Chapter 24 - Antiseptic Drugs and Disinfectants

https://doi.org/10.1016/bs.seda.2015.06.005Get rights and content

Abstract

This review covers publications during the period July 2013 to December 2014 on adverse reactions to antiseptic drugs and disinfectants. Specific agents discussed are aldehydes (formaldehyde and glutaraldehyde), guanidines (chlorhexidine, polyhexamethylene guanidine and polyhexamethylene biguanidine), benzalkonium compounds, ethylene oxide, triclosan, halogens (sodium hypochlorite, and the iodophors iodine, polyvinylpyrrolidone, and povidone-iodine). No new data were identified for tosylchloramide and phenolic compounds. Antiseptic drugs and disinfectants continue to be used in a variety of medical and occupational settings, in certain cosmetic products as well as in the household. Several epidemiological and experimental studies have confirmed the causal association between polyhexamethylene guanidine (PHMG) use in household humidifiers and lung disease in Korea. The respiratory effects and carcinogenicity of the sterilizing agent formaldehyde are still an important subject with several new epidemiologic and mechanistic studies, most of which confirmed the association. Adverse reactions to triclosan were described in a number of publications including endocrine and immunologic effects. Iodine and povidone-iodine are also well-established topical antiseptics, but they continue to cause adverse reactions, including allergic reactions and effects on thyroid function. It was specifically warned against the use of topical iodine in preterm neonates, which may cause a high incidence (12–33 per 100) of thyroid dysfunction.

Antiseptics and disinfectants are used as preservatives and antimicrobials in numerous pharmaceutical formulations and personal care products, and their safety evaluation continues. A novel observation was the fact that all kinds of antiseptic solutions may cause microbial infections when diluted with contaminated water, by inappropriate handling, or by storing under non-sterile conditions.

Section snippets

Infection Risk

The FDA has reported a series of side effects of contaminated antiseptic solutions, ranging from localised infection at an injection site to deep infections and even fatal septicaemia. The products included all commonly used antiseptic agents such as alcohols, iodophors, chlorhexidine, and quaternary ammonium compounds. The microorganisms were introduced into the antiseptic solutions by diluting them with contaminated water, by inappropriate handling, or by storing them under non-sterile

Aldehydes [SED-15, 1439, 1513; SEDA-31, 409; SEDA-32, 437; SEDA-33, 479; SEDA-34, 377; SEDA-36, 339]

Considering all disinfectants, aldehydes have a special status as they are able to pose occupational hazards even at very low concentrations in air (SEDA-36, 339). A survey in Germany 2006–2009 shows that the use of formaldehyde releasers in cosmetics is common in 8% of all products in a random sample (n = 4680) [5M].

Drug Formulations

Chlorhexidine is used extensively in oral hygiene but can cause staining of the teeth and oral mucosa, adversely affect taste and rarely cause pain [SEDA-30, 278; SEDA-31, 416; SEDA-34, 378; SEDA-36, 340]. A survey in Germany 2006–2009 shows that chlorhexidine is not only used in medicinal products but also in cosmetics with a prevalence of about 0.2% of all cosmetic products in a random sample (n = 4680) [5M].

Skin

In a systematic Cochrane review on vaginal chlorhexidine use during labor to prevent

Sensory Systems

Reviews about the effect of glaucoma therapy on ocular surface disease (OSD) and the specific adverse effects of benzalkonium chloride were provided by Anwar et al. [37R], Inoue [38R] and Rasmussen et al. [39R]. It is believed that eye drops containing benzalkonium chloride as preservative may contribute to OSD [see also SEDA-36, 341]. An observational, cross-sectional study of patients with topically treated glaucoma was conducted (n = 233). Multivariate analysis confirmed that benzalkonium

Ethylene Oxide [SED-15, 1296; SEDA-29, 242; SEDA-34, 379; SEDA-36, 341]

Ethylene oxide is used directly in the gaseous form to sterilize drugs, hospital equipment, disposable and reusable medical items, packaging materials, foods and other items [SEDA-36, 341]. A large number of samples of herbs, spices and other dried vegetables imported to Italy contained more than 0.3 mg/kg of ethylene oxide (29% of 63 analysed samples) [46E].

Triclosan [SEDA-34, 379, SEDA-36, 342]

A survey in Germany during the period 2006–2009 [random sample (n = 4680)] shows that triclosan is used in cosmetics with a prevalence of about 1% of all cosmetic products [5M]. A first human biomonitoring study in the US for exposures occurring during pregnancy (n = 181) found that triclosan was detected in 100% of urine and 51% of cord blood samples. The results suggested that triclosan exposure is ubiquitous in the US population, even in expecting mothers and their unborn children [50c]. Due to

Teeth

Sodium hypochlorite is used to irrigate root canals in dentistry and can cause many adverse reactions [SEDA-34, 380; SEDA-36, 342]. A literature review concerning the etiology and management of complications during root canal irrigation was published [62R]. A sodium hypochlorite accident occurred in a pediatric patient (1 year, 10-month-old) who was treated for early childhood caries. Symptoms included swelling of the upper lip, moderate periorbital ecchymosis and edema of the right eye causing

Endocrine

A systematic review was conducted about thyroid dysfunction in preterm neonates exposed to topical iodine. The incidence of (transient) hypothyroidism/hyperthyrotropinaemia ranged from 12% to 33% in infants, whereas the incidence in non-exposed infants was 0%. The authors concluded that neonatal exposure to iodine-containing disinfectants causes thyroid dysfunction in infants born < 32 weeks. No studies regarding the impact of exposure on neurodevelopment were available. Currently, it would seem

References (73)

  • Y. Kato et al.

    Benzalkonium chloride accelerates the formation of the amyloid fibrils of corneal dystrophy-associated peptides

    J Biol Chem

    (2013)
  • Y. Wu et al.

    Differential effects of triclosan on the activation of mouse and human peroxisome proliferator-activated receptor alpha

    Toxicol Lett

    (2014)
  • M. Axelstad et al.

    Triclosan exposure reduces thyroxine levels in pregnant and lactating rat dams and in directly exposed offspring

    Food Chem Toxicol

    (2013)
  • T. Buhl et al.

    Contact hypersensitivity to triclosan

    Ann Allergy Asthma Immunol

    (2014)
  • Y.S. Yang et al.

    Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation

    Regul Toxicol Pharmacol

    (2015)
  • A. von Keudell et al.

    Deleterious effects of diluted povidone-iodine on articular cartilage

    J Arthroplasty

    (2013)
  • Anon

    Antiseptics: sometimes the cause of infection

    Prescrire Int

    (2014)
  • C.Y. Chang et al.

    Microbial stowaways in topical antiseptic products

    N Engl J Med

    (2012)
  • S. Lee et al.

    An outbreak of Burkholderia cenocepacia associated with contaminated chlorhexidine solutions prepared in the hospital

    Am J Infect Control

    (2013)
  • FDA

    FDA Drug Safety Communication: FDA requests label changes and single-use packaging for some over-the-counter topical antiseptic products to decrease risk of infection

    (2013)
  • W. Uter et al.

    Coupled exposure to ingredients of cosmetic products: II. Preservatives

    Contact Dermatitis

    (2014)
  • G.D. Nielsen et al.

    Recent trend in risk assessment of formaldehyde exposures from indoor air

    Arch Toxicol

    (2013)
  • S. Sallapant et al.

    Formalin-induced severe colonic necrosis

    Endoscopy

    (2013)
  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans

    Formaldehyde

    IARC Monogr Eval Carcinog Risks Hum

    (2012)
  • L.E. Beane Freeman et al.

    Mortality from solid tumors among workers in formaldehyde industries: an update of the NCI cohort

    Am J Ind Med

    (2013)
  • D. Coggon et al.

    Upper airway cancer, myeloid leukemia, and other cancers in a cohort of British chemical workers exposed to formaldehyde

    Am J Epidemiol

    (2014)
  • D. Lin et al.

    Occupational exposure to formaldehyde and genetic damage in the peripheral blood lymphocytes of plywood workers

    J Occup Health

    (2013)
  • A. Marcon et al.

    Outdoor formaldehyde and NO2 exposures and markers of genotoxicity in children living near chipboard industries

    Environ Health Perspect

    (2014)
  • H.D. Hosgood et al.

    Occupational exposure to formaldehyde and alterations in lymphocyte subsets

    Am J Ind Med

    (2013)
  • A. Bauer

    Contact dermatitis in the cleaning industry

    Curr Opin Allergy Clin Immunol

    (2013)
  • Y. Tanaka et al.

    Allergy to formaldehyde: basophil histamine-release test is useful for diagnosis

    Int Arch Allergy Immunol

    (2014)
  • H. Löffler et al.

    Allergic or irritant contact dermatitis after patch testing with alcohol—that is the point

    Contact Dermatitis

    (2012)
  • A. Ohlsson et al.

    Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection

    Cochrane Database Syst Rev

    (2014)
  • R. Toholka et al.

    Allergic contact dermatitis to chlorhexidine

    Australas J Dermatol

    (2013)
  • C. Supapvanich et al.

    Respiratory and dermal symptoms in Thai nurses using latex products

    Occup Med (Lond)

    (2013)
  • U. Mushtaq et al.

    Acute allergic reaction after intravenous saline injection: an unusual presentation of chlorhexidine allergy

    Med J Aust

    (2014)

    • Cited by (5)

    • Side effects of antiseptic drugs and disinfectants with experience of the third year of COVID-19

      2023, Side Effects of Drugs Annual

    • Antiseptic drugs and disinfectants with experience of the second year of COVID-19 pandemic-related side effects

      2022, Side Effects of Drugs Annual
      Citation Excerpt :

      Following positive patch testing, occupational hand eczema consisting of both irritant contact dermatitis and allergic contact dermatitis caused by sensitization to PHMB was diagnosed (Kolodziej et al., 2021) [A]. Sensory systems: Eye drops containing benzalkonium chloride as a preservative may contribute to ocular surface disease (see also (Lachenmeier, 2014 [R]; Lachenmeier, 2015 [R]; Lachenmeier, 2016 [R]; Lachenmeier, 2017 [R]; Lachenmeier, 2018 [R]; Lachenmeier, 2020 [R]; Lachenmeier, 2021 [R])). Based on in vitro research in human primary cultured goblet cells, cell survival was negatively correlated with benzalkonium chloride concentration in the examined eye drops (0.005%, 0.0075%, 0.01% and 0.02%) suggesting a decrease in its concentration in eye drops for chronic use (Hedengran et al., 2021) [E].

    • Antiseptic drugs and disinfectants with special scrutiny of COVID-19 pandemic related side effects

      2021, Side Effects of Drugs Annual

    • Antiseptic drugs and disinfectants

      2020, Side Effects of Drugs Annual
      Citation Excerpt :

      Polyhexamethylene guanidine (PHMG) has been used as an antiseptic, especially for the suppression of hospital infection in the Russian Federation and as a disinfectant for sterilization of household humidifiers in Korea [1R,2R,3R,4R,5R,6R]. Further evidence was gathered on the association of the disinfectant PHMG with lung disease (see Refs. [1R,2R,3R,4R,5R] for description of cases). During a nationwide study in Korea in patients who presumed their lung disease to be related to humidifier disinfectant use (n = 1199), 453 (38%) were clinically confirmed as humidifier disinfectant exposure-associated lung injury.

    • Study on biological distribution of polyhexamethylene guanidine (PHMG), a toxic household chemical, using radiolabeling and molecular imaging tools

      2022, Environmental Engineering Research
    View full text
    Copyright © 2015 Elsevier B.V. All rights reserved.