L-cystine dihydrochloride

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2018-02-27

Reliability:

1 (reliable without restriction)

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:

Please refer to the QMRF and QPRF files provided under the section attached justification.

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSAR R.6

Principles of method if other than guideline:

Estimates the log octanol-water partition coefficient, log KOW, of chemicals using an atom/fragment contribution method.

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

-4.34

Temp.:

25 °C

Remarks on result:

other: QSAR predicted value. The substance is within the applicability domain of the model.

KOWWIN Program (v1.68) Results:

===============================

Log Kow(version 1.68 estimate): -4.34

Experimental Database Structure Match:

Name    : CYSTINE

CAS Num : 000056-89-3

Exp Log P: -5.08

Exp Ref : CHMELIK,J ET AL. (1991)

 

SMILES : OC(=O)C(N)CSSCC(N)C(=O)O

CHEM  : L-cystine dihydrochloride

MOL FOR: C6 H12 N2 O4 S2

MOL WT : 240.29

 

TYPE	NUM	LOGKOW FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	2	-CH2-  [aliphatic carbon]	0.4911	0.9822
Frag	2	-CH    [aliphatic carbon]	0.3614	0.7228
Frag	2	-NH2   [aliphatic attach]	-1.4148	-2.8296
Frag	2	-COOH  [acid, aliphatic attach]	-0.6895	-1.3790
Frag	1	-SS-   [disulfide]	0.5497	0.5497
Factor	1	Multi-aliphatic carboxylic acids	-0.5865	-0.5865
Factor	1	Amino acid (alpha-position) correction	-2.0238	-2.0238
Const		Equation Constant		0.2290
NOTE		Zwitterionic calculation made for all Amino Acids

 

Log Kow  = -4.3352

Conclusions:

Using KOWWIN v1.68 the logPow of the test item was calculated to be -4.34 at 25 °C. The substance is within the applicability domain of the model. Thus, the estimation can be considered accurate.

Executive summary:

The logPow was calculated using KOWWIN v1.68 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using KOWWIN v1.68 the log Kow of the test item was calculated to be -4.34 at 25 °C (EPI Suite, 2014).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Reference 2

Endpoint:

partition coefficient

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because the substance does not dissolve in water or in octanol

Justification for type of information:

The performance of the partition coefficient (n-octanol / water) test according to OECD guideline 107 respectively OECD guideline 117 is not possible due to insufficient solubility of the test item in n-octanol saturated with phosphate buffer respectively the very low calculated log Pow.

Reference 3

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2018-08-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

GLP compliance:

no

Type of method:

other: expert statement

Partition coefficient type:

octanol-water

Key result

Remarks on result:

not determinable

Results from analytical validation

Table 1. Accuracy data in saturated phosphate buffer

Nominal concentration (mg/L)	Peak Area (mAU*min)	Concentration (mg/L)	Mean concentration (mg/L)	Accuracy (%)
5 mg/L	n.a. n.a. n.a. n.a.	n.c. n.c. n.c. n.c.	n.c.	-
50 mg/L	0.5166 0.6593 0.5974 0.5624	1.81 2.29 2.08 1.96	2.04	4.1
Mean accuracy (%)				n.c.

n.c.: not calculated
n.a.: no signals detectable

Table 2. Accuracy data in saturated octanol

Nominal concentration (mg/L)	Peak Area (mAU*min)	Concentration (mg/L)	Mean concentration (mg/L)	Accuracy (%)
1 mg/L	n.a. n.a. n.a. n.a.	n.c. 0.34 n.c. n.c.	0.34	6.8
5 mg/L	n.a. n.a. n.a. n.a.	n.c. n.c. n.c. n.c.	n.c.	-
Mean accuracy (%)				n.c.

n.c.: not calculated
n.a.: no signals detectable

Higher concentrations in n-octanol saturated with phosphate buffer could not be measured due to the poor solubility of the test item.

Conclusions:

Due to the insufficient solubility and detectability in n-octanol saturated with phosphate buffer and the very low calculated logPow (-4.34), the determination of the partition coefficient (n-octanol/water) test according to OECD TG 107 respectively 117 is technically not possible.

Description of key information

Due to the insufficient solubility and detectability in n-octanol saturated with phosphate buffer and the very low calculated logPow (-4.34), the determination of the partition coefficient (n-octanol/water) test according to OECD TG 107 respectively 117 is technically not possible.

Therefore the logPow of the test item was calculated to be -4.34 at 25 °C using KOWWIN v1.68. The partition coefficient of cystine was experimentally determined to be -5.08.

Key value for chemical safety assessment

Log Kow (Log Pow):

-5.08

at the temperature of:

25 °C

Additional information

Due to the insufficient solubility and detectability in n-octanol saturated with phosphate buffer and the very low calculated logPow (-4.34), the determination of the partition coefficient (n-octanol/water) test according to OECD TG 107 respectively 117 is technically not possible (reference 4.7-2, 4.7-3).

The logPow was calculated using KOWWIN v1.68 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using KOWWIN v1.68 the log Kow of the test item was calculated to be -4.34 at 25 °C (EPI Suite, 2014) (reference 4.7-1).

The QSAR estimation was performed with L-cystine, the partition coefficient of which was esperimentally determined and included in the training set of KOWWIN, EpiSuite. The partition coefficient of cystine was determined to be -5.08 (Chemlik, J, et. al., 1991).

 

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.