Zirconium tetrabutanolate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The target substance is hydrolytically unstable with hydrolysis half-life less than 5 minutes. The hydrolysis products have been identified to be 1-butanol and hydrated zirconium dioxide. The properties and toxiciteis of the hydrolysis products are therefore used for read-across.

Reference 2

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

distribution

excretion

metabolism

Qualifier:

no guideline followed

Principles of method if other than guideline:

n-[1-14C]Butanol was mixed with corn oil and administered by gavage to male Charles River CD (SD) rats in doses of 4.5, 45, or 450 mg/kg bw. The excretion of the n-[1-14C]Butanol was examined.

GLP compliance:

not specified

Radiolabelling:

yes

Remarks:

C14

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Route of administration:

oral: gavage

Vehicle:

corn oil

Dose / conc.:

4.5 mg/kg bw (total dose)

Dose / conc.:

45 mg/kg bw (total dose)

Dose / conc.:

450 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

not specified.

Type:

distribution

Results:

highest concentrations: liver 3.88 % at 8 h, blood 0.74 % at 8 h, kidney 0.24 % at 4 h, other tissue < 0.12 %

Type:

excretion

Results:

Elimination of administered dose 450 mg/kg bw: > 44 % within 4 h, 69.3 % at 8 h, 83.3 % at 24 h

Type:

other: remaining radioactivity in carcass

Results:

at 4 h: 42.2 %; at 8 h: 27.2 %; at 24 h: 12.3 %

Metabolites identified:

yes

Details on metabolites:

About 75 % of the radioactivity was detected as 1-butanol, presumably both as an O-sulfate (44.4 %) and as an O-glucuronide (30.7 %). Urea accounted for the remainder of the radioactivity.

Conclusions:

no bioaccumulation potential based on study results

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No studies were conducted on the target substance, zirconium tetrabutanolate. As the target substance hydrolyses rapidly (half-life < 5 minutes) the intrinsic properties are related to hydrolysis products of the target substance. The hydrolysis products include 1-butanol and non-hazardous zirconium dioxide. This information is used as a supporting evidence on the toxicity of the target substance in CSA.

 

1-butanol is readily absorbed through the skin, intestinal tract, and lungs (Sander, 1933; Theorell and Bonnichsen, 1951; Winer, 1958; Merritt and Tomkins, 1959; Wartburg et al., 1964) and is eliminated after metabolism primarily by alcohol and aldehyde dehydrogenases. Two hours after rats (strain not specified) were given an oral dose of 2,000 mg/kg body weight, the maximum blood-alcohol concentration was 500 mg/l (Gaillard and Derache, 1965). After four hours, the concentration dropped to 150 mg/l, and only 0.03% of the administered dose was excreted in the urine after eight hours.

In another study, CD rats excreted 83.3% of the dose (450 mg/kg body mass) as carbon dioxide and 4.4% in the urine after 24 hours (DiVincenzo and Hamilton, 1979). Beagle dogs dermally exposed through an absorption cell on the thorax absorbed the compound at a rate of 8.8 mg/min per cm 2 over a 60-minute period (DiVincenzo and Hamilton, 1979). In an inhalation study, beagle dogs exposed to 50 ppm BA over a 6-hour period absorbed approximately 55% of the inhaled vapor (DiVincenzo and Hamilton, 1979). (Adapted from UNEP 2004).

 

Overall, 1-butanol is rapidly absorbed, metabolized, and excreted in rats. Accumulation of n-butanol or its metabolites is unlikely to occur.