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Administrative data

Description of key information

The acute oral LD50 value in rats was > 2000 mg/kg bw. Although an acute inhalation with this substance was not performed, inhalation studies with other metal chelates showed that these substances are not toxic (4-h LC50 value > 5 mg/L). In addition, acute dermal toxicity studies with other metal chelates showed that LD50 values were in excess of 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well performed and reported GLP study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
cat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species: rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC)
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Ear- and tailmark

Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation
Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).

Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures.
Route of administration:
oral: gavage
Vehicle:
acetone
Details on oral exposure:
Method: oral gavage, using plastic feeding tubes.
Fasting: animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
Frequency: single dosage on Day 1.
Dose level (volume): 2000 mg/kg (2.81 mL/kg) body weight.
Dose volume calculated as (dose level (g/kg) / density (g/mL)) x 1.85 (A correction was made for purity of the test substance (correction factor 1.85)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Mortality/Viability: twice daily.
Body weights: days 1 (pre-administration), 8 and 15.
Clinical signs: at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not needed, limit test
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was shown by one animal 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 of the animals.


Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 was 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 (2011) including the most recent partial revisions.

EDTA-Zn(NH4)2 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. Hunched posture was noted in one animals on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of EDTA-Zn(NH4)2 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.

Based on these results, EDTA-Zn(NH4)2does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) andRegulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The key study was conducted according to GLP and guidelines. Sufficient data is available also for the other metal-chelates (see also read across document in section 13) for the interpretation of study results.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Other studies with metal-chelates of EDTA (EDTA-MnNa2, EDTA-FeNa, EDTA-CuNa2) showed very limited acute toxicity (4-h LC50 > 5 mg/L). In addition, a study with Ca-DTPA showed a 2-h LC50 > 1.15 mg/L. See also read across document in section 13.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Other studies with metal-chelates of EDTA (EDTA-Fe(NH4)2OH, EDTA-FeNa) showed very limited acute toxicity (LD50 > 2000 mg/kg bw). See also read across document in section 13.

Additional information

The oral and inhalation route for the endpoint acute toxicity are covered. A third route is not reqired by Regulation 1907/2006. In addition, the absorption via the skin is expected to be very low (EU RAR, 2004).

Justification for selection of acute toxicity – oral endpoint

Study in rats, according to OECD guideline 423.

Justification for classification or non-classification

Based on the very low toxicity of EDTA-Zn(NH4)2 via the oral route, and the expected very low toxicity via the inhalation route and taking into account the very low dermal absorption of EDTA-compounds, no classification is needed for acute toxicity.