Reaction mass of 2,2'-(Ethylenedioxy)diethanol and 3,6,9-Trioxaundecane-1,11-diol

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: ASTM (American Society for Testing and Materials) Subcommittee E 47.01, Draft No. 1, "Draft proposed standard practice for conducting renewal life cycle toxicity tests with Daphnia magna"

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Purity, including information on contaminants, isomers, etc.: technical grade (around 85-90%)

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Age at study initiation (mean and range, SD): less than 24 h of age
- Feeding during test : yes
- Food type: trout chow (Rangen's) and Algae (S. capricornutum)
- Amount:15 mg(l trout chow and app. 10 mg/l algae
- Frequency: three times per week

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

240 - 310 mg/L

Test temperature:

21 - 23 °C

pH:

7.2 - 8.5

Dissolved oxygen:

5.0 - 7.5 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: Beaker
- Type (delete if not applicable): closed
- Material, size, headspace, fill volume: glass, 200 mL
- Aeration: no
- Renewal rate of test solution (frequency/flow rate): each Monday, Wednesday and Friday
- No. of organisms per vessel: 4 of 11 beakers contained 5 daphnids each for measurement of survival and growth, 7 of 11 beakers contained 1 daphnid each for measurement of reproduction
- No. of vessels per concentration (replicates):11
- No. of vessels per control (replicates): 11

TEST MEDIUM / WATER PARAMETERS
- Intervals of water quality measurement: once per week on new an 2-day-old test solution. Tempurature was recorded daily.

OTHER TEST CONDITIONS
- Adjustment of pH: no


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
survival and reproduction were measured on the renewal days
growth was measured on Days 7 and 21

TEST CONCENTRATIONS
- Test concentrations: five or more concentration and control

Key result

Duration:

21 d

Dose descriptor:

EC50

Effect conc.:

33 911 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

7 500 - 15 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

> 15 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks:

and survival

Details on results:

7d: EC50 = 40538 mg/L; NOEC > 15000 mg/L
14d: EC50 = 39356 mg/L; NOEC > 15000 mg/L

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: ASTM E-47.01, Draft No. 2

Principles of method if other than guideline:

- ASTM E-47.01, Draft No. 2, 1982 (Standard Practice for Conducting Life-Cycle Toxicity Tests With Saltwater Mysid Shrimp)

GLP compliance:

no

Analytical monitoring:

yes

Details on sampling:

- Concentrations: TEG concentrations in test water were measured weekly

Vehicle:

no

Test organisms (species):

Americamysis bahia (previous name: Mysidopsis bahia)

Test type:

flow-through

Water media type:

saltwater

Limit test:

no

Total exposure duration:

23 d

Test temperature:

25 +/- 2 °C

pH:

7.77 - 7.83

Dissolved oxygen:

6.8 - 7.2 mg/L

Salinity:

20 +/- 2 parts per hundred

Nominal and measured concentrations:

- Concentrations (mg/L): 3.2, 10, 32, 100, 320, 1000 (nominal)
- Concentrations (mg/L): ND*, 10, 31, 102, 380, 1000 (measured)

Key result

Duration:

23 d

Dose descriptor:

LC50

Effect conc.:

> 1 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Key result

Duration:

23 d

Dose descriptor:

NOEC

Effect conc.:

>= 1 000 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

reproduction

Details on results:

In the entire life-cycle toxicity test with Mysidopsis bahia, survival, average number of young released in the first brood per female, and number of
reproductively active females in the TEG treatments were not significantly different from that of seawater control.

Conc. nominal [mg/L]	Conc. measured [mg/L]	Survival [%]	Reproductivity  [%]	Day of first brood	Average Number of Young in first brood per Female
control	ND	77	33	18	3.2
3,2	ND	71	38	19	4.2
10	10	73	34	18	4.5
32	31	63	41	19	5.7
100	102	58	48	19	5.5
320	380	67	45	19	4.7
1000	1000	58	39	20	3.8

Reference 3

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
ECOSAR v2.00

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the toxicity to aquatic organisms: Daphnids: 48-h EC50; this data can be used to support the assessment regarding the toxicity of a substance to
aquatic organisms (see also attached QPRF).

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v2.00: Estimation of chronic toxicity to Daphnids for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Test organisms (species):

other: Daphnids

Water media type:

freshwater

Total exposure duration:

16 d

Remarks on exposure duration:

chronic exposure (duration not specified)

Duration:

16 d

Dose descriptor:

other: Chronic Value (ChV)

Effect conc.:

4 288 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: chronic toxicity (not specified)

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"; The substance is in the applicability domain of the model.

Reference 4

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Principles of method if other than guideline:

Reproduction test with the waterflea Daphnia magna under standardised test conditions.

GLP compliance:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: American Scientific Products Co.
- Purity, including information on contaminants, isomers, etc.: anayltical grade

Analytical monitoring:

no

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Age at study initiation (mean and range, SD): <= 24 h old
- Source: Laboratory stocks cultured at EG&G Bionomics
- Feeding during test yes
- Food type: combination of Rangen Salmon Starter fish food suspension and the unicellular green algae Selenastrum capricornutum
- Amount: Rangen Salmon Starter fish food suspension (5 mg/mL) and the unicellular green algae Selenastrum capricornutum ( 1-2 X 10' cells/mL).
- Frequency: 2 .5 mL of fish food suspension and 1 .0 mL of algae suspension three times daily on weekdays and once daily on weekends

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

28 d

Hardness:

170 mg/L CaCO3

Test temperature:

21°C

pH:

7.3 - 7 .7

Dissolved oxygen:

6.9 - 8.2 mg/L

Nominal and measured concentrations:

Test concentrations (nominal): 0, 1400, 2800, 5500, 11000, and 22000 µL/L
During flowthrough tests performed with triethylene glycol at 19°C, Cardwellet nl. (1978) found that mean measured concentrations remained very close to the nominal concentrations (110% of nominal for triethylene glycol).

Details on test conditions:

TEST SYSTEM
- Test vessel: Aquaria
- Material, size, headspace, fill volume: glass, 1.75 L
- Aeration: no
- Type of flow-through (e.g. peristaltic or proportional diluter): proportional diluter
- Renewal rate of test solution (frequency/flow rate): 4 or 5 aquarium volumes per day
- No. of organisms per vessel: 20
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4

TEST MEDIUM / WATER PARAMETERS
- Intervals of water quality measurement: The dissolved oxygen concentration, temperature, total hardness, alkalinity, specific conductance and pH of the solutions were monitored every weekday within one replicate aquarium of each treatment level and controls .

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16 hr light, 8 hr darkness
- Light intensity: 3-6 hlx

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Adult survival was determined weekly and determination of offspring production were made on weekdays between days' 7 and 28

TEST CONCENTRATIONS
- Range finding study: yes
- Results used to determine the conditions for the definitive study: The approximate threshold response concentrations during the acute toxicity tests were selected as the highest test concentrations during the chronic toxicity tests.

Duration:

28 d

Dose descriptor:

NOEC

Effect conc.:

>= 5 500 other: µl/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Duration:

28 d

Dose descriptor:

NOEC

Effect conc.:

> 6 160 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Remarks on result:

other: converted value from 5500 µl/L

Remarks:

for details see 'Any othe information on results incl. tables'

Details on results:

Survival:
Survival of daphnids was not significantly affected at exposure concentrations of 22000 µL/L during the initial 7 days. Between test day 7 and 14 all daphnids exposed to the highest concentration died. Survival of daphnids exposed to 11000 µL/L was uneffected through the initial 14 days but was significantly reduced by test day 21. Survival of daphnids exposed to 5500 µL/L or lower concentrations was uneffected during the 28 days test duration.
Reproduction:
Daphnids exposed to 11000 µL/L produced offspring in numbers comparable to the controls through test day 13 but subsequently produced significantly fewer offspring relative to the controls. The number of offspring produced by daphnids exposed to 5500 µL/L or lower concentrations was comparable to the number of offspring produced by control daphnids.

Conc.nominal [µL/L]	Survival [%]	Survival [%]	Survival [%]	Survival [%]
	day7	day14	day21	day28
control	99	96	94	91
1400	100	98	91	89
2800	100	94	88	86
5500	100	92	90	86
11000	98	86	55	29
22000	91	0	0	0

Convertion of 5500 µ/L:

m = Rho * V

Per Liter: V = 5500 µL = 5.5 mL = 0,0055 L

Rho (Diethylen glycol density) = 1,12 g/cm³ = 1120 000 mg/L

m = 0,0055 L * 1120 000 mg/L = 6160 mg

Overall, 5500 µL = 6160 mg/L

Reference 5

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
ECOSAR v2.00

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the toxicity to aquatic organisms: Daphnids: 48-h EC50; this data can be used to support the assessment regarding the toxicity of a substance to
aquatic organisms (see also attached QPRF).

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v2.00: Estimation of chronic toxicity to Daphnids for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Test organisms (species):

other: Daphnids

Water media type:

freshwater

Total exposure duration:

16 d

Remarks on exposure duration:

chronic exposure (duration not specified)

Duration:

16 d

Dose descriptor:

other: Chronic Value (ChV)

Effect conc.:

8 888 mg/L

95% CI:

8 889

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: chronic toxicity (not specified)

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"; The substance is in the applicability domain of the model.

Description of key information

Overall, experimental and estimated chronic values are clearly greater than 1 mg/L regarding classification limits and also greater than 10 mg/L, which the limit concentration in long-term toxicity testing; therefore, long-term effects on aquatic invertebrates are not to be expected.

Additional information

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met.

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labelling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

For the assessment of the substance (Q)SAR results were used for the estimation of the long-term toxicity to aquatic invertebrates. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment.

Assessment

2,2'-(ethylenedioxy)diethanol 3,6,9-trioxaundecane-1,11-diol (EC 907-131-0) is a multi-constituent substance. The main constituents of EC 907-131-0 are triethylene glycol (TGE, CAS 112-27-6, 10-80% w/w) and tetraethylene glycol (Tetra-EG, CAS 112-60-7, 10-80% w/w). Since no data on the long-term toxicity to fish of the reaction mass of 2,2'-(ethylenedioxy)diethanol 3,6,9-trioxaundecane-1,11-diol are available, the assessment is based on the available data for the main components triethylene glycol (CAS 112-27-6) and tetraethylene glycol (112-60-7).

For the substance triethylene glycol (CAS 112 -27 -6) two key studies and one supporting study are available.

One key and one supporting study measured the effect of triethylene glycol on the reproduction of Daphnia magna (Adams & Heidolph, 1985; LeBlanc & Surprenant, 1983). One study was conducted according to the national standard ASTM (E 47.01, Draft No. 1, "Draft proposed standard practice for conducting renewal life cycle toxicity tests with Daphnia magna"). In this test the Daphnids were exposed to triethylene glycol for 21 days. Based on reproduction the reported NOEC is > 15000 mg/L triethylene glycol (nominal, Adams & Heidolph, 1985).  Supporting reproduction study was conducted under standartised test conditions. The 21 -d NOEC was determined to be > 6120 mg/L (converted from 5500 µL/L, nominal, LeBlanc, 1983).

The second key study with the saltwater shrimp Mysidopsis bahia was conducted according to the standard of ASTM (E-47.01, Draft No. 2, 1982 (Standard Practice for Conducting Life-Cycle Toxicity Tests With Saltwater Mysid Shrimp). The test organisms were exposed to triethylene glycol in a flow-through system for 23 days. Up to the highest test concentration of 1000 mg/L no effect on the reproduction of the saltwater shrimps were observed (nominal, analytically verified, Montgomery et al., 1985).

Additionaly, for both constituents the long-term toxicity to aquatic invertebrates was determined using a valid QSAR model (ECOSAR v2.0; BASF SE, 2022). The ChV for CAS 112-27-6 and CAS 112-60-7 were predicted to be 4288 and 8888 mg/L, respectively. The substance is within the applicability domain of the model.

Overall, experimental and estimated chronic values are clearly greater than 1 mg/L regarding classification limits and also greater than 10 mg/L, which the limit concentration in long-term toxicity testing; therefore, long-term effects on aquatic invertebrates are not to be expected.