Contact Sensitization to Formaldehyde in Veterinary Medicine - An Unexplored Field in Occupational Health.

BACKGROUND: Veterinary staff and students could be exposed to formaldehyde - a ubiquitous agent, common cause of contact allergy. AIM: To evaluate the incidence of contact sensitization to formaldehyde in exposures in veterinary medicine. SETTINGS AND
DESIGN: A cross-sectional study was conducted during July-December 2017.
MATERIALS AND METHODS: A total of 206 individuals were included, patch tested with formaldehyde 1.0%/aq - 36 veterinary medicine students, 20 veterinarians, 47 students and 28 trainees of dental medicine, 41 dental professionals, and 35 non-occupationally exposed individuals.
RESULTS: The incidence of contact sensitization to formaldehyde among the whole studied population was 48.1%, highest being among the students of veterinary medicine (94.4%) and the veterinarians (85%). With very high significance, the sensitization incidence was higher in the groups of students of veterinary medicine and veterinarians, if compared to the control group (P < 0.001); (P = 0.004), dental professionals (P < 0.001); (P = 0.001), trainees of dental medicine (P < 0.001); (P = 0.005), and students of dental medicine three-fourth year of education (P < 0.001); (P = 0.001). Significantly, higher was the incidence of contact allergy in the control group if compared to those of dental professionals (P = 0.033) and dental students three-fourth year of education (P = 0.028).
CONCLUSIONS: The exposure to formaldehyde during the education in veterinary medicine and practice could be an important risk factor for the onset of contact sensitization. Stricter preventive measures are needed to reduce veterinary student's and lecturer's exposures. Equipment of dissection tables with local exhaust ventilation system could reduce the concentration of formaldehyde in the gross anatomy laboratory.

INTRODUCTION

Formaldehyde (F) is a ubiquitous chemical agent, a part of our general outdoor and indoor residential environment and is sometimes difficult to distinguish the roles of environmental and occupational exposures.[12] Formaldehyde has found numerous applications in the medical science and practice. It is an inexpensive biocidal preservative used in a wide range of products, such as tissue specimen and cadaveric preservation solutions, nail polish, wrinkle-free fabrics, and so on.

Formalin, an aqueous solution 37% (w/v) of formaldehyde (CH2O, CAS no. 50-00-0), is the chemical most commonly used for embalming. Embalmers, anatomists, technicians, medical, dental, or veterinary students during anatomy laboratory sessions with formaldehyde-preserved tissues are among the people who have high exposure to formaldehyde.[3] On the other hand, instructors demonstrating or observing students are also at risk of exposure to formaldehyde as a component of the preservative solution. Formaldehyde exposure in gross anatomy dissection may occur by different routes, including inhalation or direct contact with the skin[4567] or accidently splashes in eyes,[8] or ingestion into the gastrointestinal tract.[9]

In veterinary medicine, gross anatomy describes the normal structures of different kinds of animal bodies. Formaldehyde levels, measured in the breathing zone during anatomical dissection in veterinary medicine, were below the maximum allowable concentration in all specimens except for a 300 kg horse cadaver.[10] Increased formaldehyde concentrations in the working area can be caused by a work environment that facilitates the spillage of formalin; poor condition of cadavers, which causes embalming fluid to leak; a high formaldehyde concentration in the air (>0.50 ppm) or in cadaveric tissues (0.22 ppm); poor ventilation in the dissection rooms; lack of strict and appropriate guidelines for handling embalmed cadavers and prosected specimens; or ignorance of consequences of formalin exposure.[11] Veterinary medicine exposures are also possible when used as a fumigation agent against bacterial contamination.[12131415]

Despite the trend for restricting its use, formaldehyde remains an ingredient of some dental materials such as root canal filling materials, formocresol, sealers and cements, and so on.[16] A large group of sealers/cements, including the commonly used Endomethasone, Riebler's paste, N2, AH26, several composite resins, among others, contain substantial amounts of paraformaldehyde and are able to leach formaldehyde into water in amounts sufficient to cause local allergic reactions.[16] The release of formaldehyde from some endodontic materials – root canal-filling sealers was evaluated and highest release of formaldehyde in the case of freshly mixed samples was demonstrated.[1718] Formaldehyde is formed as an oxidation product of the residual methyl methacrylate monomer and may be released from methacrylate-based dental materials, such as composites and denture bases.[19202122]

Formaldehyde is a common cause of contact allergy, and has been named by the American Contact Dermatitis Society Contact Allergen of the Year for 2015.[23] In our previous studies, irritant and skin-sensitizing effects of formaldehyde among dental students exposed during their practical education were well documented.[2425] No studies were found in the available literature concerning the incidence of contact sensitization to formaldehyde among veterinary medicine students and lecturers.

The aim of the present study was to evaluate the incidence of contact sensitization to formaldehyde in exposures in veterinary medicine and to compare it with the one in dental medicine exposures.

MATERIAL AND METHODS

Subjects

A total of 206 individuals were included in the present study, divided into the following groups:

First main group – A total of 56 individuals exposed in veterinary medicine, including: 36 students of veterinary medicine 3–6 years from the Faculty of Veterinary Medicine at the University of Forestry, Sofia, exposed to formaldehyde during their practical training in animal anatomy and pathological anatomy and 20 veterinarians from the Faculty of Veterinary Medicine at the University of Forestry, Sofia, exposed to formaldehyde during the practical training of the students of animal anatomy and pathological anatomy, as well as during their scientific and research activities.

Second main group – A total of 115 individuals occupationally exposed to formaldehyde in dental medicine, including: 47 students of dental medicine three-fourth year of education from the Faculty of Dental Medicine at the Medical University, Sofia, exposed during their practical training in preclinical and clinical disciplines, 28 trainees of dental medicine 6th year of education from the Faculty of Dental Medicine at the Medical University, Sofia, exposed during the clinical work with patients; and 41 occupationally exposed dental professionals from the Faculty of Dental Medicine at the Medical University, Sofia – lecturers in clinical disciplines and nurses.

Control group – A total of 35 individuals without occupational exposure to formaldehyde. The subjects included in the study were selected according to the following inclusion criteria: occupational exposure in dental or veterinary medicine, directly or through the work environment, formaldehyde as an ingredient of dental materials or embalming fluids, gender, and age characteristics. Exclusion criteria: specific and non-specific desensitization therapy or intake of anti-allergic medicaments at the time of the study.

The participants in the study were recruited on a voluntary principle, informing them about the benefits of the study. All the surveyed were provided with specially elaborated forms with information for the purposes of the study and a declaration of informed consent for participation.

The age and gender characteristics of the studied groups are presented in Table 1.

Table 1

Age and gender characteristics of the studied groups

Studied groups	Total n/%	Men n/%	Women n/%	Mean age±SD
Control group	35 (17.0)	13 (37.1)	22 (62.9)	46.49±17.29
Dental professionals	41 (19.9)	13 (31.7)	28 (68.3)	49.10±13.58
Trainees of dental medicine	27 (13.1)	11 (40.7)	16 (59.3)	26.52±2.89
Students of dental medicine three-fourth year of education	47 (22.8)	16 (59.3)	24 (51.1)	21.54±1.80
Students of veterinary medicine	36 (17.5)	21 (58.3)	15 (41.7)	22.00±1.64
Veterinarians	20 (9.7)	14 (70.0)	6 (30.0)	39.50±11.76
Total	206 (100.0)	95 (46.1)	111 (53.9)	33.80±15.79

Skin patch testing

Skin patch testing with formaldehyde was performed, according to the Jadassohn & Bloch classical methods for diagnosis of contact allergy, by placing the allergen (formaldehyde – 1.0%/aq, Art. nr. F002A, Chemotechnique Diagnostics) in IQ-Ultra hypoallergenic patches of Chemotechnique Diagnostics (IQ Chambers®, Vellinge, Sweden). The obligatory condition for testing was the absence of anti-allergic medication before placing the patches and during the study. Patches with allergens were applied and remained on the back of the tested subjects for 48 h. The test was read several hours after removal of the patches. For the interpretation of the test result the following scheme was used (International Contact Dermatitis Research Group – ICDRG):

(−) Negative reaction

? Doubtful reaction

+ Weak reaction (non-vesicular)

++ Strong reaction (edematous or vesicular)

+++ Extreme reaction (ulcerative or bullous)

IR Irritant reaction.

Statistical methods

The statistics were calculated with the SPSS 19.0. Available for cross-tabulation statistics were used: Chi-square test, Fisher exact test for statistical significance (values of P < 0.05 were accepted as statistically significant).

RESULTS

To assess the incidence of contact sensitization to formaldehyde among the studied population, we performed a comparative analysis between control group and the occupationally exposed individuals (including dental professionals, veterinarians, dental students, and students of veterinary medicine). The results are presented in Table 2.

Table 2

Incidence of positive patch test reactions to formaldehyde among the occupationally exposed individuals and the control group

	Groups		Total
	Control group n/%	Occupationally exposed n/%
With sensitization	16/45.7	83/48.5	99/48.1
Without sensitization	19/54.3	88/51.5	107/51.9
Total	35/100.0	171/100.0	206/100.0

As demonstrated, the incidence of sensitization to formaldehyde among the whole studied population was high and was observed in 99 individuals (48.1%). The patch tests results were positive among 57 men (60%) and 42 women (37.8%) – Table 3.

Table 3

Incidence of positive patch test reactions to formaldehyde according to gender characteristics

	Groups		Total
	Men n/%	Women n/%
With sensitization	57/600	42/37.8	99/48.1
Without sensitization	38/40.0	69/62.2	107/51.9
Total	95/100.0	111/100.0	206/100.0

The statistical analysis revealed a significantly higher incidence among men ( χ2 = 10.07, P = 0.002). Since men predominated in the groups of veterinarians and the students of veterinary medicine, we evaluated the incidence of sensitization according to the gender characteristic in the control group, and the results were confirmed – the sensitization incidence again was higher among men (61.5%).

In Table 4 we present the summarized results on the incidence of positive patch test reactions to formaldehyde in the groups defined by us according to the type of exposure.

Table 4

Incidence of positive patch test reactions for formaldehyde in the groups according to the type of exposure

	Groups						Total
	Control group n/%	Dental professio-nals n/%	Trainees of dental medicine n/%	Students of dental medicine n/%	Students of veterinary medicine n/%	Veterinarians n/%
With sensitization	16/45.7	9/22.0	12/44.4	11/23.4	34/94.4	17/85.0	99/48,1
Without sensitization	19/54.3	32/78.0	15/55.6	36/76.6	2/5.6	3/15.0	107/51.9
Total	35	41	27	47	36	20	206

Evidently, highest was the incidence of sensitization among the group of students of veterinary medicine (94.4%), followed by the one in the group of veterinarians (85%). When comparing the incidence of sensitization between the groups exposed in veterinary practice and the control group, a significantly lower incidence of sensitization was established for the latter group than in the groups of students of veterinary medicine (χ2 = 20.23, P < 0.001) and veterinarians (χ2 = 8.19, P = 0.004).

We also performed a comparative intergroup statistical analysis of the incidence of sensitization among the individuals occupationally exposed in dental practice and in veterinary medicine. We established a significantly higher incidence among the trainees of dental medicine if compared to dental professionals (χ2 = 3.86, P = 0.049), as well as, with very high statistical significance, among students in veterinary medicine (χ2 = 40.85, P < 0.001) and veterinarians (χ2 = 21.85, P = 0.001), if compared to dental professionals.

The incidence of sensitization among the students of veterinary medicine was also higher, with high statistical significance, if compared to the one among trainees of dental medicine (χ2 = 19.58, P = <0.001) and among the students of dental medicine three-fourth year of education (χ2 = 41.45, P = <0.001). Similar are the results concerning the incidence of sensitization among veterinarians if compared to the one among the trainees of dental medicine (χ2 = 7.99, P = 0.005) and dental students three-fourth year of education (χ2 = 21.88, P = 0.001).

The intergroup statistical analysis between the groups exposed in dental practice and the control group confirmed our previous results – a significantly higher frequency of contact sensitization to formaldehyde was established in the control group if compared to those of dental professionals (χ2 = 4.52, P = 0.033) and dental students three-fourth year of education (χ2 = 4.83, P = 0.028).

DISCUSSION

Formaldehyde is a widely used organic compound in several applications (hard thermoset resins, adhesives, disinfectants, tissue fixatives, and so on) in its free form or released by formaldehyde releaser products. Its use is under control due to its toxic, carcinogenic, and allergenic properties.[26]

In the gross anatomy laboratory – a compulsory subject in medical, dental, and veterinary education – students and instructors are exposed to formaldehyde, which is emitted from cadavers and embalming fluid during dissection. The main exposure of students of veterinary medicine appears during the first year of their education and high exposure could adversely affect their health.[27] Common effects of formaldehyde exposure are various symptoms caused by irritation of the mucosa in the eyes and upper respiratory tract. Studies documented that veterinary students had a high prevalence of nasal itching, eyes burning, excessive lacrimation, eyes redness, headache, and respiratory distress and male students were more affected than females, as well as decreases pulmonary function tests in students after gross anatomy dissection and anatomy; staff members had nasal itching, burning and congestion, eyes burning and redness, excessive lacrimation, cough and respiratory distress, mouth dryness, and headache.[2829]

The use of formaldehyde is so ubiquitous that it has always been present in the baseline series of patch tests.[30] Sensitization rates to formaldehyde are lower in Europe in comparison with the United States due to stricter regulations regarding its use.[31] A Danish survey found extensive use of formaldehyde in various product types used occupationally, which can be regarded as problematic, in particular for the sensitized worker.[32] Sensitization to formaldehyde is relevant in our population, especially in the healthcare sector. The results from a study performed by Prodi et al. (2016) suggest a significant association between healthcare work, hand/forearm dermatitis, and sensitization to formaldehyde.[33]

None was found in the available literature regarding the incidence of sensitization to formaldehyde in veterinary education and practice exposures. Takahashi et al. (2007) tested by patch test for formaldehyde medical students at the beginning and end of a human anatomy laboratory course and established that only 3.3% of the students became positive to 1% formaldehyde at the end of the anatomy course.[34]

The results from the present study confirmed the high incidence of sensitization to formaldehyde among the studied population (48.1%), men being at significantly increased risk. Further, the incidence of sensitization among the students of veterinary medicine and the group of veterinarians was very high (94.4% vs. 85%). No similar results were found in the available literature to compare with, but basing on our finding we could conclude that the type and degree of exposure to formaldehyde in veterinary medicine imposes a serious risk of contact sensitization.

Concerning the incidence of contact sensitization to formaldehyde in dental medicine exposure, the results achieved were in concordance with our previous findings and confirmed that it was lower if compared with both the control group and the groups exposed in veterinary medicine, dental trainees being at a higher risk if compared with dental professionals.

Based on the results obtained in the present study, we could conclude that exposure to formaldehyde during the education in veterinary medicine, as well as, at some less extend, in veterinary practice, is an important risk factor for the onset of contact sensitization.

The toxicity of formaldehyde is of concern to all people working closely with its sources. Stricter preventive measures are needed to reduce student's exposure to formaldehyde during the process of practical education in veterinary medicine. Students should be provided with safety instructions during the gross anatomy sessions and to follow precautionary measures, including periodical risk assessment to evaluate the extent of risk on students and staff. Yamato et al.[35] and Kikuta et al.[36] suggested installation of dissection tables equipped with local exhaust ventilation system to reduce the concentration of formaldehyde vapors. Although it is not the practice, students should have access to goggles, respirators, as well as masks to reduce the intake of formaldehyde.[29] Switching to alternative preservative methods, such as freezing, is a safer way of tissues preservation than using formaldehyde.[28]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.