2,2-dimethylpropane-1,3-diamine

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

other: handbook value

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

Data from authoritative online data compendium. Methods not reported.

GLP compliance:

not specified

Type of method:

other: Data from authoritative online data compendium

Water solubility:

1 000 g/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: pH not given

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Water solubility estimated using the atom fragment methodology by WATERNT v1.01

GLP compliance:

no

Type of method:

other: QSAR

Specific details on test material used for the study:

- SMILES Code: NCC(CN)(C)C

Water solubility:

1 000 000 mg/L

Temp.:

25 °C

Remarks on result:

other: Substance within application domain of the model.

Remarks:

the maximum solubility was applied

Type	Num	Water Solubility Fragment Description	Coefficient	Value
Frag	2	-CH3 [aliphatic carbon]	-0.3213	-0.6425
Frag	2	-CH2- [aliphatic carbon]	-0.5370	-1.0740
Frag	2	-NH2 [aliphatic attach]	1.9656	3.9312
Frag	1	-tert Carbon [3 or more carbon attach]	-0.5774	-0.5774
Const		Equation Constant		0.2492
NOTE		Maximum solubility (1,000,000 mg/L) Applied!

Log Water Sol (moles/L) at 25 dec C = 0.9906
Water solubility (mg/L) at 25 dec C = 1E+006

Executive summary:

QPRF: Estimation of water solubility using WATERNT v1.01 (EPI Suite v4.11)

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint		Water solubility at 25 °C
		Dependent variable		Water solubility
3.2	Algorithm (OECD Principle 2)	Model or submodel name		WATERNT
		Model version		v. 1.01
		Reference to QMRF		QMRF: Estimation of water solubility using WATERNT v1.01 (EPI Suite v4.11)
		Predicted value (model result)		See “Results and discussion”
		Input for prediction		Chemical structure via CAS number or SMILES
		Descriptor values		- Fragment constants - Correction factors
3.3	Applicability domain (OECD principle 3)	Domains:
		1) Molecular weight		See assessment below
		2) Number of occurrence of fragments and correction factors		See assessment below
3.4	The uncertainty of the prediction (OECD principle 4)	According to REACH Guidance Document R.7a, (Nov. 2012), solubility in water is difficult to model accurately. The experimental error on solubility measurements can be quite high (generally reckoned to be about 0.5 log unit).
		Statistical accuracy	Training set		Validation set
		n	1128		4636
		Correlation coefficient (r^2)	0.940		0.815
		Standard deviation (log units)	0.537		1.045
		Absolute mean error (log units)	0.355		0.815
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The water solubility of a substance depends on its affinity for water as well as its affinity for its own crystal structure. WATERNT uses a "fragment constant" methodology to predict the water solubility.  In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the estimate.

 

References

- US EPA (2012). On-Line WATERNT User’s Guide.

 

 

Assessment of estimation domain via molecular weight, estimated water solubility, fragments and correction factors:

Part 1: Fragments

Fragment Description		Coefficient	Number of compounds containing fragment	Maximum occurences in any one compound	No. of instances of each bond found for the current substance
-CH3	[aliphatic carbon]	-0.32127	612	6	2
-CH2-	[aliphatic carbon]	-0.53702	416	14	2
-NH2	[aliphatic attach]	1.96561	58	2	2
-tert Carbon	[3 or more carbon attach]	-0.57735	81	4	1

Applicability domain

Training set:	Molecular weight	Water solubility
Minimum	30.30	4.00E-07
Maximum	672.62	miscible
Average	187.73	---

Assessment

Molecular weight:	Molecular weight within range of training set.
Water solubility:	Estimated water solubility within range of training set.

Reference 3

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Principles of method if other than guideline:

Water solubility estimated from log Kow using WSKOW v1.42

GLP compliance:

no

Type of method:

other: QSAR

Specific details on test material used for the study:

- SMILES Code: NCC(CN)(C)C

Water solubility:

1 000 000 mg/L

Temp.:

25 °C

Remarks on result:

other: Water solubility calculated based on estimated/experimental log Kow of -0.26. Substance within application domain of the model.

Log Kow (estimated) : -0.26
Log Kow (experimental): not available from database
Log Kow used by Water solubility estimates: -0.26

Correction(s)	Value
Amine, aliphatic	1.008

Log Water Solubility (in moles/L) : 1.279
Log Water Solubility (in moles/L) : 0.991 (Applied Upper Limit)
Water Solubility at 25 deg C (mg/L): 1e+006

Executive summary:

QPRF: WSKOWWIN v1.42 (31 Oct. 2013)

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Water solubility at 25 °C
		Dependent variable	Water solubility
3.2	Algorithm (OECD Principle 2)	Model or submodel name	WSKOWWIN
		Model version	v. 1.42
		Reference to QMRF	Estimation of Water Solubility using WSKOWWIN v1.42 (EPI Suite v4.11) (QMRF)
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	Chemical structure via CAS number or SMILES
		Descriptor values	- log Kow - molecular weight - melting point - Correction factors
3.3	Applicability domain (OECD principle 3)	Domains:
		1) Molecular weight (range of test data set: 27.03 to 627.62 g/mol; On-Line WSKOWWIN User’s Guide, Ch. 7.2.2 Estimation Domain)	Substance (not) within range (102.18 g/mol)
		2) Log Kow (range of test data set: -3.89 to 8.27; On-Line WSKOWWIN User’s Guide, Ch. 7.2.2 Estimation Domain)	Substance (not) within range (log Kow = -0.26)
3.4	The uncertainty of the prediction (OECD principle 4)	According to REACH Guidance Document R.7a, (Nov. 2012), solubility in water is difficult to model accurately. For this reason, as well as the fact that the experimental error on solubility measurements can be quite high (generally reckoned to be about 0.5 log unit), the prediction of aqueous solubility is not as accurate as is the prediction of octanol/water partitioning.
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The water solubility of a substance depends on its affinity for water as well as its affinity for its own crystal structure. In general, substances with high melting points have poor solubility in any solvent.

 

References

- US EPA (2012). On-Line WSKOWWIN User’s Guide.

 

 

Assessment of estimation domain and applied correction factors:

 

Correction factors

Correction Factor shown in WSKOWWIN Program	With MP Coef	Without MP Coef	No. in Dataset	Correction factor identified in compound
Amine, aliphatic	0.838	1.008	37	1

Equation estimate of water solubility

The following discusses the correction factor in the table

Liquid Amines [Amine, Aliphatic]: applies only to liquids that contain a primary, secondary or tertiary amine. The amine must have only aliphatic carbon attachments (as with all correction factors, a carbon attachment does not include the carbonyl function). For equation 19 (which includes solids and liquids), it also applies to the same amines; however, any structure that contains an acetamide, acid or imide is excluded.

Applicability domain

Training set: Molecular weights	Minimum	Maximum
	27.03	672.62
Assessment of molecular weight	Molecular weight within range of training set.
Training set: log Kow	Minimum	Maximum
	-3.89	8.27
Assessment of log Kow	Molecular weight within range of training set.
Training set: Water solubilities (mg/L)	Minimum	Maximum
	4.00E-07	completely soluble
Assessment of water solubility	Estimated water solubility within range of training set.

Description of key information

The water solubility was found to be 1000 g/L according to authoritative online database (GESTIS). Additionally, two QSARs were performed (WSKOW v1.42 and WATERNT v1.01), which both estimated a water solubility of 1000 g/L at 25 °C (the maximum solubility was applied).

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. Furthermore according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort.

 

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 labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

 

For the assessment of the test substance (Q)SAR results were used for water solubility. 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.