3-(dimethylamino)propylurea

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

09 December 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2014

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

GLP compliance:

no

Type of method:

other: shaking an aliquot of the test item with successive amounts of purified water followed by a visual check for undissolved test item and check for colloidal dispersed matter by observation of a Tyndall effect via laser beam.

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: Manufacturer, UA21412002
- Purity, including information on contaminants, isomers, etc.: Content: 75% 3-(N,N-Dimethyl)propyl-urea and 25% Polyethylenglycol

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store container tightly closed at a well-ventilated place. Store in the original container. Do not store with acids.

Key result

Water solubility:

> 1 000 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

500 mg/L

Incubation duration:

10 min

Temp.:

22 °C

Remarks on result:

completely miscible

Key result

Water solubility:

> 1 000 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

100 mg/L

Incubation duration:

10 min

Temp.:

22 °C

Remarks on result:

completely miscible

First Experiment

At first, nominal 100 mg test item were weighed out in a graduated 10 mL cylinder and successive amounts of water were added.

Table 1. Results of the Preliminary Test

Volume of added water [mL]	Test item [mg]	Test item concentration (nominal) [g/Lsolvent]	Homogenous solution (visual) [yes/no]
0.1	102.4	1024	Yes, no Tyndall-effect
0.2		512	Yes, observable Tyndall-effect
0.5		205	Yes, observable Tyndall-effect
1		102	Yes, observable Tyndall-effect
2		51	Yes, observable Tyndall-effect, foaming
5		20	Yes, observable Tyndall-effect, foaming
10		10	Yes, observable Tyndall-effect, foaming

Second Experiment

For the second experiment, nominal 500 mg test item were used.

Table 2. Results of the Preliminary Test

Volume of added water [mL]	Test item [mg]	Test item concentration (nominal) [g/Lsolvent]	Homogenous solution (visual) [yes/no]
0.1	499.6	5000	Yes, no Tyndall-effect
0.2		2500	Yes, no Tyndall-effect
0.5		1000	Yes, no Tyndall-effect
1		500	Yes, observable Tyndall-effect
2		250	Yes, observable Tyndall-effect
5		100	Yes, observable Tyndall-effect
10		50	Yes, observable Tyndall-effect

Third Experiment

For the third experiment, nominal 10 mg test item were weighed out in a 100 mL graduated cylinder.

Table 3. Results of the Preliminary Test

Volume of added water [mL]	Test item [mg]	Test item concentration (nominal) [g/Lsolvent]	Homogenous solution (visual) [yes/no]
1	12.7	13	Yes, observable Tyndall-effect
2		6	Yes, observable Tyndall-effect
5		2.5	Yes, observable Tyndall-effect
10		1.3	Yes, observable Tyndall-effect
20		0.6	Yes, observable Tyndall-effect
50		0.25	Yes, observable Tyndall-effect
100		0.13	Yes, observable Tyndall-effect

Of this last volume of 100 mL with a concentration of nominal 0.13 g/L, 1 mL was diluted with1 and 2 mL purified water and afterwards filled up to 5 and 10 mL, corresponding to concentrations of 65, 43, 26 and 13 mg/L. The Tyndall-effect remained observable for all concentrations.

Conclusions:

No separation of the test item from the aqueous phase could be observed for any concentration, with a lack of colloidal dispersed matter at concentrations that could be interpreted as a solution of water in the test item. Thus, the water solubility of the test item was estimated at ambient temperature to be fully miscible.

At “lower” concentrations at and below approx. 1000 g/L, a Tyndall-effect was observed. It was assumed that this Tyndall-effect might be caused by the polyethylene glycol, which is a significant compound of the test item.

The specific determination of the water solubility via shake flask method is not possible, as no two-phase system of (saturated) solution and undissolved test item could be achieved.

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

02 Febraur 2023

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE :Water Solubility (EPISUITE), V. 1.0

2. MODEL (incl. version number): WSKOW v1.43 and WATERNT™ v1.01©

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CN(C)CCCNC(=O)(N)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
- Defined endpoint: water solubility
- Unambiguous algorithm: The estimation methodology used by WSKOWWIN (Meylan and Howard, 1994a,b) is described in the following document prepared for the U.S. Environmental Protection Agency (OPPT): Upgrade of PCGEMS Water Solubility Estimation Method (May 1994). A companion document (Validation of Water Solubility Estimation Methods Using Log Kow for Application in PCGEMS & EPI) also discusses the methodology.

Two equations are used for estimating water solubilty:
Eq. 1: log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Corrections
Eq. 2: log S (mol/L) = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + Corrections
(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids]) .

Corrections are applied to 15 structure types (eg. alcohols, acids, selected phenols, nitros, amines, alkyl pyridines, amino acids, PAHS, multi-nitrogen types, etc); application and magnitude depends on available MP.
Equation 2 is used when a measured MP is available; otherwise, equation 1 is used.

The model based on 2D parameter calculated by WATERNT™ v1.01© program (part of EPISUITE) which estimates the water solubility of organic compounds at 25oC.
The program and estimation methodology were developed at Syracuse Research Corporation for the US Environmental Protection Agency. The estimation methodology is based upon a "fragment constant" method very similar to the method of the KOWWIN Program which estimates octanol-water partition coefficients. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups, ACF) and coefficient values of each fragment or group are summed together to yield the solubility estimate. An improvement of water solubility is developed by adding of correction factors to the AFC method. In general the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures
A journal article by Meylan and Howard (1995) describes the KOWWIN program methodology.
Calculations are based on:
Eq 1: log WatSol (moles/L) = Σ(fi * ni) + Σ(cj * nj) + 0.24922
where Σ(fi * ni) is the summation of fi (the coefficient for each atom/fragment) times ni (the number of times the atom/fragment occurs in the structure) and Σ(cj * nj) is the summation of cj (the coefficient for each correction factor) times nj (the number of times the correction factor is applied in the molecule)

Principles of method if other than guideline:

- Software tool(s) used including version: Water Solubility (EPISUITE), V. 1.0
- Model(s) used: This is a model based on 2D parameter calculated by WSKOWWIN v1.42© program (part of EPISUITE) which estimates the water solubility (WSol) of an organic compound using the compounds log octanol-water partition coefficient (Kow).
- Model description: see field 'Justification for non-standard information', 'Attached justification' and/or 'Cross-reference' The estimation methodology used by WSKOWWIN (Meylan and Howard, 1994a,b) is described in the following document prepared for the U.S. Environmental Protection Agency (OPPT): Upgrade of PCGEMS Water Solubility Estimation Method (May 1994). A companion document (Validation of Water Solubility Estimation Methods Using Log Kow for Application in PCGEMS & EPI) also discusses the methodology.
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'Cross-reference'

- Software tool(s) used including version: Water Solubility (fragments) (EPISUITE)
- Model(s) used: This is a model based on 2D parameter calculated by WATERNT™ v1.01© program (part of EPISUITE) which estimates the water solubility of organic compounds at 25°C.
- Model description: This is a model based on 2D parameter calculated by WATERNT™ v1.01© program (part of EPISUITE) which estimates the water solubility of organic compounds at 25°C.
The program and estimation methodology were developed at Syracuse Research Corporation for the US Environmental Protection Agency. The estimation methodology is based upon a "fragment constant" method very similar to the method of the KOWWIN Program which estimates octanol-water partition coefficients. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups, ACF) and coefficient values of each fragment or group are summed together to yield the solubility estimate. An improvement of water solubility is developed by adding of correction factors to the AFC method. In general the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures
A journal article by Meylan and Howard (1995) describes the KOWWIN program methodology.
Calculations are based on:
Eq 1: log WatSol (moles/L) = Σ(fi * ni) + Σ(cj * nj) + 0.24922
where Σ(fi * ni) is the summation of fi (the coefficient for each atom/fragment) times ni (the number of times the atom/fragment occurs in the structure) and Σ(cj * nj) is the summation of cj (the coefficient for each correction factor) times nj (the number of times the correction factor is applied in the molecule)

- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'Cross-reference'

GLP compliance:

no

Type of method:

other: QSAR

Key result

Water solubility:

> 229 000 - <= 1 000 000 mg/L

Conc. based on:

other: Water Solubility from Kow and segment

Temp.:

25 °C

Remarks on result:

completely miscible

Key value for chemical safety assessment

Water solubility:

1 000 g/L