1,1'-[[3-(dimethylamino)propyl]imino]bispropan-2-ol

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

May 2022

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
EPI Suite v4.1
2. MODEL (incl. version number)
ECOSAR v1.11
The following sub-models are covered for this QSAR analysis, all predicting 48 hour LC50 values for freshwater invertebrates:
-Aliphatic Amines
-Neutral Organic SAR
-Aldehydes (Mono)
-Aliphatic Amines-acid
-Neutral Organics-acid
-Neutral Organics
-Aldehydes (Mono)-acid
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
ECOSAR only requires a chemical structure as SMILES as input. All SMILES codes are available in
the attached QPRF.
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.
5. APPLICABILITY DOMAIN
ECOSAR predictions were also made for acute aquatic toxicity to algae and fish. Only for the substance group Aliphatic amines were invertebrates the most sensitive species. Whereas the structural similarity between the test chemicals and the training set appeared to be limited, a substructure search showed that all substructures occurred in one or more chemicals of the training and/or validation set. A detailed assessment of the applicability domain of this model can be found in the attached QPRF.
6. ADEQUACY OF THE RESULT
The main purpose of this QSAR analysis, was to assess the aquatic toxicity of the predicted biodegradation products of JeffCat DPA (CAS# 63469-23-8) for use in the PBT/vPvB assessment. All predicted effects concentrations were well above the screening criterion for any of the substances to fulfill the T criterion. Therefore, the predictions can be considered appropriate for this use.

Reason / purpose for cross-reference:

other: KOWWIN v1.68 prediction of log Kow of the compounds used in this QSAR analysis as input to estimate the acute toxicity to invertebrates.

Reason / purpose for cross-reference:

other: Record describing the biodegradation products of DPA (CAS# 63469-23-8) predicted by EAWAG-BBD PPS, for which the acute toxicity to invertebrates is estimated.

Principles of method if other than guideline:

Estimation of the acute aquatic toxicity to freshwater invertebrates using ECOSAR v4.11.

GLP compliance:

no

Specific details on test material used for the study:

Predictions were made for the 41 biodegradation products predicted by the EAWAG-BBD PPS tool.

Details on test organisms:

Freshwater invertebrates

The table below lists the ECOSAR v4.11 predictions for the compounds for which invertebrates were the most sensitive species. All results are available in the QPRF.

Name	ECOSAR Aliphatic amine 48 hr LC50 for invertebrates (mg/L)
CC(O)CN(CCC(=O))CC(C)O	364.91
CNCCCN(CC(C)O)CC(C)O	200.284
CC(O)CN(CCCN(C)C)CC(=O)(C)	196.38
CC(O)CNCCCN(C)C	127.462
CC(O)CNCC(C)O	169.835
CN(C)CCC=O	72.783
CC(O)CN(CCC(=O)(O))CC(C)O	243000
CC(O)CN(CCCN)CC(C)O	357.541
CNCCCN(CC(C)O)CC(=O)(C)	246.647
CNCCC=O	84.196
CNCCCNCC(C)O	156.205
CC(O)CN(CCC(=O))CC(=O)(C)	449.025
CN(C)CCCN(CC(=O)(C))CC(=O)(C)	137.178
CN(C)CCCNCC(=O)(C)	88.744
CC(O)CNCC(=O)(C)	208.037
CC(O)CNCCC=O	275.606
CN(C)CCCN	71.65
CC(O)CN	148.947
CN(C)CCC(=O)(O)	51682.398
CC(O)CNCCC(=O)(O)	190000
CC(O)CN(CCC(=O)(O))CC(=O)(C)	299000
CC(O)CN(CCCN)CC(=O)(C)	439.982
CC(O)CNCCCN	270.688
NCCC=O	135.4
CC(=O)CN	102.204
CC(=O)CN(CCC(=O))CC(=O)(C)	313.2
CC(=O)CNCC(=O)(C)	144.433
CC(=O)CNCCC=O	191.345
CNCCC(=O)(O)	61100.922
CNCCCN(CC(=O)(C))CC(=O)(C)	172.179
CNCCCNCC(=O)(C)	108.623
CNCCCN	83.02
CC(=O)CN(CCC(=O)(O))CC(=O)(C)	209000
CC(=O)CNCCC(=O)(O)	132000
CC(=O)CNCCCN	187.953
CN	28.328

Conclusions:

Overall, a very low aquatic toxicity to invertebrates was estimated for the modelled compounds. The lowest LC50 obtained for aquatic invertebrates within the substances identified as aliphatic amines, was 28.328 mg/L.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2001-12-18 to 2001-12-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no analytical verification

Qualifier:

according to guideline

Guideline:

ISO 6341 (Water quality - Determination of the Inhibition of the Mobility of Daphnia magna Straus (Cladocera, Crustacea))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): TOYOCAT-RX4
- Substance type: clear yellowish liquid
- Physical state: liquid
- Analytical purity: 93.1 % (GC)
- Impurities (identity and concentrations): not reported
- Lot/batch No.: 080401
- Expiration date of the lot/batch: 25 October 2002
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in dark

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION
- Preparation of stock solution of 100 mg/L in ISO medium.
- Method: due to the substance's good solubility no special treatment other than magnetic stirring for a short period was necessary
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no, the substance completely dissolved in the test medium at the concentrations tested
- Preparation of test concentrations by subsequent dilutions of the stock in the test medium.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Strain: not reported
- Source: not reported, breeding performed at study laboratory
- Age at study initiation (mean and range, SD): < 24 hours
- Method of breeding:
* 250 of new born daphnids, i.e. less than 3 days old, were kept in 10 liters of medium in an all-glass culture vessel during 4 weeks
* after 7 days of cultivation half of the medium was renewed twice a week
* at 18-22 °C, constant within 1°C
* feeding: daily, a suspension of fresh water algae
* medium: M7 (Elendt, 1990)
- Feeding during test: no

ACCLIMATION
Test animals were not acclimated to test conditions.
Test conditions (temperature, light/dark cycle) similar as during culturing.

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

250 mg/L as CaCO3

Test temperature:

19.6-20.5 °C (blank control)

pH:

pH at start: 8.1 (blank control), 8.2 (0.1 mg/L and 1.0 mg/L), 8.4 (10 mg/L) and 9.4 (100 mg/L)
pH at end: 7.8 (blank control) and 8.4 (100 mg/L )

Dissolved oxygen:

oxygen concentration at start: 9.0 mg/L (blank control) and 9.1 mg/L (100 mg/L)
oxygen concentration at end: 9.4 mg/L (blank control and 100 mg/L)

Salinity:

not applicable

Nominal and measured concentrations:

Nominal: control + 0.1-1.0-10-100 mg/L
(combined range-finding/limit test)

Details on test conditions:

TEST SYSTEM
- Test vessel: all-glass
- Material, size, fill volume: glass, 100 mL, 80 mL
- Aeration: not during test
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 2 (100 mg/L), 1 (dilutions)
- No. of vessels per control (replicates): 2

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: ISO medium prepared from ultra-pure water (i.e. tap water purified by reverse osmosis (milli-RO) and subsequently passed over activated carbon and ion-exchange cartridges)
- Culture medium different from test medium: yes
- Intervals of water quality measurement: pH and oxygen concentration were measured at start and end of test (i.e. after 48 h), measurement of temperature daily in one control vessel

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16 h light daily

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- immobilisation at 24 h and 48 h

TEST CONCENTRATIONS
- Only range finding study performed (because of results used as limit test)
- Spacing factor for test concentrations: 10
- Test concentrations: blank control, 0.1, 1.0, 10 and 100 mg/l
- Results used to determine the conditions for the definitive study: this study was a combined limit and range-finding test

Reference substance (positive control):

yes

Remarks:

K2Cr2O7

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

No immobile daphnids were observed in any of the concentrations tested.

Results with reference substance (positive control):

The actual responses in this reference test potassium dichromate were within the ranges of the expected responses at the different concentrations. Hence, the sensitivity of the used batch of D.magna was in agreement with the historical data collected in the test laboratory.
The 24-h EC50 was 1.3 mg/L with 95 % fiducial limits of 1.0-1.8 mg/L
The 48-h EC50 was 0.55 mg/L with 95 % fiducial limits of 0.48-0.69 mg/L

Reported statistics and error estimates:

No statistics used (no effects observed).

Analytical verification of test concentrations was not included in the test. As the substance is highly soluble in water (miscible) and does not contain any hydrolysable groups, the nominal test concentration is taken as the actual exposure concentration over the test duration. Stability in aqueous solution was confirmed in a recent acute fish toxicity study (Vaughan, 2012) in which the substance was determined to be stable in test dilution water (not further specified) over a 96h period at 120 mg/L, 15 °C, pH 7.5-7.9 and a 16h light and 8h dark photoperiod.

Validity criteria fulfilled:

yes

Conclusions:

During a range-finding study at concentrations up to 100 mg/L, the test substance did not cause immobilization in juvenile Daphnia magna after 48 h of exposure. Therefore the range-finding study can be considered as a definitive limit test resulting in a 48-h EC50 > 100 mg/L.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-10-28 to 2016-12-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: OECD Guidance Document, No.23, September 2000, "Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Daphnia sp., Acute Immobilization Test stipulated in the "Testing Methods for New Chemical Substances"

Version / remarks:

(March 31, 2011, No. 0331-7, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare; March 29, 2011, No. 5, Manufacturing Industries Bureau, Ministry of Economy, Trade and Industry; No. 110331009, Environmental Policy Bureau, Ministry of the Environment, Japan; latest revision, December 21, 2015, No. 1221-1, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare; December 9, 2015, No. 1, Manufacturng i Industries Bureau, Ministry of Economy, Trade and Industry; No. 1512211, Environmental Policy Bureau, Ministry of the Environment, Japan)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Chemical name: Reaction product of 3-dimethylaminopropylamine and propylene oxide with 1,1'-[(3-dimethylaminopropyl)imino]-bis-2-propanol and 1-[(3-dimethylaminopropyl)(2-hydroxy-1-methylethyl)amino]-2-propanol as main component
- Name of test material (as cited in study report): DMAPA-2PO
- CAS number: CAS 63469-23-8 (1,1'-[(3-(dimethylaminopropyl)imino)]-bis-2-propanol)
- Molecular formula: C11H26N2O2 (main component)
- Molecular weight: 218.3 (main component)
- Substance type: yellow liquid
- Physical state: liquid
- Analytical purity: 100 %
- Impurities (identity and concentrations): not reported
- Lot/batch No.: 5Y1024
- Expiration date of the lot/batch: NA
- Stability under test conditions: stable
- Storage condition of test material: cooll and dark place

Analytical monitoring:

yes

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The test sample of 330 mg was weighed and then mixed to dilution water of 3L and stirred to produce a stock solution of 110 mg/L. Required volumes of the stock solution and dilution water were mixed and stirred in a preparation container to prepare the test solution which was divided into each test vessel. In addition, the pH of the 110 mg/L stock solution was adjusted to it of the dilution water with 1 mol/L hydrochloric acid solution to prepare pH adjusted stock solution. Required volumes of the pH adjusted stock solution and dilution water were mixed and stirred in a preparation container to prepare the pH adjusted test solution which was divided into each test vessel.
- Evidence of undissolved material (e.g. precipitate, surface film, etc): final test solutions were clear and colourless

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water-flea
- Source: The University of Sheffield, UK, July 9, 1990
- Age at study initiation (mean and range, SD): < 24 h (from parental daphnids of more than 2 weeks old, maximum age 4 weeks)
- Feeding during cultivation: Chlorella vulgaris of 0.1- 0.2 mgC (Organic carbon content)/day per Daphnia was fed to the parents once a day.
- Feeding during test: no

ACCLIMATION
- Acclimation period: Y mmg daphnids produced by parents that were cultured in this laboratory were used. The parents to obtain young daphnids were bred in the same quality of water (dechlorinated tap water), water temperature (20±1°C) and photoperiod (16-hour light/8-hour dark) as used in the test. The parent animals used for the test were same lot and their age and survival rate were 14-day old and 100%, respectively.

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Hardness:

28 mg/L as CaCO3

Test temperature:

pH unadjusted:
20.0 - 20.2 °C
pH adjusted:
20.2 - 20.3 °C

pH:

pH unadjusted:
7.9 - 9.6 mg/L
pH adjusted:
8.8 - 8.9 mg/L

Dissolved oxygen:

> 3 mg/L

Salinity:

not relevant

Conductivity:

not relevant

Nominal and measured concentrations:

Range finder:
Nominal concentrations: 10 and 100 mg/L

Measured concentrations (static) at t=0h: 6.35, 86.5, 96.9 mg/L (pH adjusted)
Measured concentrations (static) at t=48h: 6.10, 83.8 mg/L

Final test:
Nominal concentrations (pH unadjusted): 21.7, 32.6, 48.9, 73.3, 110 mg/L
Nominal concentrations (pH adjusted): 21.7, 32.6, 48.9, 73.3, 110 mg/L

Measured concentrations (pH unadjusted) at t=0h: n.d., 13.3, 25.9, 39.2, 67.7, 95.8 mg/L
Measured concentrations (pH unadjusted) at t=48h: n.d., 12.2, 27.5, 36.4, 59.96, 99.6 mg/L

Measured concentrations (pH adjusted) at t=0h: 14.5, 27.3, 44.2, 71.4, 109 mg/L
Measured concentrations (pH adjusted) at t=48h: 13.9, 26.1, 40.8, 69.6, 122 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: beaker
- Type (delete if not applicable): Transparent plastic lid
- Material, size, headspace, fill volume: 100 mL, glass beaker filled with 100 mL
- Aeration: not during the test
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4
- Test medium: adjusted ISO medium

OTHER TEST CONDITIONS
- Photoperiod: 16h light daily

EFFECT PARAMETERS MEASURED (with observation intervals if applicable): Immobility was defined as those organisms which are not able to swim within 15 seconds after gentle agitation of the test container and was monitored after 24 and 48 hours of continuous treatment with the test substance.

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 1.5
- Range finding study
- Test concentrations: 10 and 100 mg/L
- Results used to determine the conditions for the definitive study: yes

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Key result

Duration:

48 h

Dose descriptor:

EC50

Remarks:

pH unadjusted

Effect conc.:

> 97.7 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC50

Remarks:

pH adjusted

Effect conc.:

> 115 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Mortality of control: none
- Other adverse effects control: no
- Abnormal responses: none

Results with reference substance (positive control):

- Results with reference substance valid? yes
- Mortality: no
- EC50/LC50: 48-h EC50 = 0.14 mg/L. This value was within the stipulated range (mean± 2S.D.) [mean ± S.D.: 0.23±0.06 mg/L (n=97)] to background data in this laboratory.

Reported statistics and error estimates:

Since more than 50% immobility could not be obtained in the exposure level, the ECso value was estimated as ">maximum test concentration"

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of DMAPA-2PO to Daphnia magna was determined in a 48 hour static test according to OECD guideline 202. Based on geometric mean concentrations, the 48-h EC50 were > 97.7 mg/L (pH unadjusted) and > 115 mg/L (pH adjusted). It was concluded that the test item has no remarkable acute effect on the test item. The results of the test can be considered reliable without restriction.

Description of key information

The study of Adachi (2016) is selected as key study for endpoint coverage. It investigated the acute toxicity of the substance to Daphnia magna in a 48h static test according to the OECD guideline 202. Based on geometric mean concentrations, a 48h-EC50 was determined to be >115 mg/L (with adjusted pH). The study is given a Klimisch score of 1 and was conducted under GLP.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

> 115 mg/L

Additional information

Two studies were performed with the test substance to investigate the acute toxicity to aquatic invertebrates.

 

In the first study from Adachi (2016), which was considered as key study, the acute toxicity of the test substance to Daphnia magna was determined in a 48-hour static test according to the OECD guideline 202. Based on geometric mean concentrations, the 48-h EC50 were determined to be > 115 mg/L. It was concluded that the test item has no remarkable acute effect on daphnia.

 

The second study from Migchielsen (2002) is selected as a supporting study. It is a limit test performed under GLP conditions and according to the OECD guideline 202.  An EC50 > 100 mg/L based on nominal concentrations was found for juvenile Daphnia magna after an exposure period of 48 hours in a static test. The study however was given a Klimisch score of 2 as no analytical measurements were performed.

 

Additionally, a QSAR analysis was carried out to assess the aquatic toxicity of the predicted biodegradation products of the substance for use in the PBT/vPvB assessment. Estimations were carried out using ECOSAR v1.11. All predicted effects concentrations were above the screening criterion for any of the substances to fulfill the T criterion (the lowest 48h-LC50 obtained for aquatic invertebrates was 28.3 mg/L).