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Physical & Chemical properties

Water solubility

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Reference
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2017
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
Qualifier:
according to
Guideline:
other: REACH Guidance on QSAR's R.6, QSAR used and validated for the endpoints that would be derived during a OECD Guideline 105 Water Solubility (1995)
Specific details on test material used for the study:
SMILES: CCCCN(CCCC)CN(CCCC)CCCC
Key result
Water solubility:
13.6 mg/L
Conc. based on:
other: Test item constituent
Temp.:
25 °C
Remarks on result:
other: (Q)SAR predicted value
Details on results:
Water solubility of N,N,N',N'-tetrabutylmethanediamine was predicted using the iSafeRat® water solubility module giving as the input the log KOW (5.7) which was predicted using the iSafeRat® Log KOW module with the molecular structure (SMILES code) as the input.

Applicability domains

a. Domains:

i. Descriptor domain
The log KOW used as the descriptor for this prediction was reliably predicted using the iSafeRat® log KOW module and it falls within the descriptor domain of the model between a log KOW of -0.642 to 8.48. N,N,N',N'-tetrabutylmethanediamine falls within the response domain of the training set between a log water solubility (in log (mol/L)) of -6.33 to -1.56.

ii. Structural fragment domain
Currently, the water solubility module of the iSafeRat® Holistic HA-QSAR can reliably predict the water solubility for non-polar organic compounds and several oxygenated and nitrogen-containing compounds. N,N,N',N'-tetrabutylmethanediamine as an amine can be taken into account for water solubility predictions. All chemical groups within the molecular structure are taken into account by the model.

iii. Mechanism domain
Water solubility of the substance is determined using log KOW as the descriptor. The submodel used is dependent on the capability of the substance to participate in hydrogen bonding with water and octanol. iSafeRat® Holistic HA-QSAR includes the following submodels:
•Water Solubility submodel for NonPolar Organic compounds: for compounds which are neither donor, nor acceptor for hydrogen bonds (e.g. alkanes, halides, alkenes, thiols… etc.)
•Water Solubility submodel for Oxygenated, NonHydroxylated compounds (classical): for hydrogen bond acceptor compounds which are not donors (e.g. ethers, mono-esters, ketones, aldehydes, epoxides, lactones, carbonates, (meth)acrylates)
•Water Solubility submodel for Oxygenated, NonHydroxylated compounds (diesters): specific submodel for diester compounds.
•Water Solubility submodel for Oxygenated, Hydroxylated compounds: for hydrogen bond acceptor and donor compounds (i.e. alcohols, ethoxylated alcohols, lactates and carboxylic acids).
•Water Solubility model for Alkyl/Alkoxyphenols compounds: for hydrogen bond acceptor and donor compounds which can participate to strong hydrogen bonds.
•Water Solubility model for Amino compounds: for hydrogen bond acceptor and donor compounds which can be ionised (i.e. primary, secondary and tertiary amines).

iv. Metabolic domain, if relevant
Not relevant.

b.Structural analogues:
Proprietary.

c.Considerations on structural analogues
Not relevant.

Water solubility of N,N,N',N'-tetrabutylmethylenediamine was predicted as log Water Solubility = -3.978 at 25 °C.

Water solublity of N,N,N',N'-tetrabutylmethylenediamine is equal to 13.6 mg/L at 25 °C.
Conclusions:
The water solubility of N,N,N',N'-tetrabutylmethylenediamine, estimated using the iSafeRat holistic HA-QSARv 1.8, was 28.5 mg/L at 25°C (95 % confidence intervals: # - # mg/L).

The QSAR model meets the criteria set out in section 1.3 of Annex XI to REACH and can be considered a reliable endpoint.
Executive summary:

Water solubility of N,N,N',N'-tetrabutylmethanediamine was predicted using the iSafeRat® water solubility module giving as an input the log Kow which was predicted using the iSafeRat® Log Kow module with the molecular structure (SMILE notation) as the input.

The log Kow, used as the descriptor for this prediction, was reliably predicted (log Kow = 5.7) using the iSafeRat® log Kow module and it falls within the descriptor domain of the model between a log Kow of 0.642 to 8.48. N,N,N',N'-tetrabutylmethanediamine falls within the response domain of the training set between a log water solubility (in log (mol/l)) of -6.33 to -1.56.

Water solubility of the substance at 25 °C, determined using log Kow as the descriptor, was estimated to be 28.5 mg/L (95 % CI: 21.3 - 38.1 mg/L) (log water solubility = -3.978 mol/L at 25 °C).

Description of key information

Constituent 1: N,N,N',N'-tetrabutylmethylenediamine = 28.5 mg/L; REACH guidance on QSAR's R.6, OECD 105 "Water Solubility" (1995), Thomas, P. (2018).

Constituent 1: N,N,N',N'-tetrabutylmethylenediamine water solubility within the substance Reaction Mass of N,N,N',N'-tetrabutylmethylenediamine and N-butylbutan-1-amine (dibutylamine) = 18.8 mg/L; REACH guidance on QSAR's R.6, OECD 105 "Water Solubility" (1995), Thomas, P. (2018).

Key value for chemical safety assessment

Water solubility:
18.8 mg/L
at the temperature of:
25 °C

Additional information

Water solubility of N,N,N',N'-tetrabutylmethanediamine was predicted using the iSafeRat® water solubility module giving as an input the log Kow which was predicted using the iSafeRat® Log Kow module with the molecular structure (SMILE notation) as the input.

The log Kow, used as the descriptor for this prediction, was reliably predicted (log Kow = 5.7) using the iSafeRat® log Kow module and it falls within the descriptor domain of the model between a log Kow of 0.642 to 8.48. N,N,N',N'-tetrabutylmethanediamine falls within the response domain of the training set between a log water solubility (in log (mol/l)) of -6.33 to -1.56.

Water solubility of the substance at 25 °C, determined using log Kow as the descriptor, was estimated to be 28.5 mg/L (95 % CI: 21.3 - 38.1 mg/L) (log water solubility = -3.978 mol/L at 25 °C).

However, due to interaction of the two main constituents within the mixture, the solubilities within the mixture of each constituent are liable to change. Therefore, the water solubility of the constituents of the Reaction mass of N,N,N',N'-tetrabutylmethylenediamine and N-butylbutan-1-amine (dibutylamine) (as a whole) were estimated using a thermodynamically based calculation and individual constituent QSAR inputs from iSafeRat v.1.8.

The water solubility was determined using a calculation method based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as Quantitative Structure-Activity Relationship (QSAR) models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004).

Table 1      Water solubility values for each constituent anticipated during an OECD 105 water solubility test at 25 ºC

Constituent name

Water solubility

(mg/L)

N,N,N’,N’-tetrabutylmethylenediamine

18.8