Reaction mass of disodium [2,2'-(ethane-1,2-diylbis{[2-(hydroxy-kO)benzyl]imino-kN})diacetato-kO(4-)]zinc(2-) and sodium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September-December 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted and well documented study under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

ZnHBED

IUPAC Name:

ZnHBED

Constituent 2

Reference substance name:

disodium [2,2'-(ethane-1,2-diylbis{[2-(hydroxy-kO)benzyl]imino-kN})diacetato-kO(4-)]zinc(2-)

Cas Number:

1263416-97-2

Molecular formula:

C20 H20 N2 Na2 O6 Zn

IUPAC Name:

disodium [2,2'-(ethane-1,2-diylbis{[2-(hydroxy-kO)benzyl]imino-kN})diacetato-kO(4-)]zinc(2-)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The animals were quarantined and observed daily for 5 days. A general medical -veterinary examination was performed on the day of the introductionof the animals to the quarantine, whereas a detailed medical-veterinary examination was performed before the beginning of the experiment. Only animals without any clinical signs were introduced to the experiment. The animals were randomized to the experiment. Their sex and body weights were taken into account. All animals were marked individually. One 8-week-old animal weighing 182 g (dose of 2000 mg/kg b.w. ) was used in the sighting study. Four 9-week-old animals whose average body weight was 187 g (dose of 2000 mg/kg b.w.) were used in the main study.

Housing conditions
During the quarantine, the sighting study, and the main study, the animals were kept in air-conditioned rooms under the following conditions:
- air temperature: 20 – 23 °C
- relative ai r humidity: 35 – 61%
- artificial fluorescent lighting; lighting cycle: 12 hours light/12 hours dark
- facility air exchange: about 16 times/hour [SOP/T/9].
The animals were kept in plastic cages covered with wi re bar lids. The dimensions of the cages were 58 x 37 x 21 cm (length x width x height). In the sighting study, the animals were caged individually,whereas in the main study, there were four of them per cage.

The animals were given ad libitum access to the “Murigran” standard granulated laboratory fodder and drinking tap water.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test item at a single dose of 2000 mg/kg b.w. was administered in the form of an aqueous solution in a volume of 0.5 mL/100 g b.w. using a metal stomach tube. One milliliter of the administered solution contained 400 mg of the test item (dose of 2000 mg/kg b.w.).

Doses:

2000 mg /kg b.w.

No. of animals per sex per dose:

4 animals (female)

Control animals:

not specified

Details on study design:

The experiment commenced with a sighting study in which the test item at a single dose of 2000 mg/kg b.w was administered to one animal.
On the grounds of the sighting study results, four animals used in the main study were given the test item at a dose of 2000 mg/kg b.w. (the animal from the sighting study which had been given the dose of 2000 mg/kg b.w. was included in the main study).
Before the administration, the animals had been fasted for about 19 hours. The test item in the form of an aqueous solution in a volume of 0.5 mL/100 g b.w. was administered using a metal stomach tube. After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. Body weights of the animals were determined on days 0 (di rectly before the administration of the test item), 7, and 14. After the 14-day observation period, the animals were euthanized and subjected to a necropsy
and a detailed gross examination.

Results and discussion

Preliminary study:

The test item at a single dose of 2000 mg/kg b.w. was administered to one animal. The test item was administered in the form of an aqueous solution in a volume of 0.5 mL/100 g b.w. using a metal stomach tube. One milliliter of the administered solution contained 400 mg of the test item (dose of 2000 mg/kg b.w.). No signs of toxicity were stated. The animal survived the experiment.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed. All animals (4) survived the test.

Clinical signs:

other: No clinical signs were obserwed.

Gross pathology:

The animals did not exhibit any pathological changes.

Other findings:

No other findings were observed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the grounds of the obtained results, the test item, i.e. Zn (II) HBED can be classified to the following categories:
- category 5 / unclassified – according to the Globally Harmonized System (GHS),
- agents which are beyond categorization – according to the Regulation (EC) No. 1272/2008 of the European Parliament and of the Council of December 16, 2008 on classification, labelling, and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC and amending Regulation (EC) No. 1907/2006.

Executive summary:

Following single administration of the test item at a dose of 2000 mg/kg b.w. to one animal used in the sighting study, no signs of toxicity were stated. The animal survived the experiment. Following single administration of the test item at a dose of 2000 mg/kg b.w. to the next four animals used in the main study, no signs of toxicity were stated. All animals survived the experiment. During the 14-day experiment, body weight gain was stated in all animals. Gross examinations did not reveal any pathological changes in the examined animals.