Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

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.
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:
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

Referenceopen allclose all

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.
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:
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
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:
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.