1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C12-14(even numbered) acyl) derivs., hydroxides, inner salts

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

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

Key result

Duration:

21 d

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:

reproduction

Reported statistics and error estimates:

Steel-Test

Conclusions:

Three of the Daphnia magna reproduction tests were conducted in reconstituted dilution water resulting in 21 d NOEC values of 0.03, 0.32, and 0.932 mg a.i./L. Based on the test results using 2/3 reconstituted dilution water and 1/3 pond water (21 d NOEC=0.9 mg a.i./L), it can be assumed that the presence of pond water has little or no influence, as the results are comparable to those obtained in the newly performed study in which analytical monitoring of the test substance concentration was performed using state-of-the-art equipments and techniques and which seems to be the most reliable study.
The very low 21 d NOEC and LOEC of 0.03 and 0.1 mg a.i./L determined in one test could not be confirmed by the other studies and based on the available data this discrepancy could not be resolved. Therefore a weight of evidence approach seems to be justified taking into account the 21 d NOEC values of 0.03, 0.32, 0.9, and 0.932 mg a.i./L. The calculation yielded a 21 d NOEC of 0.3 mg a. i./L as the geometric mean with respect to reproduction.

Description of key information

The long-term toxicity of C8-18 AAPB and C8 -18 and C18 unsatd. AAPB was investigated in four studies conducted according to OECD Guideline 211, in some reports cited as OECD Guideline 202, part II Daphnia sp., Reproduction Test. It was considered appropriate to evaluate the studies using a weight of evidence approach.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

0.3 mg/L

Additional information

No experimental data are available for C12-14 AAPB.

However, adequate and reliable long-term toxicity data to aquatic invertebrates are available for the closely related source substances C8-18 AAPB and C8-18 and C18 unsatd. AAPB (Coco AAPB).

A justification for read-across is given below.

 

In the first study the 21 d toxicity of C8-18 AAPB to Daphnia magna was investigated according to OECD Guideline 211 (Daphnia magna Reproduction Test) under semi-static conditions. The analytically determined concentrations of C8-18 AAPB in the freshly prepared test media of the analysed test concentrations of 0.32, 1.0, and 3.2 mg/L varied from 101 to 124 % of the nominal concentrations, the mean measured values of all measurements amounted from 104 to 118 % of the respective nominal value. In the test media samples taken out of the actual biological test (including algal food), the test substance concentration could not be quantified due to disturbance of the measurements by the algae. However, additional stability controls showed that C8-18 AAPB was sufficiently stable in the test media (but without algal food and Daphnia) during the longest test medium renewal periods of 72 h. The 21 d NOEC and LOEC based on survival and reproduction were determined to be 0.03 and 0.1 mg a.i./L nominal, respectively. These very low values could not be confirmed in the other studies. Based on the available data this discrepancy could not be resolved.

 

In the second study the 21 d toxicity of C8-18 and C18 unsatd. AAPB to Daphnia magna was investigated according to OECD Guideline 211 (Daphnia magna Reproduction Test) under semi-static conditions. The 21 d NOEC and LOEC values were determined to be 0.32 and 0.56 mg a. i./L in respect to reproduction. The most sensitive endpoint was release of the first brood (21 d NOEC=0.18 mg a. i./L; 21 d LOEC=0.32 mg a. i./L nominal each).

 

In the third study the 21-day-chronic toxicity of C8-18 AAPB (30 % active matter) to Daphnia magna was investigated according to OECD Guideline 211 (Daphnia magna Reproduction Test) under semi-static conditions. The test was performed in a mixture of 2/3 reconstituted water and 1/3 pond water. Per concentration 20 daphnids (ten per beaker) were kept in bulk culture. After 7 d 10 daphnids with eggs in the brood pouch were separated and kept individually. The remaining daphnids were observed for mortality rates (unhealthy and damaged daphnids were excluded). At the start of the treatment periods the measured concentrations (photometric) ranged from 76.7 to 117 % of the nominal values and at the end of the exposure period from 76.3 to 96.9 %. Additionally performed stability controls showed that the test substance was sufficiently stable in the test media during the renewal periods. The 21-day NOEC and LOEC based on reproduction were 0.9 and 3.6 mg active substance/L nominal.

 

In the newly performed 21-day-chronic, semi-static reproduction tests conducted according to OECD Guideline 211 (Daphnia magna Reproduction Test) and EU Method C.20 (Daphnia magna Reproduction Test), the influence of natural ingredients in environmental aquatic systems on the chronic toxicity of C8-18 AAPB (28.4 % active matter) to Daphnia magna was investigated. Daphnids were exposed to control, and test chemical at nominal concentrations of 0.0284, 0.091, 0.290, 0.932 and 2.98 mg a.i./L (dilution water according to Elendt). Samples of all concentrations and control were analytically verified via LC-MS/MS on days 0, 2, 14 (fresh media, 0 h) and on days 2, 5, 16 (old media, 48/72 h). The recovery rates of fresh and old media of the biologically relevant concentration levels were > 80 %. The 21-day NOEC and LOEC based on reproduction were 0.932 and 2.98 mg active substance/L nominal, respectively (CEFIC/CESIO [ICCA Initiative] Alkylamidopropyl Betaines Consortium (2006a))

 

An additional study with same study design was conducted with natural river water. The study is described and compared to the study with reconstituted water as follows in the SIAR CAPB 2006.

“The test with natural river water resulted in a NOEC on reproduction of ≥ 2.98 mg active substance/l and a LOEC greater than 2.98 mg active substance/l (21 d-NOEC ≥ 10.5 mg product/l; 21 d-LOEC > 10.5 mg product/l). In these two studies additional parameters were investigated (e. g. first appearance of juveniles, intrinsic rate of natural increase). In the study with natural river water weak (but statistically significant) effects on the intrinsic rate were observed at all concentrations ≥ 0.32 mg product/L, showing no concentration effect relationship. Only at 10.5 mg/L a significant decrease in intrinsic rate and a significant effect on the first appearance of juveniles was determined. With reconstituted water the effect levels of reproduction rate, intrinsic rate, and first appearance were comparable. The test substance concentration was sufficiently stable at the relevant concentrations. Thus, humic acids and other natural ingredients have only a slight influence on the toxicity of C8-18 AAPB to Daphnia magna. The variation in the effect values described above could not be clarified.”

 

Conclusion

Three of the Daphnia magna reproduction tests were conducted in reconstituted dilution water resulting in 21 d NOEC values of 0.03, 0.32, and 0.932 mg a.i./L. Based on the test results using 2/3 reconstituted dilution water and 1/3 pond water (21 d NOEC=0.9 mg a.i./L), it can be assumed that the presence of pond water has little or no influence, as the results are comparable to those obtained in the newly performed study in which analytical monitoring of the test substance concentration was performed using state-of-the-art equipments and techniques and which seems to be the most reliable study.

As already mentioned above, the very low 21 d NOEC and LOEC of 0.03 and 0.1 mg a.i./L determined in one test could not be confirmed by the other studies and based on the available data this discrepancy could not be resolved. Therefore a weight of evidence approach seems to be justified taking into account the 21 d NOEC values of 0.03, 0.32, 0.9, and 0.932 mg a.i./L. The calculation yielded a 21 d NOEC of 0.3 mg a. i./L as the geometric mean with respect to reproduction.

 

 

Justification for read-across

For details on substance identity and detailed (eco)toxicological profiles, please refer also to the general justification for read-across given 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 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 long-term toxicity data to aquatic invertebrates

 

Endpoints	Source substances		Target substance
	C8-18 AAPB	C8-18 and C18 unsatd. AAPB	C12-14 AAPB
Long-term toxicity to aquatic invertebrates	WoE.Long-term toxicity to aquatic invertebrates: 97862-59-4_9.1.5_IUA_1995_OECD 202   Weight of evidence   OECD Guideline 211 (Daphnia magna Reproduction Test) (cited as OECD Guideline 202, part 2 (Daphnia sp., Reproduction Test)) Daphnia magna, semi-static, freshwater 21 d NOEC = 0.032 mg/Lact. ingr. (nominal) based on: survival and reproduction rate 21 d LOEC = 0.1 mg/Lact. ingr. (nominal) based on: survival and reproduction rate   Reliability: 1 (reliable without restriction), GLP	WoE.Long-term toxicity to aquatic invertebrates: 61789-40-0_9.1.5_Unilever Research_1990   Weight of evidence   OECD Guideline 211 (Daphnia magna Reproduction Test) (cited as OECD Guideline 202, part 2 (Daphnia sp., Reproduction Test)) Daphnia magna, semi-static, freshwater   21 d NOEC = 0.32 mg/Lact. ingr. (nominal) based on: reproduction 21 d LOEC = 0.56 mg/Lact. ingr. (nominal) based on: reproduction 21 d NOEC = 0.56 mg/Lact. ingr. (nominal) based on: mortality 21 d LOEC = 1 mg/Lact. ingr. (nominal) based on: mortality   Reliability: 2 (reliable with restrictions), GLP	No data, read-across
	WoE.Long-term toxicity to aquatic invertebrates: 97862-59-4_9.1.5_THG_1991d_OECD 202   Weight of evidence   OECD Guideline 211 (Daphnia magna Reproduction Test) (cited as OECD Guideline 202, part 2 (Daphnia sp., Reproduction Test)) Daphnia magna, semi-static, freshwater 21 d NOEC = 0.9 mg/Lact. ingr. (nominal) based on: reproduction 21 d LOEC = 3.6 mg/Lact. ingr. (nominal) based on: reproduction   Reliability: 1 (reliable without restriction), GLP
	WoE.Long-term toxicity to aquatic invertebrates: 97862-59-4_9.1.5_CEFIC_CESIO_2006a_OECD 211   OECD Guideline 211 (Daphnia magna Reproduction Test) Daphnia magna, semi-static, freshwater   21 d NOEC = 0.932 mg/Lact. ingr. (nominal) based on: reproduction 21 d LOEC = 2.98 mg/Lact. ingr. (nominal) based on: reproduction   Reliability: 1 (reliable without restriction), GLP

 

Three of the reproduction tests were conducted in reconstituted dilution water resulting in 21 d NOEC values of 0.03, 0.32, and 0.932 mg a.i./L. Based on the test results using 2/3 reconstituted dilution water and 1/3 pond water (21 d NOEC=0.9 mg a. i./L), it can be assumed that the presence of pond water has little or no influence, as the results are comparable to those obtained in the newly performed study in which analytical monitoring of the test substance concentration was performed using state-of-the-art equipments and techniques and which seems to be the most reliable study.

The very low 21 d NOEC and LOEC of 0.03 and 0.1 mg a.i./L determined in one test could not be confirmed by the other studies, and based on the available data this discrepancy could not be resolved. Therefore a weight of evidence approach was applied calculating the geometric mean of the available NOEC. This resulted in a21 d NOEC of 0.3 mg a.i./L with respect to reproduction.

 

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 toOECD Guideline 211 and were reliable or reliable with restrictions (RL1-2, GLP).

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 substances as 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 C8-18 AAPB and C8-18 and C18 unsatd. AAPB are also valid for the target substance C12-14 AAPB.

A weight of evidence approach was applied taking into account the 21 d NOEC values of 0.03, 0.32, 0.9, and 0.932 mg a.i./L. The calculation yielded a 21 d NOEC of 0.3 mg a.i./L as the geometric mean with respect to reproduction.