Butyraldehyde

Repeated dose toxicity: inhalation

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Reference 2

Reference Type:

publication

Title:

No information

Author:

Ballantyne B et al

Year:

1986

Bibliographic source:

The Toxicologist 6, 59

Reference 3

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

Test material information

Constituent 1

Reference substance name:

Butyraldehyde

EC Number:

204-646-6

EC Name:

Butyraldehyde

Cas Number:

123-72-8

Molecular formula:

C4H8O

IUPAC Name:

butanal

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 or test system 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).