Trimethyl-3-[(1-oxo-10-undecenyl)amino]propylammonium methyl sulphate

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study results generated by reliable QSAR model.

Justification for type of information:

QSAR prediction

Qualifier:

no guideline followed

Principles of method if other than guideline:

The QSAR model, Ecological Structure Activity Relationships (ECOSAR) Class Program to estimate long-term toxicity to invertebrates.

GLP compliance:

no

Analytical monitoring:

not required

Vehicle:

no

Test organisms (species):

other: Daphnid

Limit test:

no

Reference substance (positive control):

not required

Dose descriptor:

other: Chronic value

Effect conc.:

29 mg/L

Nominal / measured:

estimated

Conc. based on:

other: QSAR modelled data

Basis for effect:

other: QSAR modelled data

Remarks on result:

other: Calculated for Amide component

Dose descriptor:

other: Chronic value

Effect conc.:

101 mg/L

Nominal / measured:

estimated

Conc. based on:

other: QSAR modelled data

Basis for effect:

other: QSAR modelled data

Remarks on result:

other: Neutral Tertiary Amine component

Acute toxicity data are available for the substance, although long-term toxicity data are unavailable. Instead the registrant has undertaken QSAR modelling using the US EPA’s ECOSAR model in order to generate long-term toxicity data for the substance.

ECOSAR deals with cationic surfactants including quaternary ammoniums as a special case.  The QSARs for cationic surfactants are linear and the ecotoxicity potential is related to the size of the hydrophobic component (i.e. number of carbons – the QSAR are different where carbon chain is greater than C16, or less than C16).  However, the model cannot specifically account for the amide group in the the substance molecule (or the double bond at the end of the alkyl chain).  Furthermore, the QSAR for quaternary ammoniums only provides acute toxicity data and these acute toxicity value are low (ca. 1-2 mg/l) for quaternary ammoniums with an average carbon chain of 14. These estimated values are much lower than the measured laboratory values.  It may be reasonable, given the structure of the molecule, to model a lower average carbon chain for the substance, but there is no guidance or accepted experience for using ECOSAR for this type of situation. Furthermore, significant hydrolysis of the amide seems unlikely at relatively neutral pH in the environment.

The ECOSAR operation manual states that “quaternary ammonium compounds (four carbons are bound to the nitrogen) are an exception [to organic ammonium salts] since reduction (e.g., loss of hydrogens) at neutral pH is unlikely; however, these are classified as surfactants.” Instead, the neutral quaternary ammonium compound with four alkyl groups on the nitrogen has been modelled using the ECOSAR programme, but not as a ‘special class’ surfactant due to the reasons described above. However, the compound is unlikely to form the corresponding amine (i.e. loss of an alkyl group) under normal environmental conditions.

Using an ECOSAR approach based on modelling the quaternary ammonium ion provides chronic toxicity data for three trophic levels (Table 1). The SMILES notation used in the assessment for Rewocid 185 UTM is C (=O) (CCCCCCCCC=C) NCCCN{+} (C) (C) C. The most conservative chronic value (equivalent to the geometric mean of a NOEC and LOEC) is for fish (0.5 mg/l).  It can be assumed that the ECOSAR amide predictions provide a worst case estimate for the long-term toxicity of the substance to aquatic organisms; in particular fish appear to be the most sensitive organisms to both the substance and its analogue substance methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate. The most sensitive organisms in both lab and modelled data are algae for acute toxicity. The algae are several orders of magnitude more sensitive than fish and invertebrates. However, the chronic data indicate much more similar sensitivities across the three trophic levels and indicate fish are the most sensitive.  It is not clear why the sensitivities vary so dramatically in the model and the trend changes between acute and chronic data sets. This presents an uncertainty with the ECOSAR approach.

  

Table 1: ECOSAR chronic aquatic toxicity data (rounded values)
		CAS 94313-91-4		CAS 10595-49-0
Organism	Toxicity Test	Value for Amide (mg/l)	Value for Neutral Tertiary Amine (mg/l)	Value for Amide (mg/l)	Value for Neutral Tertiary Amine (mg/l)
Fish	Chronic	0.5	236	0.3	73
Invertebrate	Chronic	29	101	13	36
Algae	Chronic	8	135	5	60

In addition, the methylsulphonate counter ion (SMILES notation CS(=O)(=O)O) was evaluated in ECOSAR and the chronic value for invertebrates was 81,495 mg/l. The modelled results indicate that the amide component of the substance's structure drives the assessment.

Validity criteria fulfilled:

not applicable

Conclusions:

A chronic value of 0.5 mg/l relating to the amide structure is provided from modeled results for long-term toxicity of the substance to invertebrates.

Executive summary:

A QSAR-modelled approach using the US EPA's ECOSAR model was used to derive chronic toxicity data for invertebrates based on the amide and neutral tertiary amine components of the test substance structure. The most sensitive chronic value of 29 mg/l was derived for invertebrate species based on the amide structure.

Description of key information

A chronic value of 29 mg/l is provided for long-term toxicity to invertebrates based on reliable QSAR model results.

Using an ECOSAR approach based on modelling the quaternary ammonium ion provides chronic toxicity data for three trophic levels of aquatic organisms. The most conservative chronic value (equivalent to the geometric mean of a NOEC and LOEC) for invertebrates is 29 mg/l. The modelled QSAR data show that ECOSAR amide predictions provide a worst case estimate for the long-term toxicity of the substance to aquatic organisms; in particular fish appear to be the most sensitive organisms to both the substance and its analogue substance methyl trimethyl-3-[(1-oxododecyl)amino]propylammonium sulphate and invertebrates appear to be the least sensitive organisms.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

29 mg/L