Bisguanidinium phosphate

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 on guanidinium phosphate (CAS 5423-22-3, EC 226-551-9) is used to fill data gaps for bisguanidinium phosphate (CAS 5423-23-4, EC 226-552-4), in accordance with Regulation No 1907/2006 (REACH), Annex XI. The basis for this read-across is the “Read-Across Assessment Framework” (RAAF) (ECHA 2017). The read-across hypothesis for the analogue approach is that both salts bisguanidinium phosphate and guanidinium phosphate result in the identical cat- and anion in a water based environment and have consequently similar (eco)toxicological and fate properties. According to the RAAF this approach is covered by scenario 2: “Different compounds have the same type of effect(s)”.
“This scenario covers the analogue approach for which the read-across hypothesis is based on different compounds with qualitatively similar properties. For the REACH information requirement under consideration, the property investigated in a study conducted with one source substance is used to predict properties that would be observed in a study with the target substance if it were to be conducted. Qualitatively 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)
In this read-across approach data on guanidinium phosphate (CAS 5423-22-3, EC 226-551-9) is used to fill data gaps for bisguanidinium phosphate (CAS 5423-23-4, EC 226-552-4).
The target substance bisguanidinium phosphate and the source substance guanidinium phosphate are phosphate salts of the base guanidine.
With a pKb of 0.4, guanidine is a strong base. Therefore, in neutral water guanidine occurs fully protonated as its conjugate acid guanidinium cation. Most guanidine derivatives are in fact salts containing guanidinium cation as the conjugate acid. The source and the target substances are phosphate salts of guanidine consisting of guanidinium cation as conjugate acid and phosphate anion as conjugate base. The relation between guanidinium cation and the phosphate anion is 2:1 in the target substance and 1:1 in the source substance. As a consequence, the conjugate base in the target substance is a hydrogenphosphate (HPO4), whereas in the source substance it is a dihydrogenphosphate (H2PO4).

3. ANALOGUE APPROACH JUSTIFICATION
Based on the structural similarity, the similarity in physical chemical properties and the QSAR predicted similarity in the (eco)toxicological profile, the read-across approach is justified. Thus, the available studies for the source substance guanidinium phosphate were used to fill data gaps for bisguanidinium phosphate for several environmental and toxicological endpoints. Since phosphates are endogenous compounds occurring in nature in considerable amounts, the guanidinium ions are considered to trigger the (eco)toxicity of bisguanidinium phosphate. To account for the higher guanidine content in the target substance bisguanidinium phosphate (2:1) when compared to the source substance guanidinium phosphate (1:1), the hazard values found for the source substance in experimental studies were calculated for the target substance (please refer to 'Any other information on results').
Regarding short-term toxicity to invertebrates, a study according to OECD Guideline 202 and GLP is available for the source substance guanidinium phosphate. D. magna was exposed to guanidinium phosphate under static conditions at the following nominal concentrations: 0 (blank control), 0.1, 1, 10, and 100 mg/L. The test substance induced no immobilization in daphnia at the highest tested nominal exposure concentration of 100 mg/L. Thus, the EC50 (48h) was >100 mg/L based on analytically confirmed nominal concentrations. The study is considered to be reliable without restrictions. Considering the guanidinium content, this corresponds to an EC50 of > 68.81 mg/L for the target substance bisguanidinium phosphate (please refer to 'Any other information on results').

4. DATA MATRIX
The data matrix is included in the Read Across Statement attached in Section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

assessment report

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 68.81 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Measured concentrations: Analysis of the samples taken from the 100 mg/L concentration showed that the actual concentration was in agreement with nominal and remained stable during the test period (97-107%). Given this result the EC50-value was based on the nominal test concentration.

- Biological results: A single daphnid was found immobilized at the highest test concentration (100 mg/L). For the lower test concentrations and the blank control no immobilized daphnids were observed.

- Acceptability of the test:
1. In the control, no daphnids became immobilised.
2. The oxygen concentration at the end of the test was ≥3 mg/L in control and test vessels.

Results with reference substance (positive control):

- Potassium dichromate (K2Cr2O7): The 48h-EC50 was 0.53 mg/L (95% confidence interval between 0.49 and 0.62 mg/L)

calculation of hazard values for bisguanidine phosphate

Guanidinium content in guanidinium phosphate

MW (guanidinium phosphate) = 157.04 g/mol

MW (guanidinium ion) = 60.07 g/mol

proportion of guanidinium ion in guanidinium phosphate = MW (guanidinium ion) / MW (guanidinium phosphate) = 60.07 / 157.04 = 0.38

Guanidinium content in bisguanidinium phosphate

MW (bisguanidinium phosphate) = 216.11 g/mol

MW (guanidinium ion) = 60.07 g/mol

proportion of guanidinium ion in bisguanidinium phosphate = 2 * MW (guanidinium ion) / MW (bisguanidinium phosphate) = 2 * 60.07 / 216.11 = 0.56

EC50 (guanidinium phosphate) = > 100 mg/L

EC50 (guanidinium ion) = EC50 (guanidinium phosphate) * 0.38 = > 38.25 mg/L

EC50 (bisguanidinium phosphate) = > 38.25 mg/L / 0.56 = > 68.81 mg/L

Validity criteria fulfilled:

yes

Conclusions:

The 48h-EC50 for Daphnia magna exposed to guanidine phosphate (1:1) was >100 mg/L. Considering the guanidinium content, for the target substance bisguanidinium phosphate, this corresponds to an EC50 of > 68.81 mg/L.

Executive summary:

In a 48-h acute toxicity study conducted according to OECD guideline 202, water fleas (Daphnia magna) were exposed to guanidine phosphate (1:1) under static conditions at the following nominal concentrations: 0 (blank control), 0.1, 1, 10 and 100 mg/L. The test substance induced no immobilization in daphnids at a nominal exposure concentration of 100 mg/L. The 48h-EC50 was >100 mg/L based on analytically confirmed nominal concentrations. The study is considered to be reliable without restrictions. Considering the guanidinium content, for the target substance bisguanidinium phosphate, this corresponds to an EC50 of > 68.81 mg/L.

Description of key information

Read across: OECD 202, D. magna, GLP, EC50 (48 h) > 68.81

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

68.81 mg/L

Additional information

Regarding short-term toxicity to invertebrates, a study according to OECD Guideline 202 and GLP is available for the source substance guanidinium phosphate. D. magna was exposed to guanidinium phosphate under static conditions at the following nominal concentrations: 0 (blank control), 0.1, 1, 10, and 100 mg/L. The test substance induced no immobilization in daphnia at the highest tested nominal exposure concentration of 100 mg/L. Thus, the EC50 (48h) was >100 mg/L based on analytically confirmed nominal concentrations. The study is considered to be reliable without restrictions. Considering the guanidinium content, this corresponds to an EC50 of > 68.81 mg/L for the target substance bisguanidinium phosphate.