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EC number: 238-694-4
CAS number: 14644-61-2
The overall results of the test formulation
analyses were within the limits of acceptance for concentration (15% of
the theoretical concentration).
Effects on fertility - via oral route
No information on zirconium sulfate is available to cover this endpoint.
Therefore read across from zirconium acetate experimental data (another
'water soluble' zirconium compound) is proposed. The read across
justification is included in Section 13 of IUCLID.
The systemic toxic effects of the read across substance zirconium
acetate (aqueous solution containing 40.7% of the active ingredient
zirconium acetate) after repeated dosing, as well as any toxic effects
on reproduction and development were investigated in Sprague Dawley rats
up to early lactation (day 4 post partum) by Rossiello (2013). The study
was performed according to OECD guideline 422 and under GLP principles.
Three groups of 10 males and 10 females each received the test item, by
oral gavage, at 100, 300 and 1000 mg zirconium acetate/kg bw/day. A
similar constituted control group received the vehicle alone during the
The test item was diluted in purified water (vehicle) at concentrations
of 10, 30 and 100 mg of zirconium acetate/mL. Chemical analyses of the
formulated test item were performed during the study and the overall
results were within the limits of acceptance.
The overall dosing period was 32 days for males, which included 2 weeks
before pairing and continuously thereafter up to the day before necropsy
and up to 50 days for females including 2 weeks before pairing
thereafter during pairing, gestation and lactation periods until day 3
The parental animals were followed for daily clinical signs, weekly body
weight, food consumption, neurotoxicity assessment, oestrous cycle,
mating performance, clinical pathology evaluation including haematology
and clinical chemistry and offspring delivery. A detailed macroscopic
examination, organ weights and histopathology including the
spermatogenic cycle were performed.
Pups were also checked for sex, body weight, clinical signs and
No mortality occurred in the study. No treatment-related findings were
observed either during the in vivo phase or at post mortem examination
of parent animals.
Microscopically, treatment-related finding was seen in males receiving
300 and 1000 mg/kg bw/day consisting of minimal focal vacuolation of
squamous epithelium (limiting ridge) of non-glandular region of the
stomach. This change may be attributed to a local irritant effect of the
compound administered by oral gavage and since humans do not have
forestomach or structure analogous to forestomach, it is not considered
of toxicological relevance.
In addition, no abnormalities were found at the evaluation of the
spermatogenic cycle. No treatment-related effects were observed in the
number of oestrous cycle, pre-coital intervals, copulatory and fertility
indices between treated and control groups. No significant differences
were observed in the number of implantations, corpora lutea, total
litter size, pre-implantation loss, pre-birth loss and gestation length
between control and treated groups.
No effects were noted on reproduction and development at any dose. On
the basis of the results obtained in the study, the NOAEL (No Observed
Adverse Effect Level) for reproduction/developmental toxicity could be
considered >= 1000 mg/kg bw/day (expressed as zirconium acetate
anhydrous form), i.e. the highest dose tested.
This study was considered reliable with restrictions (Klimisch 2) to
reflect the read across status. The read across justification is
attached to IUCLID Section 13.
Annex IX testing
An OECD 422 test (Rossiello, 2013) has been performed with the read
across substance zirconium acetate, another 'water soluble' zirconium
compound. The test was performed in compliance with GLP principles. The
test results indicate that zirconium acetate is a substance of low
toxicological potential as the NOAEL for reproduction/developmental
toxicity was considered to be >=1000 mg/kg bw/day, the highest dose
tested. In addition, and based on the assessment of the available data,
low absorption of zirconium acetate is expected. This is also the case
for zirconium sulfate (see Section 7.1). Further, low toxicity is also
expected based on the available acute and subacute experimental data for
zirconium acetate and/or zirconium sulfate (or other 'water soluble'
zirconium compounds). Taking into account all available information, it
can be concluded that zirconium acetate does neither affect fertility
nor mating performance in rats of both sexes at doses up to and
including 1000 mg/kg bw/day. Similar results would be expected for other
'water soluble' zirconium compounds such as zirconium sulfate.
Therefore, no further testing seems to be scientifically required for
zirconium sulfate and thus, and for animal welfare reasons, no
two-generation study (or extended one-generation study) additional test
Effects on development: oral routeNo key experimental information is available for zirconium sulfate. Therefore, the results of an OECD 422 study with the read across substance zirconium acetate (another 'water soluble' zirconium compound with similar behaviour as zirconium sulfate), in which no adverse effects on developmental toxicity parameters were observed, is used as key information to cover this endpoint. Based on this information, no testing is currently deemed necessary for zirconium sulfate.
Developmental effects: oral route
No information on the potential developmental toxicity is available on
zirconium sulfate. Therefore read across from zirconium acetate (another
'water-soluble' zirconium compound with similar behaviour as zirconium
sulfate) is proposed. The results of the OECD 422 study performed with
zirconium acetate by Rossiello (2013) showed that the susbtance is of
low toxicological potential, as the NOAEL for reproductive/developmental
toxicity was considered to be >= 1000 mg/kg bw/day (the highest dose
tested). Furthermore no effects were observed in litter and sex ratios
and any of the parameters evaluated for pups (clinical signs) and no
treatment-related findings were recorded at necropsy in decedent pups
and in pups sacrified at term (Day 4 post partum).
Based on the toxicokinetics assessment (IUCLID Section 7.1) extremely
low absorption of zirconium is expected, even when animals are exposed
orally to 'water soluble' zirconium compounds such as zirconium acetate
and zirconium sulfate. This is reflected in the fact that no adverse
effects have been observed in available short-term and/or subacute
toxicity studies with 'water soluble' zirconium compounds. Therefore,
and taking into account all available information (no developmental
effects, extremely low absorption and toxicity), no further testing is
scientifically justified for zirconium sulfate (i.e. OECD 414), and, for
animal welfare reasons, no additional study is proposed.
The read across justification is included in Section 13 of IUCLID.
Based on the available data for the read across substance zirconium
acetate (another 'water soluble' compound with similar behaviour as
zirconium sulfate) and according to the criteria of the DSD and CLP
Regulation, zirconium sulfate should not be classified for toxicity to
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