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Diss Factsheets

Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTIS study report.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Human Sensory Irritation Thresholds Five Ketones Final Report
Author:
National Technical Information Service
Year:
1965
Bibliographic source:
National Technical Information Service, OTS0206267, April 27, 1965
Reference Type:
secondary source
Title:
Acute Inhalation (LC50) & Human Sensory Irritation Studies On Cyclopentanone, Isophorone, Dihydroisophorone, Cyclohexanone, and Methyl Isobutyl Ketone
Author:
National Technical Information Service
Year:
1965
Bibliographic source:
National Technical Information Service, OTS0572861, November 8, 1965,

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Sensory irritation threshold in humans was determined for the test substance 3,3,5-trimethylcyclohexanone by exposing them to human volunteers at gradually increasing concentration levels.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3,5-trimethylcyclohexan-1-one
EC Number:
212-855-9
EC Name:
3,3,5-trimethylcyclohexan-1-one
Cas Number:
873-94-9
Molecular formula:
C9H16O
IUPAC Name:
3,3,5-trimethylcyclohexan-1-one
Test material form:
liquid
Details on test material:
- Name of test material :3,3,5-trimethylcyclohexan-1-one
- IUPAC name: 3,3,5-Trimethylcyclohexanone
- Molecular formula :C9H16O
- Molecular weight :140.224
- Smiles notation :C1(C[C@@H](CC(C1)=O)C)(C)C
- InChl :1S/C9H16O/c1-7-4-8(10)6-9(2,3)5-7/h7H,4-6H2,1-3H3
- Substance type: Organic
- Physical state: liquid
Specific details on test material used for the study:
- Name of test material :3,3,5-trimethylcyclohexan-1-one
- Molecular formula :C9H16O
- Molecular weight :140.224
- Smiles notation :C1(C[C@@H](CC(C1)=O)C)(C)C
- InChl :1S/C9H16O/c1-7-4-8(10)6-9(2,3)5-7/h7H,4-6H2,1-3H3
- Substance type: Organic
- Physical state: liquid

Test animals

Species:
other: Human
Strain:
other: Not applicable
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
No data
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 min
Concentrations:
1st exposure: 15, 20, 37, 69, and 96 ppm
2nd exposure: 12 ppm
No. of animals per sex per dose:
6 human volunteers
Control animals:
not specified
Details on study design:
Week No.1 consisted of exposure to several concentrations of a documented ketone similar to those being tested. Week No. 2 consisted of exposure (first exposure series) of test group to the test compound at increasing concentrations until sensory irritation thresholds were
established. Week No.4 consisted of confirmatory exposures (second exposure series) of each group of six subjects to its respective test compound, first at the concentration established as the sensory irritation threshold and then at additional concentrations, if deemed necessary. A second series of test runs two weeks later was used for Confirmatory purposes. All phases of the study were under the supervision of a physician.
Statistics:
Complete volatilization of test substance was not assured but there was no deposition of the material coated in the aerosol chamber or face masks of the subjects. The threshold value value calculated from a plot of the number of responses versus concentration. In deriving these curves. the eye. nose or throat irritation responses were used. The odour response was not included. The maximum number of responses possible at any concentration was 18 (six subjects x three modalities). The threshold line was arbitrarily selected at six responses. 'The concentration at each ketOne corresponding to the point Where the response curve crosses the threshold line is reported as the sensory irritation threshold. Odor was detectable in all subjects at the lowest concentration studied. This data therefore represent something above the odor threshold.

Results and discussion

Effect levels
Key result
Sex:
not specified
Dose descriptor:
other: Sensory irritation threshold
Effect level:
0.12 mg/L air
Based on:
test mat.
Exp. duration:
7 min
Mortality:
No
Clinical signs:
other: Throat, eye, and nasal irritation.
Body weight:
No data
Gross pathology:
No data
Other findings:
5/6 subjects responded at the lowest level in the first test series and 6/6 at a slightly lower level in the second series.

Any other information on results incl. tables

Human Sensory: Irritation

Odor

mg/l

ppm

mg/l

ppm

0.12

20

0.07

12

*Approximate equivalent as ppm (v/v) assuming complete vaporization

Throat, eye, and nasal irritation occurred at the lowest concentration employed, 0.069 mg/liter of' air (approximately 12 ppm expressed as a vapor concentration). At concentrations of 0.212 mg/liter of' air (approximately 37 ppm expressed as a vapor concentration) and 0.548 mg/liter of' air (approximately 95 ppm expressed as a vapor concentration) during the initial session, one subject removed his face mask. This subject reported skin irritation at a concentration of 0.548 mg/liter of air. During the first session, after four exposures at increasing concentrations (0.117 mg/liter of air, 0.212 mg/liter of air, 0.393 mg/liter of air, and 0.548 mg/liter of air), the subjects were exposed to a concentration of 0.084 mg/liter of air (approximately 15 ppm expressed as a vapor concentration). Four out of the six subjects were able to detect compound odour at this level, but only one case of sensory irritation (eye) was recorded. This contrasts sharply with the results obtained two weeks later when these same six subjects were exposed to an even lower concentration, 0.069 mg/liter of air (approximately 12 ppm expressed as a vapor concentration). During this exposure, all six subjects detected odor (five out of six within five seconds), two subjects experienced eye irritation, one subject experienced throat irritation, and one subject experienced nasal irritation. This suggests that sensory adaptation occurred during the first exposure series at high concentrations and may be suggestive of local anesthesia of receptors, which is a known phenomenon caused by exposure to ketone vapors. Aside from this, no significant differences were noted in subject sensory irritation response between the first and second exposure series.

Applicant's summary and conclusion

Interpretation of results:
other: STOT SE-3
Conclusions:
Based on the findings of the study, the sensory irritation threshold of test substance 3,3,5-trimethylcyclohexanone after exposure by inhalation in human volunteers was determined to be 0.12 mg/l.
Executive summary:

Sensory irritation threshold in humans was determined for the test substance3,3,5-trimethylcyclohexanone by exposing (air)at gradually increasing concentration levels tosix adult volunteer subjects. Air containing the chosen concentration of the test substance was diverted from a manifold through a full-face mask. Each subject was provided with a signaling device to indicate the presence (or disappearance) of odor and eye, nose or throat irritation. Exposures to each concentration were for seven minutes and four to nine concentrations of a given substance were used at each session. A second series of test runs two weeks later was used for confirmatory purposes. In these sessions two or three concentration levels of each substance were used. During the initial series of exposures to test substance, four of the six subjects were able to detect odor; but only one subject experienced sensory irritation (eye) at 15 ppm after four previous exposures to concentrations of 20, 37, 69, and 96 ppm, in that order. Yet, during the challenge series, the same six Subjects were exposed to a concentration of 12 ppm, and all detected odor (five out of six within five seconds); eye, nasal, and throat irritation were also recorded. The sensory irritation threshold of test substance 3,3,5-trimethylcyclohexanone after exposure by inhalation in human volunteers was determined to be 0.12 mg/l.

 

Thus, based on the above study, it can be concluded that the test substance 3,3,5-trimethylcyclohexanone causes sensory irritation in human through inhalation and hence can be classified under "Category 3" of Specific target organ toxicity-single exposure (STOT SE-3) as per CLP regulation.