Pregnant and breast-feeding healthcare workers appear to be well within safe exposure limits and can use alcohol-based hand rubs without risk to fetus or baby, a researcher reported recently in Portland, OR, at the annual meeting of the Association for Professionals in Infection Control and Epidemiology (APIC).

“The internal doses of ethanol associated with frequent use of hand sanitizers and scrubs are hundreds of times lower than the concentration that might be related to [reproductive] developmental effects,” said Andrew Maier, PhD, CIH, DABT, associate professor of environmental health at the University of Cincinnati. “That is good news. Based on this, there is no significant risk of developmental reproductive [effects] from repeated use of these types of materials. The exposure that one can get from using these products is way below the concentrations that cause these kinds of effects.”

The FDA requested information in 2015 on the safety of active ingredients in healthcare antiseptics, saying solutions and products are being used in the absence of data on long-term effects to healthcare workers. Alcohol-based healthcare antiseptics are not only ubiquitous and used frequently throughout the day in healthcare settings, they are essentially a standard of care, given their recommendation by the CDC. Though some have noted there is no established safety threshold for fetal alcohol syndrome, the FDA would have to find compelling evidence to limit the use of alcohol rubs in hospitals. An unintended consequence could be an increase in healthcare-associated infections that already kill tens of thousands of patients annually.

Studies undertaken by researchers and industry are expected to demonstrate adequate safety data to the FDA, which has recommended continuing to use the alcohol rubs while the review is in process.

The FDA requested that “maximal use” trials be conducted to ensure the safety of frequent use of alcohol-based hand rubs by healthcare workers.

“This is the new thinking from FDA and they are doing this with all drugs now,” said David Macinga, PhD, director of regulatory affairs and clinical science at GOJO Industries, Inc., in Akron, OH. “We used to see studies under typical use, and now FDA is saying we want to see safety studies done under what’s called ‘maximum’ use conditions. If you think about these alcohol hand rubs, they want to see studies done at the maximum number of uses that may be done in a single day by a single person.”

Breaking Down Data

A recently published study2 used a retrospective review of the literature and analysis of two other studies that utilized hand hygiene electronic compliance monitoring (ECM) systems. The researchers found the greatest use of alcohol rubs was recorded by an ECM system in a medical ICU.

“In 95% of nursing shifts, individual nurses used alcohol-based hand rubs 141 times or less per shift, and 15 times or less per hour,” the authors reported.

Maier reviewed that study and other data involving alcohol exposures in animals and its presence in common products in a review of the issue at APIC. Maier disclosed receipt of grant funding and research support from GOJO Industries, which manufactures hand cleaners and other healthcare products.

“We’re really focusing our assessments on developmental effects — reproductive developmental toxicity,” Maier said. “The key question is making sure the exposure level is well below the concentrations where the effect might be caused. That is the margin of safety assessment.”

Evaluating data that included some 250 published studies on the reproductive effects of alcohol consumption, Maier predictably found that the majority of those involved consumption of alcoholic drinks.

“They show that binge drinking or ingestion of high levels of alcohol do cause developmental effects,” he said. “That’s no surprise to most folks in occupational health, but the question is what happens at smaller, very low levels of exposure?”

That is a much harder question to answer, but Maier pointed out at the onset that the tracking systems in place by FDA and other bodies have not identified any link between alcohol hand rubs used in healthcare and reproductive effects in workers. Maier also looked at animal toxicology studies on alcohol and reproductive effects.

“Two big findings came out of our evaluation of the animal toxicology data,” he said. “One is that it is the peak drug concentration that is really the driver for these developmental effects. It’s not the average, low-dose exposure you might have — it is high-dose peaks that are driving these types of responses.”

The blood alcohol concentration (BAC) level where developmental effects begin to occur in the animal data is 150 mg per 100 mls of blood, he said.

“Above that concentration in the blood, you start to see effects in animal toxicology studies,” Maier said. “Below that concentration, you don’t see effects. We are starting to see this boundary for the onset of effects. So, obviously, we want to make sure that the [human] exposures are maintained well below those types of concentrations.”

Scenarios Tested

A variety of different scenarios were evaluated that reflected topical application of the alcohol hand rubs under conditions representative of average use, high use, and maximal use for two different products. Maier looked at the BAC that would be predicted for the various scenarios and compared that to the threshold for safety in the animal toxicity studies.

“For example, for average use, basically the amount of exposure is 380 [times] lower than the concentration that would potentially cause adverse effects,” he said. “We have a margin of safety there of around 380-fold, which is a pretty large margin.”

High use resulted in a BAC of 0.75, 200-fold less than the threshold for reproductive effects. Maximum use estimates of a BAC of 0.94 still fell within a wide margin of safety, 160 times less than the threshold of concern. Overall, the various scenarios of hand hygiene with alcohol rubs was 160 to 680 times lower than the threshold for developmental effects, he said.

Maier then contrasted those levels with ethanol alcohol in various fruits, noting that the average use of hand rubs over a healthcare shift resulted in an alcohol exposure equivalent to eating a ripe banana. In addition, the FDA defines drinks with no more than 0.5% of alcohol as nonalcoholic beverages, Maier said. The maximum use of alcohol rubs resulting in a BAC of 0.94 compares to one nonalcoholic beverage with a BAC of 1.20.

“The amount of ethanol blood concentration for hand sanitizers is pretty much similar to the low-dose exposures you would get from fruits,” he said. “In both cases, the margin between those BACs and the amount of concentration that might be associated with onset of developmental effects is quite large. These can be considered safe by traditional FDA standards. Ethanol sanitizers are safe for their intended use as [hand] hygiene products.”

REFERENCES

  1. Food and Drug Administration. Safety and Effectiveness of Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record. Fed Reg May 1, 2015: http://1.usa.gov/1SDshKy.
  2. Boyce JM, Polgreen PM, Monsalve M, et al. Frequency of Use of Alcohol-Based Hand Rubs by Nurses: A Systematic Review. Infect Control Hosp Epidemiol 2017;38:189–195.