Introduction

Biocidal products are commonly used in residential, commercial, and public facilities to prevent the spread of infectious diseases1. Recently, the importance of disinfection has increased owing to the spread of infectious diseases, such as coronavirus disease 2019 (COVID-19)2. Thus, strengthening the disinfection of multi-use facilities, such as offices, medical facilities, public transportation, and restaurants, is essential to prevent the spread of COVID-193. However, concerns have been raised regarding the damage induced by misuse and overexposure to biocidal products, as their indiscriminate use has increased since the COVID-19 crisis4. The use of biocides is strictly regulated worldwide, and efforts are being made to ensure their efficient management5. The Federal Insecticide Fungicide Rodenticide Act (FIFRA) in the United States was enacted in 1972 while the Biocide Product Regulation (BPR) was enacted in the European Union (EU) in 1998 to establish and regulate laws for the management of biocidal products6,7. The Korean Household Chemical Products and Biocides Safety Act (K-BPR) was enacted in 2019 to ensure comprehensive safety management of biocides8.

Most previous studies have explored current practices and working environments related to disinfection and biocidal product usage patterns, specifically focusing on their application in both residential and multiuse facilities. The use of disinfectants and biocides has increased owing to the spread of COVID-19, and a risk of secondary exposure for the general population could arise as the emitted substances remain and are released into indoor spaces9. Sodium hypochlorite exhibits an acute health effect and reacts with ammonia both indoors and outdoors to produce chloramine (NH2Cl) gas, which can cause respiratory problems10. In a study comprising children indirectly exposed to biocides, the use of bleach as a disinfectant at home and school increased the frequency of respiratory symptoms and other associated infections11. In addition, a survey of non-occupationally exposed adults and elderly people revealed a dose–response relationship, indicating that asthma symptoms were more likely to occur when irritating disinfectants, such as bleach and ammonia, were used on a weekly basis12.

Disinfectants are essential for preventing the spread of COVID-19. However, health risks might arise when the general population enters or remains in a recently disinfected area. To address this concern, this study evaluates the exposure and toxicity of biocidal products used by disinfection workers and determines the safe re-entry time for the general population. The hazard quotient (HQ) calculations and risk assessment models provide critical insights into the temporal dynamics of exposure levels. These findings could help establish enhanced safety guidelines and mitigate potential health risks from residual biocides in indoor environments.

Methods

Interview survey

Interview surveys were conducted using a questionnaire and by recruiting disinfection companies in the metropolises of Seoul, Busan, Daejeon, Daegu, and Gwangju, South Korea, from April to September 2021. A total of 300 disinfection workers participated in interview surveys conducted over a period of 10 days within 2 weeks, while considering the frequency of disinfection at each location. In addition to survey responses, direct field observations were conducted to improve the accuracy of exposure assessment. The researcher accompanied the disinfection workers during their tasks to evaluate key exposure factors, including the amount of disinfectant used, exposure duration, and biocidal active substances. Based on the survey responses and field observations, a total of 4762 exposure cases were identified and categorized according to the type of biocidal products used and the site of application. The volume of the room was measured using a laser distance meter (SMART-300, Korea). The total amount of disinfectant sprayed at the site was determined using the difference in weight before and after. To ensure data reliability, a cross-validation process was applied by comparing self-reported data with direct measurements from field observations. If inconsistencies were detected, additional interviews with disinfection workers were conducted to verify the accuracy of reported exposure cases. The disinfectants and pesticide-active substances used for disinfection were selected as targets, and the weight fraction and dilution factor of each product were investigated, as shown in Table 1. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects and their legal guardian. This study was approved by the Institutional Review Board of Daegu Catholic University (IRB No. CUIRB-2022-056).

Table 1 Weight fractions and dilution factors of the active substances in biocidal products.
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Toxicity values for the active substances in biocidal products

Inhalation and absorption through the skin were selected as the exposure routes depending on the purpose and type of product used. As shown in Table 2, the toxicity of the active substances in the biocidal product was assessed based on official and reliable experimental reports as well as studies13,14,15,16,17,18,19,20,21,22. To determine the dose level at which adverse effects can occur, point of departure (POD) values, such as the no observed adverse effect level (NOAEL) and no observed adverse effect concentration (NOAEC), were employed. The toxicity reference concentration (RfC) and reference dose (RfD) for the general population were calculated by applying the ECHA’s assessment factor (AF) based on reliable toxicity values23.

Table 2 Weight fractions and dilution factors of the active substances in biocidal products.
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Assessing exposure and health risk

Secondary exposure is assumed to occur when the general population remains in or enters the site after disinfection24. Secondary exposure scenarios include inhalation due to the volatilization of disinfectants and pesticides that remain on surfaces after disinfection and dermal exposure from contact with active substances that remain on surfaces. (Eq. 1) and (Eq. 2) were employed for the inhalation and dermal exposure algorithms, with reference to the RIVM report24. The fraction released into the air (F) was obtained using the inhalation algorithm of the European Center for Ecotoxicology and Chemical Toxicology (ECETOC), which assigns a value between 0.001 and 1 based on the vapor pressure of the substance25. Air changes per hour (ACH) were applied using the default value of 0.6 h−1 for all sites based on the exposure factors provided by the Ministry of Environment (MoE) of Korea26. By applying the Korean general exposure factors, the secondary exposure time and emission duration by site were 0.51 h for bars, 1.62 h for transportation, 2.45 h for other sites, 4.28 h for work and school, and 14.90 h for homes27. The surface area of the exposed skin, including the arms, hands, and calves, was assumed to be 6888.74 cm2, assuming that short sleeves and shorts were worn during the summer27.

$$C_{a} = \frac{{A_{o} \times W_{f} /t_{r} \times F}}{q \times V} \times 1 - e^{ - qt} \times e^{{ - q\left( {t - t_{r} } \right)}}$$
(1)

where Ca is the substance concentration in the indoor air (mg/m3), Ao is the product amount (mg), Wf is the weight fraction of the substance in the product, tr is the emission duration (h), F is the fraction released into the air, q is the room ventilation rate (h-1), V is the room volume (m3), and t is the exposure time (h).

$${L}_{d}={A}_{c}\times {W}_{f}\times {A}_{s}$$
(2)
$${A}_{c}=\frac{{A}_{o}}{({S}_{max}\times {10}^{4})}$$

where Ld is the dermal load (mg), Ac is the dislodgeable amount (mg/cm2), Wf is the weight fraction of the substance in the product, As is the surface area of the exposed skin (cm2), Ao is the amount of product (mg), and Smax is the room-floor area (m2).

The assigned protection factor (APF) was applied to calculate the inhalation exposure for the general population. The exposure concentration (Cexp) was calculated using (Eq. 3), which accounts for the APF of 10 resulting from mask usage, as all members of the general population were wearing half-masks as a precaution against COVID-1928. The dermal load (Ld) was calculated by considering the absorption fraction and body weight of the general population in the dermal dose (Dder) in the exposure algorithm, as shown in (Eq. 4)29.

$${C}_{exp}={C}_{a}\times n\times \frac{{t}_{n}}{24}\times \frac{1}{APF}$$
(3)

where Cexp is the exposure concentration (mg/m3), Ca is the concentration of the substance in the indoor air (mg/m3), n is the frequency of use of the biocidal products, tn is the exposure duration per use (h/use), and APF is the assigned protection factor.

$${D}_{der}={L}_{d}\times abs\times N\times \frac{1}{BW}$$
(4)

where Dder is the dermal dose (mg/kg/day), Ld is the dermal load (mg), abs is the absorption fraction (fraction), N is the frequency of biocidal product use (use/day), and BW is the body weight (kg).

The hazard quotient (HQ) of a non-carcinogenic active substance was derived by calculating Cexp and Dder using the exposure algorithm and dividing them by RfC and RfD, respectively, as shown in (Eq. 5)30. The hazard index (HI) was evaluated by adding the inhalation hazard quotient (HQinh) and dermal hazard quotient (HQder), as shown in (Eq. 6). An HI of 1 or greater indicates a potential health risk31.

$${HQ}_{inh}=\frac{{C}_{exp}}{RfC}, { HQ}_{der}=\frac{{D}_{der}}{RfD}$$
(5)

where HQinh is the inhalation hazard quotient (mg/m3), Cexp is the exposure concentration, RfC is the reference concentration (mg/m3), HQder is the dermal hazard quotient (mg/kg/day), Dder is the dermal dose (mg/kg/day), and RfD is the reference dose (mg/kg/day).

$$HI=\sum HQ$$
(6)

where HI is the hazard index and HQ is the hazard quotient.

Results

Exposure factors for the general population

The exposure factors of 4762 cases were divided into disinfectants (2806 cases) and pesticides (1956 cases) according to the site. The averages and standard deviations of the usage amount and room volume by location are listed in Table 3. Detached houses had the highest amount of disinfectant and pesticide usage, with an average of 49,468.44 ± 173,721.19 mg, followed by public baths, with an average of 2625.45 ± 3737.11 mg. The gymnasium had the largest room volume for disinfection of 58,852.32 ± 105,116.98 m3 and the detached houses had the smallest room volume of 136.33 ± 92.37 m3. The average disinfectant usage was 5948.50 ± 72,434.76 mg and the average pesticide usage was 201.61 ± 305.91 mg, which is approximately 30-fold lower than the amount of disinfectant usage.

Table 3 Exposure factors for biocidal products according to the general population based on location.
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Dose–response assessment of active substances

Sodium hypochlorite and sodium dichloroisocyanurate (C3Cl2N3NaO3) were considered to emit chlorine gas and an NOAEC of 1.5 mg/m3 was used as the toxicity value13. The toxicity values of benzalkonium chloride (BKC) and quaternary ammonium compound (QAC) were 0.22 mg/m3 and 0.11 mg/m3, respectively. These values were reported by the U.S. RED and the Korea Occupational Safety and Health Agency (KOSHA), respectively15,17. Oral toxicity values of 600 mg/kg/day for oxone (KHSO5) and 2400 mg/kg/day for ethanol (C2H6O) were used and were obtained from the ECHA and OECD reports13,14. By consulting ECHA’s pesticide assessment report, the toxicity values for deltamethrin (C22H19Br2NO3), λ-cyhalothrin (C23H19ClF3NO3), etofenprox (C25H28O3) and permethrin (C21H20Cl2O3) were determined18,20,21,22. Finally, the toxicity values for cypermethrin (C22H19Cl2NO3) was obtained from the U.S. RED reports19. Table 4 shows the RfC and RfD values applied to the general population using the ECHA AF23.

Table 4 Reference concentration (RfC) and reference dose (RfD) values according to a dose–response assessment of the active substances based on the general population.
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Exposure assessment

The Cexp and Dder values for the 11 active substances were calculated using the exposure algorithm and are presented in Table 5. Ethanol had the highest Cexp of 2.28E+01 mg/m3, whereas sodium dichloroisocyanurate had the lowest concentration of 4.66E−13 mg/m3. Ethanol had the highest Dder (6.47E−03 mg/kg/day) while sodium dichloroisocyanurate had the lowest Dder (1.54E−13 mg/kg/day).

Table 5 Estimated exposure concentration (Cexp) and dermal dose (Dder) of the active substances in biocidal products in the general population.
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Health risk assessment

The values of HQinh, HQder, HI, and the HQinh/HQder ratios for the 11 active substances are presented in Table 6. Ethanol had the highest HQinh (1.48E+02) while sodium dichloroisocyanurate had the lowest HQinh (1.74E−10). Ethanol had the highest HQder (5.39E−04) while sodium dichloroisocyanurate had the lowest HQder (9.99E−14), with a value of less than 1, indicating no potential health risks. Ethanol was associated with a potential health risk, with an HI greater than 1, whereas the remaining 10 active substances had values ranging from 1.74E−10 to 7.71E−04, with HI values of less than 1, implying no potential health risk. Ethanol had the highest HQinh/HQder ratio of 2.73E+05 while λ-cyhalothrin had the lowest ratio of 7.94E−01.

Table 6 Estimated inhalation hazard quotient (HQinh), dermal hazard quotient (HQder), and hazard index (HI) of the active substances in biocidal products in the general population.
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Discussion

Exposure factors, such as usage amount, room volume, and information about biocidal products, were evaluated through interview surveys with disinfection workers. Cexp and Dder were calculated using an algorithm for 11 active substances in the biocidal products, and risk assessment was performed by applying RfC and RfD, which are toxicity values for the general population.

The increased use of disinfectants in homes and public facilities is due to the enhanced disinfection guidelines implemented during the COVID-19 pandemic3. As disinfection has been strongly recommended to prevent the spread of COVID-19, detached houses were found to have the highest usage per unit volume of disinfectants. Therefore, the use of disinfectants has significantly increased compared to that of pesticides to prevent the spread of COVID-19 and maintain a safe indoor environment32. Consequently, the active substances of biocidal products that remain on the disinfected surface pose potential health risks33.

Ethanol has a high vapor pressure, and its fraction released into the air is 1. The volatility and high weight fraction of the active substance are expected to affect Cexp, and the results were similar to those of previous studies34. Ethanol and sodium hypochlorite are volatile and short-lived, whereas the other active substances are nonvolatile compounds that remain in the indoor environment for longer periods35. In a study that obtained actual measurements after the spraying of a disinfectant, QAC, which has a low vapor pressure, was found to be primarily deposited on the floor, whereas alcohol, which has a high vapor pressure, mainly evaporated into the air36.

The 10 active substances had an HQinh/HQder ratio greater than 1, indicating that inhalation exposure had a greater effect than dermal. Dermal exposure is not considered when calculating body surface area (BSA) when clothes are worn29. The risk assessment for secondary exposure to the active substances, except for ethanol, did not reveal an HI ≥ 1, indicating no potential health risk. Spraying ethanol with a weight fraction of 30% or more can cause rapid changes in the chemical composition of indoor air, and increased concentrations of volatile organic compounds (VOCs) and particles after spraying can be harmful to one’s health through inhalation exposure37. The concentration of ethanol was higher than that of the other active substances because it was used in a stock solution with a high weight fraction of 83%. Ethanol accounts for 70–90% of the concentration of active substance recommended by the World Health Organization (WHO). However, spraying these substances is associated with a high risk of inhalation exposure38. Calculating the change in HQ for each active substance over time is crucial for suggesting a safe entry time after disinfection for the general population. The median values of 266.12 m3 and 2.45 h were used for the volume of the site and duration of emission, while the average value in Table 2 was used for the amount of disinfectants and pesticides used. As shown in Fig. 1, sodium hypochlorite, a highly volatile active substance, poses a potential health risk for up to 4 h after disinfection, while ethanol poses a risk for up to 7 h. Therefore, the general population may face health risks from secondary exposure to the active substances if they enter the room immediately after disinfection.

Fig. 1
figure 1

Trend in the hazard quotient of the active substances over time; (a) volatile active substances; and (b) non-volatile active substances.

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The significance of exposure and risk assessment in the general population is increasing owing to the persistence of COVID-19. Of note, the actual exposure concentration of the active substance may differ from the estimated concentration calculated using the exposure algorithm, which serves as a limitation of this study. However, considering the difficulty in measuring secondary exposure, an algorithm can be used to estimate the health risks of each active substance. Although this study incorporated site volume, the potential for underestimation exists in larger spaces, such as gymnasiums and viewing facilities. Therefore, attempting the application of personal volumes, such as 2 m3 and 5 m3, would be appropriate39,40.

Conclusions

Exposure and risk assessments were conducted for 11 types of biocidal substances, with specific focus on the general population that may be indirectly exposed to these substances after a disinfection protocol. The RfC and RfD values for the general population were derived using the representative toxicity values for each active substance. Ethanol and sodium hypochlorite pose potential health risks if an individual is present in or enters the room immediately after disinfection. Therefore, the spraying of disinfecting biocides should be avoided and replaced with a method that involves soaking a cloth to disinfect the surface.