Sodium salts of [[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid (1-3 Na:1)

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to microorganisms, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to Annex 4 of the CSR and IUCLID Section 13 for justification of read-across within the DTPMP category.

Reason / purpose for cross-reference:

read-across source

Duration:

30 min

Dose descriptor:

EC0

Effect conc.:

> 2 500 mg/L

Nominal / measured:

nominal

Conc. based on:

other: active acid

Reference 2

Endpoint:

toxicity to microorganisms, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

In an environmental context the speciation will be controlled by the prevailing conditions and ions present, and will be the same regardless of the starting form. The properties of the members of the category are consistent across all endpoints. The category hypothesis is that all the members are various ionised forms of the same parent acid. The main assumption is that sodium and potassium are not significant in respect of all the properties under consideration. For ammonium salts the properties and role of ammonia are given due consideration. In dilute aqueous conditions of defined pH a salt will behave no differently to the parent acid, at identical concentration of the particular speciated form present and will be fully dissociated. Hence some properties (measured or expressed in aqueous media, e.g. ecotoxicity) for a salt can be directly read-across (with suitable mass correction) to the parent acid and vice versa, and from one salt to another.

Justification for read-across between ATMP acid and DTPMP sodium salt:
DTPMP acid is a member of the DTPMP category, which is comprised of the acid form and various salts of the same acid. DTPMP is an example of the aminomethylenephosphonic acid class. The justification for read across of a property to a DTPMP registration data set from a study conducted with a different phosphonate is considered as scenario 2.

The registration substance shares a common chemistry to other aminomethylenephosphonates which incorporate alkyl backbones with one or more tertiary amine centres and multiple methylphosphonate groups present. DTPMP acid (CAS 15287-60-8) has three amine centres (five methylphosphonate groups), connected by ethyl chains. ATMP acid (CAS 6419-19-8) has three methylphosphonate groups connected by a central amine nitrogen. Typically, impurities include residual inorganic acids/salts and organic by-products from manufacturing. As well as being structural analogues, both phosphonates have consistent chemical properties including high MW (573 and 299 respectively), very low log Kow (<-3 for both substances) and are highly soluble in water. Both DTPMP and ATMP are very strong chelators with the ability to bind to inorganic surfaces. They undergo photodegradation and bind strongly and effectively irreversibly to substrates including soil and sediment. The substances in question generally posses similar physicochemical properties and are not readily biodegradable.

In addition to the similarity in physico-chemical properties, the read-across for this short-term exposure endpoint is supported by similar short-term aquatic ecotoxicity. Both DTPMP and ATMP indicate very low short-term toxicity to freshwater invertebrates (7500 and 300 mg/l respectively). Short-term toxicity to fish is also low for DTPMP and ATMP with LC50 values of 216 and 160 mg/l respectively and furthermore long-term NOEC for toxicity to fish is around 25 mg/l for both substances. In the present context, the effect of the alkaline metal counter-ion will not be significant. For ammonium salts, the role of ammonia is given due consideration. In biological systems and the environment, polyvalent metal ions will be present, and the phosphonate ions show very strong affinity to them. Further information on the analogue read-across from the ATMP category to the DTPMP category is presented in IUCLID Section 13 and Annex 5 of the CSR.


Justification for read-across between HEDP acid and DTPMP sodium salt:
DTPMP acid is a member of the DTPMP category, which is comprised of the acid form and various salts of the same acid. DTPMP is an example of the aminomethylenephosphonic acid class. The justification for read across of a property to a DTPMP registration data set from a study conducted with a different phosphonate is considered as scenario 2.
The registration substance shares a common chemistry to other aminomethylenephosphonates which incorporate alkyl backbones with one or more tertiary amine centres and multiple methylphosphonate groups present. DTPMP acid (CAS 15287-60-8) has three amine centres (five methylphosphonate groups), connected by ethyl chains. HEDP acid (CAS 2809-21-4) is a bisphosphonate structure with two phosphonate functional groups attached to ethanol. Typically, impurities include residual inorganic acids/salts and organic by-products from manufacturing.

Whilst not directly structurally comparable, both phosphonates have consistent chemical properties including very low log Kow (<-3 for both substances) and are highly soluble in water. Both DTPMP and HEDP are very strong chelators with the ability to bind to inorganic surfaces. They undergo photodegradation and bind strongly and effectively irreversibly to substrates including soil and sediment. The substances in question generally possess similar physicochemical properties and are not readily biodegradable.

In addition to the similarity in physicochemical properties, the read-across for this short-term exposure endpoint is supported by similar short-term aquatic ecotoxicity. Both DTPMP and HEDP indicate very low short-term toxicity to freshwater invertebrates (7500 and 530 mg/l respectively). Short term toxicity to fish is also low for both DTPMP and HEDP with LC50 values of 216 and 200 mg/l respectively. In the present context, the effect of the alkaline metal counter-ion will not be significant. For ammonium salts, the role of ammonia is given due consideration. In biological systems and the environment, polyvalent metal ions will be present, and the phosphonate ions show very strong affinity to them. A data matrix of the available physicochemical, environmental fate and ecotoxicology data for the DTPMP and HEDP categories is attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Duration:

30 d

Dose descriptor:

NOEC

Effect conc.:

200 mg/L

Conc. based on:

other: Phosphonate active acid equivalent

Basis for effect:

other: Sewage gas production volume

Remarks on result:

other: This result is read across from both ATMP-H and HEDP-H

Reference 3

Endpoint:

toxicity to microorganisms, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Non-quantitative study of effect of increasing concentration of test substance on the sewage treatment process

GLP compliance:

not specified

Vehicle:

no

Test organisms (species):

activated sludge

Test type:

not specified

Water media type:

not specified

Limit test:

no

Duration:

30 d

Dose descriptor:

NOEC

Effect conc.:

200 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

other: sewage gas production volume

Duration:

30 d

Dose descriptor:

LOEC

Effect conc.:

500 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

other: sewage gas volume reduced and fermentation delayed

Details on results:

At 50 mg/L Dequest 2000 showed no effects.
At 100 and 200 mg/L the start of fermentation was delayed, but constant gas volume was achieved in the same period as in the control.
At 500 mg/L Dequest 2000, the system was strongly disturbed, as indicated by a late beginning of fermentation, and greatly reduced sewage gas production volume.

Conclusions:

A non-standard study of effects on sewage treatment plant micro-organisms was conducted according to generally accepted scientific principles but lacks detail in the study report. The result of a lack of effects on respiration up to 200 mg/L provides reliable evidence.

Reference 4

Endpoint:

toxicity to microorganisms, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Principles of method if other than guideline:

Method: other: DIN 38412

GLP compliance:

not specified

Analytical monitoring:

not specified

Test organisms (species):

Photobacterium phosphoreum

Total exposure duration:

30 min

Details on test conditions:

Type: aquatic

Duration:

30 min

Dose descriptor:

EC0

Effect conc.:

> 2 500 mg/L

Nominal / measured:

nominal

Conc. based on:

other: active acid

Result expressed as nominal concentration. Properties of the
test substance and evidence from other studies (where
concentrations were measured) indicate that nominal and
measured concentrations are likely to be in good agreement.

Reference 5

Endpoint:

toxicity to microorganisms, other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Non-quantitative study of effect of increasing concentration of test substance on the sewage treatment process

GLP compliance:

not specified

Vehicle:

no

Test organisms (species):

activated sludge

Test type:

not specified

Water media type:

not specified

Limit test:

no

Duration:

30 d

Dose descriptor:

NOEC

Effect conc.:

200 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

other: sewage gas production volume

Duration:

30 d

Dose descriptor:

LOEC

Effect conc.:

500 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

other: sewage gas volume reduced and fermentation delayed

Details on results:

At 50 mg/L HEDP showed no effects.
At 100 and 200 mg/L the start of fermentation was delayed, but constant gas volume was achieved in the same period as in the control.
At 500 mg/L HEDP, the system was strongly disturbed, as indicated by a late beginning of fermentation, and greatly reduced sewage gas production volume.

Conclusions:

A non-standard study of effects on sewage treatment plant micro-organisms was conducted according to generally accepted scientific principles but lacks detail in the study report. The result of a lack of effects on respiration up to 200 mg/L provides reliable evidence.

Description of key information

The available data provide a general weight of evidence of a lack of inhibition of micro-organisms at concentrations up to ca. 200 mg/L (read-across from ATMP-H and HEDP-H).

Key value for chemical safety assessment

EC10 or NOEC for microorganisms:

200 mg/L

Additional information

A reliability 4 30-minute EC₀ value of >2500 mg/L has been determined for the effects of DTPMP-H on the bioluminescence of the bacterium, Photobacterium phosphoreum (Grohmann and Horstmann, 1989).

A non-standard study of effects on sewage treatment plant micro-organisms was conducted according to generally accepted scientific principles but lacks detail in the study report. The study reports a lack of effects on respiration for 30 days up to 200 mg/L with ATMP-H and HEDP-H.

The data can be directly read across to DTPMP (1-3Na) because they are structural analogues, have similar physicochemical properties and are not readily biodegradable. Please refer to the Target EPSR for further information on the read-across.

All these studies have been used as weight of evidence to determine the low toxicity of DTPMP to microorganism toxicity. The data from ATMP-H and HEDP-H have been used to determine the PNEC because they represent the lowest values for this endpoint.

The acid and salts in the DTPMP category are freely soluble in water and, therefore, the DTPMP anion is fully dissociated from its cations when in solution. Under any given conditions, the degree of ionisation of the DTPMP species is determined by the pH of the solution. At a specific pH, the degree of ionisation is the same regardless of whether the starting material was DTPMP-H, DTPMP (1-3Na), DTPMP (5-7Na), DTPMP-xK, DTPMP (xNH4) or another salt of DTPMP.

 

Therefore, when a salt of DTPMP is present in test media or the environment, the following is present (separately):

1. DTPMP is present as DTPMP-H or one of its ionised forms. The degree of ionisation depends upon the pH of the media and not whether DTPMP-H, DTPMP (1-3Na), DTPMP (5-7Na), DTPMP-xK, DTPMP (xNH4), or another salt was used for testing.

2. Disassociated ammonium, potassium or sodium cations. The amount of ammonium, potassium or sodium present depends on which salt was added.

3. Divalent and trivalent cations have much higher stability constants for binding with DTPMP than the sodium, potassium or ammonium ions so would preferentially replace them. These ions include calcium (Ca²⁺), magnesium (Mg²⁺) and iron (Fe³⁺). Therefore, the presence of these in the environment or in biological fluids or from dietary sources would result in the formation of DTPMP-dication (e.g. DTPMP-Ca, DTPMP-Mg) and DTPMP-trication (e.g. DTPMP-Fe) complexes in solution, irrespective of the starting substance/test material.