Hydrogen peroxide

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study results are considered as reliable with restrictions. A guideline is not available and the publication is well documented, but gives incomplete data on the subjective ratings and pulmonary function parameters for individual participants of the study so that a detailed examination of the study results is not possible.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2012

Materials and methods

Type of study / information:

Acute effects of exposure to vapors of hydrogen peroxide in humans

Test guideline

Qualifier:

no guideline available

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen peroxide

EC Number:

231-765-0

EC Name:

Hydrogen peroxide

Cas Number:

7722-84-1

Molecular formula:

H2O2

IUPAC Name:

hydrogen peroxide

Test material form:

other: vapor

Method

Ethical approval:

other: according to Helsinki declaration and approval by the Regional Ethical Review board, Stockholm

Details on study design:

The study examined the acute irritation and inflammatory effects of short-term inhalation exposure to hydrogen peroxide vapours. Eleven healthy human volunteers (six females, five males) aged 20 to 38 years were exposed in three separate sessions to clean air (control), 0.5 ppm (0.7 mg/m3) or 2.2 ppm (3.08 mg/m3) in a 20-m3 exposure chamber for durations of 2 hours per session. Potential effects caused by short-term inhalation exposure to hydrogen peroxide vapours were evaluated by means of subjective ratings of a list of effects and measurements of pulmonary function, nasal and eye parameters and inflammatory markers before, during, immediately after exposure and after a recovery period.

Details on exposure:

TYPE OF EXPOSURE:
Inhalation/Dermal (whole-body exposure in exposure chamber)
All subjects were exposed during resting conditions while seated in a 20 m3 exposure chamber with controlled climate (23.4 °C, 27% relative humidity, 18 to 20 air changes per hour).

TYPE OF EXPOSURE MEASUREMENT:
The air concentration of hydrogen peroxide in the exposure chamber was continuously monitored and logged in parallel on two electrochemical detectors (Sensor XS EC H2O2, PACIII, Dräger, Germany). The correctness of the factory-calibrated detectors was checked by adding known amounts of hydrogen peroxide to Tedlar bags filled with 9.6 L of clean air to obtain final concentrations of 0.5, 1 and 2 ppm. The response of both detectors was similar and proportional to the spiked concentrations. The recovery was 88% (95% confidence interval from 79 to 101%, n = 15) and 80% (95% confidence interval from 72 to 89%), respectively. The air concentrations measured with the two detectors were corrected for the detector response.

Examinations and symptom ratings:
The human participants were asked to fill in questionnaires and rate ten perceived symptoms in a Visual Analog Scale form. These symptoms were 1) discomfort in the eyes: burning, irritated or runny eyes, 2) discomfort in the nose: burning, irritated or runny nose, 3) discomfort in the throat or airways, 4) breathing difficulties, 5) solvent smell, 6) headache, 7) fatigue, 8) nausea, 9) dizziness and 10) feeling of intoxication. The ratings were done immediately before the experiments, during the exposure (at 3, 60 and 118 minutes) and after exposure (at 145, 330 and 1440 minutes from onset of exposure). Pulmonary function parameters (vital capacity, forced vital capacity, forced expiratory volume in one second, peak expiratory flow and forced expiratory flow at 25%, 50% and 75% of forced vital capacity) were measured prior to, directly after and 3.5 hours after exposure. The blocking index as a measure of nasal airway resistance was calculated as the difference between the mouth and the nasal peak expiratory flow values divided by the mouth peak expiratory flow. The breathing frequency was also measured. Nasal swelling was assessed by acoustic rhinometry before, immediately after and 3.5 hours after exposure. The volumes of the nasal cavity of each nostril were measured between 0 and 22 mm and between 23 and 54 mm from the opening of the nostrils. The minimum nasal cross-sectional areas between 0 and 22 mm and between 23 and 54 mm were also determined. Eye blinking was monitored throughout the exposure period by electromyography. Finally, inflammatory markers in blood were analysed in venous plasma or serum collected before, 3.5 and 22 hours after exposure. The analysed markers included interleukin-6, C-reactive protein (CRP), serum amyloid A, fibrinogen, factor VIII, von Willebrand-factor and Clara cell protein (CC16).

EXPOSURE LEVELS:
The nominal concentrations were 0, 0.5 and 2.2 ppm. The measured hydrogen peroxide concentrations in the air of the exposure chamber during the experiments were, on average, 0.48 (SD 0.05) and 2.2 (SD 0.19) ppm.

EXPOSURE PERIOD:
The participants were exposed for durations of 2 hours per session. Participants were exposed at three separate occasions. The exposure sessions were separated by at least one week.

EXPOSURE GROUP:
Persons exposed: six women and five men (20 to 38 years old, weight not reported)
Known Diseases: Healthy non-smokers without chronic diseases

The volunteers participating in the study were students recruited by advertisement at Karolinska Institutet. A medical examination including clinical blood chemistry tests and a pregnancy test for female participants. All participants were informed about the design of the study, the possible health hazards and their right to immediately and unconditionally interrupt exposure. Each participant signed a written consent after the presentation of oral and written information.

Results and discussion

Results:

Clinical Signs:
Subjective ratings: The median rating of smell, irritation and other symptoms during exposure to hydrogen peroxide were generally low. There was a large inter-individual variation in the rating of the symptoms and women tended to rate significantly higher in almost all ratings, compared to men at some time-points.

Results of examinations
Pulmonary function: The vital capacity was significantly affected in the experiment, but this effect was not related to exposure and the largest increase was seen for exposure to clean air at 3.5 hours after exposure. The blocking index – the difference between the mouth and the nasal peak expiratory flow values divided by the mouth peak expiratory flow – was significantly higher directly after exposure to 2.2 ppm hydrogen peroxide.
Nasal measurements: A significant difference in nasal volume between exposure conditions was seen, which was not dose-dependent.
Eye measurements: There was a slight, but not statistically significant increase in the blink frequency at 0.5 ppm and 2.2 ppm compared to control exposure.
Inflammatory markers: No significant exposure-related effects on the markers of inflammation and coagulation were detected.

Applicant's summary and conclusion

Conclusions:

The findings of the Swedish human volunteer study by Ernstgård et al (2012) give only weak evidence of local effects, possibly a swelling or mild irritation of the airways, during short-term inhalation exposure of humans to hydrogen peroxide vapour in the range of a few parts per million. The study setup with a single exposure to hydrogen peroxide over a period of 2 hours allows some conclusion on the potential local effects in the respiratory tract: There is no irritation at an exposure level of 0.5 ppm and there is no irritation or there are a few signs of very mild irritation at 2.2 ppm. Further, there seems to be large inter-individual variability in the occurrence of local effects.

The markers of inflammation and coagulation gave no indication of an inflammatory response after cease of exposure. This may indicate that local effects caused by acute inhalation exposure to hydrogen peroxide levels up to 2.2 ppm are mild and fully reversible within a short period of time of non-exposure. These findings agree with a previously seen NOEC for respiratory irritation of 5 mg/m3 after short-term inhalation exposure of 32 human volunteers to hydrogen peroxide vapours for 5 minutes up to 4 hours (Kondrashov 1977).

No conclusion on local effects in the respiratory tract caused by longer-term or repeated dose inhalation exposure can be drawn from the results of the Swedish study.