Choline hydroxide

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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
Please refer also to Read Across Statement attached in Section 13

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In this read-across approach data choline chloride are used to fill data gaps for choline hydroxide, in accordance with Regulation No 1907/2006 (REACH), Annex XI. The basis for this read-across approach is the “Read-Across Assessment Framework” (RAAF) (ECHA 2017). The read-across hypothesis for the analogue approach is that choline hydroxide and choline chloride exhibit a similar (eco)toxicological profile. This is due to the fact that both choline salts as quaternary alkylammonium salts dissociate readily into the respective ions when getting into contact with water and the choline cation is what is left to be considered (US EPA, 2010). Thus, the different choline salts are used to for hazard assessment. According to the RAAF this approach is covered by scenario 1: “(Bio)transformation to common compound(s)”.
“This scenario covers the analogue approach for which the read-across hypothesis is based on (bio) transformation to common compound(s). For the REACH information requirement under consideration, the property investigated in a study conducted with one source substance is used to predict the properties that would be observed in a study with the target substance if it were to be conducted. Similar properties or absence of effect are predicted. The predicted property may be similar or based on a worst-case approach.” (ECHA 2017).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
2-hydroxy-N,N,N-trimethylethanaminium chloride
Molecular formula: C5H14ClNO
SMILES: [Cl-].C[N+](C)(C)CCO
CAS: 67-48-1
Purity: not specified

Target chemical:
Choline hydroxide
Molecular formula: C5H15NO2
SMILES: [OH-].C[N+](C)(C)CCO
CAS: 123-41-1
Purity: 96 %

3. ANALOGUE APPROACH JUSTIFICATION
Upon contact with water, choline hydroxide is expected to dissociate into the cationic form (choline) and the anionic form (hydroxide ions); the hydroxy moiety dissociates and essentially ceases to exist upon mixing with water in preparation for application and in the body. The latter will be even skipped because both choline hydroxide and choline chloride are only distributed as aqueous solution, i.a. due to their hygroscopic properties. The choline cation is what is left to be considered (US EPA, 2010). Due to the structural similarities, i.e. the identical organic cation, which contains a positively charged nitrogen, and small, negatively charged inorganic anion (for choline base: Hydroxide), this is a reasonable and scientifically expectable conclusion, which allow one to draw the generalized conclusion, that Choline salts in general dissociate readily in water into the corresponding positively charged quaternary hydroxyl alkylammonium ion and the negatively charged inorganic anion (OECD SIDS, 2004). The choline cation therefore, is the moiety of interest. Based on the fact that in the environment and in biological fluids the same compounds are formed from the source and the target substances, the same (eco)toxicological profile of choline hydroxide and choline chloride is expected. Therefore, the read-across approach is justified. Thus, the available studies for the source substance choline chloride were used to fill data gaps for choline hydroxide for several environmental and toxicological endpoints.

Reason / purpose for cross-reference:

read-across source

Duration:

24 h

Dose descriptor:

EC0

Effect conc.:

250 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

>= 500 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

24 h

Dose descriptor:

EC100

Effect conc.:

>= 500 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

125 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

>= 500 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

> 500 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

EC0(3h): 500 mg/L, EC50(3h) >= 500 mg/L, EC100(3h) > 500 mg/L
EC0(6h): 500 mg/L, EC50(6h) >= 500 mg/L, EC100(6h) > 500 mg/L

Results with reference substance (positive control):

Not applicable.

Reported statistics and error estimates:

No statistics or error estimates reported.

Table 1. Test animals able to swim

Concentration  [mg/L]	Test animals able to swim after
	0h	3h	6h	24h	48h
0.00	20	20	20	20	20
31.25	20	20	20	20	20
62.50	20	20	20	20	20
125.00	20	20	20	19	16
250.00	20	20	20	14	11
500.00	20	20	20	20	20

Validity criteria fulfilled:

yes

Remarks:

Scientific criteria for acute toxicity testing to aquatic invertebrates seemed to be fulfilled.

Conclusions:

The study report describes a valid study, conducted according to EU Method C.2. No information about GLP compliance available. Available data confirm that the experiment was well-performed. The test substance was not toxic to Daphnia magna up to a concentration of 500 mg/L during an exposure duration of 48 h.

Executive summary:

The acute toxicity of Choline chloride towards the aquatic invertebrate Daphnia magna was investigated according to EU Method C.2. (BASF AG, 1988). Test concentrations were chosen as followed: 0 (control), 31.25, 62.50, 125, 250 and 500 mg/L. Four replicates of each concentration were included. The mobility and the corresponding EC0, EC50 and EC100 values were determined after 3, 6, 24 and 48 hours. The highest concentration tested at which an effect =< 10 % occurred was referred to as EC0. Physico-chemical measurements (temperature, pH and dissolved oxygen content) were measured at the beginning and termination of the experiment. At the start, the temperature was recorded as 18.75 °C and the pH 7.8. The exposure duration was 48 h. After this time, the final results were reported as: EC0(48h): 125 mg/L, EC50(48h) >= 500 mg/L and EC100(48h) >= 500 mg/L. No analytical verification and no statistical methods were implemented in the experiment.

Based on the fact that in the environment and in biological fluids the same compounds are formed from the source and the target substances, the choline moiety is the considered fraction of the source substance. Thus, this conclusion can also be drawn for the target substance choline hydroxide.

Description of key information

There are no studies on the Short-term toxicity to aquatic invertebrates available for the source substance choline hydroxide.

 

However, there are studies available for the close analogue Choline chloride. The results showed no toxicity observed even at highest concentration level tested.
RA_CAS 67-48-1_Daphnia magna_EU Method C.2: EC0(48h): 125 mg/L, EC50(48h) ≥ 500 mg/L, EC100(48h) ≥ 500 mg/L

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

500 mg/L

Additional information

Toxicological effects of Choline hydroxide towards aquatic invertebrates were not investigated experimentally.

To fulfil this endpoint, a read-across to Choline chloride (CAS 67-48-1) is intended, since both substances possess a strong structural similarity and substance characteristics. For the detailed justification of this procedure, please refer to the separate read-across statement by Chemservice S.A. (2013).

Choline chloride was used as test substance in an experiment according to EU Method C.2 with the freshwater invertebrate Daphnia magna (BASF AG, 1988). Test concentrations were chosen as followed: 0 (control), 31.25, 62.50, 125, 250 and 500 mg/L. Four replicates of each concentration were included. The mobility and the corresponding EC0, EC50 and EC100 values were determined after 3, 6, 24 and 48 hours. The highest concentration tested at which an effect ≤ 10 % occurred was referred to as EC0. Physico-chemical measurements (temperature, pH and dissolved oxygen content) were measured at the beginning and termination of the experiment. At the start, the temperature was recorded as 18.75 °C and the pH 7.8. The exposure duration was 48 h. No toxicity was observed even at highest concentration level tested, therefore, the results were reported as: EC0(48h): 125 mg/L, EC50(48h) ≥ 500 mg/L and EC100(48h) ≥ 500 mg/L. No analytical verification and no statistical methods were implemented in the experiment.