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Administrative data

acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
May-June 2010
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study carried out under GLP
Justification for type of information:
Members of the aminocarboxylic acid (ethylenediamine-based) chelants chemical category possess similar molecular structures that contain common functional groups. All members have a molecular structure with an ethylenediamine or a diethylenetriamine backbone, which has 4 or 5 acetic acid groups attached to the nitrogens. The diethylenetriamine struc¬tures contain five acetic acid groups (DTPA); the ethylenediamine structure has four acetic acid groups (EDTA).
Therefore, all category members have identical functional groups (DTPA and EDTA) and have an ethylene-diamine-backbone. It is the presence of multiple carboxylic acid groups on the amine that provides chelants with their unique metal ion chelating or sequestering properties. This common property is the important feature to consider in assessing the aquatic and mammalian toxicity of chelants and in justifying their consideration as a category.
The substantial body of evidence that chelants are not directly toxic to aquatic and mammalian organisms but exert their influence by affecting mineral balance, together with the fact that the backbone structures of the chelants in the category have qualitative similar affinities for metals supports the inclusion of these chelants in a category. Subtle differences in toxicity due to the presence of calcium, magnesium, manganese, ferric (or ferrous) iron, copper or zinc can be explained by their affinity towards these metals and their ability to supply or deny metals to organisms.
As tested substance EDTA-MnNa2 and target substance DTPA-MnNa3 have the same metal cation and the chelating agents (EDTA and DTPA) are very similar structure, the results obtained for EDTA-MnNa2 are also valid for DTPA-MnNa3.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to guideline
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']manganate(2-)
EC Number:
EC Name:
Disodium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']manganate(2-)
Cas Number:
Molecular formula:
Disodium; 2-[2-(bis(carboxylatomethyl)amino)ethyl-(carboxylatomethyl)amino]acetate; manganese(+2) cation
Details on test material:
Chemical name: Ethylenediaminetetraacetic acid, manganese disodium complex
Purity: 92.3%
Batch no: CFC 9380
Expiry date: 31 August 2012

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: ca. 10 weeks old
- Weight at study initiation:
- Fasting period before study: animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: group housing of 3 animals per cage
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days

- Temperature (°C): 19.6 – 21.5
- Humidity (%): 38-75
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 27 May To 16 June 2010

Administration / exposure

Route of administration:
oral: gavage
Details on oral exposure:
Study was started with 3 females, later on 3 other females were treated.
Method: Oral gavage, using plastic feeding tubes.
Frequency: Single dosage, on Day 1.
Dose level (volume): 2000 mg/kg (10 mL/kg) body weight.
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily observations on mortality, clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15, weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no
Not needed in a limit test

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Clinical signs:
Piloerection or hunched posture were noted in all animals on Day 1
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain
Gross pathology:
No abnormalities were found at macroscopic post mortem examination
Other findings:

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Migrated information
Because no mortality was observed, the oral LD50 is in excess of 2000 mg/kg bw.
Executive summary:

The study was carried out based on the guidelines described in:

- OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

- Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"

- EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

- JMAFF guidelines (2000) including the most recent partial revisions.

EDTA-MnNa2 was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Piloerection or hunched posture were noted in all animals on Day 1. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of EDTA-MnNa2 in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.