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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable well documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
other: microfiche
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Principles of method if other than guideline:
other: subacute inhalation study (9 day vapour inhalation toxicity study)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Cyclohex-3-ene-1-carbaldehyde
EC Number:
202-858-3
EC Name:
Cyclohex-3-ene-1-carbaldehyde
Cas Number:
100-50-5
Molecular formula:
C7H10O
IUPAC Name:
cyclohex-3-ene-1-carbaldehyde
Details on test material:
tetrahydrobenzaldehyde (THBA), purity: 99.6%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Duration of treatment / exposure:
6 hours/day for 5 consecutive days, after 2 days without exposure, the animals were exposed for additional 4 consecutive days
Frequency of treatment:
6 hours/day for 5 consecutive days, after 2 days without exposure, the animals were exposed for additional 4 consecutive days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 75, 250, 500 ppm
Basis:

No. of animals per sex per dose:
10 animals per sex and dose, in addition: control and 500 ppmgroups: 5 animals per sex for the 4-week recovery period
Control animals:
yes, sham-exposed

Results and discussion

Effect levels

Dose descriptor:
LOAEC
Effect level:
75 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: decrease in body weight gain, minimal to mild epithelial hyperplasia/dysplasia of tissues from the nasal mucosa

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Mean THBA concentrations were 77.4 (+/- 6.0), 244 (+/- 18.8), and 479 (+/- 38.2) ppm. There were no mortalities prior to the scheduled sacrifices.

Urine staining and periocular swelling were observed in animals from the 500 ppm exposure group during the exposure regime and during the recovery period. On study day 12, body weight was decreased for the male and female animals from the 500 ppm exposure group. Body weight gain was decreased for male and female animals from all exposure groups during the first week of the exposure regime. During the second week of the exposure regime, the body weight gain was decreased for the males from 250 and 500 ppm exposure groups. Also, during the second week of exposure regime, female animals had decreased body weight gain, except those from the 250 ppm exposure group on Day 8. During the recovery period, the female animals from the 500 ppm exposure group had decreased body weight gain until the fourth week of recovery. For the first week of the exposure regimen, male animals from the 250 and 500 ppm exposure groups had decreased food consumption values. Also, for the first week, the female animals from the 75, 250, and 500 ppm exposure groups had decreased food consumption values. For the second week, female animals from the 500 ppm exposure group still had decreased food consumption values.

Clinical pathologic findings at the end of the exposure regime included decreased platelet counts for male animals from the 250 and 500 ppm exposure groups and for female animals from the 500 ppm exposure group. At the end of the recovery period, the platelet counts were not decreased. After the exposure regime, total urine volumes were decreased for the male and female animals from the 250 and 500 ppm exposure groups. Male animals from the 250 and 500 ppm exposure groups and female animals from the 500 ppm exposure group had increased urine osmolality. Male and female animals from the 500 ppm exposure group had decreased urine pH and increased frequency of higher ketone concentrations. At the recovery period sacrifice, these values were not different from control values.

At the end of the exposure regimen, urine staining of the urogenital region and swelling of the periocular tissues were observed for both sexes of animals from the 500 ppm exposure group. These findings were resolved upon recovery. In the male and female animals from the 250 and 500 ppm exposure groups, mild to moderate injury to the tissues of the nasal mucosa was observed, as evidenced by rhinitis, epithelial necrosis, and a varity of degenerative and/or regenerative lesions of the epithelium including vacuolization, hyperplasia, dysplasia, and squamous metaplasia. Minimal or mild epithelial hyperplasia/dysplasia was found in some animals from the 75 ppm group, which was probably related to THBA exposure. Male animals were slightly more affected than female animals. At the recovery period sacrifice, most of the lesions were resolved.

Applicant's summary and conclusion