Formaldehyde and Glutaraldehyde IgM

Formaldehyde is an organic compound. Formaldehyde-based materials are common to the manufacture of automobiles. Formaldehyde-containing resins – melamine formaldehyde, ureaformaldehyde, phenolformaldehyde, carbamide formaldehyde – are used as a binder in plywood and particleboard production, home furnishings, household cleaners, paints, textiles, landscape and yard products, medicinal and personal care products, pesticides, fire retardation, increased water repellency, stiffness, carpeting made with synthetic fibers, and wrinkle-resistance in fabric finishing; paper products treated with formaldehyde include paper bags, waxed paper, paper towels, and disposable sanitary products; in the health care industry, formaldehyde is used in disinfectants, preservatives, and embalming fluid. Thus, formaldehyde exposure occurs in multiple home and work environments. Formaldehyde has been classified as a known human carcinogen by the International Agency for Research on Cancer.

Glutaraldehyde is an organic compound. Glutaraldehyde is commonly used to disinfect medical and dental equipment; it is also used for industrial water treatment and as a preservative. The variety of uses for glutaraldehyde includes:

- cold sterilizer in the health care industry

- tanning agent

- biocide in metalworking fluids and in oil and gas pipelines

- antimicrobial in water-treatment systems

- slimicide in paper manufacturing

- preservative in cosmetics

- disinfectant in animal housing tissue fixative in histology and pathology labs

- hardening agent in the development of X-rays

- embalming solutions

- preparation of grafts and prostheses

- various clinical applications

In the healthcare industry, glutaraldehyde is most often used to disinfect equipment that cannot be heat sterilized such as dialysis instruments, surgical instruments, suction bottles, bronchoscopes, endoscopes, and ear, nose, and throat instruments. The possible routes of exposure to formaldehyde are ingestion, inhalation, dermal absorption and, rarely, blood exchange as in dialysis.

Because formaldehyde is so soluble, it is quickly absorbed in the respiratory and the gastrointestinal tracts.

Inhalation exposure to formaldehyde has been identified as a potential cause of asthma. Inhalation of formaldehyde leads to the formation of DNA–protein crosslinks, DNA single-strand breaks, chromosomal aberrations, sister chromatid exchange and gene mutation in human cells in vitro. This mechanism may be the cause of the carcinogenic, mutagenic and sensitizing action of formaldehyde. The most common adverse health effects resulting from formaldehyde exposure include:

- respiratory tract irritation

- increased incidence of infectious diseases

- sensitization

- mutagenic

- carcinogenic action

In March of 1986, a railroad tanker car containing 190,000 pounds of ureaformaldehyde resin underwent uncontrolled venting in Crown Point, Alaska. Following the event, residents of Crown Point showed significantly high IgM and IgG titers to formaldehyde. Symptoms included nasal congestion, sore throat, headache, cough, conjunctivitis, fatigue, rash, dizziness, diarrhea, shortness of breath, nausea, and nose bleeds; additionally, 50% of residents had recurrent, unresolved health complaints approximately 60 days following the spill. 

Studies on healthcare workers (laboratory, dental, hospital, veterinary), show that personnel in these industries are among the most affected by formaldehyde exposure. Formaldehyde is a well-known mucous membrane irritant and a primary skin sensitizing agent associated with both contact dermatitis (Type IV allergy), and immediate, anaphylactic reactions (Type I allergy).

Significantly increased sensitization rates common to the healthcare sector were found for the vaccine preservative thimerosal, as well as for glutaraldehyde, formaldehyde and glyoxal. In a 5-year study conducted by the University of Kansas, 468 patients were patch tested to glutaraldehyde. A higher than expected co-reactivity between glutaraldehyde and formaldehyde was noted among healthcare workers, which cannot fully be explained by concomitant exposure. A significantly increased risk for occupational allergic dermatitis was induced most frequently by glutaraldehyde. It is therefore of great practical importance to evaluate the appearance of concomitant sensitization to glutaraldehyde and formaldehyde, respectively. 

In dental practice it is common to have concomitant exposures to formaldehyde and glutaraldehyde. Chronic inhalation of glutaraldehyde caused considerable non-neoplastic lesions in the noses of study rats and mice. Glutaraldehyde disinfectant replacement in the hospital setting can cause a rapid increase in the environmental pollution levels for short periods of time. 

The detection of antibodies to Formaldehyde + Glutaraldehyde bound to human protein in serum indicates a breakdown in immunological tolerance and induction of chemical intolerance. Formaldehyde and Glutaraldehyde can bind to human tissue proteins and form neo-antigens. These new antigens are comprised of the haptenic chemical plus the tissue antigen. The formation of neo-antigens initiates an immune response, which may result in antibody production against the chemical and the human tissue. Continued exposure to the chemical and the subsequent production of antibodies against various tissue antigens, may result in autoimmune reactivity.

References:

- World Health Organization. Formaldehyde. Air quality guidelines (2nd ed). Regional Office for Europe, Copenhagen, Denmark, 2001: Chapter 5, p 8.

- Lyapina M, Kisselova-Yaneva A, Krasteva A, et al. Allergic contact dermatitis from formaldehyde exposure. J IMAB, 2012; 18(4):255-262.

- Bernstein RS, Stayner LT, Elliott LJ, et al. Inhalation exposure to formaldehyde: an overview of its toxicology, epidemiology, monitoring, and control. Am Ind Hyg Assoc J, 1984; 45(11):778- 785.

- Madison RE, Broughton A, Thrasher JD. Immunologic biomarkers associated with an acute exposure to exothermic byproducts of a ureaformaldehyde spill. Environ Health Perspect, 1991; 94:219-223.

- Shaffer MP, Belsito DV. Allergic contact dermatitis from glutaraldehyde in health-care workers. Contact Dermatitis, 2000; 43(3);150-156.

- Schnuch A, Uter W, Geier J, et al. Contact allergies inhealthcare workers. Results from the IVDK. Acta Derm Venerol, 1998; 78(5):358-363.

- Krecisz B, Kiec-Swierczynska M. The role of formaldehyde in the occurrence of contact allergy. [Article in Polish] Med Pr, 1998; 49(6):609-614.

- van Birgelen AP, Chou BJ, Renne RA, et al. Effects of glutaraldehyde in a 2-year study in rats and mice. Toxicologic Sci, 2000; 55(1):195-205.

- Pacenti M, Dugheri S, Boccalon P, et al. Evaluation of the Occupational Exposure to Glutaraldehyde in some Endoscopic Services in an Italian Hospital. Indoor Built Environ, 2006; 15(1):63–68.