Diammonium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']cuprate(2-)

Acute Toxicity: oral

Administrative data

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

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:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diammonium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']cuprate(2-)

EC Number:

268-018-3

EC Name:

Diammonium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']cuprate(2-)

Cas Number:

67989-88-2

Molecular formula:

C10H12CuN2O8.(NH4)2

IUPAC Name:

copper(2+) ion 2-({2-[(carboxylatomethyl)(carboxylmethyl)amino]ethyl}(carboxymethyl)amino)acetate diamine

Test material form:

other: solution

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

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 (10 mL/kg) body weight.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 females (300 mg/kg bw); 3 females (2000 mg/kg bw)

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

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

All animals died at 2000 mg/kg bw; no mortality occurred at 300 mg/kg bw.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 is in excess of 300 mg/kg bw but lower than 2000 mg/kg bw