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EC number: 237-529-3
CAS number: 13826-66-9
No key information is available on the effects of zirconium dinitrate
oxide on fertility. Therefore, the endpoint is covered using a read
across study performed with zirconium acetate, a water-soluble zirconium
compound with similar behaviour as zirconium dinitrate oxide.
Rossiello (2013) performed a combined repeated dose toxicity study with
reproduction/developmental toxicity screening via oral route in rats
according to OECD guideline 422. This Klimisch 1 study was performed in
compliance with GLP guidelines. A NOAEL of >=1000 mg/kg bw/day
(expressed as zirconium acetate anhydrous) was derived for
reproduction/developmental toxicity. No adverse effects on any of the
relevant parameters were observed up to and including at the highest
dose tested. This result is considered relevant for zirconium dinitrate
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:
Because no reliable information could be identified on the effects of
zirconium dinitrate oxide on fertility, the endpoint is covered using a
read across study performed with zirconium acetate, a water-soluble
zirconium compound with similar behaviour as zirconium dinitrate oxide.
The systemic toxic effects of zirconium acetate 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, a treatment-related finding was seen in males receiving
300 and 1000 mg/kg bw/day consisting of minimal focal vacuolation of the
squamous epithelium (limiting ridge) of the non-glandular region of the
stomach. This change may be attributed to a local irritating effect of
the compound administered by oral gavage and since humans do not have a
forestomach or any structure analogous to the 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 cycles, 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.
In conclusion, 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 zirconium acetate
anhydrous form), i.e. the highest dose tested. This result is considered
relevant for zirconium dinitrate oxide too. The read across
justification is attached to IUCLID Section 13.
No data are required under Annex VIII on this endpoint, except for the screening for developmental toxicity, which is described under IUCLID Section 7.8.1, and covered by the OECD 422 study performed with the read across substance zirconium acetate (Rossiello, 2013). No adverse effects have been observed on any of the parameters evaluated for pups.
See explanation under toxicity to reproduction.
Based on the available data for the read across substance zirconium
acetate, a water-soluble zirconium compound with similar behaviour as
zirconium dinitrate oxide, and according to the criteria of the CLP
Regulation, zirconium dinitrate oxide should not be classified for
toxicity to reproduction.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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