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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.
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:
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

Description of key information

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.