Registration Dossier

Ecotoxicological information

Endpoint summary

Administrative data

Description of key information

72 hr ErC50 = 2.40 (2.28 – 2.54) mg a.i./L; 72 hr ErC10 =0.494 (0.437 – 0.557) mg a.i./L (OECD TG 201; Pseudokirchneriella subcapitata; RL1; GLP)

no classification for aquatic acute; Aquatic Chronic 3

Additional information

For the target substance Amphopropionates C12-18 a concentration range finding study in Daphnia magna as well as a toxicity study in algae is available. Short-term toxicity tests to fish and aquatic invertebrates are available for the structurally related source substances Amphopropionate C8 and Amphoacetates C8-C18. Further supporting data are available for the source substance Acrylic acid. A justification for read-across is given below.

 

Short-term toxicity to fish

The 96 h LC50 of Amphopropionate C8 (50.6% a.i.) to carp (Cyprinus carpio) was > 100 mg a.i./L.  The EC50 and NOEC values, based on mortality/sublethal effects, were both > 100 mg a.i./L.  No visible sublethal effects were observed under the conditions of the present test. 

 

The 96 h LC50 of to Amphoacetates C8-C18 to rainbow trout (Oncorhynchus mykiss) was 4.2 mg/L, nominal (based on solids content).

 

The 96 h LC50 of Amphoacetates C8-C18 to zebra fish (Danio rerio) was 8.5 mg/L, nominal (based on solids content).

 

The 96 h LC50 of Acrylic acid to Oncorhynchus mykiss was reported to be 27 mg/L.

 

Long-term toxicity to fish

According to REACh Regulation, Annex IX, 9.1.6. long-term toxicity testing shall be proposed by the registrant if the chemical safety assessment according to Annex I indicates the need to investigate further the effects on aquatic organisms.

 

Short-term toxicity to aquatic invertebrates

The 48–hr-acute toxicity of Amphopropionates C12-18 (40% in water) to Daphnia magna was studied in a screening test according to OECD Guideline 202 (2004) with deviations under static conditions.  The 48 hr EC50 was 76.8 mg/L (nominal). Based on measured concentrations, the 48 h EC50 was 13.2 mg/L (95% c.i. 1.72 - 17.22 mg/L).

As this study was designed only as dose range finding study, it is not fully in compliance with the testing guideline. Thus, it is assigned a Klimisch score of 3. Nevertheless, it is used in a weight-of-evidence-approach.

 

The 48-hr-acute toxicity of Amphoacetates C8-C18 to Daphnia magna was examined in two studies according to OECD Guideline 202 under static conditions. The 48 h EC50 was in the range of 2.5 mg/L to17.9 mg/L.

 

The 48 h EC50 of Amphopropionate C8 (50.6% a.i.) to Daphnia magna was >100 mg a.i./L.

 

Supporting data are available for Acrylic acid: The 48 h EC50 of acrylic acid to Daphnia magna was 47 mg/L.

 

The 48 h EC50 obtained in the dose range finding study conducted with the target substance Amphopropionates C12-18 was 13.2 mg/L (95% c.i. 1.72 - 17.22 mg/L) and thus higher than the effect concentrations obtained with the source substance Amphoacetates C8-C18. Acrylic acid did not show considerable toxicity to aquatic invertebrates. Therefore, the value of the source substance Amphoacetates C8-C18 is also protective for the target substance Amphopropionates C12-18.

 

Long-term toxicity to aquatic invertebrates

According to REACh Regulation, Annex IX, 9.1.5. long-term toxicity testing shall be proposed by the registrant if the chemical safety assessment according to Annex I indicates the need to investigate further the effects on aquatic organisms.

 

Toxicity to aquatic algae and cyanobacteria

In a test conducted according to OECD Guideline 201, the cultures of Pseudokirchneriella subcapitata were exposed to Amphopropionates C12-18 at nominal concentrations of 0 (control), 0.10, 0.316, 1.00, 3.16, 10mg a.i./L (corresponsing to geom. mean measured concentrations of 0.0966, 0.317, 0.878, 2.95, 9.08 mg a.i./L) for 72 h under static conditions.The glass walls of the test vessels were saturated with the test solutions prior to initiating the exposure.

The 72 h ErC50 and ErC10 were determined to be 2.4 and 0.494 mg a.i./L, respectively.

 

Supporting data are available for the source substances Amphoacetates C8-C18, Amphopropionate C8 and Acrylic acid:

 

Supporting data on the source substances Amphopropionate C8 (ErC50 =65 mg/L, NOEC <4.6 mg/L) and Amphoacetates C8-18 (ErC50 ranging from 10 to 30 mg/L, NOEC ranging from <3.1 to 3.6 mg/L) are available.

 

The 72 h NOEC(growth rate), ErC10, ErC50 of acrylic acid to Scenedesmus subspicatus were 0.016 mg/L, 0.03 mg/L and 0.13 mg/L, respectively.

 

Toxicity to microorganisms

The toxicity of Amphopropionates C12-18 (40% a.i.) to microorganisms was investigated during a ready biodegradation study according to OECD guideline 301 F (1992), Manometric Respirometry Test and OECD guideline 301 A (1992), DOC Die Away Test, each over a period of 28 days and using an inoculum obtained from activated sludge from a predominantly domestic sewage treatment plant.

Inoculum blank, procedural/functional control with the reference substance Sodium acetate and a toxicity control were performed.

No inhibitory effects on activated sludge microorganisms were noted in both studies at 70 mg/L or 100 mg/L, respectively. For chemical safety assessment the geometric mean of both studies of 83.7 mg/L will be used.

 

Conclusion

The most sensitive organism was algae. Thus, the 72 h ErC50 of 2.4 mg/L is used to derive the PNECs.

Based on acute toxicity values >1 mg/L, no classification for aquatic acute toxicity is required according to GHS Regulation EC No 1272/2008.

Chronic toxicity values between 0.1 and 1 mg/L were obtained with algae, and the substance is readily biodegradable. Thus, according to GHS Regulation EC No 1272/2008, Amphopropionates C12-18 is classified as Aquatic Chronic 3.

 

Justification for read-across

For details on substance identity and detailed toxicological profiles, please refer also to the general justification for read-across given at the beginning of the CSR and attached as pdf document to IUCLID section 13.

This read-across approach is justified based on structural similarities as well as on a similar toxicological profile. The target and source substances contain the same functional groups. Thus a common mode of action can be assumed.

 

 

Structural similarity and functional groups

The target substance Amphopropionates C12-18 is manufactured from fatty acids (C12-18, C18unsatd.) and aminoethylethanolamie (AEEA) to form 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-C17 odd-numbered, C17unsatd. alkyl) derivs. This is further reacted with 2-propenoic acid in the presence of sodium hydroxide (alternatively, sodium 2-propenoate can be used) and water. The molar relation between 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-C17, C17unsatd. alkyl) derivs. and 2-propenoic acid is somewhat below 1:1. Most of the excess 2-propenoic acid is stripped off by distillation. However, a small amount remains in the aqueous solution.

 

The source substance Amphopropionate C8 is manufactured from capric acid andaminoethylethanolamine (AEEA) to form 1-(2-Hydroxyethyl)-2-Heptylimidazoline. Excess AEEA is removed from the reaction mixture by distillation at elevated temperature. In a further step 2-propenoic acid is added to form Amphopropionate C8. Most of the excess 2-propenoic acid is stripped off by distillation. However, a small amount remains in the aqueous solution.

 

The source substance Amphoacetates C8-C18 is manufactured from 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and chloroacetic acid in the presence of sodium hydroxide. The molar relation between 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs.and chloroacetic acid ranges from 1:1 to 1:2. As by-product, hydrochloric acid is formed during the reaction, that is neutralized with adding more sodium hydroxide.

 

 

Differences

Chain length:

The source substance Amphopropionate C8 contains shorter C chains, whereas the major C chain in the target substance is C12.

In general the absorption declines with increasing alkyl chain length (Ramirez et al. 2001). Therefore the source substances with the shorter alkyl chain lengths are assumed to represent a worst-case scenario due to higher absorption rates than the target substance.

 

Degree of unsaturation:

In contrast to the source substance Amphopropionate C8, the target substance Amphopropionates C12-18 as well as the source substance Amphoacetates C8-C18 contain some amounts of unsaturated C18 chains.

An increase in the degree of unsaturation may lead to a slightly higher irritation potential (HERA, 2002; Stillman, 1975; Aungst, 1989). Apart from that, fatty acids irrespective of their degree of unsaturation are in general non-toxic. For other endpoints, this difference in composition is of no toxicological relevance.

Propionate vs. acetate functions:

The target substance Amphopropionates C12-18 contains propionate functions, whereas thesource substance Amphoacetates C8-C18 contains acetate functions. The shorter acetate chains might lead to slightly higher absorption.

 

Presence of residual acrylic acid:

The target substanceAmphopropionates C12-18 as well as the source substance Amphopropionate C8 may contain some small amounts of residual acrylic acid, in contrast to the source substance Amphoacetates C8-C18.

As algae are the most sensitive organisms towards acrylic acid, a toxicity study with algae was performed on the target substance itself. Moreover, supporting data from a concentrationrange finding study in Daphnia magnaperformed with the target substance is available as well as supporting data on the toxicity of acrylic acid to aquatic invertebrates and fish.

 

 

Comparison of ecotoxicity data

 

Target substance

Source substances

 

 

Endpoint

Amphopropionates C12-18

Amphopropionate C8

Amphoacetates C8-C18

Acrylic acid

Acute toxicity to fish

No data, read-across

WoE_RA_Short-term toxicity to fish_64265-45-8_9.1.3_Evonik_2008_OECD203

 

OECD TG 203, static, freshwater, Cyprinus carpio

 

96 h LC50 > 100 mg a.i./L, analytically verified nominal conc.

 

1 (reliable without restriction), GLP

WoE_RA_Short-term toxicity to fish: 931-291-0_9.1.3._Rhodia_1995

 

OECD TG 203, semi-static, freshwater, Oncorhynchus mykiss

 

96 h LC50 = 4.2 mg a.i./L, nominal

 

2 (reliable with restrictions), GLP

sup_RA_Short-term toxicity to fish: 79-10-7_9.1.3._EU RAR_2002

 

guideline not specified, flow-through, freshwater, Oncorhynchus mykiss

 

96 h LC50 = 27 mg/L, meas.

 

2 (reliable with restrictions), no data on GLP

 

 

 

WoE_RA_Short-term toxicity to fish: 931-291-0_9.1.3._Cognis_2001

 

OECD TG 203, static, freshwater, Danio rerio

 

96 h LC50 = 8.5 mg a.i./L, analytically verified nominal conc.

 

1 (reliable without restriction), GLP

 

Short-term toxicity to aquatic invertebrates

WoE_Short-term toxicity to aquatic invertebrates_93820-52-1_9.1.1_Evonik_2016_OECD202

 

OECD TG 202, static, freshwater, Daphnia magna

 

48 h EC50 = 13.2 mg a.i./L (95% c.i. 1.72 - 17.22 mg/L), nominal

 

3 (not reliable), non-GLP dose range finding study

WoE_RA_Short-term toxicity to aquatic invertebrates_64265-45-8_9.1.1_Evonik_2008_OECD202

 

OECD TG 202, static, freshwater, Daphnia magna

 

48 h EC50 > 100 mg a.i./L, analytically verified nominal conc.

 

1 (reliable without restriction), GLP

WoE_RA_Short-term toxicity to aquatic invertebrates: 931-291-0_9.1.1_Cognis_2001

 

OECD TG 202, static, freshwater, Daphnia magna

 

48 h EC50 =17.9 mg a.i./L, analytically verified nominal conc.

 

1 (reliable without restriction), GLP

sup_RA_Short-term toxicity to aquatic invertebrates: 79-10-7_9.1.1._EU RAR_2002

 

guideline not specified, static, freshwater, Daphnia magna

 

48 h EC50 = 47 mg/L, meas.

 

2 (reliable with restrictions), no data on GLP

 

 

 

WoE_RA_Short-term toxicity to aquatic invertebrates: 931-291-0_9.1.1_Evonik_1992

 

OECD TG 202, static, freshwater, Daphnia magna

 

48 h EC50 = 2.5 mg a.i./L, nominal

 

2 (reliable with restrictions), GLP

 

Toxicity to aquatic algae and cyanobacteria

key_Toxicity to aquatic algae and cyanobacteria: 93820-52-1_9.1.2_Evonik_2016_OECD201

 

OECD TG 201, static, freshwater, Pseudokirchnerella subcapitata

 

72 h ErC10 = 0.494 mg a.i./L (95% c.i. 2.28 – 2.54 mg/L (geom.. mean measured))

72 h ErC50 = 2.4 mg a.i./L (95% c.i. 0.437 – 0.557 mg/L (geom.. mean measured))

 

1 (reliable without restriction), GLP

sup_RA_Toxicity to aquatic algae and cyanobacteria_64265-45-8_9.1.2_Evonik_2008_OECD201

 

OECD TG 201, static, freshwater, Pseudokirchnerella subcapitata

 

72 h NOEC < 4.6 mg a.i./L,

72 h ErC50 = 65 mg a.i./L (95% c.i. 42-99 mg/L), analytically verified nominal conc.

 

1 (reliable without restriction), GLP

sup_RA_Toxicity to aquatic algae and cyanobacteria: 931-291-0_9.1.2._Rhodia_2001_OECD201

 

OECD TG 201, static, freshwater, Pseudokirchnerella subcapitata

 

72 h NOEC = 3.6 mg a.i./L,

72 h ErC50 = 28.5 mg a.i./L (95% c.i. 25.3 - 33.2 mg/L), nominal

 

2 (reliable with restrictions), GLP

sup_RA_Toxicity to aquatic algae and cyanobacteria: 79-10-7_9.1.2._EU RAR_2002

 

guideline not specified, static, freshwater, Scenedesmus subspicatus

 

72 h NOEC (growth rate) = 0.016 mg/L, meas.

72 h ErC10 = 0.03 mg/L, meas.

72 h ErC50 = 0.13 mg/L, meas.

 

2 (reliable with restrictions), no data on GLP

 

 

 

sup_RA_Toxicity to aquatic algae and cyanobacteria: 931-291-0_9.1.2._Rhodia_1995_OECD201

 

OECD TG 201, static, freshwater, Pseudokirchnerella subcapitata

 

72 h NOEC = 3.2 mg a.i./L,

72 h ErC50 = 10 mg a.i./L (95% c.i. 9 – 12 mg/L), nominal

 

2 (reliable with restrictions), GLP

 

 

 

 

sup_RA_Toxicity to aquatic algae and cyanobacteria: 931-291-0_9.1.2._Evonik_1998_OECD201

 

OECD TG 201, static, freshwater, Desmodesmus subspicatus

 

72 h NOEC < 3.1 mg a.i./L,

72 h ErC10 = 6.5 mg a.i./L

72 h ErC50 = 30 mg a.i./L, analytically verified nominal conc.

 

2 (reliable with restrictions), GLP

 

 

Short-term toxicity to fish

No experimental data are available for the target substance.

In an acute toxicity study according to OECD Guideline 203 in Cyprinus carpio conducted with Amphopropionate C8, the 96 h LC50 was > 100 mg a.i./L.  The EC50 and NOEC values, based on mortality/sublethal effects, were both > 100 mg a.i./L.

 

The 96 h LC50 of Amphoacetates C8-C18 to Oncorhynchus mykiss was 4.2 mg/L (based on solids content).

 

The 96 h LC50 of Amphoacetates C8-C18 to Danio rerio was 8.5 mg/L (based on solids content).

 

The 96 h LC50 of acrylic acid to Oncorhynchus mykiss was reported to be 27 mg/L.

 

The lowest 96 h LC50 of 4.2 mg/L obtained with the source substance Amphoacetates C8-C18 will be used for chemical safety assessment.

 

Short-term toxicity to aquatic invertebrates

The 48–hr-acute toxicity of Amphopropionates C12-18 (40% in water) toDaphnia magnawas studied in a screening test according to OECD Guideline 202 (2004) with deviations under static conditions.  Daphnids were exposed to control and test item at nominal concentrations of 1, 10 and 100 mg/L for 48 hr.  Immobilization was observed daily.  The 48 hr EC50 was 76.8 mg/L (nominal). Based on measured concentrations, the 48 h EC50 was 13.2 mg/L (95% c.i. 1.72 - 17.22 mg/L).

 

The 48 h EC50 of Amphoacetates C8-C18 to Daphnia magna was 2.5 mg/L (based on solids content).

 

The 48 h EC50 of Amphopropionate C8 was >100 mg a.i./L.

 

The 48 h EC50 of acrylic acid to Daphnia magna was 47 mg/L.

 

Toxicity to algae and cyanobacteria

In a test conducted according to OECD Guideline 201 with Pseudokirchneriella subcapitata the 72 h ErC10 and ErC50 of Amphopropionates C12-18 were 2.4 and 0.494 mg a.i./L, respectively.

 

Supporting data on the source substances Amphopropionate C8 (ErC50 =65 mg/L, NOEC <4.6 mg/L) and Amphoacetates C8-18 (ErC50 ranging from 10 to 30 mg/L, NOEC ranging from <3.1 to 3.6 mg/L) are available.

 

The 72 h NOEC(growth rate), ErC10, ErC50 of acrylic acid to Scenedesmus subspicatus were 0.016 mg/L, 0.03 mg/L and 0.13 mg/L, respectively.

 

 

Quality of the experimental data of the analogues:

The available data are adequate and sufficiently reliable to justify the read-across approach.

The key studies were conducted according to OECD Guidelines 201, 202 and 203, respectively, and are reliable or reliable with restrictions (RL1-2). The concentration range finding study in Daphnia conducted with the target substance is not fully compliant with the guideline requirements and thus, was assigned RL=3. 

The test materials used in the respective studies represent the source substance as described in the hypothesis in terms of substance identity and minor constituents.

Overall, the study results are adequate for the purpose of classification and labelling and risk assessment.

 

 

Conclusion

The structural similarities between the source and the target substances presented above and in more detail in the general justification for read-across support the read-across hypothesis. Adequate and reliable scientific information indicates that the source and target substances have similar ecotoxicity profiles.

The most sensitive organisms was found to be algae (72 h ErC50 =2.4 mg/L). This result was considered as an appropriate starting point for deriving PNECs for the aquatic compartment (including sediment).