1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C12-18(even numbered) acyl) derivs., hydroxides, inner salts

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
see "General Justification for Read-Across" attached to IUCLID section 13

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Mutual read across from the AAPBs to one another is justified:

a) Based on the information given in section 1, it can be concluded that all AAPBs mentioned above are similar in structure, since they are manufactured from similar resp. identical precursors under similar conditions and all contain the same functional groups. Thus a common mode of action can be assumed.
b) The content of minor constituents in all products are comparable and differ to an irrelevant amount.
c) The only deviation within this group of substances is a minor variety in their fatty acid moiety, which is not expected to have a relevant impact on intrinsic toxic or ecotoxic activity and environmental fate. Potential minor impact on specific endpoints will be discussed in the specific endpoint sections.

The read-across hypothesis is based on structural similarity of target and source substances. Based on the available experimental data, including key physico-chemical properties and data from toxicokinetic, acute toxicity, irritation, sensitisation, genotoxicity and repeated dose toxicity studies, the read-across strategy is supported by a quite similar toxicological profile of all five substances.
The respective data are summarised in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see "General Justification for Read-Across" attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see "General Justification for Read-Across" attached to IUCLID section 13

4. DATA MATRIX
see "General Justification for Read-Across" attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

72 h

Dose descriptor:

EC50

Remarks:

geometric mean of all available studies

Effect conc.:

1.5 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

growth rate

Key result

Duration:

72 h

Dose descriptor:

NOEC

Remarks:

geometric mean of all available studies

Effect conc.:

0.3 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

growth rate

Conclusions:

In a weight of evidence approach, considering all available information for the endpoint aquatic toxicity, the ecotox profile of C8-18 AAPB is characterised by an acute aquatic toxicity in the range of >1 to ≤ 10 mg/L. For practical reasons (to name a value for the algae effect concentration) the algae study with the lowest acute effect result within this range is used for the assessment of algae toxicity: 72h-ErC50 = 1.5 mg a.i./L, 72h-NOEC = 0.3 mg a.i./L.

Description of key information

The toxicity of C8-18 AAPB, Coco AAPB and C12 AAPB to fresh water and salt water algae was investigated in 8 valid studies. In a weight of evidence approach, considering all available information for the endpoint aquatic toxicity, the ecotox profile of C8-18 AAPB is characterised by an acute aquatic toxicity in the range of >1 to ≤ 10 mg/L. For practical reasons (to name a value for the algae effect concentration) the algae study with the lowest acute effect result within this range is used for the assessment of algae toxicity: 72h-ErC50 = 1.5 mg a.i./L, 72h-NOEC = 0.3 mg a.i./L.

Key value for chemical safety assessment

EC50 for freshwater algae:

1.5 mg/L

EC10 or NOEC for freshwater algae:

0.3 mg/L

Additional information

No experimental data are available for C12-18 AAPB.

However, algal toxicity studies in freshwater and saltwater algae are available for the closely related source substances C12 AAPB, C8-18 AAPB and C8-18 and C18 unsatd. AAPB (Coco AAPB). A justification for read-across is given below.

 

The toxicity of C8-18 AAPB, C8-18 and C18 unsatd. AAPB and C12 AAPB to fresh water and salt water algae was investigated in 8 valid studies,7 fresh water algae studies with Desmodesmus subspicatus and Pseudokirchnerella subcapitata (72h-ErC50 1.5 - > 334 mg/L a.i.) and one marine algae study with Skeletonema costatum (72 -h- ErC50 0.97 mg/L a.i.).

 

In a weight of evidence approach, considering all available information for the endpoint aquatic toxicity, the ecotox profile of C8-18 AAPB is characterised by an acute aquatic toxicity in the range of >1 to ≤ 10 mg/L. For practical reasons (to name a value for the algae effect concentration) the algae study with the lowest acute effect result within this range is used for the assessment of algae toxicity: 72h-ErC50 = 1.5 mg a.i./L, 72h-NOEC = 0.3 mg a.i./L.

 

Data included in the weight of evidence approach

1. In a test conducted according to DIN 38412, part 9 (comparable to OECD Guideline 201), the cultures of Desmodesmus subspicatus were exposed to C8-18 and C18 unsatd. AAPB at nominal concentrations of 0.003, 0.009, 0.03, 0.09, 0.3, 0.9, 3.0 mg a.i./L under static conditions for 72 h. Originally, the data were evaluated according to the test guideline (DIN 38412, Part 9) using the EDV-program of Mr. Holtmann (Henkel KGaA). Based on today knowledge, this calculation model is no longer valid or only valid with restriction. Therefore, a recalculation of the 72 h EC50 values was performed taking into account the OECD principles. The 72 h ErC50, EbC50, and NOEC were found to be 1.5, 0.57, and 0.3 mg a.i./L nominal, respectively.

 

2. In a 72 hour toxicity study conducted according to OECD Guideline 201 (Alga, Growth Inhibition Test) and EU Method C.3 (Algal Inhibition test), the cultures of Desmodesmus subspicatus were exposed to C8-18 and C18 unsatd. AAPB (30.9 % active matter) at nominal concentrations of 0.97, 1.93, 3.86, 7.72, 15.45, 30.9 mg active substance/L under static conditions. The 72 h NOEC, LOEC and EC50 values based on growth rate were 3.86, 7.73 and 9.86 mg a.i./L nominal, respectively. The 72 h NOEC, LOEC and EC50 values based on biomass were 1.93, 3.86 and 5.31 mg a.i./L nominal, respectively. There were no compound related phytotoxic effects. This toxicity study is regarded as reliable without restriction and satisfies the requirements of the guideline.

 

3. In a 72 hour acute toxicity study, the cultures of Desmodesmus subspicatus were exposed to C12 AAPB at nominal concentrations of 0.03, 0.096, 0.3, 0.96, 3, 9.6 mg a.i./L / under static conditions in accordance with the OECD Guideline 201 (2006).  The 72 h ErC50 value based on inhibition of specific growth rate was 3.15 mg a.i./L, the 72 h EyC50 value based on yield inhibition was 1.01 mg a.i./L, respectively. The 72 h NOEC based on growth rate and yield was determined to be 0.3 mg a.i./L nominal. No abnormalities were noted. The test item effects were observed to be reversible at the test concentrations 0.32 - 32 mg test mat. /L. (0.096 - 9.6 mg a.i./L). This toxicity study is classified as reliable without restriction and satisfies the requirements of the OECD Guideline 201 Alga, Growth inhibition test (2006).

 

4. In a 72 hour toxicity study conducted according to OECD Guideline 201 (Alga, Growth Inhibition Test), the cultures of Desmodesmus subspicatus were exposed to C8 -18 AAPB at nominal concentrations of 0, 0.098, 0.31, 0.98, 3.1, 9.8, and 31 mg active substance/L under static conditions. The 72 h ErC50 and 72 h EbC50 were 14.7 and 9.2 mg active substance/L nominal, respectively.  There were no compound related phytotoxic effects. This study is regarded as reliable with restrictions and satisfies the guideline requirements for a toxicity study with freshwater algae.

 

5. The toxicity of C8-18 and C18 unsatd. AAPB to Scenedesmus subspicatus was investigated in a study conducted according to OECD Guideline 201 (Alga, Growth Inhibition Test), EU Method C.3 (Algal Inhibition test) and ISO 8692 (Water Quality - Fresh Water Algal Growth Inhibition Test with Scenedesmus subspicatus and Selenastrum capricornutum). Scenedesmus subspicatus was exposed to nominal concentrations of 0 (control), 1.0, 1.8, 3.2, 5.6, and 10.0 mg a.i./L for 72 h under static conditions. The 72 h EC50 and NOEC based on biomass and growth rate were determined to be 5.6 (growth rate) and 4.66 (biomass) and 1.8 mg a.i./L nominal (growth rate and biomass), respectively. This study is regarded as reliable with restrictions.

 

6. The toxicity of Coco AAPB to Selenastrum capricornutum was investigated in a study conducted according to OECD Guideline 201 (Alga, Growth Inhibition Test), EU Method C.3 (Algal Inhibition test) and ISO 8692 (Water Quality - Fresh Water Algal Growth Inhibition Test with Scenedesmus subspicatus and Selenastrum capricornutum). Selenastrum capricornutum was exposed to nominal concentrations of 0 (control), 0.56, 1.0, 1.8, 3.2, 5.6, and 10.0 mg a.i./L for 96 h under static conditions. The 96 h ErC50, EbC50 and NOEC were determined to be >10 (growth rate) and ca. 8 (biomass) and 3.2 mg a.i./L nominal (growth rate and biomass), respectively. This study is regarded as reliable with restrictions.

 

7. In a test conducted according to OECD Guideline 201, the cultures of Desmodesmus subspicatus were exposed to C8-18 and C18 unsatd. AAPB at nominal concentrations of 0 (control), 4, 10, 25, 63, 158, and 395 mg dry residue/L for 72 h under static conditions. The stability of the test item was measured via TOC measurements. The recovery rate was >80%. After 72 h, the measured values differed from freshly prepared solutions by < 20%. The 72 h EC50 were determined to be 37.2 (biomass) and >334 mg a.i./L nominal (growth rate), respectively. This study is regarded as reliable with restrictions.

 

8. The toxicity of C8-18 and C18 unsatd. AAPB to the marine phytoplankton Skeletonema costatum was investigated in a study conducted according to ISO 10253 (Water quality - Marine Algal Growth Inhibition Test with Skeletonema costatum and Phaeodactylum tricornutum). Cultures of Skeletonema costatum in the exponential growth phase were exposed to nominal concentrations of 0.32, 1.0, 3.2, 5.6, and 10 mg product/L corresponding to 0.01, 0.36, 1, 2, and 3.6 mg a.i./L under static conditions for 72 h. The 72 h ErC50 and NOEC values were determined to be 2.05 mg product/L and 1 mg product/L (nominal each), respectively.

Effect concentrations based on a.i. as named in study report CoA (certificate of analysis) (= solids - sodium chloride) and recalculated for a.i. of registration substance composition (IUCLID chapter 1.2): 72 h ErC50: 1.21 mg a.i./L, 72 h NOEC: 0.59 mg a.i./L.

Effect concentrations based on a.i. as named in study report CoA (certificate of analysis) (= solids - sodium chloride): 72 h ErC50: 0.74 mg a.i./L, 72 h NOEC: 0.36 mg a.i./L.

This toxicity study is regarded as reliable without restriction.

 

Justification for read-across

For details on substance identity and detailed (eco)toxicological profiles, please refer also to the general justification for read-across attached as pdf document to IUCLID section 13.

 

This read-across approach is justified based on structural similarities. All AAPBs contain the same functional groups. Thus a common mode of action can be assumed.

The only deviation within this group of substances is a minor variety in their fatty acid moiety (chain length and degree of unsaturation), which is not expected to have a relevant impact on intrinsic ecotoxicological properties.

 

a. Structural similarity and functional groups

Alkylamidopropyl betaines (AAPBs) are – with the exception of C12 AAPB - UVCB substances (Substances of Unknown or Variable composition, Complex reaction products or Biological materials), which are defined as reaction products of natural fatty acids or oils with dimethylaminopropylamine and further reaction with sodium monochloroacetate. AAPBs are amphoteric surfactants, which are characterized by both acidic and alkaline properties.

 

Their general structure is:

 

R-C(O)-NH-(CH₂)₃-(N(CH₃)₂)⁺-CH₂-C(O)O^-

R = fatty acid moiety

 

The fatty acids have a mixed, slightly varying composition with an even numbered chain length from C8 to C18. Unsaturated C18 may be included. Consequently, the AAPBs differ by their carbon chain length distribution and the degree of unsaturation in the fatty acid moiety. However, Lauramidopropyl betaine (C12 fatty acid derivate) is the major ingredient of all AAPBs covered by this justification as listed in table 1 “Substance identities” of the general justification for read-across.

 

The substances under evaluation share structural similarities with common functional groups (quaternary amines, amide bonds and carboxymethyl groups), and fatty acid chains with differences in chain length and degree of saturation.

 

b. Differences

Differences in acute ecotoxicity of the AAPBs could potentially arise from the following facts:

-Different amounts of different carbon chain lengths (carbon chain length distribution):

Higher amounts of higher chain lengths and corresponding lower amounts of lower chain length could result in a rising average lipophilicity. However, the main component for all AAPBs is C12 AAPB. Relevant effects on ecotoxicity are not to be expected.

- Different amounts of unsaturated fatty ester moieties:

Effects may be expected for e.g. physical state, but are not considered to be of relevance for ecotoxicity.

 

Comparison of toxicity to aquatic algae and cyanobacteria

 

Endpoint	Source substances			Target substance
	C8-18 AAPB	C8-18 and C18 unsatd. AAPB	C12 AAPB	C12-18 AAPB
Toxicity to aquatic algae and cyanobacteria	WoE.Toxicity to aquatic algae and cyanobacteria: 97862-59-4_9.1.2_THG_1993e_OECD 201 Weight of evidence OECD Guideline 201 (Alga, Growth Inhibition Test),Scenedesmus subspicatus (new name: Desmodesmus subspicatus), freshwater, static 72 h EC50 = ca. 14.7 mg/L,act. ingr. (nominal) based on: growth rate   72 h EC50 = ca. 9.2 mg/L,ingr. (nominal) based on: biomass   Reliability: 2 (reliable with restrictions), GLP	WoE.Toxicity to aquatic algae and cyanobacteria: 61789-40-0_9.1.2_Henkel_1992_DIN 38412 part 9   Weight of evidence DIN 38412, part 9: Bestimmung der Hemmwirkung von Wasserinhaltsstoffen auf Grünalgen, Desmodesmus subspicatus (reported as Scenedesmus subspicatus), freshwater, static   72 h EC50 = ca. 1.5 mg/L,act. ingr. (nominal) based on: growth rate 72 h NOEC = ca. 0.3 mg/L,act. ingr. (nominal) based on: biomass 72 h EC50 = ca. 0.57 mg/L,act. ingr. (nominal) based on: biomass   Reliability: 2 (reliable with restrictions), GLP	WoE.Toxicity to aquatic algae and cyanobacteria: 4292-10-8_9.1.2_Betaines consortium_2007_OECD 201 Weight of evidence   OECD Guideline 201 (Alga, Growth Inhibition Test),Desmodesmus subspicatus, freshwater, static   72 h EC50 = 3.15 mg/L,act. ingr. (nominal) based on: growth rate (2.82 - 3.51 mg act. ingr./L) 72 h EC20 = 1.31 mg/L,act. ingr. (nominal) based on: growth rate (1.11 - 1.48 mg act. ingr./L) 72 h EC10 = 0.825 mg/L,act. ingr. (nominal) based on: growth rate (0.663 - 1.01 mg act. ingr./L) 72 h NOEC = 0.3 mg/L,act. ingr. (nominal) based on: growth rate 72 h LOEC = 0.96 mg/L,act. ingr. (nominal) based on: growth rate   72 h EC50 = 1.01 mg/L,act. ingr. (nominal) based on: yield inhibition (0.801 - 1.29 mg act. ingr./L) 72 h EC20 = 0.558 mg/L,act. ingr. (nominal) based on: yield inhibition (0.396 . 0.603 mg act. ingr./L) 72 h EC10 = 0.426 mg/L,act. ingr. (nominal) based on: yield inhibition (0.287 - 0.603 mg act. ingr./L) 72 h NOEC = 0.3 mg/L,act. ingr. (nominal) based on: yield inhibition 72 h LOEC = 0.96 mg/L,act. ingr. (nominal) based on: yield inhibition   Reliability: 1 (reliable without restriction), GLP	No data, read-across
		WoE.Toxicity to aquatic algae and cyanobacteria: 61789-40-0_9.1.2_CEFIC_CESIO_2006b_OECD 201 Weight of evidence   OECD Guideline 201 (Alga, Growth Inhibition Test),Desmodesmus subspicatus, freshwater, static   72 h NOEC = 3.86 mg/Lact. ingr. (nominal) based on: growth rate 72 h EC50 = 9.86 mg/Lact. ingr. (nominal) based on: growth rate (95% c.i. 9.33 - 10.4 mg/L) 72 h LOEC = 7.73 mg/Lact. ingr. (nominal) based on: growth rate 72 h EC50 = 5.31 mg/Lact. ingr. (nominal) based on: biomass (95% c.i. 5.06 - 5.53 mg/L) 72 h NOEC = 1.93 mg/Lact. ingr. (nominal) based on: biomass 72 h LOEC = 3.86 mg/Lact. ingr. (nominal) based on: biomass   Reliability: 1 (reliable without restriction), GLP
		WoE.Toxicity to aquatic algae and cyanobacteria.61789-40-0_9.1.2_Acute-algae_Unilever_A19_AL-L17-01 Weight of evidence OECD Guideline 201 (Alga, Growth Inhibition Test),Desmodesmus subspicatus (reported as Scenedesmus subspicatus), freshwater, static   72 h NOEC = 1.8 mg/Lact. ingr. (nominal) based on: biomass and growth rate 72 h EC50 = 4.66 mg/Lact. ingr. (nominal) based on: biomass 72 h EC50 = 5.6 mg/Lact. ingr. (nominal) based on: growth rate   Reliability: 2 (reliable with restrictions), no GLP
		WoE.Toxicity to aquatic algae and cyanobacteria.61789-40-0_9.1.2_Acute-algae_Unilever_A18_AL-L474-01   Weight of evidence OECD Guideline 201 (Alga, Growth Inhibition Test),Selenastrum capricornutum (new name: Pseudokirchnerella subcapitata), freshwater, static   96 h NOEC = 3.2 mg/Lact. ingr. (nominal) based on: biomass and growth rate 96 h EC50 > 10 mg/Lact. ingr. (nominal) based on: growth rate   96 h EC50 = ca. 8 mg/Lact. ingr. (nominal) based on: biomass   Reliability: 2 (reliable with restrictions), no GLP
		WoE.Toxicity to aquatic algae and cyanobacteria: 61789-40-0_9.1.2_Hüls_1996_EEC 92-69 C3 weight of evidence EU Method C.3 (Algal Inhibition test) (cited as Directive 92/69/EEC, C.3,Desmodesmus subspicatus (reported as Scenedesmus subspicatus), freshwater, static   72 h EC50 > 334 mg/Lact. ingr. (nominal) based on: growth rate 72 h EC10 = 37.2 mg/Lact. ingr. (nominal) based on: growth rate 72 h NOEC = 10 mg/Lact. ingr. (nominal) based on: biomass   Reliability: 2 (reliable with restrictions), GLP
		WoE.Toxicity to aquatic algae and cyanobacteria.61789-40-0_9.1.2_Marine_72h_Skeletonema costatum_Rhodia_Mirataine-BET-C37_ISO_2008   weight of evidence ISO 10253 (Water quality - Marine Algal Growth Inhibition Test with Skeletonema costatum and Phaeodactylum tricornutum),Skeletonema costatum, saltwater, static   72 h NOEC 0.36 mg/Lact. ingr. (nominal) based on: growth rate 72 h EC50 0.74 mg/Lact. ingr. (nominal) based on: growth rate (95% c.i.: 0.7-0.78 mg a.i./L) 72 h NOEC 1 mg/Ltest mat. (nominal) based on: growth rate 72 h EC50 2.05 mg/Ltest mat. (nominal) based on: growth rate (95% c.i.: 1.94-2.17 mg product/L)   Reliability: 1 (reliable without restriction), GLP

 

72 h ErC50 values were in the range of 0.74 to >334 mg/L; 72 h NOEC (or EC10) values were in the range of 0.3 to 37.2 mg/L.

In a weight of evidence approach, considering all available information for the endpoint aquatic toxicity, the ecotoxicity profile of the AAPBs is characterised by an acute aquatic toxicity in the range of >1 to ≤ 10 mg/L. For practical reasons (to name a value for the algae effect concentration) the algae study with the lowest acute effect result within this range is used for the assessment of algae toxicity: 72h-ErC50 = 1.5 mg a.i./L, 72h-NOEC = 0.3 mg a.i./L.

 

Quality of the experimental data of the analogues:

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

The available studies were conducted according to OECD Guideline 201 or EU method C.4 (marine algae: ISO 10253) and were reliable (RL1) or reliable with restrictions (RL2).

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

Based on structural similarities of the target and source substancesas presented above and in more detail in the general justification for read across, it can be concluded that the available data from the source substances C12 AAPB, C8-18 AAPB and C8-18 and C18 unsatd. AAPB are also valid for the target substance C12-18 AAPB.