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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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

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:

96 h

Dose descriptor:

LC50

Remarks:

(freshwater fish: Pimephales promelas)

Effect conc.:

1.11 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95% c.i.: 0.54-1.68 mg a.i./L

Key result

Duration:

96 h

Dose descriptor:

NOEC

Remarks:

(marine fish: Cyprinodon variegatus)

Effect conc.:

1.1 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

mortality (fish)

Conclusions:

For freshwater fish (Pimephales promelas) the lowest 96 h LC50 was determined to be 1.11 mg a.i./L nominal, and for marine fish (Cyprinodon variegatus) 1.1 mg a.i./L nominal.

Description of key information

Reliable results on the acute toxicity of C8-18 AAPB and C8-18 and C18 unsatd. AAPB and the prolonged toxicity of C8-18 AAPB to fresh water fish obtained from guideline studies are available. For marine fish a limit test conducted according to guideline is available.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

1.11 mg/L

Marine water fish

Marine water fish

Effect concentration:

1.1 mg/L

Additional information

No experimental data are available for C12-14 AAPB.

However, short-term toxicity studies in freshwater and saltwater fish 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.

 

Freshwater fish

Tests withC8-18 and C18 unsatd.AAPB:

In a semi-static test conducted according to OECD Guideline 203 and EU Method C.1 usingPimephales promelas as test organism a 96 h LC50=1.11 mg a. i./L (nominal; no analytical monitoring of test substance concentration; pH not adjusted; pH range: 7.2 -7.6) was determined. In two semistatic tests conducted according to OECD Guideline 203 and/or EC Method C.1 with Danio rerio (pH adjusted) and Cyprinus carpio (pH not adjusted; pH range: 7.8 -8.2) 96 h LC50 values of ca. 2 mg a. i./L (nominal) and 1.9 mg a.i./L (nominal), respectively, were derived. Analytical monitoring of test substance concentrations was not conducted in the test with Danio rerio. In the semi-static test with Cyprinus carpio the concentration of C8-18 and C18 unsatd. AAPB was stable during the incubation time which has been shown by analytical monitoring via TOC (non-specific method).

 

Tests with C8-18 AAPB:

The acute toxicity of C8-18 AAPB towards fish (Danio rerio) was investigated in a study conducted according to OECD Guideline 203 (Fish, Acute Toxicity Test) and ISO 7346-1 (Determination of the Acute Lethal Toxicity of Substances to a Freshwater Fish [Brachydanio rerio Hamilton-Buchanan (Teleostei, Cyprinidae) ] - Part 1: Static Method). The 96 h LC50 was found to be 15 mg/L nominal (no information whether this value refers to test material or active matter).

Furthermore the results of a prolonged fish toxicity test are available. In this 28-d toxicity study conducted according to OECD Guideline 204, rainbow trouts (Oncorhynchus mykiss) were exposed to C8-18 AAPB under flow-through conditions. The 28-d NOEC and LOEC values were 0.16 and 0.5 mg a. i./L nominal based on mortality and sub-lethal effects.

 

Saltwater fish

The acute toxicity of C8-18 and C18 unsatd. AAPB to the marine fish Cyprinodon variegatus was investigated in a study conducted according to OECD Guideline 203 (Fish, Acute Toxicity Test) adapted by OSPARCOM (2005 -11) for marine testing of offshore chemicals. In this limit test conducted under semi-static conditions, the fish were exposed to a single concentration of 3 mg product/L nominal (corresponding to 1.1 mg a. i./L) for 96 h. No effects were observed at 1.1 mg a. i./L nominal.

 

Conclusion

For freshwater fish (Pimephales promelas) the lowest 96 h LC50 was determined to be 1.11 mg a.i./L nominal, and for marine fish (Cyprinodon variegatus) 1.1 mg a.i./L nominal.

The obtained results were considered to be valid for the AAPBs.

 

 

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 6.1 (Aquatic toxicity).

 

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 short-term fish toxicity data

 

Endpoints	Source substances		Target substance
	C8-18 AAPB	C8-18 and C18 unsatd. AAPB	C12-14 AAPB
Short-term toxicity to fish	key(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	key.Short-term toxicity to fish.61789-40-0_9.1.3_Acute_fish_Unilever_AT-R728-01 key study OECD Guideline 203 (Fish, Acute Toxicity Test) Pimephales promelas, semi-static, freshwater 96 h NOEC = 0.54 mg/L,act. ingr. (nominal)  96 h LC100 = 1.68 mg/L,act. ingr. (nominal)  96 h LC50 = 1.11 mg/L,act. ingr. (nominal) based on: mortality (95% c.i.: 0.54-1.68 mg a.i./L)   Reliability: 1 (reliable without restriction), no GLP	No data, read-across
	sup.Short-term toxicity to fish.97862-59-4_9.1.3_EOC_Lovap_1995_OECD 203   supporting study   OECD Guideline 203 (Fish, Acute Toxicity Test)   Brachydanio rerio (new name: Danio rerio), static, freshwater 96 h LC50 = 15 mg/Ltest mat. (nominal) based on: mortality 96 h LC100 = 21.5 mg/Ltest mat. (nominal) based on: mortality 96 h LC0 = 10.7 mg/Ltest mat. (nominal) based on: mortality   Reliability: 2 (reliable with restrictions), no GLP	key (marine).Short-term toxicity to fish.61789-40-0_9.1.3_Marine_Cyprinodon variegatus_Rhodia_Mirataine-BET-C-37_OECD203_2008 key study   similar to OECD Guideline 203 (Fish, Acute Toxicity Test) (adapted by OSPARCOM (2005-11) for marine testing of offshore chemicals) Cyprinodon variegatus, semi-static, saltwater   96 h NOEC = 1.1 mg/Lact. ingr. (nominal) based on: mortality   Reliability: 2 (reliable with restrictions), GLP
		sup.Short-term toxicity to fish: 61789-40-0_9.1.3_Henkel_2001_OECD 203 supporting study   OECD Guideline 203 (Fish, Acute Toxicity Test) Brachydanio rerio (new name: Danio rerio), semi-static, freshwater   96 h LC100 = ca. 2.4 mg/Lact. ingr. (nominal) based on: mortality 96 h LC50 = ca. 2 mg/Lact. ingr. (nominal) based on: mortality 96 h LC0 = 1.7 mg/Lact. ingr. (nominal) based on: mortality   Reliability: 2 (reliable with restrictions), no GLP
		sup.Short-term toxicity to fish: 61789-40-0_9.1.3_Hüls_1996_EEC 92-69 C1   supporting study EU Method C.1 (Acute Toxicity for Fish) Cyprinus carpio, semi-static, freshwater 96 h LC50 = 1.9 mg/Lact. ingr. (nominal) based on: mortality   96 h LC0 = 1.4 mg/Lact. ingr. (nominal) based on: mortality    96 h LC100 = 2.5 mg/Lact. ingr. (nominal) based on: mortality   Reliability: 2 (reliable with restrictions), GLP
		RL4_Short-term toxicity to fish: 61789-40-0_9.1.3_THG_1980c_DIN 38 412_48h   Supporting study   DIN 38412 Leuciscus idus   48 h LC0 = 2.5 mg/L based on: mortality   48 h LC100 = 5 mg/L based on: mortality   Reliability: 4 (not assignable), no GLP

 

LC50 values were in the range from 1.1 to 15 mg/L for different species.

For freshwater fish (Pimephales promelas) the lowest 96 h LC50 was determined to be 1.11 mg a.i./L nominal. For marine fish (Cyprinodon variegatus) the lowest 96 h LC50 was 1.1 mg a.i./L nominal.

 

Quality of the experimental data of the analogues:

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

Two key studies with freshwaster fish have been identified, which were conducted according toOECD Guideline 204 (C8-18 AAPB, RL1, GLP) andOECD Guideline 203 (C8-18 and C18 unsatd. AAPB, RL1, no data on GLP), respectively.

A further key study with marine fish was conducted similar to OECD Guideline 203 (C8-18 and C18 unsatd. AAPB, RL2, GLP)

One supporting study conducted withC8-18 AAPB (RL2) and two supporting studies conducted withC8-18 and C18 unsatd. AAPB(RL 2) according toEU Method C.1 or OECD Guideline 203 are reported.

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 substancesC8-18 AAPB and C8-18 and C18 unsatd. AAPB are also valid for the target substance C12-14 AAPB.

 

The obtained LC50 values were in the same range for freshwater and marine fish:For freshwater fish (Pimephales promelas) the lowest 96 h LC50 was determined to be 1.11 mg a.i./L nominal, and for marine fish (Cyprinodon variegatus) 1.1 mg a.i./L nominal.