Zinc, [1,2,3-propanetriolato(2-)-.kappa.O1,.kappa.O2]-, homopolymer, stereoisomer

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From September 19, 2008 to October 7, 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

zinc(2+) 3-hydroxypropane-1,2-bis(olate)

EC Number:

700-107-9

Cas Number:

87189-25-1

Molecular formula:

(C3H6O3Zn)n

IUPAC Name:

zinc(2+) 3-hydroxypropane-1,2-bis(olate)

Details on test material:

- Substance type: Organic
- Physical state: Powder
- Storage condition of test material: At room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as stated in the report: Wistar rat strain Crl:Wl (Han) outbred
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 11-12 weeks
- Weight at study initiation: group 1: 183-208 g / group 2: 181-199 (body weight variation did not exceed +/-20% of the sex mean)
- Sex: female (nulliparous and non-pregnant)
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm), containing sterilized sawdust as bedding material (Litalabo, SPPS, Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet ad libitum: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water ad libitum: tap water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions
- Number of animal per dose group: 3

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-21.2°C
- Humidity (%): 43-75%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h artificial fluorescent light and 12h darkness per day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Volume applied: 10 ml/kg bw (2000 mg/kg bw)
- Justification for choice of vehicle: selection based on trial formulations performed at Notox and on test substance data supplied
- Specific gravity: 1.036
- Formulations (w/w, 4 grams substance with 17 grams vehicle) were prepared within 4h prior to dosing. Homogeneity was accomplished to a visually acceptable level.

ACUTE TOXIC CLASS METHOD:
- Method: Oral gavage, using plastic feeding tubes
- Frequency: single dosage, on day 1
- Dose level (volume): 2000 mg/kg bw (10 mL/kg) bw

Doses:

2000 mg/kg (10 mL/kg) bw

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days

OBSERVATIONS:
- Frequency of observation for mortality/viability: twice daily
- Frequency of weighing: Days 1 (pre-administration), 8 and 15
- Frequency of observation for clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy: At the end of the observation period (day 15), all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal abnormalities were recorded.

Statistics:

Electronic data capture:
REES Centron Environmental Monitoring System version SQL 2.0 (REES scientific, Trenton, NJ, USA) and
TOXDATA version 8.0 (NOTOX BV, 's-Hertogenbosch, The Netherlands)
No statistical analysis was performed.

Results and discussion

Preliminary study:

Dose: 2000 mg/kg bw
No mortality occured
Hunched posture was noted in all animals between days 1 and 8 and piloerection was noted in all animals between days 1 and 4. Uncoordinated movements were observed among the animals on day 1.
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.
No abnormalities were found at macroscopic post mortem examination of the animals.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: none of the animals died

Mortality:

No mortality occured.

Clinical signs:

other: Hunched posture was noted in all animals between days 1 and 8 and piloerection was noted in all animals between days 1 and 4. Uncoordinated movements were observed among the animals on day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 1: Mean body weights in gram (Dose level: 2000 mg/kg bw)

Test day	1	8	15
Group 1 females	197 +/- 13	222 +/- 15	230 +/- 22
Group 2 females	188 +/- 10	206 +/- 15	215 +/- 15

Body weights on day one were assessed before application of test article.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met