (8.6 - 8.8). It was considered to be caused by test substance. pH of the test solutions were not adjusted during test period.
- Photoperiod:
- Light intensity: 16:8 hours, light-darkness cycle

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :

VEHICLE CONTROL PERFORMED: yes/no

RANGE-FINDING STUDY
- Test concentrations:
- Results used to determine the conditions for the definitive study:

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Key result

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Details on results:

- Mortality of parent animals: 0% at 100 mg/L
- No. of offspring produced per day per female:
- Body length and weight of parent animals:
- Type and number of morphological abnormalities:
- Type and number of behavioural abnormalities:
- Number of males and females (parental)
- Time to first brood release or time to hatch: All parental daphnids (both control and concentration, 100 mg/L) had first brood after 8 days.
- Egg development time
- Brood size
- Time to sexual maturity
- Type and magnitude of biochemical changes
- Other biological observations:
- Effect concentrations exceeding solubility of substance in test medium:

Results with reference substance (positive control):

- Results with reference substance valid? yes
- Relevant effect levels: 48 h EC50 = 0.75 mg/L
- Other:

Conclusions:

The long-term toxicity of 4-ethylmorpholine to aquatic invertebrates was assessed in an OECD 211 study with Daphnia magna. The following effect values resulted based on the reproduction: NOEC (21 d) = 100 mg/L (MOE, Japan, 2003).

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

read across from related substance

Justification for type of information:

Read-across from structural analogue (4-ethylmorpholine). Justification of this read-across approach is included in section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Key result

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Conclusions:

No reliable data for this endpoint with the target substance is available. Data generated with the related substance 4-ethylmorpholine is used for endpoint coverage. The long-term toxicity of 4-ethylmorpholine to aquatic invertebrates was assessed in an OECD 211 study with Daphnia magna. The following effect values resulted based on the reproduction: NOEC (21d) = 100 mg/L (MOE, Japan, 2003). The same is assumed to be correct for the target substance.

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 4-ethyl morpholine, yielding a NOEC value of 100 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

100 mg/L

Additional information

The long-term toxicity of the structural analogue 4-ethylmorpholine to aquatic invertebrates was assessed in an OECD 211 study with Daphnia magna. The following effect values resulted based on the reproduction: NOEC (21 d) = 100 mg/L (MOE, Japan, 2003). The justification for read-across within this endpoint can be found in section 13.