Choline hydroxide

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
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:

96 h

Dose descriptor:

LC50

Effect conc.:

> 10 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 1 % Significance level

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

10 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

Neither any symptoms nor any mortality occurred during the exposure duration.

Results with reference substance (positive control):

LC50(48h): ~ 32 mg/L (Determined: 1988-04-18)

Reported statistics and error estimates:

Determination / calculation of the median lethal concentration (LC50) and, if possible, the LC5 and LC95 was performed by Probit Analysis after 1, 4, 24, 48, 72 and 96 hours.
Reference: Finney, D.J., Probit Analysis, Cambr. Univ. Press, 3rd Ed., 1971. Certain aspects of this method have been modified (Details: Internal SOP).

Validity criteria fulfilled:

yes

Remarks:

Scientific criteria for acute toxicity testing to fish seemed to be fulfilled.

Conclusions:

The study report describes a valid study, conducted equivalent to a national guideline (DIN 38412). No information about GLP compliance available. Available data confirm that the experiment was well-performed. The test substance was not toxic to fish up to a concentration of 10000 mg/L during an exposure duration of 96 h.

Executive summary:

Choline chloride (with an active ingredient content of 78 %) was tested for its toxicity towards the freshwater fish Leuciscus idus (Golden orfe) with an exposure time of 96 hours (BASF AG, 1988). The experiment was conducted equivalent to the German guideline DIN 38412. After a range-finding study (LC50(96h) > 10000 mg/L), two concentration were fixed as followed: 5000 mg/L and 10000 mg/L. The concentrations exceeded the normal upper limit for acute studies because it was the aim to test higher concentrations for classification of hazards to water. The test substance was added to the test water without any pretreatment, based on its easily solubility. Chloroacetamide served as positive control, resulting in a LC50(48h) of about 32 mg/L. This lethal concentration corresponds to the normal sensitivity. The test temperature was set at 21 °C and the pH was around 8. 10 animals per concentration were used, a control was also included. Thus, the biomass loading rate was 4.7 g/L. Probit analysis was used as statistical method. Neither any abnormalities nor mortality was recorded during the experiment. Therefore, the LC50(96h) is > 10000 mg/L and the NOEC(96h): 10000 mg/L.

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 fish available for the source substance choline hydroxide.

 

However, there are studies available for the close analogue Choline chloride. The study results showed no toxicity observed even at highest concentration level tested.
RA_CAS 67-48-1_Leuciscus idus_DIN 38412: LC50(96h) > 10000 mg/L, NOEC(96h): 10000 mg/L (applies for 78 % and 50 % Choline Chloride)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

LC50

Effect concentration:

10 000 mg/L

Additional information

Choline hydroxide was not investigated experimentally regarding toxicological effects towards fish. Valid results are available for the reliable read-across substance Choline chloride (CAS 67-48-1). Both substances possess comparable substance characteristics, based on the chemical structure. For the detailed justification of this procedure, please refer to the separate read-across statement by Chemservice S.A. (2013).

Choline chloride (with active ingredient contents of 78 % and 50 % in a second experiment) was tested for its toxicity towards the freshwater fish Leuciscus idus (Golden orfe) with an exposure time of 96 hours (BASF AG, 1988). The experiment was conducted equivalent to the German guideline DIN 38412. After a range-finding study (LC50(96h) > 10000 mg/L), two concentration levels were fixed as followed: 5000 mg/L and 10000 mg/L. The concentrations exceeded the normal upper limit for acute studies because it was the aim to test higher concentrations for classification of hazards to water organisms. The test substance was added to the test water without any pretreatment, based on its easily solubility. Chloroacetamide served as positive control, resulting in a LC50(48h) of about 32 mg/L. This lethal concentration corresponds to the normal sensitivity. The test temperature was set at 21 °C and the pH was around 8. Ten animals per concentration were used, a control was also included. Thus, the biomass loading rate was 4.7 g/L. Probit analysis was used as statistical method. Neither any abnormalities nor mortality was recorded during the experiment. The LC50(96h) is determined to be > 10000 mg/L and the NOEC(96h): 10000 mg/L.