1. Formaldehyde: An overview Treatment of Verrucae Matt Dilnot

2. Conversions 1 ppm = 1.25 mg/m3 1 ppm = 1.25 mg/m3 1 mg/m3 = 0.8 ppm (at 20 °C and 1013 hPa) 1 mg/m3 = 0.8 ppm (at 20 °C and 1013 hPa) 1 ppb (v/v) = 1.23 mg/m3 1 ppb (v/v) = 1.23 mg/m3 1 µg/m3 = 0.813 ppb (v/v) 1 µg/m3 = 0.813 ppb (v/v) Formalin 10% = formaldehyde 28mg/mL Formalin 10% = formaldehyde 28mg/mL Odour Threshold :.5 – 1.0 ppm Odour Threshold :.5 – 1.0 ppm

3. Overview Formaldehyde (H2C=O) Formaldehyde (H2C=O) Very soluble in water Very soluble in water Flammable, colourless, reactive and readily polymerized gas at normal room temperature and pressure Flammable, colourless, reactive and readily polymerized gas at normal room temperature and pressure Normal part of environment e.g. Methane Cycle, decaying organic matter, forest fires Normal part of environment e.g. Methane Cycle, decaying organic matter, forest fires Normal part of fruit and vegetables (3-100 mg/kg) Normal part of fruit and vegetables (3-100 mg/kg) One of the largest man made chemicals One of the largest man made chemicals Used in all major manufacturing industries Used in all major manufacturing industries e.g. plastics, glues, chemical reactions Normal home – 0.014 to 0.042 mg/m 3 Normal home – 0.014 to 0.042 mg/m 3 Natural background - < 1 µg/m 3 - mean 0.5 µg/m 3 Natural background - < 1 µg/m 3 - mean 0.5 µg/m 3

4. WHO Average Daily Exposure Food 9.4 mg/d Food 9.4 mg/d Inhalation 1 mg/d Inhalation 1 mg/d Water.15 mg/d Water.15 mg/d Total: 10.55 mg/d

5. Overview Normal physiological substance Normal physiological substance –Endogenous formaldehyde 3-12ng/g tissue –Liver 22mg/min Essential for protein synthesis Essential for protein synthesis Normal part of Lipid Metabolism Normal part of Lipid Metabolism

6. Formaldehyde Metabolism Converted by enzymes in erythrocytes and liver Converted by enzymes in erythrocytes and liver Metabolised rapidly to formate and formic acid Metabolised rapidly to formate and formic acid Formic acid oxidized to CO 2 and Water Formic acid oxidized to CO 2 and Water Formate is converted to sodium salt and excreted or used in biosynthesis Formate is converted to sodium salt and excreted or used in biosynthesis Liver converts 22mg/minute of formaldehyde to carbon dioxide Liver converts 22mg/minute of formaldehyde to carbon dioxide Intravenous infusion: half-life of 1.5 minutes Intravenous infusion: half-life of 1.5 minutes

8. Formaldehyde Blood Levels ControlExposed Rats (14.4 ppm, 2 hrs) 18 mg/m 3 2.242.25 Monkeys (6 ppm, 4 weeks) 7.5 mg/m 3 2.421.84 Humans (1.9 ppm, 40 mins) 2.375 mg/m 3 2.612.77 Normal Environmental Ambient ~3.0 ppb (peak 8.3 ppb).02 mg/m3

9. Specific Cellular Actions Biocide class Biocide class Cross-linking in the cell membrane Cross-linking in the cell membrane Damages cell contents – cross-linking Damages cell contents – cross-linking –Nucleic Acids –Amino Acids

10. Carcinogenicity WHO classification “probable carcinogen” WHO classification “probable carcinogen” Naso-pharangeal cancer in mice and rats at high concentrations. Inhalation (18-25 mg/m 3 ) Naso-pharangeal cancer in mice and rats at high concentrations. Inhalation (18-25 mg/m 3 ) (Normal home – 0.014 to 0.042 mg/m 3 ) (Normal home – 0.014 to 0.042 mg/m 3 ) 900 to 1250 times normal daily exposure. Humans can only tolerate 5-6.2 mg/m 3 for 30 mins. 900 to 1250 times normal daily exposure. Humans can only tolerate 5-6.2 mg/m 3 for 30 mins. SCCs in 50% of rats @ 25 mg/m 3, 6 hours a day, 5 days a week, 2 years. SCCs in 50% of rats @ 25 mg/m 3, 6 hours a day, 5 days a week, 2 years. 10-20 fold increase in cell proliferation of lungs. 10-20 fold increase in cell proliferation of lungs.

11. Carcinogenicity Naso-pharangeal carcinogenicity appears to be only risk Naso-pharangeal carcinogenicity appears to be only risk –Inhalation doesn’t increase blood concentrations regardless of inhaled concentration Remember it is poisonous!!

12. Cancer Epidemiology 2 studies following ~7500 UK workers in formaldehyde factories over ~20-40 years 2 studies following ~7500 UK workers in formaldehyde factories over ~20-40 years No cases of nasopharangeal cancer No cases of nasopharangeal cancer UK death records reports 3 cases of nasopharangeal cancers in Doctors. None worked with formaldehyde (e.g. pathologists) UK death records reports 3 cases of nasopharangeal cancers in Doctors. None worked with formaldehyde (e.g. pathologists)

13. Summary High concentration vapours for extended periods are only reasonable risk High concentration vapours for extended periods are only reasonable risk Exposure to normal environmental formaldehyde is safe with no measurable changes to body function/blood levels Exposure to normal environmental formaldehyde is safe with no measurable changes to body function/blood levels Exposure to formalin 10% on skin is safe Exposure to formalin 10% on skin is safe Formaldehyde is Poisonous!

14. Uses in Dermatology Hyperhidrosis – Mechanism, probable destruction of sweat glands Hyperhidrosis – Mechanism, probable destruction of sweat glands -cidal to most lines of cells – bacteria, fungus, viruses, skin cells. -cidal to most lines of cells – bacteria, fungus, viruses, skin cells. Treatment of Burns Treatment of Burns Verrucae Verrucae –Cytotoxic to Skin –Irritates skin –Thins skin

15. Dermal Exposure Absorption is non-existent or negligible Absorption is non-existent or negligible Only a local effect Only a local effect There is no accumulation in body or skin There is no accumulation in body or skin Is a skin irritant and can cause allergic contact dermatitis – Can’t differentiate Is a skin irritant and can cause allergic contact dermatitis – Can’t differentiate Dermatitis is caused only by concentrations > 2% Formaldehyde Dermatitis is caused only by concentrations > 2% Formaldehyde Is non-toxic to immune system Is non-toxic to immune system

16. Formalin Commercial formaldehyde is 34.7 – 36% with buffering/diluting substances Commercial formaldehyde is 34.7 – 36% with buffering/diluting substances Dilute with water e.g. 5 ml formaldehyde with 45 ml water = formalin 10% Dilute with water e.g. 5 ml formaldehyde with 45 ml water = formalin 10% Formalin 10% is actually ~3.47% formaldehyde Formalin 10% is actually ~3.47% formaldehyde Vapours with head directly over Formalin bottle may measure up to 3mg/m 3 Vapours with head directly over Formalin bottle may measure up to 3mg/m 3

17. Study 1 Vickers CFH. Treatment of plantar warts in children. Br Med J 1961; ii: 743-5 Vickers CFH. Treatment of plantar warts in children. Br Med J 1961; ii: 743-5 200 Children 6-8 weeks with 3% Formaldehyde 200 Children 6-8 weeks with 3% Formaldehyde 80% clearance rate 80% clearance rate

18. Study 2 Anderson I, Shirreffs E. The treatment of Plantar Warts. Br J Dermatol 1963: 75: 29-32 Anderson I, Shirreffs E. The treatment of Plantar Warts. Br J Dermatol 1963: 75: 29-32 Comparison: Formaldehyde soaks v Water soaks and saccharose by mouth. Comparison: Formaldehyde soaks v Water soaks and saccharose by mouth. Results: No difference between groups. Results: No difference between groups.

19. Study 3 Formaldehyde 10% +/- MCA Jennings MB. Unpublished 2004. New York College. Jennings MB. Unpublished 2004. New York College. N=46 N=46 4 weeks formaldehyde 10% 4 weeks formaldehyde 10% Then divide 2 groups placebo v MCA 2 weekly (both continued formaldehyde 10%) Then divide 2 groups placebo v MCA 2 weekly (both continued formaldehyde 10%) Once daily application for less than 20 secs. Once daily application for less than 20 secs. Lazerformaldehyde ® Roll-on by Pedinol Lazerformaldehyde ® Roll-on by Pedinol Continued for further 8 weeks Continued for further 8 weeks Results: Both ~75% cure rate Results: Both ~75% cure rate

20. Case Study 23 y.o. female 23 y.o. female Multiple Mosaic Warts, present 2 years Multiple Mosaic Warts, present 2 years Treatments from 2 Pods and GP Treatments from 2 Pods and GP Sal acid, Multiple Liq.Nitrogen, Wartner, Occlusion Sal acid, Multiple Liq.Nitrogen, Wartner, Occlusion Worked as florist, damp feet and shoes, suffers chilblains Worked as florist, damp feet and shoes, suffers chilblains

21. Treatment regime Apply Formalin 10% to affected area Apply Formalin 10% to affected area Apply with cotton bud for ~ 1min. Apply with cotton bud for ~ 1min. Once or twice daily Once or twice daily Debride once weekly with file/sand paper/pumice stone Debride once weekly with file/sand paper/pumice stone No masking of area No masking of area Review at 4 weeks Review at 4 weeks