Iron(3+) ion dipotassium 2-({2-[bis(carboxylatomethyl)amino]ethyl} (carboxylatomethyl)amino)acetate; hydrate

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

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:

other: Guideline study conducted in compliance with GLP regulations

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
EDTA-metal complexes are very similar in their chemical structure and fate because they are salts of EDTA anion and metal cations where the metal ion valency can vary from 1+ to 3+. The EDTA anion has in all cases a similar ecotoxicity. The toxicity of the EDTA-metal ion complex depends on the toxicity of the free metal ion. Both EDTA-Iron complexes and EDTA-sodium complexes were found to have a similar ecotoxicity in the short term toxicity test. Read across of the long term aquatic invertebrate results from EDTA-NaH2 (source chemical) to EDTA-Fe(OH)K2 is therefore considered justified.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source chemical for the long term toxicity to aquatic invertebrates is EDTA-NaH2 (CAS no 139-33-3) the target chemical for this endpoint is EDTA-Fe(OH)K2.

3. ANALOGUE APPROACH JUSTIFICATION
There is no long term ecotoxicity data on aquatic invertebrates available for EDTA-FeK or EDTA-Fe(OH)K2. For EDTA-Na2H2 (CAS no 139 -33 -3) however a NOEC of 25 mg/L was observed in a 21 day long term aquatic invertebrates study with Daphnia magna. For this registration dossier no long term vertebrate study is required but considering the margin to 1 mg/L and the results of the acute daphnia tests, it can be concluded with high probability that EDTA-Fe(OH)K2 will not be chronically harmful to aquatic invertebrates. Based on the comparable results observed for EDTA-Na2H2 and the key acute study performed with EDTA-FeNa in the acute daphnia tests, it is considered justified to use the long term EDTA-Na2H2 data for read across to EDTA-Fe(OH)K2. As a worst-case no molecular weight correction is applied (30% difference). To compensate for the uncertainty for read across an additional assessment factor of 2 will be applied in the long term PNEC derivation.

4. DATA MATRIX
Read across document see Chapter 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: EEC Guideline XI/681/86, Draft 4: "Prolonged toxicity study with Daphnia magna: Effects on reproduction"

Principles of method if other than guideline:

For the statistical evaluation of the LOEC and NOEC Duncan's new multiple range test was used.

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

Samples for analysis were taken in the 1st, the 2nd and the 3rd week of the test. For each concentration the freshly prepared test solution (unstocked) and the corresponding 48 h or 72 h old test solution (stocked with daphnids) were analyzed.

Vehicle:

no

Details on test solutions:

At the beginning of the test and before changing the test solutions, a stock solution of the test substance was freshly prepared. A defined amount of the substance was weighed out and suspended directly in the test medium by stirring (about 10 min at 22+/-1 °C). The nominal concentrations of the stock solutions were 100 mg/L. By dilution of the stock solutions with test medium, the nominal test concentrations were prepared.

Test organisms (species):

Daphnia magna

Details on test organisms:

Species: Daphnia magna STRAUSS
Supplier: Institut National de Recherche Chimique Appliquée, France, 1978
Culture: The daphnids are cultured under standard conditions in the Laboratory for Experimental Ecology of BASF AG, Ludwigshafen

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Hardness:

Total hardness: 2.20 - 3.20 mmol/L

Test temperature:

19.9 - 21.7 °C

pH:

7.5-8.5

Dissolved oxygen:

Oxygen content: 8.0 - 9.6 mg/L

Nominal and measured concentrations:

Test concentrations (nominal): 100; 50.0; 25.0; 12.5; 6.25; 3.13 and 1.56 mg/L. (Dilution factor: 2)

Details on test conditions:

TEST PROCEDURE
- Semistatic procedure: Change of test solution three times a week.
- Test water: synthetic M4-medium
Alkalinity up to pH 4.3: 0.80 - 1.00 mmol/L
Molar ratio Ca:Mg: about 4 : 1
Conductivity: 550 - 650 µS/cm
- Number of animals/vessel: 1
- Number of replicates/concentration: 10
- Number of replicates/control: 10
- Age of the animals at the start of the test: 2 - 24 h
- Age of stock animals: 2 - 4 weeks
- Light: Artificial light, OSRAM L58 W31 warm white day : night-rhythm = 16 : 8 hours
- Removal of young from test beakers and counting: daily
- Check of the study and recording (mortality, hatching of young): daily
- Feeding: daily
- Measurement of temperature: Continuously in an extra vessel
- Measurement of pH and oxygen: At the start of the test and at each change of test solution in the 48
- or 72-hour-old solution in one parallel at each concentration

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Duration:

21 d

Dose descriptor:

LOEC

Effect conc.:

50 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Duration:

21 d

Dose descriptor:

other: LC0

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Analytically found relative minimum and maximum concentrations of the test substance in the test solutions
at different times of the test (with and without daphnids). The values are given in percent of the nominal concentrations:


 Time   /   Stocked with   /  Minimum    /    Maximum    /
  [h]   /    daphnids      /    [%]      /      [%]      /
-----------------------------------------------------------
   0    /     no           /   80.8      /     166.7     /
 48/72  /     no           /   92.8      /     166.7     /
 48/72  /     yes          /   95.2      /     173.1     /
-----------------------------------------------------------
M4-water caused a background value of about 1 mg/L "Trilon BD". Regarding to this and to the precision of the analytical method, most concentrations found corresponded to the expected values.


Validity criteria:

In the control:
- the mortality of parent animals up to the end of the test was <= 10 %.
- the mean number of living young per parent animal that survived the  test was >= 60.
- the coefficient of variation for the mean number of living young per parent animal that survived the test was   <= 25 %.
- The NOEC of the control substance 3,4-dichloroaniline was 2.5 ug/L, the LOEC was 10 ug/L and LC0 was > 10 ug/L. 

The validity criteria were fulfilled by the test.


Control:
In the control the first young were observed at day 7. In the highest concentration tested, at which the daphnids produced young (100 mg/L), the first young were observed at day 13.

Description of key information

There is no long term ecotoxicity data on aquatic invertebrates available for EDTA-FeK or EDTA-Fe(OH)K2. For EDTA-Na2H2 (CAS no 139 -33 -3) however a NOEC of 25 mg/L was observed in a 21 day long term aquatic invertebrates study with Daphnia magna. For this registration dossier no long term vertebrate study is required but considering the margin to 1 mg/L and the results of the acute daphnia tests, it can be concluded with high probability that EDTA-Fe(OH)K2 will not be chronically harmful to aquatic invertebrates. Based on the comparable results observed for EDTA-Na2H2 and the key acute study performed with EDTA-FeNa in the acute daphnia tests, it is considered justified to use the long term EDTA-Na2H2 data for read across to EDTA-Fe(OH)K2. As a worst-case no molecular weight correction is applied (30% difference). To compensate for the uncertainty for read across an additional assessment factor of 2 will be applied in the long term PNEC derivation.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

25 mg/L

Additional information

The long-term toxicity of EDTA-Na2H2 to Daphnia magna was measured in a 21d reproduction test according to GLP criteria [BASF AG, 1998]. After 21 days of exposure a NOEC of 25 mg/L was observed.

As a worst-case no molecular weight correction is applied (30% difference) for read-across.