Hydroxy(2-methylprop-2-enoato-O)zinc

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 August - 20 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 423 with a minor deviation: the temperature recorded in the animal room was sometimes outside of the target ranges

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

the temperature recorded in the animal room was sometimes outside of the target ranges

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxy(2-methylprop-2-enoato-O)zinc

EC Number:

264-202-2

EC Name:

Hydroxy(2-methylprop-2-enoato-O)zinc

Cas Number:

63451-47-8

Molecular formula:

C4H6O3Zn

IUPAC Name:

hydroxy(2-methylprop-2-enoato-O)zinc

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Hydroxy(2-methylprop-2-enoato-O)zinc
- Physical state: White powder
- Analytical purity: > 85.5%
- Lot/batch No.: Y1109025
- Date of receipt: 05 July 2012
- Expiration date of the lot/batch: 03 December 2012
- Storage condition of test material: Room temperature, protected from humidity

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 210 g (range: 194-228 g)
- Fasting period before study: Animals were fasted overnight before treatment. Food was given approximately 4 h after administration of the test item.
- Housing: Animals from the same group were housed by three in polycarbonate cages with stainless steel lids (Tecniplast 2154, 940 cm²).
- Diet: SSNIFF R/M-H pelleted maintenance diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Tap water (filtered with a 0.22 µm filter), ad libitum
- Acclimation period: 5 or 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 50 ± 20 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % methylcellulose aqueous

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: As heterogeneous suspension at 200 mg/mL was obtained with drinking water treated by reverse osmosis, the test item was tested with 0.5% methylcellulose aqueous solution. A homogenous suspension was obtained at the concentration of 200 mg/mL in 0.5% methylcellulose aqueous solution. Therefore, 0.5 % methylcellulose aqueous was selected as vehicle.
- Lot/batch no. (if required): 068K0020

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
- Test item was administered as a homogenous suspension in the vehicle. The test item was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle. Dose formulations preparations were prepared on the day of each administration. The dose formulations were stored at room temperature and delivered to the study room in brown flasks.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose level was 300 mg/kg bw for ethical reasons.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

- First assay: 3 females/dose (300 and 2000 mg/kg bw)
- Confirmatory assay: 3 females (2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Each animal was checked for mortality and morbidity, frequently during the hours following administration, then at least once a day until the end of the observation period, including weekends and public holidays. Each animal was observed after treatment as follows: at least once during the first 30 minutes, periodically during the first 4 h, then once a day, at approximately the same time, for the recording of clinical signs.
Bodyweight: Body weight of each animal was recorded the day of group allocation then on the day of treatment and on Days 8 and 15.
- Necropsy of survivors performed: Yes; On completion of the observation period, animals were deeply anesthetized by an intraperitoneal injection of pentobarbital sodium and euthanized by exsanguination and macroscopic examination was performed.

Statistics:

None

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No unscheduled deaths and no clinical signs were observed in any animals.

Mortality:

- No mortality was observed.

Clinical signs:

other: - No clinical signs were observed.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 7.2.1/1: Body weight

 

Sex	Female
Group	Historical control data	1	2	3
Dose-level (mg/kg)	0	300	2000	2000
Body weight
Day 1	219	197	211	221
Day 8	264	245	243	261
Day 15	284	260	261	276
Body weight change
Days 1-8	+44	+48	+32	+40
Days 8-15	+20	+16	+18	+16
Days 1-15	+64	+63	+50	+56

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the oral LD50 for Hydroxy(2-methylprop-2-enoato-O)zinc is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a GLP acute oral toxicity study performed according to OECD Guideline 423, groups of 3 female Sprague Dawley [Rj Han: SD] rats were given a single oral (gavage) dose of Hydroxy(2-methylprop-2-enoato-O)zinc at 300 and 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality or clinical signs were observed. When compared to laboratory historical control data, a trend to a slightly lower mean body weight gain was observed in females treated at 2000 mg/kg bw (group 2, first assay) during the first week of study. No macroscopic abnormalities were observed at study termination. In this study, the oral LD50 of the test item was therefore considered to be higher than 2000 mg/kg bw.

Under the test conditions, the oral LD50 for Hydroxy(2-methylprop-2-enoato-O)zinc is higher than 2000 mg/kg bw in female rats. Therefore, according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008), it is not classified for acute oral toxicity.