Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: key study carried out according to OECD guideline no 401 indicating for trizinc bis(orthophosphate) LD50 > 5000 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 trizinc bis(orthophosphate)

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:
other: Used in EU risk assessment for zinc phosphate, guideline study,
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
not specified
Details on test animals and environmental conditions:
No data
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
No data
Doses:
Not specified
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Preliminary study:
Not applicable
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
no effects
Body weight:
no effects
Gross pathology:
no effects
Other findings:
None

None

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 oral rat is >5000 mg zinc phosphate/kg bw
Executive summary:

Zinc phosphate was tested in an oral limit test according to OECD guidelines using Wistar rats. No mortality occurred and no signs of toxicity was observed. The LD50 is >5000 mg zinc phosphate/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: used in EU risk assessment for zinc oxide, guideline study, reliable with restrictions
Qualifier:
equivalent or similar to
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 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 m ± 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
Mortality:
no mortality
Clinical signs:
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:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
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
5 700 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

With LD50 values consistently exceeding 2,000 mg/kg bw, slightly soluble or insoluble zinc compounds such as zinc oxide (LD50 ranges between 5,000 and 15,000mg/kg bw), zinc phosphate (LD50 is >5,000mg/kg bw), zinc metal (LD50 >2,000mg/kg bw) or zinc sulphide (LD50 is >15,000mg/kg bw), show very low level of acute oral toxicity. Moreover, zinc oxide and zinc metal were further shown to be of low acute inhalation toxicity (i.e., LC50 values of > 5.7 and >5.41 mg/L/4hrs). Given the common characteristics shared via their solubility characteristics, the remaining slightly soluble zinc compounds are also considered to be of low acute inhalation toxicity. There are no available data on which to evaluate acute dermal toxicity forslightly soluble or insoluble zinc compounds, however, acute dermal toxicity can be considered to be low in view of the poor absorption by this route.

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

The slightly soluble and insoluble zinc compounds (i.e., zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal and zinc sulphide)

are of low acute, dermal and inhalation toxicity not requiring a classification for acute toxicity according to the EC criteria.