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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
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:
other: as mentioned below
Principles of method if other than guideline:
Prediction is done using 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 (IUPAC name): 3,7-bis(diethylamino)phenoxazin-5-ium acetate
- Molecular formula: C22H29N3O3
- Molecular weight: 383.489 g/mol
- Smiles notation: c1c2nc3ccc(cc3[o+]c2cc(N(CC)CC)c1)N(CC)CC.C(C)(=O)[O-]
- InChl: 1S/C20H26N3O.C2H4O2/c1-5-22(6-2)15-9-11-17-19(13-15)24-20-14-16(23(7-3)8-4)10-12-18(20)21-17;1-2(3)4/h9-14H,5-8H2,1-4H3;1H3,(H,3,4)/q+1;/p-1
- Substance type: Organic
- Physical state: Solid
Analytical monitoring:
not specified
Vehicle:
not specified
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
0.349 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Intoxication

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" )  and "c" )  and "d" )  and ("e" and "f" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Peroxy Acids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 6) ONLY

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.00445

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.45

Validity criteria fulfilled:
not specified
Conclusions:
The median Effective concentration (EC50) value for chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate acetate on Daphnia magna in a 48 hour study was estimated to be 0.349 mg/L on the basis of effects on intoxication
Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). EC50 value was estimated to be 0.349 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate is considered to be toxic to aquatic environment and can be considered to be classified in

aquatic acute 1/ chronic 1 category as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). EC50 value was estimated to be 0.349 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1 / chronic 1 category as per the CLP classification criteria.

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
0.349 mg/L

Additional information

Predicted data for the target chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate(CAS No. 79916-07-7) and various supporting weight of evidence studies for its closest read across substances with logKow as the primary descriptorwere reviewed to summarize the following information:

 

Short term toxicity on aquatic invertebrate of target chemical3,7-bis(diethylamino)phenoxazin-5-ium acetate(CAS No. 79916-07-7)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 0.349 mg/l for Daphnia magna for 48 hr duration.

 

In a weight of evidencestudy from authoritative database (HSDB and ECOTOX database, 2017) of the read across chemical 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232-93-7),short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs. The study was based on the effects of the read across compound 2 -(diethylamino)-6 -methylpyrimidin-4 -yl methyl methoxy(sulfanylidene)phosphonate on Daphnia magna in a static fresh water system at a temperature of 21°C and a pH range of 7.4 to 7.9, respectively. Dissolved oxygen of water was ≥7.8 mg/l. Daphnia magna (Water flea) of < 24 hr old neonate was used as a test organism. Based on effect on intoxication of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 0.00044 mg/l (95% C. I. interval = 0.00037 to 0.00051 mg/l), respectively.

 

Another long term toxicity to Gammarus pulex L. study was carried out for 144 hrs for the same read across chemical 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonate (CAS no. 29232 -93 -7) (Nathan Mcloughlin et. al; 2000). Gammarus pulex L. (scud) was used as a test organism during the study. The study was based on the effects of the read across compound 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonate on Gammarus pulex L. in a static fresh water system at a temperature of 15± 1°Cand a pH of 7.3, respectively. Dissolved oxygen of water was 7.75mg/l. Test organism Adult male G. pulex L. (length > 5 mm) were collected from Crags Stream (National Grid Reference SK 477745; Clowne, Derbyshire, UK). Test animals were fed ad libitum on fungally conditioned alder leaves (Alnus glutinosaL.). Test organisms were maintained in the laboratory for one week before use in experiments. Animals were maintained at 15± 1°C with a photoperiod of 12 h of light and 12 h of dark in an artificial pond water. Five different nominal test chemical concentrations were used for the study. They were 0.001, 0.0025, 0.005, 0.01 and 0.015 mg/l (1, 2.5, 5, 10, and 15mg/L), respectively. Glass tube was used as a test vessel during the study. Gammarus were held individually, without food, in glass tubes (length, 80 mm; diameter, 15 mm) fitted with a 1-mm mesh base. Each treatment consisted of a set of 30 tubes suspended in a 3-L glass aquarium containing 2 L of test solution or artificial pond water (control). Animals were observed at exposure times of 24, 48, 72, 96, 120, and 144 h, and dead animals were recorded and removed at each exposure. Animals were considered to be dead if no appendage movement was visible during a 20-s observation period. Dissolved oxygen, pH, and conductivity were determined daily for each chemical treatment and control using handheld meters (Models 9071, 3310, and 4071; Jenway, Dunmow, UK). All data were checked for normality using normal probability plots. The LC50 values were calculated using probit analysis, and effective concentration estimates were calculated using linear interpolation methods. All statistical analyses were based on actual exposure concentrations and conducted at a significance level of 0.05. The test solutions were changed daily, and all tests were conducted at 15618with a photoperiod of 12 h of light and 12 h of dark. Concentrations of 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite in test solutions were determined using gas chromatography/mass spectrometry analysis (Model 5988; Hewlett-Packard, Avondale, PA, USA) with detection limits of 0.02mg/L for 2 -(diethylamino)-6 -methylpyrimidin-4 -yl methyl methoxy(sulfanylidene)phosphonite. No significant differences were found in dissolved oxygen, pH, or conductivity between treatments (F<0.9,p >0.05). The mean values ± standard deviations across all treatments were 7.75±0.4 mg O2/L, 7.3±0.2 pH units, and 577±11µS/cm, respectively. For test chemical, the LC50 was still decreasing with increasing exposure time, even after 144 h. Based on effect on mortality of the test organism Gammarus pulex L., the 24, 48, 72, 96, 120 and 144 hr EC50 value was determined to be 0.01832, 0.00549, 0.00382, 0.00278, 0.00214 and 0.00145 mg/l, respectively. Thus, based on the 24 hr EC50 value (0.01832), it can be concluded that the substance 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite can be considered as toxic to aquatic organisms and thus can be considered to be classified in aquatic acute 1/ chronic 1 category as per the CLP classification criteria.

 

For the read across chemical 4-(dimethylamino)-3-methylphenyl N-methylcarbamate (CAS no. 2032-59-9) from authoritative database (ECOTOX database, 2017),short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs. The study was based on the effects of the read across compound 4 -(dimethylamino)-3 -methylphenyl N-methylcarbamate on Daphnia magna in a static fresh water system at a temperature of 17°C, pH 7.1 and hardness of water was 42 mg/l CaCO3. Daphnia magna (Water flea) was used as a test organism. Based on effect on intoxication of the test organism Daphnia magna (Water flea), the 48 hr EC50 value was determined to be 0.32 mg/l (95% C. I. = 0.271 to 0.378 mg/l), respectively.

 

Thus, based on the overall reported results for target chemical3,7-bis(diethylamino)phenoxazin-5-ium acetate(OECD QSAR toolbox version 3.3, 2017) and for its read across substance (fromauthoritative database ECOTOX, HSDB and peer reviewed journal),it can be concluded that the test substance3,7-bis(diethylamino)phenoxazin-5-ium acetatecan be considered as toxic to aquatic invertebrates and can be considered to be classified in aquatic acute 1/ chronic 1 category as per the CLP classification criteria.