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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:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non standard method, limited report

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1977

Materials and methods

Type of study / information:
Asthma, rhinitis and urticaria can be provoked by the test substance and the occurrence of asthma induced by the test substance has been reported.
Endpoint addressed:
other: respiratory sensitisation after oral challenge
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Fourteen asthma patients with a history of exacerbations occurring after ingestion of orange drinks containing the test substance were given provocation tests by drinking solution of the test substance in water.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
No data given

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
The pre-treatment forced-expiratory volume in 1 sec (FEV1) was measured, using a vitalograph spirometer, at least three times at 5 min intervals or unit such time as values differed by not more than 10%. The test substance was dissolved in 250 mL water, equivalent to a large glassful, and sipped to completion over a period of 1 to 2 min. This method of ingestion is the normal way of taking an orange drink, and was preferred to administration by capsule, since, in addition to absorption by the gut, it allows for the possibility of absorption by the oral mucosa, which is a route that must be considered as possible methodological weakness arising from the impossibility of preparing placebo solutions.
The test substance was given in sequential doses of 20 mg, 80 mg and 300 mg in 250 mL water at 40 min intervals. The FEV1 was measured following ingestion of each dose of the test substance at 10 min intervals for 30 min. A decrease in FEV1 of 12% or more below the pretreatment level was recorded as a positive response.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: ingestion

TYPE OF EXPOSURE MEASUREMENT: The pre-treatment forced-expiratory volume in 1 sec (FEV1) was measured.

EXPOSURE LEVELS: The test substance was given in sequential doses of 20 mg, 80 mg and 300 mg at 40 min intervals.

EXPOSURE PERIOD: 30 min

POSTEXPOSURE PERIOD: 10 min

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:

Results and discussion

Results:
Four of the ten patients who reacted to provocation tests were sensitive to the test substance. Although the mean intervals between challenge and maximal depression of FEV1 was 20 min for the test substance, the onset of symptoms and earliest measurable changes usually occurred 10-20 min after the test substance.

Any other information on results incl. tables

The doses of the test substance at which falls in FEV1 occurred, the magnitued of fall in FEV1 and the interval between ingestion and the maximal fall in FEV1 is shown.

Additive

Case No.

Dose (mg)*

Max. FEV1 fall (%)

Times of max. FEV1 fall (min)

The test substance

1

120

25

30

2

120

23

20

4

120

33

20

7

20

26

10

mean

95

27

20

* The smallest dose of the test substance to which the patients responded.

Applicant's summary and conclusion

Conclusions:
Four of the ten patients who reacted to provocation tests were sensitive to the test substance, as was measured as a fall in FEV1. The test substance sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher.
Executive summary:

Fourteen asthma patients with a history of exacerbations occurring after ingestion of orange drinks were given provocation tests by drinking solution of the test substance in water at 20, 80 and 300 mg/250 mL.

Four of the ten patients who reacted to provocation tests were sensitive to the test substance, as was measured as a fall in FEV1. The test substance sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher.