Zirconium tetrabutanolate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

chronic toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, this substance is hydrolytically unstable with hydrolysis rate estimated to be less than 5 minutes. The hydrolysis products have been identified to be 1-butanol and zirconium dioxide. The discussion of toxicity is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

secondary data from authority reviewed summary

Qualifier:

according to guideline

Guideline:

other: other

Principles of method if other than guideline:

Four groups of male and female rats (30/sex/group) were administered daily by gavage 0, 30, 125 or 500 mg/kg bw/d for either 6 or 13 weeks.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6 weeks

Frequency of treatment:

daily

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

30 mg/kg bw/day (nominal)

Dose / conc.:

125 mg/kg bw/day (nominal)

Dose / conc.:

500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

30

Control animals:

yes

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Ataxia and hypoactivity (lasting less than 1 h) were observed 2 to 3 minutes after dosing in both sexes of the high-dose group (500 mg/kg bw/d) during the final 6 weeks of dosing.

Mortality:

mortality observed, non-treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 125 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

other: no effects observed

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

500 mg/kg bw/day (nominal)

System:

central nervous system

Organ:

other: general effect on CNS

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

yes

Conclusions:

No treatment related signs were observed in the 30 or 125 mg/kg bw /d treatment groups, the latter value being the no-observed adverse effect level (NOAEL)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

125 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

According to hydrolysis test results, this substance is hydrolytically unstable with hydrolysis rate estimated to be less than 5 minutes. The hydrolysis products have been identified to be 1-butanol and zirconium dioxide. The discussion of toxicity is based on the hydrolysis/degradation products.

Reference 2

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

authority reviewed.

Qualifier:

according to guideline

Guideline:

other: other

Principles of method if other than guideline:

disturbance of rotarod performance

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

6 h/d, 5 d/wk for 3 months

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

disturbance of rotarod performance

Duration of treatment / exposure:

3 months

Dose / conc.:

150 mg/m³ air

Dose / conc.:

310 mg/m³ air

No. of animals per sex per dose:

24

Control animals:

yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Key result

Dose descriptor:

LOEL

Effect level:

ca. 50 ppm

Based on:

test mat.

Sex:

male

Basis for effect level:

clinical signs

other: rotarod performance

Reference 3

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OTS 798.2450 (90-Day Inhalation Toxicity)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6 h/d, 5 d/week. For 65 days

Dose / conc.:

0 ppm

Dose / conc.:

500 ppm

Dose / conc.:

1 500 ppm

Dose / conc.:

3 000 ppm

No. of animals per sex per dose:

15

Control animals:

yes, concurrent vehicle

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

reduced activity levels (less movement, decreased alertness, and slower response)

Mortality:

no mortality observed

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 500 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

1 500 ppm

System:

central nervous system

Organ:

other: central nervous system

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

yes

Conclusions:

n-butyl acetate NOAEL of 500 ppm was reported for systemic effects in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

676 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

As the target substance hydrolyses rapidly (half-life < 5 minutes) the intrinsic properties are related to hydrolysis products of the target substance. The toxicity evaluation of the hydrolysis product – 1-butanol was used for assessment.

 

Oral
The most sensitive indicator of oral effect was ataxia and hypoactivity at 500 mg/kg bw /d, the highest dose tested; this is typical of alcohol CNS depression. There was no clear evidene of other systemic toxicity. Slight effects on haematological parameters were noted in female rats at 500 mg/kg bw/d after 6 weeks, but not after 13 weeks of dosing. The NOAEL was 125 mg/kg bw/d. (US EPA 1986)

 

Inhalation

In an inhalative study at 50 and 100 ppm level, neurological effects were observed. Neurological effects were assessed by rotarod performance. The LOEL was 50 ppm (Korsak et al. 1994).

 

In another inhalative study incorporating structure surrogate, n-butyl acetate (NBAc), rats were exposed to 500, 1500 and 3000 ppm NBAc for 13 weeks. No systemc, organ-specific toxicit was observed. A NOAEL of 500 ppm was reported fro systemic effects in rats (David et al., 1998) The equivalent values for 1-butanol, corrected for molecular weight, was 223 ppm (equivalent to 676 mg/m3). (Adapted from UNEP 2004)

 

Dermal

No adequate dermal study was available for 1-butanol.

Justification for classification or non-classification

Based on the NOAEL (oral) and NOAEC (inhalation) 1 -butanol, there is no need for classification of the target substance in accordance with the criteria of CLP Regulation.