1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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 limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine
- Molecular formula :C13H18Cl2N2
- Molecular weight :273.205 g/mol
- Smiles notation : N1(c2cc(Cl)ccc2)CCN(CC1)CCCCl
- InChl : 1S/C13H18Cl2N2/c14-5-2-6-16-7-9-17(10-8-16)13-4-1-3-12(15)11-13/h1,3-4,11H,2,5-10H2
- Substance type:Organic
- Physical state:Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

23.6 - 24.7°C

pH:

test start: 8.5 -8.6
test end: 9.3 - 9.6

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

132.757 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" or "d" )  and "e" )  and "f" )  and ("g" and "h" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides by Protein binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Basesurface narcotics by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "f"

Similarity boundary:Target: ClCCCN1CCN(c2cccc(Cl)c2)CC1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.495

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.53

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine on Desmodesmus subspicatus in a 72 hour study was estimated to be 132.76 mg/L on the basis of effects on growth rate.

Executive summary:

Using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 1 -(3 -chloro phenyl)-4 -(3 -chloropropyl)piperazine (CAS: 39577 -43 -0). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 132.76 mg/l for Desmodesmus subspicatus for 72 duration. Based on this value, it can be concluded that the test chemical 1 -(3 -chlorophenyl) -4 -(3 -chloropropyl)piperazine was likely to be non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

Description of key information

Using the EPI Suite ECOSAR version 1.10, the short term toxicity on green algae was predicted for test substance 1 -(3 -chloro phenyl)-4 -(3 -chloropropyl)piperazine (CAS: 39577 -43 -0). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 132.76 mg/l for Desmodesmus subspicatus for 72 duration. Based on this value, it can be concluded that the test chemical 1 -(3 -chlorophenyl) -4 -(3 -chloropropyl)piperazine was likely to be non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

132.76 mg/L

Additional information

Various predicted data for the target chemical 1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine(CAS No. 39577-43-0) and weight of evidence study for its read across substancewere reviewed to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine(CAS No. 39577-43-0) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 132.76 mg/l for Desmodesmus subspicatus for 72 duration. Based on this value, it can be concluded that the test chemical 1 -(3 -chlorophenyl) -4 -(3 -chloropropyl) piperazine was likely to be non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidence study from authoritative database (J-CHECK, 2017) of the read across chemical 1 -Chlorooctane (CAS no. 111 -85 -3), short term toxicity to green algae study was carried out for 72 hrs. The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). The study was based on the effects of the read across compound 1 -Chlorooctane on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be > 0.27 and 0.27 mg/l, respectively and on the basis of AUG, the 72 hr EC50 and NOEC value was determined to be > 4.4 and 0.18 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1 -Chlorooctane can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 1 -Chlorooctane can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

In an another study from peer reviewed journal (Kuo-Pei Tsai and Chung-Yuan Chen, 2007) for the read across chemical 1,1,2 -trichloroethane (CAS no. 79 -00 -5), short term toxicity to Pseudokirchneriella subcapitata (green algae) study was carried out for 48 hrs. The study was based on the effects of the read across compound 1,1,2 -trichloroethane on green algae in a static fresh water closed system at a temperature of 24±1°C and pH 7.0, respectively. Test compound was tested at least twice (i.e; range finding test and definitive test). Stock solutions was freshly prepared, and its concentrations was analyzed using high performance liquid chromatography (HPLC; 2996 Photodiode Array Detector; Waters, Millford, MA, USA). At the beginning of the definitive test, one treatment concentration, which was closest to the estimated EC50, was selected for concentration check. The concentration of toxicant was then analyzed by HPLC. Normally, the difference between the nominal and measured concentration was within the range of 1 to 6%. Pseudokirchneriella subcapitata UTEX 1648 was used as a test organism obtained from University of Texas at Austin, Austin, TX, USA. Biochemical Oxygen Demand (BOD) test bottles of 300 ml volume was used as a test vessel for the study. The BOD bottles were completely filled, with no headspace left. A water seal was provided to ensure a closed test environment. The bottles were placed in an orbital shaker operated at 100 rpm. Algal growth medium with no ethylene-diaminetetera-acetic acid content was used for toxicity testing. The initial pH for the growth medium was 7.9, and the initial inoculated cell density was 15,000 cells/ml. All test were conducted in triplicate. The population density of the algae was determined using an electronic particle counter (Coulter Electronics, Luton, UK). The inhibition rate on the net increase of algal cell density was also calculated. Based on effect on growth rate of the test organism Pseudokirchneriella subcapitata, the 72 hr EC50 value was determined to be 105.42 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1,1,2 -trichloroethane can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

For the same read across chemical 1,1,2 -trichloroethane (CAS no. 79 -00 -5),short term toxicity to Chlamydomonas spp. (green algae) study was carried out for 96 hrs (ECOTOX database, 2017). The study was based on the effects of the read across compound 1,1,2 -trichloroethane (CAS no. 79 -00 -5) on Chlamydomonas spp. in a static fresh water system at a pH 8.0. Chlamydomonas spp. (green algae) was used as a test organism. Based on effect on growth rate of the test organism Chlamydomonas spp.(green algae), the 96 hr EC50 value was determined to be 260 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1,1,2 -trichloroethane can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical1-(3-chlorophenyl)-4-(3-chloropropyl)piperazine(OECD QSAR toolbox version 3.3, 2017) and for its read across substance (fromauthoritative database J-CHECK, ECOTOX and peer reviewed journal),it can be concluded that the test substance 1 -(3 -chlorophenyl)-4 -(3 -chloropropyl)piperazine can be considered as non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.