Bis(5-oxo-L-prolinato-N1,O2)zinc

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 May 2016 to 14 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(5-oxo-L-prolinato-N1,O2)zinc

EC Number:

239-473-5

EC Name:

Bis(5-oxo-L-prolinato-N1,O2)zinc

Cas Number:

15454-75-8

Molecular formula:

C10H12N2O6Zn

IUPAC Name:

(3'aR)-3,3',6,6'-tetraoxo-3a,3'a,4,4',5,5',6,6'-octahydro-3H,3'H-1,1'-spirobi[pyrrolo[1,2-c]1-oxa-3-aza-2-zincacyclopentane]-1,1-bis(ylium)-2,2'-diuide

Test material form:

solid: particulate/powder

Details on test material:

- Physical appearance: White to off-white powder
- Storage conditions: Controlled room temperature (15-25°C, below 70 RH%), protected from light

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15 to 25 ºC, below 70 RH %), protected from light.

Test animals

Species:

rat

Strain:

other: CRL: (WI)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Only specified as young adult.
- Weight at study initiation: 218 to 269 g
- Housing: Individual caging in Type II polypropylene/polycarbonate cages.
- Diet: Ad libitum; the food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Water: Tap water from the municipal supply, as for human consumption, from a 500 mL bottle, ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.9 to 25.0 °C
- Humidity: 32 to 62 %
- Air changes: 15 to 20 air exchanges per hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10 % (5 x 5 cm)
- Type of wrap if used: Sterile gauze pads (approximately 5 x 5 cm were placed on the skin of the rats to cover the dampened test material. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw
- For solids, paste formed: The test material was dampened with sufficient water before application to ensure good contact with the skin.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test material and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

- Necropsy of survivors performed: Yes
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

- Other examinations performed: The body weights were recorded on Day 0 (before test material administration) and on Days 7 and 14 just before necropsy.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test material did not cause mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test material during the 14 days observation period.

Gross pathology:

There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal LD50 value of the test material was found to be > 2000 mg/kg bw in male and female CRL:(WI) rats.

Executive summary:

An acute dermal toxicity study was performed with test material in CRL:(WI) rats, in accordance with the standardised guideline OECD Guideline No.: 402, under GLP conditions.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test material was applied as a single dermal 24-hour exposure followed by a 14-day observation period. The test material was applied to the shaven backs of the animals to cover approximately 10 % of the total body surface area, it was applied on a gauze pad kept in contact with the skin using an adhesive patch. The trunk of the animal was then wrapped with semi-occlusive plastic wrap for 24 hours.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

The test material did not cause any mortality at 2000 mg/kg bw, there were no systemic clinical or local dermal signs observed throughout the study. Body weight gains of the treated animals showed no indication of a test-material related effect. There were no macroscopic findings to report. 

Under the conditions of this study, the acute dermal LD50 value of the test material was found to be above 2000 mg/kg bw in male and female CRL:(WI) rats.