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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:
30 September - 21 October 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Wistar (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8-10 weeks old).
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: 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.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

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.

IN-LIFE DATES: From: 30 September - 21 October 2014
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.
Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 1970 mg/kg body weight

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.
Doses:
1970 mg/kg body weight
No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
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.
- Necropsy of survivors performed: 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.
- Other examinations performed: none.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture and piloerection were noted for all animals on Days 1 and/or 2.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of EDTA-ZnK2 in Wistar rats was established to exceed 1970 mg/kg body weight. Since the difference with the intended dose level was less than 2%, it was considered that the obtained results would be comparable to those that would be obtained at 2000 mg/kg bw. Therefore it was considered that the oral LD50 value of EDTA-ZnK2 exceeded 2000 mg/kg body weight. Based on the results and 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-ZnK2 does 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) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
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 classification or non-classification

Based on the very low toxicity of EDTA-ZnK2 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.