Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only secondary literature available

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1999

Materials and methods

Principles of method if other than guideline:
other: subacute dermal 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:
no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
not specified
Duration of treatment / exposure:
Union Carbide corporation
Frequency of treatment:
Union Carbide corporation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.1, 0.25, 0.75 ml(kg bw/day
Basis:

No. of animals per sex per dose:
control and high dose group: 15 rats per sex; low and mid level groups: 10 rats per sex
Control animals:
yes, concurrent no treatment

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
0.1 other: ml/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Histopathology: Minimal to slight changes of the skin
Dose descriptor:
LOAEL
Effect level:
0.25 other: ml/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: mild to moderate skin irritation, histopathology: changes of the skin, of the kidneys (females only)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

At the 0.75 ml/kg/day:

Two of the fifteen females were found dead during the first week of the study; based on an assessment of morphologic abnormalities, a cause of death was not determined. The remaining females and all fifteen males survived. The survivors in this group had decreased weight gains and increased water consumption, compared to the control values. Histopathology of the kidneys of the females revealed focal mineral deposits. Severe, reversible skin irritation was seen at the dose site of all 0.75 ml/kg/day animals. Histopathology of the site of topical application of THBA revealed surface accumulation of inflammatory cells/cell debris and/or necrotic debris, squamous cell hyperplasia, hyperkeratosis, dermal necrosis and ulcers and acute to subacute-chronic inflammation, edema and hypertrophy/hyperplasia of sebaceous glands. No evidence of THBA induced toxicity was seen in the feed consumption, physical evaluations, neurobehavioral studies, hematology, clinical chemistry, urinalysis or organ weight values of these animals.

At 0.25 ml/kg/day:

All 0.25 ml/kg/day animals survived to the end of the treatment period, and were free of test material related clinical signs. However, mild to moderate skin irritation was seen at the dose site; histopathology of the dose site revealed changes similar to those seen in the 0.75 ml/kg/day group but were less severe. Histopathology of the kidneys (females only) also revealed changes which were similar to those seen in the 0.75 ml/kg/day group, but were less severe. No evidence of THBA induced toxicity was seen in the body weights, feed consumption, water consumption, neurobehavioral studies, hematology, clinical chemistry, urinalysis or organ weight values of the 0.25 ml/kg/day animals.

At 0.10 ml/kg/day:

There were no treatment-related deaths in the 0.10 ml/kg/day animals, and all animals were free of clinical signs and significant skin irritation. Histopathology of the dose site revealed changes similar to those seen in the 0.75 ml/kg/day group but were minimal to slight in severity. No evidence of THBA induced toxicity was seen in the body weights, feed consumption, water consumption, neurobehavioral studies, hematology, clinical chemistry, urinalysis or organ weight values of the 0.10 ml/kg/day animals. Except for the skin lesions discussed previously, there were no significant microscopic changes seen in these animals which could be attributed to administration of THBA.

Applicant's summary and conclusion