Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: key study carried out according to OECD guideline no 401 indicating for zinc metal LD50 > 2000 mg/kg bw
Acute inhalation toxicity: key study carried out according to OECD guideline no 403 indicating for zinc metal LC50 > 5.41 mg/L/4hrs

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
used in EU risk assessment report for Zinc metal
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
no further details provided
Route of administration:
oral: feed
Vehicle:
maize oil
Details on oral exposure:
In this study very fine zinc powder, labelled as “Zincstaub, superfein 620”, was given as a suspension in maize oil
Doses:
one dose of 2000 mg zinc/kg bw
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no further information
Statistics:
no information
Preliminary study:
no information
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality observed
Clinical signs:
piloerection in all females, diarrhoea in one female
Body weight:
no adverse effects reported
Gross pathology:
no adverse effects reported
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 >2000 mg/kg bw
Executive summary:

A limit study with Wistar rats was carried out according to OECD guideline no. 401 to assess the oral LD50. Apart from piloerection in all females and diarrhoea in one female, no mortality or clinical signs were observed after dosing of 2000 mg zinc/kg bw during the 14 day observation period. In this study very fine zinc powder, labelled as “Zincstaub, superfein 620”, was given as a suspension in maize oil. The particle size was not given in this study, but according to the accompanying letter from the industry the particle diameter was 5 μm. An LD50-value of > 2000 mg/kg bw was reported

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
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: no data
Details on inhalation exposure:
Of the particles, 85% had an aerodynamic diameter ≤8.2 μm and 27% ≤5 μm. The mass median aerodynamic diameter was determined to be 6.2 μm with a geometric standard deviation of 1.7.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
> 5.41 g Zn/m3 air (the highest attainable concentration)
No. of animals per sex per dose:
according to guideline study
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: as per guideline
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes
Statistics:
as per guideline
Preliminary study:
no information
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 410 mg/m³ air
Mortality:
No mortalities occurred during the 14-day observation period.
Clinical signs:
other: other:
Body weight:
no information
Gross pathology:
Abnormalities at necropsy consisted of lung changes (white spots on three or all five lung lobes) in two males and four females
Other findings:
none

none

Interpretation of results:
GHS criteria not met
Conclusions:
LC50 greater than 5.41 g /m3
Executive summary:

An LC50-value of > 5.41 g /m3air (the highest attainable concentration for the same very fine zinc powder, labelled as “Zincstaub superfein 620”) for a single 4-hour exposure period was found in a nose only exposure study in Wistar rats carried out according to OECD guideline no. 403. Of the particles, 85% had an aerodynamic diameter ≤8.2 μm and 27% ≤5 μm. The mass median aerodynamic diameter was determined to be 6.2 μm with a geometric standard deviation of 1.7. Clinical signs after exposure consisted of visually decreased breathing rate (first 2 days) and sluggishness in all animals (only shortly after exposure) and blepharospasm in two male and two female rats (first day). No mortalities occurred during the 14-day observation period. Abnormalities at necropsy consisted of lung changes (white spots on three or all five lung lobes) in two males and four females.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 410 mg/m³

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 metal does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).


Based on the results of the available acute inhalation rat study, zinc metal 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 metal 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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