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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only 8 volunteers studied. Because of the limited number of subjects, it was not possible to evaluate the relevance of the tendency towards increased airway diameters.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Uptake, distribution and elimination of α-pinene in man after exposure by inhalation
Author:
Falk AA, Hagberg MT, Löf AE, Wigaeus-Hjelm EM and Zhiping W
Year:
1990
Bibliographic source:
Scand J Work Environ Health 16(5):372-8

Materials and methods

Type of study / information:
Subjective perception of irritation of eyes, nose and throat and effects on the central nervous system and pulmonary functions in human volunteers were studied during exposure to (+)-alpha-pinene by inhalation (2 h, 50 W).
Endpoint addressed:
other: Subjective perception of irritation of eyes, nose and throat and effects on the central nervous system and pulmonary functions
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The toxicokinetics of (+) and (-)-alpha-pinene was studied in human volunteers exposed by inhalation (2 h, 50 W) in an exposure chamber on four occasions. Subjective perception of irritation of eyes, nose and throat and effects on the central nervous system and pulmonary functions were also studied.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
Name of test material (as cited in study report): alpha-pinene
Source: Aldrich, Federal Republic of Germany
Purity: 98 %

Method

Ethical approval:
confirmed, but no further information available
Remarks:
study was approved by the Regional Ethical Committee at the Karolinska Institute, Solna, Sweden.
Details on study design:
Subjects: Eight healthy men, with a mean (range) age of 31 (24-39) years and weight of 80 (71-96) kg participated in the study. The subjects were not occupationally exposed to solvents and were instructed to refrain from drinking alcoholic beverages for at least 2 days before each exposure. All the participants were given a general medical examination preceding the experiment and were judged to be healthy.

Experimental design: The subjects were exposed to α-pinene for 2 h during light physical exercise (50 W on a bicycle ergometer) in an exposure chamber on four occasions. Two subjects were exposed on each occasion. The concentrations were 10, 225 and 450 mg/m3 for (+)-α-pinene and 450 mg/m3 for (-)-α-pinene. The sequence of the exposure concentrations was based on a Latin square 4 x 4 design. The subjects were informed of the experimental design but were not told the exposure sequence. The volume of the chamber was 12 m3. The air was changed 10 times/h. To prevent the solvent from leaking from the chamber into the surroundings, the inlet flow was 115 m3/h and the outlet flow was 135 m3/h. The solvent was injected into the inflowing air stream by means of a high-performance liquid chromatographic pump (Gilson 302).
Exposure assessment:
measured

Results and discussion

Results:
- Five subjects experienced irritation of their eyes, nose, and throat during the high exposures.
- No statistically significant acute changes in lung function parameters and the tendency of change was towards increased bronchial diameter rather than bronchoconstriction.

Any other information on results incl. tables

Table 7.10.5/1: Preexposure lung function values and the percentage of change 30 min after a 2-h inhalation exposure (50 W) to (+)-α-pinene at concentrations of 10 and 450 mg/m3

 

FEV 1,0 (L)

VC (L)

RV (L)

PEF (L)

MEF50 (L/s-1)

sGaw (L/kPa/s)

Raw (kPaxs/L)

Preexposure values

4.8 ± 0.6

6.6 ± 0.7

2.9 ± 1.1

12.7 ± 2.8

5.2 ± 1.1

2.1 ± 1.0

0.14 ± 0.05

Percentage of change after 30 min

 

 

 

 

 

 

 

10 mg/m3

0.5 ± 0.1

-0.1 ± 13

-5.8 ± 24

0.4 ± 13

1.7 ± 5.6

16 ± 55

-25 ± 23

450 mg/m3

3.4 ± 4.7

0.8 ± 6.4

1.5 ± 26

3.2 ± 12

5.5 ± 7.6

5.4 ± 49

-25 ± 26

FEV1.0 = forced expiratory volume in 1 s, VC = vital capacity , RV = residual volume, PEF = peak expiratory flow, MEF50 = mean expiratory flow at 50 % of the VC, sGaw = conductance, Raw = resistance

Applicant's summary and conclusion

Conclusions:
There was a statistically significant exposure-response relationship among five subjects who experienced a subjective perception of irritation of eyes, noise and throat, especially at high exposures. Short-time exposure to (+)-alpha-pinene did not give rise to acute changes in lung function 30 min after the exposure.
Executive summary:

In this study, eight male volunteers were exposed to 10, 225 and 450 mg/m3 of (+)-alpha-pinene and 450 mg/m3 of (-)-alpha-pinene

by inhalation (2h with physical exercise workload of 50 W) in a 12 m3 exposure chamber on four occasions. The sequence of exposure concentrations was not the same amongst the volunteers. The subjects were not occupationally exposed to solvents and instructed to refrain from drinking alcoholic beverages for at least 2 days before each exposure. Their general health status was checked prior to the experiment. Continuous monitoring of alpha-pinene concentration in the exposure chamber air during each exposure; alpha-pinene concentrations at selected intervals in exhaled air, in blood and in urine, during and after each exposure were performed. Subjective perception of irritation of eyes, nose and throat and effects on the central nervous system, pulmonary functions before, during and after each exposure were studied.

 

There was a statistically significant exposure-response relationship among five subjects who experienced a subjective perception of irritation of eyes, noise and throat, especially at high exposures. Short-time exposure to (+)-alpha-pinene did not give rise to acute changes in lung function 30 min after the exposure.