Choline hydroxide

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Endpoint:

toxicity to microorganisms, other

Remarks:

Growth inhibition test according to Brinkmann and Kühn

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). 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:

17 h

Dose descriptor:

EC10

Effect conc.:

112.9 mg/L

Nominal / measured:

nominal

Conc. based on:

dissolved

Basis for effect:

growth inhibition

Duration:

17 h

Dose descriptor:

EC50

Effect conc.:

132.8 mg/L

Nominal / measured:

nominal

Conc. based on:

dissolved

Basis for effect:

growth inhibition

Duration:

17 h

Dose descriptor:

other: EC90

Effect conc.:

278.2 mg/L

Nominal / measured:

nominal

Conc. based on:

dissolved

Basis for effect:

growth inhibition

Details on results:

No further details available.

Results with reference substance (positive control):

Not applicable.

Reported statistics and error estimates:

A standard deviation was calculated from the individual values.

Table 1. Extinktion Measurement after 17 h at 436 nm

Concentration	Inoculated	Non-inoculated	Difference	% of the control
Control		0.405
50 mg/L	0.425	0.000	0.425	104.81
100 mg/L	0.471	0.000	0.471	116.10
150 mg/L	0.062	0.000	0.062	15.24
200 mg/L	0.066	0.000	0.066	16.29
250 mg/L	0.061	0.000	0.061	15.05
300 mg/L	0.025	0.000	0.025	6.11

Validity criteria fulfilled:

yes

Remarks:

Basic validity criteria were fulfilled. National guideline study.

Conclusions:

Only basic information given. The test substance was found to be non-toxic towards Pseudomonas putida (EC50(17h): 132.80 mg/L). The study is classified as reliable with restrictions (Klimisch 2).

Executive summary:

The toxicity of Choline chloride (dissolved in water) towards Pseudomonas putida was investigated according to the German guideline DIN 38412 Part 8 (BASF AG, 2003). The experiment was conducted at 297 +/- 1 K (22.85 - 24.85 °C) for a time duration of 17 h. The test concentrations were 0 (control), 50, 100, 150, 200, 250 and 300 mg/L. The following results were obtained: EC10(17h): 112.90 mg/L, EC50(17h): 132.80 mg/L and EC90(17h): 278.20 mg/L, respectively.

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 toxicity to microorganisms available for the source substance choline hydroxide.

However, there is a study available for the close analogue Choline chloride.

 

RA_CAS 67-48 -1_Pseudomonas putida_DIN 38412 Part 8: EC10(17h): 112.90 mg/L, EC50(17h): 132.80 mg/L

Key value for chemical safety assessment

EC50 for microorganisms:

132.8 mg/L

EC10 or NOEC for microorganisms:

112.9 mg/L

Additional information

Toxicity towards aquatic microorganisms was not investigated for Choline hydroxide.

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).

The toxicity towards aquatic microorganisms was investigated experimentally with the read-across substance Choline chloride (CAS 67-48-1). Pseudomonas putida was used as inoculum and the experiment was performed according to the German guideline DIN 38412 Part 8 (BASF AG, 2003). The time duration was 17 h at a temperature of 297 +/- 1 K (22.85 - 24.85 °C). The test concentrations were 0 (control), 50, 100, 150, 200, 250 and 300 mg/L. The following results were obtained: EC10(17h): 112.90 mg/L, EC50(17h): 132.80 mg/L and EC90(17h): 278.20 mg/L, respectively. Since the use of Choline chloride as a surrogate for Choline hydroxide is scientifically justified, and the study is classified as reliable with restrictions (Klimisch 2), the results obtained from this study are sufficient to cover this endpoint and choline hydroxide can also be considered to be non-toxic to Pseudomonas putida.