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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report date:
1965

Materials and methods

Type of study / information:
Human sensory irritation
Endpoint addressed:
eye irritation
respiratory irritation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Experiment was designed to establish the human sensory-irritation threshold of dihydroisophorone
GLP compliance:
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
Details on test material:
- Name of test material (as cited in study report): dihydroisophorone
- Origin: Esso Research and Engineering Company, 21 Dec 1964, used as received

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
- Criteria:
1. Detection of odor
2. Nose irritation
3. Eye irritation
4. Throat irritation (instead of skin irritation)
5. Mask removal
- Other information: The test substance did not vaporize immediately, but as there was no deposition on the walls of the aerosol chamber, complete vaporization was assumed. Nominal concentrations were reported.
Exposure assessment:
measured
Details on exposure:
PERSONS EXPOSED: 6
EXPOSURE
- Reason of exposure:  determination of human sensory irritation thresholds
- Type of exposure: gaseous via face mask
- Duration of exposure: 7 minutes per concentration
- Exposure concentrations / dose:   
first exposeur (week 2): 117; 212; 393; 549; 84 mg/m3   
confirmatory exposure (week 4): 69; 264 mg/m3

Results and discussion

Results:
Throat, eye and nasal irritation < 12 ppm (0.069 mg/L)

Any other information on results incl. tables

Positive observations (6 volunteers):

 

Conc.

 (mg/m3)

Nose

Eye

Throat

Odor

1.      Session

84

 

1/6

 

4/6

117

2/6

2/6

1/6

5/6

212

4/6

5/6

2/6

5/6

393

5/6

4/6

5/6

5/6

549

5/6

5/6

5/6

5/6

2.      Session

69

2/6

3/6

2/6

6/6

264

6/6

2/6

2/6

6/6


This results 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 signifant differerences were noted in subject sensory irritation response between the first and second exposure series.

Applicant's summary and conclusion

Conclusions:
In humans dihydroisophorone is irritating to eyes, nose and throat when exposed for 7 minutes at 0.069 mg/L.
Executive summary:

The irritating potential of dihydroisophorone was determined in an investigation with 6 volunteers. After exposure for 7 minutes to 0.084, 0.117, 0.212, 0.393, and 0.549 mg/L (first exposure), throat and nose irritation was reported at 0.117 mg/L and eye irritation at 0.084 mg/L. The second exposure after two weeks led to throat, eye and nose irritation at the lowest concentration tested (0.069 mg/L).

Dihydroisophorone is considered to be irritant to eyes and respiratory system. A LOAEL of 0.069 mg/L was concluded for repeated dose exposure.

100 % odor detection of dihydroisophorone was found at 0.069 mg/L at session 2.

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