3,7-bis(diethylamino)phenoxazin-5-ium acetate

Endpoint summary

Description of key information

Short term toxicity to fish

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 to fish was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). LC50 value was estimated to be 0.838 mg/l for Oryzias latipes for 96 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.

Short term toxicity to aquatic invertebrates

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.

Toxicity to aquatic algae and cyanobacteria

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 algae and cyanobacteria was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). EC50 value was estimated to be 0.578 mg/l for Pseudokirchneriella subcapitata for 72 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.

Toxicity to microorganisms

Using the OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor and considering the five closest read across substances, toxicity to microorganisms was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). IGC50 value was estimated to be 51.96 mg/l for Tetrahymena pyriformis for 48 h duration.

Additional information

Short term toxicity to fish

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 semi-static freshwater system, the lethal concentration LC50 value for the substance is estimated to be 0.838 mg/L for Oryzias latipes for 96 hr duration.

 

In a weight of evidencestudy from authoritative database (J-CHECK, 2017) of the read across chemical (peroxybis(propane-2,2-diyl))dibenzene (CAS no. 80-43-3),short term toxicity to fish study was carried out for 96 hrs. The study was performed according to OECD Guideline 203 (Fish, Acute Toxicity Test). The study was based on the effects of the read across compound (peroxybis(propane-2,2-diyl))dibenzene on Oryzias latipes in a semi-static fresh water system at a temperature of 24 ± 1°C.Test chemical concentration used for the study were 2.00, 1.43, 1.02, 0.729, 0.521 mg/l (geometric ration 1.4). Analytical methods used for the study was HPLC. The study was performed in duplicates using5 organisms per vessels (10/concentration) under room light, 16 h light – 8 h dark. Based on effect on mortality of the test organism Oryzias latipes, the 96 hr LC50 value was determined to be 0.469 mg/l.

 

For the read across chemical 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232-93-7), short term toxicity to fish (Oncorhynchus mykiss) study was carried out for 96 hrs (HSDB and ECOTOX database, 2017). The study was based on the effects of the read across compound 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232 -93 -7) on Oncorhynchus mykiss in a flow through fresh water system. Oncorhynchus mykiss (Rainbow trout) was used as a test organism. Based on effect on mortality of the test organism Oncorhynchus mykiss, the 96 hr LC50 value was determined to be 0. 404 mg/l (95% C. I. = 0.36 to 0.44 mg/l), respectively.

 

Another short term toxicity to fish (Rutilus rutilus) study from authoritative database (ECOTOX database, 2017) was carried out for 96 hrs. The study was based on the effects of the read across compound 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232-93-7) on Rutilus rutilus in a fresh water system. Rutilus rutilus (Roach) was used as a test organism. Based on effect on mortality of the test organism Rutilus rutilus, the 96 hr LC50 value was determined to be 0.84 mg/l, respectively.

 

Thus, based on the overall reported results for target chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate(OECD QSAR toolbox version 3.3, 2017) and for its read across substance (fromauthoritative database ECOTOX, HSDB and J-CHECK),it can be concluded that the test substance3,7-bis(diethylamino)phenoxazin-5-ium acetatecan be considered as toxic to aquatic fish and can be considered to be classified in aquatic acute1/ chronic 1 categoryas per the CLP classification criteria.

Short term toxicity to aquatic invertebrates

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 descriptor were 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 acute1/ chronic 1 categoryas 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 acute1/ chronic 1 categoryas per the CLP classification criteria.

Toxicity to aquatic algae and cyanobacteria

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 for toxicity to aquatic algae and cyanobacteria endpoint to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria 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 0.578 mg/l for Pseudokirchneriella subcapitata for 72 duration.

 

In a weight of evidencestudy from authoritative database (HSDB, 2017) of the read across chemical 4-(dimethylamino)-3-methylphenyl N-methylcarbamate (CAS no. 2032-59-9), short term toxicity to Chlamydomonas variabilis (green algae) study was carried out for 24 hrs. The study was based on the effects of the read across compound 4 -(dimethylamino)-3 -methylphenyl N-methylcarbamate on Chlamydomonas variabilis in a static fresh water system. Based on the inhibitory effect on the test organism Chlamydomonas variabilis, the 24 hr IC50 value was determined to be 0.0008 mg/l, respectively.

 

Another short term toxicity to aquatic algae study was carried out for 28 hrs for the same read across chemical 4-(dimethylamino)-3-methylphenyl N-methylcarbamate (CAS no. 2032-59-9) (ECOTOX database, 2017).The study was based on the effects of the read across compound 4 -(dimethylamino)-3 -methylphenyl N-methylcarbamate (CAS no. 2032 -59 -9) on algae in a static fresh water system at a temperature of 12°C. Based on effect on physiology of the test organism algae, the 28 hr EC50 value was determined to be 0.56 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 HSDB and ECOTOX),it can be concluded that the test substance3,7-bis(diethylamino)phenoxazin-5-ium acetatecan be considered as toxic to aquatic algae and cyanobacteria and can be considered to be classified in aquatic acute1/ chronic 1 categoryas per the CLP classification criteria.

Toxicity to microorganisms

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 for toxicity to microorganism endpoint to summarize the following information:

 

Toxicityto microorganismof 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, the IGC50 value was estimated to be 51.96 mg/l for Tetrahymena pyriformis for 48 h duration.

 

In a weight of evidencestudy from peer reviewed journal (Dr. D. Brown et. al, 1981) of the read across chemical 3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene ]-3-one (CAS no. 509-34-2),a screening method based on the measurement of the respiration rate of activated sludge for assessing the possible inhibitory effect of dyestuffs on aerobic waste-water bacteria. The test principle involves measuring the respiration rate of an activated sludge and comparing it with the respiration rate of the same activated sludge under identical conditions, but in the presence of the chemical under test. The test was carried out in activated sludge respiration rate apparatus with constant 20 ± 2°C and pH about 7-8. The test concentration used was 100 mg/l. OECD recommended synthetic sewage was used as feed, while activated sludge was obtained from a sewage works treating predominantly domestic sewage or from a sewage works treating predominantly industrial waste water. The respiration rate of an activated sludge and the respiration rate of activated sludge with test chemical were noted down. In order to calculate the inhibitory effect of a particular chemical at 100 mg/l test concentration its respiration rate is expressed as a percentage of the mean of the two control respiration rates. For those chemicals whose respiration rate is at least 80% of the control, the IC50 (concentration for 50% inhibition of respiration rate) is recorded as >100 mg/l. Thus, IC50 value (concentration for 50% inhibition of respiration rate) for the test chemical 3',6'-bis(diethylamino)-3H-spiro[2 -benzofuran-1,9'-xanthen]-3 -one on activated sludge (aerobic bacteria) is determined to be >100 mg/1 after 3 hrs of exposure.

 

For the read across chemical Diethyl aniline (CAS no. 91-66-7), toxicity to micro-organism (bacteria) study was carried out for 3 hrs (HPVIS, 2017). The study was performed according to a Screening Test for the Assessment of the Possible Inhibitory Effect of a Chemical Substance on Aerobic Waste Water Bacteria method. Activated sludge was used as a test organism during the study. Based on the inhibitory effect on the test organism activated sludge, the 3 hr EC50 value was determined to be > 100 mg/l.

 

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 (frompeer reviewed journal and secondary source HPVIS),it can be concluded that the IGC50 value for the test chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetatewas estimated to be 51.96 mg/l, respectively.

On the basis of above mentioned available information for short term toxicity to fish, aquatic invertebrates and toxicity to aquatic algae and cyanobacteria, test substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be considered as toxic to aquatic organisms and can be considered to be classified in aquatic acute 1/ chronic 1 category as per the CLP classification criteria.