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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary source: IUCLID 07/1997 Only insufficient documents about study available and documentation/performance of study insufficient.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979
Reference Type:
publication
Title:
No information
Author:
Ballantyne B et al
Year:
1986
Bibliographic source:
The Toxicologist 6, 59
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
no guideline followed
Guideline:
other:
Principles of method if other than guideline:
No information provided
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Butyraldehyde
- Molecular formula (if other than submission substance): Not documented
- Molecular weight (if other than submission substance): 72.1
- Smiles notation (if other than submission substance): Not documented
- InChl (if other than submission substance): Not documented
- Structural formula attached as image file (if other than submission substance): see Fig. Not documented
- Substance type: Organic
- Physical state: Liquid
- Analytical purity: 98.59 % by weight
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: Not documented
- Expiration date of the lot/batch: Not documented
- Radiochemical purity (if radiolabelling): Not documented
- Specific activity (if radiolabelling): Not documented
- Locations of the label (if radiolabelling): Not documented
- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions:Not documented
- Storage condition of test material: Not documented
- Other: Not documented

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No information provided

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: No information provided
Details on inhalation exposure:
No information provided
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information provided
Duration of treatment / exposure:
up to 13 weeks
Frequency of treatment:
6 h/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
5.44, 1.36, 0.34 mg/l (2000, 500, 125 ppm)
Basis:
no data
No. of animals per sex per dose:
25
Control animals:
yes, concurrent no treatment
Details on study design:
Post-exposure period: no data
Positive control:
No information provided

Examinations

Sacrifice and pathology:
Groups of 10 rats per sex per group were sacrificed at 6 and 13 weeks.
Other examinations:
.Animals were monitored for signs of toxicity and body weight gain during the exposure interval. Urinalysis, hematology, and blood chemistry tests were performed prior to initiation of exposure and again on 5 rats per sex per group after 6 and 13 weeks of exposure. Tissues from control and high dose (2000 ppm) animals were examined microscopically; tissues from lower-dose animals were examined if lesions were observed at the highest dose.
Statistics:
No information provided

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
effects observed, treatment-related
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
not specified
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Interim sacrifice was conducted after 6 and 13 weeks. Body weight did not show treatment-related changes. Haematological examinations revealed a significant increase in albumin in females treated with 0.34 mg/L after 63 - 64 days and in total protein in females treated with 0.34 and 5.44 mg/L after 29 days. Treatment-related histopathological changes were mainly found in the nasal cavity in all treated groups. The changes included metaplasia in the squamous epithelium of the nasal mucous membrane, rhinitis and starting atrophy of the goblet cells followed by hyperplasia. These changes were more pronounced in animals exposed 6 weeks to butyraldehyde than in those that inhaled butyraldehyde for 13 weeks.


Signs of eye and respiratory irritation (lacrimation, salivation, nasal discharge) were observed at all dose levels. There was only one death, which was not related to treatment. There were no significant differences in body weight gains between exposed and control animals. There were no differences in organ weights observed in exposed animals sacrificed at 6 and 13 weeks as compared to controls. Rats at all treatment levels had treatment-related changes in the nasal cavity, indicating an inflammatory response to chronic irritation. Changes consisted of squamous metaplasia of the mucosal epithelium, rhinitis, goblet cell atrophy, and goblet cell hyperplasia. Changes appeared to be more severe in rats sacrificed after 6 weeks of exposure than in those sacrificed at 13 weeks. No other treatment-related effects were noted.

Effect levels

Dose descriptor:
LOAEC
Effect level:
125 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No toxic effects observed at 125ppm

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the LOAEC was determined to be 125ppm.
Executive summary:

In a non verifiable repeated-dose inhalation study, groups of  male and female rats were exposed to butyraldehyde vapor by inhalation at concentrations of 0, 125, 500 and 2000 ppm ( 0.34, 1.36, and 5.44 mg/l) for 6 hr/day for 5 days/wk for 13 weeks. Rats in all exposure groups had treatment-related changes in the nasal cavity, including squamous metaplasia of the mucosal epithelium, rhinitis, goblet cell atrophy, and goblet cell hyperplasia. No other effects were observed. The LOAEC for rats in this study was 125 ppm (= 0.34 mg/L), based on local irritation in the nasal region (from SIAR draft March 2006).