2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
a detailled justification for the analogue approach can be found in Iuclid section 13 of the dossier.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

GLP compliance:

not specified

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
The substance amount required for the production of the test concentration is weighed in a plastic cup and inserted into a weighted sample receptacle.

Test organisms (species):

Leuciscus idus melanotus

Details on test organisms:

TEST ORGANISM
- Common name: Golden ide
- Source: Fish Farm Eggers, Hohenweststedt, Germany
- Age at study initiation: ca. 4 weeks
- Corpulence factor (W(g) x 100/L(cm3)): 0.8 - 1.1 g/cm
- feeding during test: none

ACCLIMATION
- Type and amount of food: Pitti Floxi-Flakes, alround food for ornamental fish
- Feeding frequency: 2x weekly
- Lighting: 12 hours per day
- Oxygen content: at least 80 % of saturation value

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

15 ± 3 °dH

Test temperature:

20 ± 0.5 °C

pH:

8.3 - 9.3

Dissolved oxygen:

5.3 - 8.1 mg O2/L

Nominal and measured concentrations:

nominal: 100, 200, 400, 600, and 800 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:
- Type: open
- Material, size, headspace, fill volume: glass container (length: 28.5; width: 21.0; height: 24.0 cm)
- Aeration: lightly aerated during the test
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- No. of vessels per vehicle control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: A mix of Cologne tap water and deionised water serves as dilution water
- Ca/mg ratio: 4:1
- Intervals of water quality measurement: after 24, 48, 72, and 96 hours

OTHER TEST CONDITIONS
- Adjustment of pH:
- Photoperiod: 12 hours per day

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : lethality, after 24, 48, 72, and 96 hours

Reference substance (positive control):

no

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

460 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

800 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Sublethal observations / clinical signs:

Table 3: mortalities during test

		Concentration (mg/L)
		control	100	200	400	600	800
24h	Absolut rel.%	0/10 0	0/10 0	0/10 0	2/10 20	2/10 20	5/10 50
48h	Absolut rel.%	0/10 0	0/10 0	0/10 0	2/10 20	5/10 50	9/10 90
72h	Absolut rel.%	0/10 0	0/10 0	0/10 0	2/10 20	7/10 70	9/10 90
96h	Absolut rel.%	0/10 0	0/10 0	0/10 0	2/10 20	8/10 80	10/10 100

The acute toxicity to fish was tested with Tris amino, a structural analogue of Tris HCl., in a OECD TG203 compliant assay. Under the conditions of this study, the structural similar Tris amino shows an LC50 of 460 mg/L and a NOEC of 100 mg/L.

Validity criteria fulfilled:

yes

Description of key information

No study with fish is available for TRIS HCl. Therefore, the assessment of short-term toxicity to fish was based on a studies conducted with the structurally similar substances TRIS AMINO and AEPD. Structural and physico-chemical similarities of the three substances, as well as similarities of short-term toxicity results with Daphnia and algae justify the read-across from AEPD and TRIS AMINO to Tris HCl in the case of short-term toxicity to fish. A publication by McFarlan and Norris (1958) is available, investigating the effect of 2 -amino-2 -(hydroxymethyl)-1,3 –propanediol (TRIS AMINO) on fish, but the test method does not comply with today’s standards for the assessment of toxicity. Therefore, the assessment of fish toxicity was based on a study conducted with AEPD (CAS 115-70-8) and supported by the above mentioned literature. The study with AEPD was conducted according to OECD guideline 203 (6.1.1 -1). The test organism Leuciscus idus melanotus was exposed to AEPD in a static system for 96 hours, at the nominal test concentrations 100, 200, 400, 600, and 800 mg/L. An LC50 of 460 mg/L was obtained. In the publication by McFarlan and Norris (1958), 29 species of fishes (in total 59 fishes), were exposed to Tris-buffer in order to determine if harmful properties existed. All but four species were marine forms. Marine fish were exposed for 12.5 h or 48 h, depending on test species. Following exposure, they were transferred to untreated water and observed for 30 days. Freshwater fish were exposed for nine days. Only one death occurred during the experiment, but it was probably due to starvation, since the fish were not fed until the fourth day.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

460 mg/L

Additional information

A publication by McFarlan and Norris (1958) is available, investigating the effect of 2 -amino-2 -(hydroxymethyl)-1,3 -propanediol (TRIS AMINO) the free base of Tris HCl on fish, but the test method does not comply with today’s standards for the assessment of toxicity. Therefore, the assessment of fish toxicity was based on a study conducted with the structurally similar substance AEPD (CAS 115-70-8) and supported by the above mentioned literature.

Structural and physico-chemical similarities of the two substances, as well as similarities of short-term toxicity results with Daphnia and algae justify the read-across from AEPD to TRIS AMINO and to Tris HC in the case of short-term toxicity to fish.

Both AEPD and TRIS HCl are well soluble in water (> 600 g/L) and have a very low vapour pressure (0.01 Pa). The relatively low partition coefficient (log Kow) of -2.31 (TRIS HCl) and -1.02 (AEPD) indicate a low potential to accumulate in biological systems. Also the log Koc is low for both substances, 2.96 and 1.87 for AEPD and TRIS HCl, respectively. Acute aquatic toxicity of > 100 mg/L indicates that both substances have low toxic potential to aquatic organisms. By calculating potential metabolites via OECD QSAR toolbox v.2.0 (2010), relevant metabolites were generated neither by the liver metabolism simulator, nor by the skin metabolism simulator, nor by the microbial metabolism simulator. The Cramer classification (related mainly to oral route) also indicates that no metabolism by cytochrome P450 enzymes in vivo is expected for TRIS HCl and AEPD.

Both OASIS and ECOSAR classification models indicate narcosis as mode of action for both substances, however it is known that for amines the toxicity can be enhanced with respect to baseline and the mode of action can be classified as “amine narcosis”. Nevertheless, as in the general case of narcosis (i.e. with absence of specific and reactive effects – which is confirmed by the presence of only amine and alcohol functional groups), log Kow is the main toxicity trigger, which is very low for both substances.

 

The study with AEPD was conducted according to OECD guideline 203 (Schopka, 1991). The test organism Leuciscus idus melanotus was exposed to AEPD in a static system for 96 hours, at the nominal test concentrations 100, 200, 400, 600, and 800 mg/L. An LC50 of 460 mg/L was obtained.

 

In the publication by McFarlan and Norris (1958), 29 species of fishes (in total 59 fishes), were exposed to Tris-buffer in order to determine if harmful properties existed. All but four species were marine forms. Marine fish were exposed for 12.5 h or 48 h, depending on test species. Following exposure, they were transferred to untreated water and observed for 30 days. Freshwater fish were exposed for nine days. One death occurred during the experiment, but it was probably due to starvation, since the fish were not fed until the fourth day.