Registration Dossier

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not a guideline study and no indication that it was performed according to GLP/GCP, but data appears well documented and scientifically acceptable.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Quantity of ethanol absorption after excessive hand disinfection using three commercially available hand rubs is minimal and below toxic levels for humans
Author:
Kramer A, Below H, Bieber N, Kampf G, Toma CD, Huebner NO, Assadian O
Year:
2007
Bibliographic source:
BMC Infect Dis 7: 117.doi: 10.1186/1471-2334-7-117

Materials and methods

Type of study / information:
Volunteer study
Endpoint addressed:
dermal absorption
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Twelve volunteers repeatedly applied three commercial hand rubs containing different concentrations of ethanol, using two exposure regimes. Blood levels of ethanol and acetaldehyde were determined immediately prior to, and up to 1.5 hrs, after application.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): Ethanol in three commercial hand rubs: Sterillium Virugard 95% w/w ethanol (hand rub A); Sterillium gel 85% w/w ethanol (hand rub B); Manorapid Synergy 55% w/w ethanol (in combination with 10% propan-1-ol) (hand rub C)
- Stability under test conditions: no data
- Storage condition of test material: no data
-Other: Both Sterillium products (hand rubs A & B) were obtained from Bode Chemie GmbH, Hamburg, Germany, whereas Manorapid Synergy (hand rub C) was obtained from Antiseptica GmbH, Pulheim, Germany.

Method

Details on study design:
Two exposure regimes were used, involving twelve volunteers (six males and six females). In the first, mimicking hygienic hand disinfection, 4 mL of each of the three hand rubs were applied and rubbed in for 30 seconds using a European standard procedure (EN 1500:1997), with a one minute waiting time (outside of the test room) between applications. A total of 20 hygienic hand disinfections were performed over a period of 30 minutes, resulting in a total exposure time with each hand rub of 10 minutes. This scenario was repeated on the next two consecutive days with the other two ethanol-based hand rubs. Volunteers were exposed to a total of 80 mL of each hand rub, corresponding to an ethanol exposure of 60.0, 56.2, and 39.6 g for hand rubs A, B, and C, respectively.

In the second exposure regime, mimicking surgical hand disinfection (started using the same volunteers 7 days after the hygienic hand disinfection experiments), 20 mL of each hand rub was applied and rubbed in for 3 minutes using a European standard procedure (EN 12791: 2004), with a five minute waiting time (outside of the test room) between applications. A total of ten surgical hand disinfections were performed over a period of 80 minutes, resulting in a total exposure time with each hand rub of 30 minutes. This scenario was repeated on the next two consecutive days with the other two ethanol-based hand rubs. Volunteers were exposed to a total of 200 mL of each had rub, corresponding to an ethanol exposure of 149.9, 140.0, and 99.0 g for hand rubs A, B, and C, respectively.

Blood was sampled prior to, and 2.5, 5, 10, 20, 30, 60, and 90 minutes after the last hygienic hand disinfection, and prior to, and 5, 10, 20, 30, 60, 90, and (for hand rub C only) 120 minutes after the last surgical hand disinfection.
Exposure assessment:
estimated

Results and discussion

Results:
For the hygienic hand disinfection, after the last application the median absorbed ethanol in the blood increased gradually and peaked after 30 minutes at 20.95 (95% CI 20.46-21.34), 11.45 (11.17-11.73), and 6.90 (6.76-7.04) mg/L with hand rubs A, B, and C, respectively. The amount of absorbed ethanol was 1365, 630, and 358 mg, therefore the proportion of absorbed ethanol was 2.3, 1.1, and 0.9% with hand rubs A, B, and C, respectively.

For the surgical hand disinfection, after the last application the median absorbed ethanol in the blood peaked after 30 minutes at 17.50 (95% CI 16.49-18.51) and 30.10 (28.09-32.11) mg/L with hand rubs A and B, respectively, and peaked after 20 minutes at 8.80 (7.34-10.26) mg/L with hand rub C. The amount of absorbed ethanol was 1067, 1542, and 477 mg, therefore the proportion of absorbed ethanol was 0.7, 1.1, and 0.5% with hand rubs A, B, and C, respectively.

The highest median acetaldehyde concentrations was 0.57 mg/L (hand rub C) 30 minutes after the last hygienic hand disinfection, and 3.99 mg/L (hand rub A) 20 minutes after the last surgical hand disinfection. After between 30 and 60 minutes, levels of acetaldehyde in the blood decreased gradually.

Applicant's summary and conclusion

Conclusions:
The absorption of ethanol was measured in the blood of twelve volunteers following repeated application of three hand rubs (containing ethanol at 95, 85, and 55%), using two exposure regimes. The median of absorbed ethanol in the blood ranged from 358 to1365 mg (corresponding to a proportion of absorbed ethanol of between 0.9 to 2.3%) after the hygienic hand disinfection regime, and ranged from 477 to 1542 mg (corresponding to a proportion of absorbed ethanol of 0.5 to 1.1%) following the surgical hand disinfection regime. It was concluded that the overall dermal and pulmonary absorption of ethanol following the two exposure regimes was below toxic levels in humans.
Executive summary:

The absorption of ethanol was measured in the blood of twelve volunteers (six male and six female) following repeated application of three hand rubs (described here as hand rubs A, B, and C) containing different concentrations of ethanol (95, 85, and 55%, respectively). Two exposure regimes (mimicking hygienic and surgical hand disinfection) were evaluated.

A total of 20 hygienic hand disinfections were performed over a period of 30 minutes, resulting in a total exposure time with each hand rub of 10 minutes. Volunteers were exposed to a total of 80 mL of each hand rub, corresponding to an ethanol exposure of 60.0, 56.2, and 39.6 g for hand rubs A, B, and C, respectively. Blood was sampled prior to, and 2.5, 5, 10, 20, 30, 60, and 90 minutes after the last hygienic disinfection. After the last application the median absorbed ethanol in the blood increased gradually and peaked after 30 minutes at 20.95, 11.45, and 6.90 mg/L with hand rubs A, B, and C, respectively. The amount of absorbed ethanol was measured as 1365, 630, and 358 mg, therefore the proportion of absorbed ethanol was calculated at 2.3, 1.1, and 0.9% with hand rubs A, B, and C, respectively.

A total of ten surgical hand disinfections were performed over a period of 80 minutes, resulting in a total exposure time with each hand rub of 30 minutes. Volunteers were exposed to a total of 200 mL of each hand rub, corresponding to an ethanol exposure of 149.9, 140.0, and 99.0 g for hand rubs A, B, and C, respectively. Blood was sampled prior to, and 5, 10, 20, 30, 60, 90 and (for hand rub C only) 120 minutes after the last surgical disinfection. After the last application the median absorbed ethanol in the blood peaked after 30 minutes at 17.50 and 30.10 mg/L with hand rubs A and B, respectively, and peaked at 20 minutes at 8.80 mg/L with hand rub C. The amount of absorbed ethanol was measured as 1067, 1542, and 477 mg, therefore the proportion of absorbed ethanol was calculated at 0.7, 1.1, and 0.5% with hand rubs A, B, and C, respectively.

It was concluded that the overall dermal and pulmonary absorption following the two exposure regimes was below toxic levels in humans.