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Description of key information

Acute oral toxicity: key study carried out according to OECD guideline no 423 indicating for zinc hydroxide LD50 > 2000 mg/kg bw


Acute inhalation toxicity: key study carried out according to OECD guideline no 403 indicating for zinc oxide LC50 > 5.7 mg/L/4hrs (read-across to zinc hydroxide)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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.
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.
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
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

none

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.

 


Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Used in EU risk assessment for zinc oxide
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
no information available
Route of administration:
inhalation
Type of inhalation exposure:
nose/head only
Vehicle:
other: no data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
Aerosol concentration was 5.7 mg/l
No. of animals per sex per dose:
10 per sex
Control animals:
yes
Details on study design:
10 male and 10 female animals per group were exposed to zinc oxide aerosol (head and nose only) for 4 h. Aerosol concentration was 5.7 mg/l and the particle size distribution had a mass median aerodynamic diameter of 4 µm ± 2.9 (GSD). Only one concentration and a control group were tested. All animals survived up to day 14 post exposure.
Statistics:
no information
Preliminary study:
no information
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 5 700 mg/m³ air
Exp. duration:
4 h
Mortality:
no mortality
Clinical signs:
other: only a dusty fur on the head, no adverse effects noted
Body weight:
no change in body weights observed
Gross pathology:
no adverse effects observed.
Other findings:
none observed

no information

Interpretation of results:
GHS criteria not met
Conclusions:
LC50 4 hours >5.7 mg ZnO/l
Executive summary:

In an acute inhalation toxicity study, 10 male and 10 female animals per group were exposed to zinc oxide aerosol (head and nose only) for 4 h. Aerosol concentration was 5.7 mg/l and the particle size distribution had a mass median aerodynamic diameter of 4mm ± 2.9 (GSD). Only one concentration and a control group were tested. All animals survived up to day 14 post exposure. Apart from a dusty fur on the head the day after the exposure, no effects were seen. Body weights developed normally. At pathological examination all organs were normal. The LC50was >5.7 mg/l.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 700 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Of significance for humans from an acute toxicity standpoint is the occurrence of metal fume fever following exposure to ultrafine particles of special grades of zinc oxide in context of very specific operations such as cutting or welding of galvanised steel. Metal fume fever is exclusively associated with freshly formed ultrafine particulate zinc oxide (<0.1 µm). As these ultrafine particles (nanoparticles) rapidly agglomerate to bigger particles, which are normally encountered at production and processing sites, at these sites there is no indication for metal fume fever. According to the response from 11 zinc companies to a questionnaire, there have been no observations of zinc metal fume fever over the last decade and in recent occupational practice (EU RAR, 2004a-f). However in light of responsible care and since no studies are available that allow the establishment of a NOAEL for metal fume fever with a reasonable degree of certainty, a LOAEL (5 mg ZnO/m3) for 2 hours (showed the typical metal fume fever symptoms beginning 4 to 8 hours after exposure and disappearing within 24 hours) can be used for metal fume fever based on the study by Gordon et al.(1992).

Justification for classification or non-classification

Based on the results of the available acute oral rat study, zinc hydroxide does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).


Based on read across from the results of the available acute inhalation rat study with zinc oxide, zinc hydroxide does not require classification for acute inhalation toxicity according to EU CLP criteria (EC 1272/2008).

There are no available data on which to evaluate acute dermal toxicity. However, acute dermal toxicity can be considered low in view of the poor absorption by this route and the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route. Therefore, zinc hydroxide does not require classification for acute dermal toxicity according to EU CLP criteria (EC 1272/2008)

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.

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