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

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

fish early-life stage toxicity

Type of information:

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

Adequacy of study:

key study

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

Duration:

37 d

Dose descriptor:

NOEC

Effect conc.:

0.135 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

other: egg hatch

Duration:

37 d

Dose descriptor:

LOEC

Effect conc.:

0.405 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

other: egg hatch

Duration:

100 d

Dose descriptor:

NOEC

Effect conc.:

0.135 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

other: length, dry weight, morphological and behavioural effects, post hatch success, overall survival

Duration:

100 d

Dose descriptor:

LOEC

Effect conc.:

0.405 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

other: length, dry weight, morphological and behavioural effects, post hatch success, overall survival

Conclusions:

The obtained NOECs of 0.135 and 0.16 mg a.i./L of C8-18 AAPB were in the same range. The obtained results were considered to be valid for the AAPBs. The NOEC of 0.135 mg a.i./L obtained from the long-term study including early life-stage was selected for further assessment and derivation of the PNEC.

Description of key information

One study for long-term toxicity to fish is available, investigating the 100– day chronic toxicity of C8 -18 AAPB conducted according to OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test).

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

0.135 mg/L

Additional information

No experimental data on long-term toxicity to fish are available for C12-14 AAPB. However, an early life stage test as well as aprolonged 28-d toxicity study conductedwith the closely related source substance C8 -18 AAPB are available.

A justification for read-across is given below.

 

In a study conducted according to OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test) and EPA OPPTS 850.1400 (Fish Early-life Stage Toxicity Test), the 100 day chronic toxicity of C8 -18 AAPB to early life stage of rainbow trout (Oncorhynchus mykiss) was investigated under flow through conditions and analytical monitoring of test material concentrations. The mean recovery rates for all concentrations were in the range of 81 – 100%. Therefore all effect values are based on nominal concentrations. The 37 day NOEC and LOEC values, based on egg hatch, were 0.135 and 0.405 mg a.i./L respectively. The 100 day overall NOEC and LOEC values were 0.135 and 0.405 mg a.i./L, respectively. The effects included were length, dry weight, morphological and behavioral effects, post hatch success and overall survival.

 

Additional data are available from a prolonged 28-d toxicity study conducted according to OECD Guideline 215 Draft 'Juvenile growth test: 28 d' (1992): Rainbow trouts (Oncorhynchus mykiss) were exposed to C8-18 AAPB under flow through conditions. A 28-d NOEC = 0.16 mg a.i./L nominal was determined based on growth (body length and mean body wet weight). At higher test concentrations of 0.5 and 1.6 mg a.i./L nominal, the growth rates could not be determined, since all fish died during the test period.

 

Conclusion

The obtained NOECs of 0.135 and 0.16 mg a.i./L of C8-18 AAPB were in the same range. The obtained results were considered to be valid for the AAPBs.

The NOEC of 0.135 mg a.i./L obtained from the long-term study including early life-stage was selected for further assessment and derivation of the PNEC.

 

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 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 fish toxicity data

 

Endpoints	Source substance	Target substance
	C8-18 AAPB	C12-14 AAPB
Long-term toxicity to fish	key.Long-term toxicity to fish: 97862-59-4_9.1.6.1_THG_2008_OECD 210 key study   OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)   Oncorhynchus mykiss, flow-through, freshwater   37 d NOEC = 0.135 mg/Lact. ingr. (nominal) based on: egg hatch 37 d LOEC = 0.405 mg/Lact. ingr. (nominal) based on: egg hatch 100 d NOEC = 0.135 mg/Lact. ingr. (nominal) based on: length, dry weight, morphological and behavioural effects, post hatch success, overall survival 100 d LOEC = 0.405 mg/Lact. ingr. (nominal) based on: length, dry weight, morphological and behavioural effects, post hatch success, overall survival   Reliability: 1 (reliable without restriction), GLP	No data, read-across
	Sup.(prolonged fish test: 28 d).Short-term toxicity to fish.97862-59-4_9.1.3_IUA_1995_OECD_204 key study OECD Guideline 204 (Fish, Prolonged Toxicity Test: 14-day Study)   Oncorhynchus mykiss, flow-through, freshwater   28 d NOEC = ca. 0.16 mg/L act. ingr. (nominal) based on: mortality   28 d LOEC = ca. 0.5 mg/L act. ingr. (nominal) based on: mortality   No deaths < 1.6 mg/L; 10/10 fish died within 4 d at >/= 1.6 mg/L   Reliability: 1 (reliable without restriction), GLP

 

The obtained NOECs of 0.135 and 0.16 mg a.i./L in both studies were in the same range. The NOEC of 0.135 mg a. i./L obtained from the long-term study including early life-stages was selected for further chemical safety assessment.

 

Quality of the experimental data of the analogues:

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

The key study was conducted according toOECD Guideline 210 (Fish, Early-Life Stage Toxicity Test; RL1, GLP). The supporting study was conducted according to OECD Guideline 204 (RL1, 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 substance C8-18 AAPB are also valid for the target substance C12-14 AAPB.

 

The 100 d NOEC of C8 -18 AAPB to Oncorhynchus mykiss was 0.135 mg a.i./L(nominal) based on length, dry weight, morphological and behavioural effects, post hatch success, overall survival.