Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Zirconium acetate considered a good surrogate for testing as this is a non-corrosive form of the substance and is water soluble
The source of data for the US Federal publication appears to lead back to a European REACH registration. The potential lead registrant has been contacted and attempts made to access the data; at the time of submission, there has been no response and the data owner is not known.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
not specified
Justification for study design:
Appears to follow OECD guidelines; accepted by peer reviewed US publication
Assumed to be GLP compliant, but no indication of data owner or testing facility provided in publication.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Not specified
Zirconium acetate considered a good surrogate for testing as this is a non-corrosive form of the substance and is water soluble

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
The substance will dissociate in water, but zirconium will remain soluble under acidic conditions of the stomach when ingested.
Duration of treatment / exposure:
Males exposed for 32 days and up to 50 days (4 days post-partum) for females. Exposure took place prior to and during mating period
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Three groups of 4 rats per sex were administered with zirconium acetate by oral gavage at doses of 100, 300 and 1000 mg/kg bw/day
Dose expressed as anhydrous form of zirconium acetate
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Not specified in review
Postmortem examinations (parental animals):
Not specified in review
Postmortem examinations (offspring):
Not specified in review

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive performance:
no effects observed

Effect levels (P0)

Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Other effects:
no effects observed

Effect levels (F1)

Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (F1)

Critical effects observed:
no

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
No clinical signs or effects on reproduction or development were reported.
The No Observed Adverse Effect Level (NOAEL) for repeated dose toxicity, reproductive toxicity and for developmental toxicity was considered to be in excess of 1000 mg/kg bw/day zirconium acetate anhydrous.
This equates to ca. 280 mg/kg/day Zr 4+ and in turn, using a nominal molecular weight of 231 for the registered substance, the NOAEL for the zirconium oxynitrate is greater than 700 mg/kg/day