Reaction mass of Ethanaminium, 2-hydroxy-N,N-dimethyl-N-[2-[(1-oxooctadecyl)oxy]ethyl]-, chloride and Ethanaminium, N,N-dimethyl-2-[(1-oxohexadecyl)oxy]-N-[2-[(1-oxooctadecyl)oxy]ethyl]-, chloride

Endpoint summary

Additional information

For the assessment of aquatic toxicity of MDEA Esterquat C18 satd. short-term and long-term toxicity data with fish, aquatic invertebrates, algae and microorganisms are not available. Therefore, aquatic toxicity is assessed by read-across to the closely related source substances MDEA-Esterquat C16-18 and C18 unsatd, MDIPA Esterquat C16-18 and C18 unsatd. and MDIPA Esterquat C18 unsatd.. A justification for read-across is given at the end of this chapter.

Short-term toxicity to fish

In a 96 h acute toxicity study according to OECD TG 203, the Zebrafish (Danio rerio), was exposed to the structurally similar source substance MDEA-Esterquat C16-18 and C18 unsatd. at nominal concentrations of 0, 1.0, 1.6, 2.5, 4.0, 6.3 and 10 mg/L under static conditions. The nominal 96 h LC50 value based on mortality was 5.2 mg/L (95% C.I.: 4.4 to 6.3 mg/L). Mortality occurred in the first 48 h. After this time, seemingly moribund organisms recovered. Within the first 48 h the test solutions at concentrations of 2.5, 4.0, 6.3, and 10 mg/L showed a Tyndall effect. The intensity increased with increasing concentrations. Precipitates were observed on the bottom of the test aquarium in the exposure concentrations of 2.5 to 10 mg/L 48 h after preparation of the test solution. These observations suggest that mortality is most likely a physical and not a toxic effect due to the undissolved particles in the water phase. The additional fish were added to the 10.0 mg/L solution after 48 h (the time the precipitates were observed). The animals survived until test termination which supports the assumption of physical effects.

Concentrations are only given as nominal, however, a long-term toxicity study in fish with measured concentrations is available resulting in a 21-day LC50 of 1.67 mg/L.

 

Similar results were obtained with the closely related read-across substances MDIPA Esterquat C16-18 and C18 unsatd. and MDIPA Esterquat C18 unsatd.:

 

In a 96-h acute toxicity study according to OECD guideline 203, adopted 17 July 1992, Carp (Cyprinus carpio, Teleostei, Cyprinidae) Linnaeus, 1758 were exposed to the source substance MDIPA-Esterquat C18 unsatd. (100% a.i) at nominal concentrations of 0 (control), 0.10, 0.32,1.0, 3.2 and 10 mg/L under semi-static conditions in the presence of 4 mg humic acid per litre (i.e. 2-4 mg dissolved organic carbon per litre). 

Measured test item concentrations were in agreement with nominal (90-93%). These concentrations remained stable during both refreshment periods (87-90% of initial). Given these results, effect parameters can be based on the nominal test concentrations.

No mortality or other clinical effect was observed at any of the test concentrations and the control during the 96-hour test period. The 96-h LC50 was >10 mg a.i./L. 

 

The 96–hr-acute toxicity of the source substance MDIPA-Esterquat C16-18 and C18 unsatd. to eggs of Danio rerio was studied under semi-static conditions according to guideline OECD guideline 236 (2013). Eggs were exposed to control and test chemical at analytically determined geometric mean concentrations of 0, 0.986, 1.90, 4.15, 8.05, and 16.0 mg/L under semi-static conditions with daily renewal. Analytics and all observations were made daily.

The 96-hour LC50 was estimated to be 11.7 mg/L with 95% confidence limits of 9.91 and 13.8 mg/L.

 

Long-term toxicity to fish

The 35-day chronic toxicity of the structurally similar source substance MDEA-Esterquat C16-18 and C18 unsatd. to early life stages of Fathead minnow (Pimephales promelas) was studied under flow-through conditions according to US EPA TSCA, 40 CFR, Part 797.1600. Fertililized eggs (25 eggs, reduction to 15 fry after hatching) were exposed to a control and measured concentrations of 0.686, 1.41, 2.68, 5.30 and 9.76 mg/L. The test system was maintained at 25 +/- 1°C and a pH of 8.0 (7.7 to 8.3). The 35-day NOEC values, based on mortality and sub-lethal effects (length, weight, pre- and post-fry reduction survival) were 0.686 mg/L, the NOEC value based on hatchability was >9.76 mg/L.

 

Short-term toxicity to aquatic invertebrates

The 24-hr acute toxicity of the structurally similar source substance MDEA-Esterquat C16-18 and C18 unsatd. to Daphnia magna was investigated under static conditions in a study conducted according to OECD TG 202 (Part I). Daphnids were exposed to 0, 0.1, 0.32, 1.0, 3.2, 10 and 32 mg/L (nominal) for 24 hours. Immobilization was observed at test termination. The 24-h EC50 was 14.8 mg/L with 95% CL of 8.4 - 26.2 mg/L (nominal each).

Observation was made at 24 h instead of 48 h as stipulated by the guideline, and concentrations are only given as nominal. However, a chronic toxicity study with Daphnia magna with measured concentrations is also available resulting in a 21-d EC50 of 1.7 mg/L.

 

Similar results were obtained with the closely related read-across substances MDIPA Esterquat C16-18 and C18 unsatd. and MDIPA Esterquat C18 unsatd.:

 

The 48–hr-acute toxicity of the source substance MDIPA-Esterquat C18 unsatd. to Daphnia magna was studied under semi-static conditions in accordance with OECD guideline 202 (2004). Daphnids were exposed to control and test chemical at nominal concentrations of 0.10, 0.32, 1.0, 3.2, 10 mg/L in the presence of 4 mg/L humic acid for 48 h. Mortality/immobilisation and sublethal effects were observed daily. The 48-hour EC50 was >8.6 mg/L (TWA, time weighted average) based on immobilisation.  

 

The 48–hr-acute toxicity of the target substance MDIPA-Esterquat C16-18 and C18 unsatd. to Daphnia magna was studied under semi-static conditions.  Daphnids (<24 h) were exposed to control and test chemical at analytically confirmed nominal concentrations of 0, 2.5, 4.5, 8.1, 14 and 25 mg/L in the presence of 4 mg/L (< 2mg/L DOC) humic acid for 48 h. Immobilisation was observed daily. 

The 48-hour EC50 was 6.7 mg/L (analytically confirmed nominal concentration) based on immobilisation.  

  

Long-term toxicity to aquatic invertebrates

The 21-day chronic toxicity of the structurally similar source substance MDEA-Esterquat C16-18 and C18 unsatd. to Daphnia magna was investigated under flow-through conditions in a study conducted according to EPA OTS 797.1330 (Daphnid Chronic Toxicity Test). Daphnids were exposed to a control and test chemical at measured concentrations of 0, 0.27, 0.47, 1.0, 2.0 and 3.9 mg/L. The 21-day EC50 based on mortality was 1.7 mg/L (95% confidence limits of 1.5 and 1.9 mg/L). The 21 -day NOEC based on survival, number of young/adult/reproduction day, and growth (length and weight) was 1.0 mg/L. Production of offspring in the treated groups indicated that MDEA-Esterquat C16-18 and C18 unsatd. has an effect on the reproduction at concentration greater than 1 mg/L.

 

Toxicity to aquatic algae and cyanobacteria

In a 72 hour acute toxicity study, the cultures of Pseudokirchneriella subcapitata, strain NIVA CHL 1 were exposed to the source substance MDIPA Esterquat C18 unsatd. at nominal concentrations of 0 (control), 0.10, 0.32, 1.0, 3.2 and 10 mg/L, corresponding to measured (TWA) concentrations of 0.042, 0.14, 0.39, 1.3 and 1.7 mg/L in the presence of 4 mg/L humic acid under static conditions in accordance with OECD guideline 201 (adopted March 23, 2006; Annex 5 corrected 28 July 2011).

Microscopic observations revealed no abnormalities.

The NOEC, EC10 and EC50 based on growth rate were 0.39, 0.54 (95% c.i. 0.10-2.9 mg/L) and 1.2 mg/L (95% c.i. 0.24-6.0 mg/L), respectively.

The NOEC, EC10 and EC50 based on based on yield were 0.39, 0.49 (95% c.i. 0.22-1.0 mg/L) and 0.95 mg/L (95% c.i. 0.44-2.1 mg/L), respectively.

All effect levels are given based on measured (TWA) concentrations.

 

In a 72 hour acute toxicity study, the cultures of Pseudokirchneriella subcapitata, strain: NIVA CHL 1 were exposed to the source substance MDIPA Esterquat C16-18 and C18 unsatd. at nominal concentrations of 0 (control), 0.25, 0.80, 2.5, 8.0 and 25 mg/L, corresponding to measured (TWA) 0.29, 0.91, 2.7, 6.2 and 25 mg/L in the presence of 4 mg/L humic acid (DOC < 2 mg/L) under static conditions in accordance with OECD guideline 201 (adopted March 23, 2006; Annex 5 corrected 28 July 2011).

Microscopic observations revealed no abnormalities.

The NOEC, EC10 and EC50 based on growth rate were 2.7, 3.2 (95% c.i. 2.5-4.1 mg/L) and 8.1 mg/L (95% c.i. 6.4-10 mg/L), respectively.

The NOEC, EC10 and EC50 based on based on yield were 0.91, 1.3 (95% c.i. 0.45-3.7 mg/L) and 4.4 mg/L (95% c.i. 1.6-12 mg/L), respectively.

All effect levels are given based on measured (TWA) concentrations.

 

Toxicity to microorganisms

In a 3-hour toxicity study, activated sludge fed with synthetic sewage was exposed to MDEA-Esterquat C16-18 and C18 unsatd. at nominal concentrations of 0, 0.54, 5.02, and 47.4 mg a.i./L in accordance with the OECD TG 209. The NOEC value based on inhibition of respiration was >47.4 mg a.i./L.

 

The most sensitive organism to the source substances was Pseudokirchneriella subcapitata in acute as well as in chronic tests. Thus, the lowest chronic toxicity value is the 72 h ErC10 in Pseudokirchneriella subcapitata of 0.54 mg/L. This value is used for the calculation of PNECs.

 

JUSTIFICATION FOR READ-ACROSS

Hypothesis for the analogue approach

This read-across is based on the hypothesis that source and target substances have similar ecotoxicological properties because they share structural similarities with common functional groups: quaternary amines, esters, and fatty acid chains with comparable length and degree of saturation. Furthermore, they are expected to hydrolyse to a comparable product (amine backbone) and common products (long chain fatty acids).

1. Substance Identity

The target substance MDEA Esterquat C18 satd. is a monoconstituent substance composed of diester of mainly saturated C18 fatty acid with MDEA (methyldiethanol amine) as amine backbone (Table 1, Figure 1).

The source substance MDEA-Esterquat C16-18 and C18 unsatd. is a UVCB substance composed of diesters of mainly saturated C16 and C18 fatty acids with MDEA (Methyldiethanol amine) as amine backbone.

The source substance MDIPA-Esterquat C18 unsatd. is a UVCB substance composed of diesters of unsaturated C18 fatty acids with MDIPA (Methyldiisopropanol amine) as amine backbone.

The source substance MDIPA-Esterquat C16-18 and C18 unsatd. is a UVCB substance composed of diesters of mainly saturated C16 and C18 fatty acids with MDIPA (Methyldiisopropanol amine) as amine backbone.

In the target and source substances, the amine function is further methylated resulting in a quaternary amine.

 

Table 1: Substance identities 

	Source substances			Target substance
	MDEA-Esterquat C16-18 and C18 unsatd.	MDIPA Esterquat C18 unsatd.	MDIPA Esterquat C16-18 and C18 unsatd.	MDEA Esterquat C18 satd.
CAS number	1079184-43-2	95009-13-5	NA	67846 -68 -8
EC number	620-174-7	305-741-6		267 -382 -0
Fatty Acid	C16-18, C18‘ (IV < 25)	C18‘, C18‘‘, C18‘‘‘ (IV = 110)	C16-18, C18‘ (IV = 20)	C18 (IV < 1)
Chain length distribution	<C16 <7%                                             C16, 16‘ 26-35% C18 42-52% C18‘ 15-20% C18‘‘,18‘‘‘ ≤ 1.5% >C18 ≤ 2%	<C16 ≤ 1% C16 ≤ 7% C18 ≤ 4% C18‘ 55-65% C18‘‘ 18-25% C18‘‘‘ 6-12% >C18 ≤ 5%	< C16: ≤ 6 % C16 20-40 % C18 35-60 % C18 unsatd.10-25 %   > C18 ≤ 5 %	C16 ≤ 8% C18 ≥ 92%
Amine	MDEA	MDIPA	MDIPA	MDEA
Anion	Chloride	Methyl sulphate	Methyl sulphate	Chloride
Purity	ca. 90% diesterquat ca. 8% monoesterquat ca. 1% Hexadecanoic acid, ca. 1% Octadecanoic acid	ca. 87% diesterquat ca. 5% monoesterquat ca. 5.5% N, N-bis(2-hydroxypropyl) -N-methylamine, mono- and diesters with fatty acids, C18 unsatd. (not quaternised) ca. 1.5% Fatty acids methyl ester, ca. 0.7% 2,2',2''-nitrilotriethanol	ca. 75% diesterquat ca. 11% monoesterquat ca. 12%. Methyldiisopropanolamine, esters with fatty acids, C16-18 (even numbered) and C18 unsatd. (not quaternised) ca. 1.6% Fatty acids ca. 1.2% fatty acids methyl esters	ca. 80% diesterquat
Impurities	n.a.	n.a.	n.a.	ca. 14% monoesterquatca. 12% non-quaternised mono-esteraminesca. 1.5% free fatty acid

 

Figure 1: Structures of the target substance MDEA Esterquat C18 satd. and the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. (see attached image file)

 

2. Analogue approach justification

This read-across is based on the hypothesis that source and target substances have similar ecotoxicological properties because they are (i) manufactured from similar resp. identical precursors under similar conditions, (ii) the metabolism pathway leads to comparable products (amine backbone and long chain fatty acids) and (iii) of their structural similarities: target and source substances are comprised of a hydrophobic (alkyl) and hydrophilic (positively charged ammonium) part; due to theses structural elements they form micelles and have surface active properties.

Based on available experimental data, including key physico-chemical properties and data from short-term ecotoxicity studies (fish, daphnia, algae), the read-across strategy is supported by a similar ecotoxicological profile of all three source substances.

The respective reliable data (RL 1 or 2) are summarised in the table below; robust study summaries are included in the Technical Dossier in the respective sections.

Ecotoxicological data are summarised in the data matrix.

 

2.1 Structural similarity

a. Structural similarity and functional groups

The target substance, MDEA Esterquat C18 satd., consists of an amine backbone (MDEA = Methyldiethanol amine) esterified mainly with the long chain fatty acid C18 saturated (IV < 1). The main reaction product is the dialkylester compound, besides that, small amounts of the monoalkylester are also be formed. The amine function is quaternised with two methyl groups. The counter ion is Chloride.

The source substance, MDEA-Esterquat C16-18 and C18 unsatd., consists of an amine backbone (MDEA = Methyldiethanol amine) esterified with long chain fatty acids C16, C18 and C18 unsaturated (IV < 25). The main reaction product is the dialkylester compound, besides that, small amounts of the monoalkylester may also be formed. The amine function is quaternised with two methyl groups. The counter ion is Chloride.

The source substance, MDIPA Esterquat C18 unsatd., consists of an amine backbone (MDIPA = Methyldiisopropanol amine) esterified with unsaturated long-chained fatty acids, C18´, C18´´, C18´´´(IV = 110). The main constituent is the dialkylester compound, next to that small amounts of the monoalkylester may be formed. The amine function is quaternised with two methyl groups. The counterion is Methosulfate.

The source substance, MDIPA Esterquat C16-18 and C18 unsatd., consists of an amine backbone (MDIPA = Methyldiisopropanol amine) esterified with long chain fatty acids C16, C18 and C18 unsaturated (IV = 20). The main constituent is the dialkylester compound, next to that small amounts of the monoalkylester may be formed. The amine function is quaternised with two methyl groups. The counterion is Methosulfate.

 The source and the target substances share structural similarities with common functional groups (quaternary amines), esters, and fatty acid chains varying in their length and degree of (un)saturation.

The amine backbones based on MDEA and MDIPA, respectively, differ only by one methyl group, all functional groups are identical.

 

b. Common breakdown products:

The ester bonds can be potentially hydrolysed, which would result in free fatty acids and Dimethyl-DEA (DEA = Diethanolamine) and Dimethyl-DIPA (DIPA = Diisopropanolamine), respectively. The fatty acids are expected to enter normal metabolic pathways and are therefore indistinguishable from fatty acids from other sources including diet.

 

c. Differences

The differences in fatty acid chain length (higher percentage of C16 in the source substance vs. corresponding higher percentage C18 in the target substance) and degree of saturation may be relevant for local effects (e.g. irritation) but are not considered to be of relevance for aquatic toxicity.

Chloride is an essential nutrient and present in all organisms; excess chloride is renally excreted (see common textbooks on biology / biochemistry). Methyl sulphate is metabolised to Sulphate and Carbon dioxide, and these are excreted via the urine and released by the lungs, respectively. The anions Chloride and Methyl sulphate are not expected to have any influence on toxicity or reactivity.

The methyl side chain of Dimethyl-DIPA which is not present in Dimethyl-DEA is not expected to enhance reactivity.

 

3. Physicochemical properties:

Table 2: Physicochemical properties

	Source substances			Target substance
Endpoints	MDEA-Esterquat C16-18 and C18 unsatd.	MDIPA Esterquat C18 unsatd.	MDIPA Esterquat C16-18 and C18 unsatd.	MDEA Esterquat C18 satd.
Molecular weight	ca. 697 g/mol	ca. 796 g/mol	ca. 761 g/mol	ca. 703 g/mol
Physical state at 20°C / 1013 hPa	solid	liquid	solid	solid
Melting point	OECD Guideline 102; RL1; GLP 54°C	OECD Guideline 102; RL1; GLP Amorphous solidification between -55 and -10°C	OECD Guideline 102; RL 1; GLP 36°C	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Boiling point	OECD Guideline 103; RL1; GLP No boiling point up to 250°C	OECD Guideline 103; RL1; GLP Decomposition at ca. 200°C	OECD Guideline 103; RL1; GLP Decomposition at > 250°C	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Surface tension	OECD Guideline 115; RL2, GLP 68.3 mN/m - not in line with the expected surface active behaviour of the substance (this is discussed below the table)	OECD Guideline 115; RL1, GLP 37.5 mN/m at 20°C	OECD Guideline 115; RL2, GLP 72 mN/m - not in line with the expected surface active behaviour of the substance (this is discussed below the table)	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Water solubility	ASTM International E 1148 – 02, GLP, RL1 17.6 mg/L at 19.7°C	ASTM International E 1148 – 02; RL1, GLP  1.22 mg/L at 20°C	OECD Guideline 105, RL 1; GLP   1.01 mg/L at 20°C	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Log Kow	Determination technically not feasible due to the surface-active properties; read-across from DODMAC 3.8	Determination technically not feasible due to the surface-active properties; read-across from DODMAC 3.8	Calculation based on Koc       4.43	Determination technically not feasible due to the surface-active properties; read-across from DODMAC 3.8
Vapour pressure	measurement is technically not feasible due to the substance properties; estimation < 1E-09 Pa at 20°C	OECD TG 104, GLP; RL1     5E-08 Pa at 20°C	OECD Guideline 104, GLP, RL 1     < 8.4E-07 Pa at 20°C	measurement is technically not feasible due to the substance properties; estimation < 1E-09 Pa at

 

The molecular weights of the target and source substances are in a comparable range. The difference in physical state and melting point is most likely due to differences in the degree of saturation of the fatty acid chains and structural differences of the amino head-group (the methyl side chain of the Dimethyl-DIPA headgroup in the source substance, which is not present in the Dimethyl-DEA headgroup in the target substance).

Experimental data on log Kow are not available for the target and source substances. A read-across approach from the structurally similar substance DODMAC (Dimethyldioctadecyl ammonium chloride) was applied, resulting in a log Kow of 3.8. For the source substance MDIPA-Esterquat C16-18 and C18 unsatd. the log Kow of 4.43 was calculated based on the available Koc (organic carbon normalised adsorption coefficient). All substances have a very low vapour pressure. The differences in order of magnitude most probably result from the differences of the applied methods (measurement vs. estimation by calculation).

The results from the studies on surface tension with the source substances MDEA-Esterquat C16-18 and C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. were not in line with the expected surface tension behaviour of the test substance. Cationic surfactants carrying two C16/C18 alkyl chains, are designed to possess surface active properties and typically exhibit surface tension values as low as 27 mN/m. However, at temperatures of 20°C, the inner-molecular mobility of the fatty acid C-chains is hindered. Corresponding to this hinderance, on the one hand, the time to reach solubilisation equilibrium is long and on the other hand, there is a tendency to form vesicles. This can be seen i.e. at the test on hydrolysis with low correlation rates for pseudo-first order curve determination for 20°C but high correlation rates at 50 and 60°C.The result obtained with the source substance MDIPA-Esterquat C18 unsatd. of 37.5 mN/m at 20°C was in the expected range for substances with this structure.

There are, however, differences in water solubility. Water solubility was determined by measurement of turbidity instead of analytical determination of concentration, since no suitable method was available to remove undissolved test substance. The standard tests for this endpoint are intended for single substances and are not appropriate for these complex substances. It is stated in the OECD guideline 105 (1995) that: “The water solubility of a substance can be considerably affected by the presence of impurities. This guideline addresses the determination of the solubility in water of essentially pure substances […]”. Although impurities are per definition not present in UVCB substances, the complex and variable composition of the target and source substances may nevertheless influence the outcome in a similar manner.

Due to differences in the methodological approach the results for the water solubility measurement are not directly comparable between the source substances. For the source substance MDEA-Esterquat C16-18 and C18 unsatd. the solubility of the test substance in water is considered equal to the intercept with the x-axis. Whereas for the source substances MDIPA Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. a baseline turbidity was calculated, and the intercept with this baseline was considered to represent the water solubility.

 

4. Metabolism

An enzymatic degradation study is not available, neither for the target substance nor for the source substances. However, data from metabolism studies (human health endpoints) with the source substance MDEA-Esterquat C16-18 and C18 unsatd. suggest ester hydrolysis. The toxicokinetics assessment is based on the available experimental data, on structural similarities and on physicochemical properties. Esterases are abundant in all organisms and ester hydrolysis is a metabolic pathway which is also present in aquatic organisms. Thus, it can be assumed, that the available toxicokinetic data from human health endpoints are also relevant for environmental endpoints.

The source and target chemicals indicate similarity in toxicokinetic behaviour based on the molecular weight of 703 g/mol (MDEA Esterquat C18 satd.), 697 g/mol (MDEA-Esterquat C16-18 and C18 unsatd.), 796 g/mol (MDIPA Esterquat C18 unsatd.) and 761 g/mol (MDIPA Esterquat C16-18 and C18 unsatd.) and very low vapour pressures of <1E-09 Pa at 20°C (MDEA Esterquats), 5E-08 Pa at 20°C (MDIPA-Esterquat C18 unsatd.) and< 8.4E-07 Pa at 20°C(MDIPA Esterquat C16-18 and C18 unsatd.) as it is shown in Table 2.

A measured log Kow for the source and target substances is not available, instead a read-across from a structurally similar substance has been applied, resulting in a log Kow of 3.8 for the MDEA-Esterquats and MDIPA Esterquat C18 satd.. For the source substance MDIPA-Esterquat C16-18 and C18 unsatd. the log Kow of 4.43 was calculated based on the available Koc

The water solubilities of the target and the source substances are in a similar order of magnitude. The differences are explained above.

 

5. Comparison of data from ecotoxicological endpoints

5.1 Ecotoxicity data of the target and source substances

As demonstrated in the data matrix (Table 3) the short-term toxicity to fish and aquatic invertebrates as well toxicity to algae are comparable for MDEA-Esterquat C16-18 and C18 unsatd., MDIPA-Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. All source substances are readily biodegradable and have a Koc in a similar range which supports the validity of the grouping approach.

Based on these data as well as on similar physicochemical properties (Table 2) and the high structural similarity between the target substance MDEA Esterquat C18 satd. and the source substances the read-across approach for short and long-term environmental toxicity is considered to be appropriate.

Table 3: General ecotoxicological profiles for the target substance MDEA Esterquat C18 satd. and all three source substances

	Source substances				Target substance
Endpoints	MDEA-Esterquat C16-18 and C18 unsatd.		MDIPA Esterquat C18 unsatd.	MDIPA Esterquat C16-18 and C18 unsatd.	MDEA Esterquat C18 satd.
Short-term toxicity to fish	OECD TG 203, static,Danio rerio, GLP, RL2   96 h LC50 = 5.2 mg/L, nominal (95% C. I.: 4.4 to 6.3 mg/L)		OECD TG 203, semi-static,Cyprinus carpio, GLP, RL1   96 h LC50 > 10 mg/L	OECD TG 236 (Fish Embryo Acute Toxicity (FET) Test),Danio rerio, RL 1, GLP 96 h LC50 = 11.7 mg/L (meas., geom. mean); 95% CL 9.91-13.8 mg/L	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Long-term toxicity to fish	US EPA TSCA, 40 CFR, Part 797.1600, Pimephales promelas, GLP, RL2 35-day NOEC = 0.686 mg/L (based on mortality (post-fry reduction) and sub-lethal effects (length and weight))		read-across MDEA-Esterquat C16-18 and C18 unsatd.	read-across MDEA-Esterquat C16-18 and C18 unsatd.	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Short-term toxicity to aquatic invertebrates	OECD Guideline 202, static,Daphnia magna, GLP, RL2 24 h EC50 = 14.8 mg/L, nominal (95% CL: 8.4 - 26.2 mg/L)		OECD Guideline 202, semi-static,Daphnia magna, GLP, RL1       48 h EC50 > 8.6 mg/L	OECD Guideline 202, semi-static,Daphnia magna, RL 1, GLP  24 h EC50 = 13 mg/L (nominal); 95% CL 11 – 16 mg/L 48 h EC50 = 6.7 mg/L (nominal); 95% CL 5.8 - 8.0 mg/L	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Long-term toxicity to aquatic invertebrates	EPA OTS 797.1330 (Daphnid Chronic Toxicity Test), GLP, RL2 21 d NOEC = 1 mg/L (mortality, reproduction, growth)		read-across MDEA-Esterquat C16-18 and C18 unsatd.	read-across MDEA-Esterquat C16-18 and C18 unsatd.	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Toxicity to aquatic algae and cyanobacteria	Read-across MDIPA Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd.		OECD Guideline 201, static,Pseudokirchnerella subcapitata, GLP, RL1   72 h ErC50 > 1.2 mg/L; 72 h ErC10 = 0.54 mg/L mg/L 72 h NOEC = 0.39 mg/L (growth rate, biomass)	OECD Guideline 201, static,Pseudokirchnerella subcapitata, RL 1, GLP   72 h ErC50 = 8.1 mg/L 72 h ErC10 = 3.2 mg/L 72 h NOEC = 2.7 mg/L (based on growth)	Read-across MDIPA Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd.
Toxicity to microorganisms	OECD Guideline 209, activated sludge, GLP, RL2   3 h NOEC = 47.4 mg/L		EU method C.11, activated sludge, GLP, RL1   3 h EC10 = 323.4 mg/L 3 h EC50 > 1000 mg/L	OECD TG 301 B (Ready Biodegradability: CO2 Evolution Test), RL 1, GLP  28 d IC10 > 28 mg a.i./L	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Biodegradation	OECD Guideline 301 B (CO2 Evolution Test), GLP, RL2 readily biodegradable		OECD guideline 301 F (Manometric Respirometry Test), GLP, RL1 readily biodegradable	OECD Guideline 301 B (Ready Biodegradability: CO2 Evolution Test), RL 1, GLP  readily biodegradable	read-across MDEA-Esterquat C16-18 and C18 unsatd.
Hydrolysis as function of pH	No data (readily biodegradable)		No data (readily biodegradable)	OECD guideline 111; RL1, GLP   pH4: t½= > 30 days at 20°C t½= 53 days at 25°C t½= 4.5 days at 50°C t½= 1.8 days at 60°C pH7: t½= > 30 days at 20°C t½= 25 days at 25°C t½= 3.4 days at 50°C t½= 1.7 days at 60°C pH9: t½= 84 days at 20°C t½= 49 days at 25°C t½= 4.2 days at 50°C t½= 1.9 days at 60°C	No data (readily biodegradable)
Adsorption/Desorption	OECD Guideline 106 (Adsorption - Desorption Using a Batch Equilibrium Method); RL 1, GLP for sludges: log Koc = 2.92 for soils: log Koc = 5.69 total: log Koc = 4.30		Log Koc (sludges and soil) = 4; read-across DODMAC	OECD Guideline 106 (Adsorption - Desorption Using a Batch Equilibrium Method); RL 1, GLP for sludges: log Koc = 1.90, for soils: log Koc = 4.89, total: log Koc = 3.69	read-across MDEA-Esterquat C16-18 and C18 unsatd.

 

Quality of the experimental data of the analogues:

The source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. have been tested in reliable (RL 1-2) GLP-compliant studies according to OECD or US EPA guidelines.

There are no uncertainties, thus the studies can be used in an analogue approach.

The available data from the source chemicals are sufficiently reliable to justify the read-across approach.

 

Classification and labelling

The target substance MDEA Esterquat C18 satd. and the source substance MDEA-Esterquat C16-18 and C18 unsatd. are not classified for any human health hazard, whereas the source substances MDIPA Esterquat C18 unsatd. and MDIPA Esterquat C16-18 and C18 unsatd. are classified for local effects (irreversible effects on the eye Category 1/Serious Eye Irritation Cat. 2, irritating to the skin Category 2).

The target and all three source substances are classified as Aquatic Chronic 3 (H412: Harmful to aquatic life with long lasting effects).

The target and all three source substances, are neither PBT nor vP/vB substances.

Table 4: Classification and labelling for target and source substances

	Source substances				Target substance
Classification Endpoints	MDEA-Esterquat C16-18 and C18 unsatd.		MDIPA Esterquat C18 unsatd.	MDIPA Esterquat C16-18 and C18 unsatd.	MDEA Esterquat C18 satd.
Physical hazards	No classification required		No classification required	No classification required	No classification required
Hazards to the aquatic environment	Aquatic Chronic 3 H412: Harmful to aquatic life with long lasting effects.		Aquatic Chronic 3 H412: Harmful to aquatic life with long lasting effects.	Aquatic Chronic 3 H412: Harmful to aquatic life with long lasting effects.	Aquatic Chronic 3 H412: Harmful to aquatic life with long lasting effects.
Hazardous to the ozone layer	No classification required		No classification required	No classification required	No classification required
Acute toxicity oral	No classification required		No classification required	No classification required	No classification required
Acute toxicity dermal	No classification required		No classification required	No classification required	No classification required
Acute toxicity inhalation	No classification required		No classification required	No classification required	No classification required
Skin irritation	No classification required		Skin irritation 2 H 315 Cause skin irritation	Skin irritation 2 H 315 Cause skin irritation	No classification required
Eye irritation	No classification required		Eye Damage 1 H318: Causes serious eye damage	Eye Irritation 2 H319: Causes serious eye irritation	No classification required
Sensitisation	No classification required		No classification required	No classification required	No classification required
Reproductive toxicity	No classification required		No classification required	No classification required	No classification required
Germ cell mutagenicity	No classification required		No classification required	No classification required	No classification required
Carcinogenicity	No classification required		No classification required	No classification required	No classification required

 

Concerning hazards to the aquatic environment, the source substances MDEA-Esterquat C16-18 and C18 unsatd., MDIPA C18 unsatd. and MDIPA C16-18 and C18 unsatd. are classified as Aquatic Chronic 3. Based on the read-across approach, this classification is also relevant for the target substance MDEA Esterquat C18 satd..

 

6. Conclusion

This read-across is based on the hypothesis that source and target substances have similar ecotoxicological properties because they are (i) manufactured from similar resp. identical precursors under similar conditions, (ii) the metabolism pathway leads to comparable products (amine backbone and long chain fatty acids) and (iii) of their structural similarities: target and source substances are comprised of a hydrophobic (alkyl chains) and hydrophilic (positively charged ammonium) part; due to theses structural elements they form micelles and have surface active properties.

Based on available experimental data, including key physico-chemical properties and data from short-term ecotoxicity studies, the read-across strategy is further supported by a similar ecotoxicological profile of all three source substances. Short-term toxicity data of the source substances obtained in fish, daphnia and toxicity data from algae are comparable. All three source substances are readily biodegradable.

Therefore, based on all available data, it can be concluded that the results of the short and long-term toxicity studies in fish, daphnia, algae and microorganisms with the source substances are likely to predict the properties of the target substance and are considered as being adequate to fulfil the information requirement of Annex VIII, 9.1.3, 9.1.4 and Annex VII, 9.1.1., 9.1.2