Zinc hydroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

Zinc hydroxide

EC Number:

243-814-3

EC Name:

Zinc hydroxide

Cas Number:

20427-58-1

Molecular formula:

H2O2Zn

IUPAC Name:

zinc hydroxide

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: solid (in the powder form), white
- Purity: 98.2%
64.6% Zn content (calculated)
- Lot/batch No.: CP4574
- Expiration date of the lot/batch: stable over time
- Storage condition of test material: room temperature, in the dark
- Particle size (typical): D10 = 1.63 µm
D50 = 7.40 µm
D90 = 164 µm
- Densitiy: 3.053 g/cm³ at 20°C

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot/batch No.of test material: CP4574
- Expiration date of the lot/batch: 13 September 2019
- Purity test date: 98.2 %
- Description:White Solid (in the powder form)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25°C, ≤70% relative humidity).
- Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face mask) for unknown materials were applied to assure personnel health and safety.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Weight at study initiation (g): 194 – 226 g
- Housing: 3 animals / cage (Type II polypropylene/polycarbonate)
- Diet: ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water: tap water from municipal supplies, as for human consumption, ad libitum.
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7-24.6
- Humidity (%): 32-73 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

A single oral gavage administration was followed by a fourteen-day observation period. On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.

Doses:

2000mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Clinical Observations: performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, 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.

Body Weight Measurement: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0), weekly thereafter and at necropsy (Day 14).

Necropsy:
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%; Lot No.: 1609291-03, Expiry date: 31 October 2019, produced by: Alfasan Nederland BV, The Netherlands). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.

Statistics:

none

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Zinc hydroxide did not cause mortality at a dose level of 2000 mg/kg bw in any animal.

Clinical signs:

other: other: All animals were symptom-free during the 14-day observation period.

Gross pathology:

There was no evidence of the macroscopic changes at necropsy at a dose level of 2000 mg/kg bw in any animal.

Other findings:

none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Tests done according to standard protocol. Good quality and considered useful for setting the reference value for acute oral toxicity (LD50>2000mg/kg)

Executive summary:

The purpose of this study was to assess the acute oral toxicity of zinc hydroxide.

As no mortality was observed in Group 1 (three Wistar rats treated at a dose level of 2000mg/kg), a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to OECD 423 and Commission Regulation(EC) No 440/2008 of 30 May2008, B.1.tris.

Under the conditions of this study, the acute oral LD₅₀value of the test item Zinc hydroxide was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.