Formaldehyde: An overview Formaldehyde: An overview

Treatment of VerrucaeTreatment of Verrucae

Matt DilnotMatt Dilnot

ConversionsConversions

• 1 ppm = 1.25 mg/m31 ppm = 1.25 mg/m3

• 1 mg/m3 = 0.8 ppm (at 20 °C and 1013 1 mg/m3 = 0.8 ppm (at 20 °C and 1013 hPa)hPa)

• 1 ppb (v/v) = 1.23 mg/m31 ppb (v/v) = 1.23 mg/m3

• 1 1 µµg/m3 = 0.813 ppb (v/v)g/m3 = 0.813 ppb (v/v)

• Formalin 10% = formaldehyde Formalin 10% = formaldehyde 28mg/mL28mg/mL

• Odour Threshold : .5 – 1.0 ppmOdour Threshold : .5 – 1.0 ppm

OverviewOverview

• Formaldehyde (H2C=O) Formaldehyde (H2C=O) • Very soluble in waterVery soluble in water• Flammable, colourless, reactive and readily polymerized Flammable, colourless, reactive and readily polymerized

gas at normal room temperature and pressuregas at normal room temperature and pressure• Normal part of environment e.g. Methane Cycle, decaying Normal part of environment e.g. Methane Cycle, decaying

organic matter, forest fires organic matter, forest fires • Normal part of fruit and vegetables Normal part of fruit and vegetables (3-100 mg/kg)(3-100 mg/kg)• One of the largest man made chemicalsOne of the largest man made chemicals• Used in all major manufacturing industriesUsed in all major manufacturing industries

e.g. plastics, glues, chemical reactionse.g. plastics, glues, chemical reactions• Normal home – 0.014 to 0.042 mg/mNormal home – 0.014 to 0.042 mg/m33

• Natural background - < 1 µg/mNatural background - < 1 µg/m33 - mean 0.5 µg/m - mean 0.5 µg/m33

WHO Average Daily WHO Average Daily ExposureExposure

• Food 9.4 mg/dFood 9.4 mg/d

• Inhalation 1 mg/dInhalation 1 mg/d

• Water .15 mg/d Water .15 mg/d

Total: 10.55 mg/dTotal: 10.55 mg/d

OverviewOverview

• Normal physiological substanceNormal physiological substance– Endogenous formaldehyde 3-12ng/g Endogenous formaldehyde 3-12ng/g

tissuetissue– Liver 22mg/minLiver 22mg/min

• Essential for protein synthesisEssential for protein synthesis

• Normal part of Lipid MetabolismNormal part of Lipid Metabolism

Formaldehyde MetabolismFormaldehyde Metabolism

• Converted by enzymes in erythrocytes and Converted by enzymes in erythrocytes and liverliver

• Metabolised rapidly to formate and formic acidMetabolised rapidly to formate and formic acid

• Formic acid oxidized to COFormic acid oxidized to CO22 and Water and Water

• Formate is converted to sodium salt and Formate is converted to sodium salt and excreted or used in biosynthesisexcreted or used in biosynthesis

• Liver converts 22mg/minute of formaldehyde Liver converts 22mg/minute of formaldehyde to carbon dioxideto carbon dioxide

• Intravenous infusion: half-life of 1.5 minutesIntravenous infusion: half-life of 1.5 minutes

Formaldehyde Blood LevelsFormaldehyde Blood Levels

ControlControl ExposedExposed

Rats Rats (14.4 ppm, 2 hrs)(14.4 ppm, 2 hrs)

18 mg/m18 mg/m33

2.242.24 2.252.25

Monkeys Monkeys (6 ppm, 4 weeks)(6 ppm, 4 weeks)

7.5 mg/m7.5 mg/m33

2.422.42 1.841.84

Humans Humans (1.9 ppm, 40 mins)(1.9 ppm, 40 mins)

2.375 mg/m2.375 mg/m33

2.612.61 2.772.77

Normal Environmental Ambient ~3.0 ppb (peak 8.3 ppb) .02 Normal Environmental Ambient ~3.0 ppb (peak 8.3 ppb) .02 mg/m3mg/m3

Specific Cellular ActionsSpecific Cellular Actions

• Biocide classBiocide class

• Cross-linking in the cell membraneCross-linking in the cell membrane

• Damages cell contents – cross-linkingDamages cell contents – cross-linking– Nucleic AcidsNucleic Acids– Amino AcidsAmino Acids

CarcinogenicityCarcinogenicity

• WHO classification “probable carcinogen”WHO classification “probable carcinogen”• Naso-pharangeal cancer in mice and rats at Naso-pharangeal cancer in mice and rats at

high concentrations. Inhalation (18-25 mg/mhigh concentrations. Inhalation (18-25 mg/m33))• (Normal home – 0.014 to 0.042 mg/m(Normal home – 0.014 to 0.042 mg/m33))

• 900 to 1250 times normal daily exposure. 900 to 1250 times normal daily exposure. Humans can only tolerate 5-6.2 mg/mHumans can only tolerate 5-6.2 mg/m33 for 30 for 30 mins.mins.

• SCCs in 50% of rats @ 25 mg/mSCCs in 50% of rats @ 25 mg/m33, 6 hours a , 6 hours a day, 5 days a week, 2 years.day, 5 days a week, 2 years.

• 10-20 fold increase in cell proliferation of 10-20 fold increase in cell proliferation of lungs.lungs.

CarcinogenicityCarcinogenicity

• Naso-pharangeal carcinogenicity Naso-pharangeal carcinogenicity appears to be only riskappears to be only risk– Inhalation doesn’t increase blood Inhalation doesn’t increase blood

concentrations regardless of inhaled concentrations regardless of inhaled concentrationconcentration

Remember it is poisonous!!Remember it is poisonous!!

Cancer EpidemiologyCancer Epidemiology

• 2 studies following ~7500 UK 2 studies following ~7500 UK workers in formaldehyde factories workers in formaldehyde factories over ~20-40 yearsover ~20-40 years

• No cases of nasopharangeal cancerNo cases of nasopharangeal cancer

• UK death records reports 3 cases of UK death records reports 3 cases of nasopharangeal cancers in Doctors. nasopharangeal cancers in Doctors. None worked with formaldehyde None worked with formaldehyde (e.g. pathologists)(e.g. pathologists)

SummarySummary

• High concentration vapours for extended High concentration vapours for extended periods are only reasonable riskperiods are only reasonable risk

• Exposure to normal environmental Exposure to normal environmental formaldehyde is safe with no measurable formaldehyde is safe with no measurable changes to body function/blood levelschanges to body function/blood levels

• Exposure to formalin 10% on skin is safeExposure to formalin 10% on skin is safe

Formaldehyde is Poisonous!Formaldehyde is Poisonous!

Uses in DermatologyUses in Dermatology

• Hyperhidrosis – Mechanism, probable Hyperhidrosis – Mechanism, probable destruction of sweat glandsdestruction of sweat glands

• -cidal to most lines of cells – bacteria, -cidal to most lines of cells – bacteria, fungus, viruses, skin cells.fungus, viruses, skin cells.

• Treatment of BurnsTreatment of Burns• Verrucae Verrucae

– Cytotoxic to SkinCytotoxic to Skin– Irritates skinIrritates skin– Thins skinThins skin

Dermal ExposureDermal Exposure

• Absorption is non-existent or negligibleAbsorption is non-existent or negligible• Only a local effectOnly a local effect• There is no accumulation in body or skinThere is no accumulation in body or skin• Is a skin irritant and can cause allergic Is a skin irritant and can cause allergic

contact dermatitis – Can’t differentiatecontact dermatitis – Can’t differentiate• Dermatitis is caused Dermatitis is caused onlyonly by by

concentrations > 2% Formaldehydeconcentrations > 2% Formaldehyde• Is non-toxic to immune systemIs non-toxic to immune system

FormalinFormalin

• Commercial formaldehyde is 34.7 Commercial formaldehyde is 34.7 – 36% with buffering/diluting – 36% with buffering/diluting substancessubstances

• Dilute with water e.g. 5 ml Dilute with water e.g. 5 ml formaldehyde with 45 ml water = formaldehyde with 45 ml water = formalin 10%formalin 10%

• Formalin 10% is actually ~3.47% Formalin 10% is actually ~3.47% formaldehydeformaldehyde

• Vapours with head directly over Vapours with head directly over Formalin bottle may measure up Formalin bottle may measure up to 3mg/mto 3mg/m33

Study 1Study 1

• Vickers CFH. Treatment of plantar Vickers CFH. Treatment of plantar warts in children. Br Med J 1961; ii: warts in children. Br Med J 1961; ii: 743-5743-5

• 200 Children 6-8 weeks with 3% 200 Children 6-8 weeks with 3% FormaldehydeFormaldehyde

• 80% clearance rate80% clearance rate

Study 2Study 2

• Anderson I, Shirreffs E. The Anderson I, Shirreffs E. The treatment of Plantar Warts. Br J treatment of Plantar Warts. Br J Dermatol 1963: 75: 29-32Dermatol 1963: 75: 29-32

• Comparison: Formaldehyde soaks v Comparison: Formaldehyde soaks v Water soaks and saccharose by Water soaks and saccharose by mouth.mouth.

• Results: No difference between Results: No difference between groups.groups.

Study 3Study 3Formaldehyde 10% +/- MCAFormaldehyde 10% +/- MCA• Jennings MB. Unpublished 2004. New York Jennings MB. Unpublished 2004. New York

College.College.• N=46N=46• 4 weeks formaldehyde 10%4 weeks formaldehyde 10%• Then divide 2 groups placebo v MCA 2 Then divide 2 groups placebo v MCA 2

weekly (both continued formaldehyde 10%)weekly (both continued formaldehyde 10%)• Once daily application for less than 20 secs.Once daily application for less than 20 secs.• LazerformaldehydeLazerformaldehyde®® Roll-on by Pedinol Roll-on by Pedinol• Continued for further 8 weeksContinued for further 8 weeks• Results: Both ~75% cure rateResults: Both ~75% cure rate

Case StudyCase Study

• 23 y.o. female23 y.o. female

• Multiple Mosaic Warts, present 2 yearsMultiple Mosaic Warts, present 2 years

• Treatments from 2 Pods and GPTreatments from 2 Pods and GP

• Sal acid, Multiple Liq.Nitrogen, Sal acid, Multiple Liq.Nitrogen, Wartner, OcclusionWartner, Occlusion

• Worked as florist, damp feet and Worked as florist, damp feet and shoes, suffers chilblains shoes, suffers chilblains

Treatment regimeTreatment regime

• Apply Formalin 10% to affected areaApply Formalin 10% to affected area

• Apply with cotton bud for ~ 1min.Apply with cotton bud for ~ 1min.

• Once or twice dailyOnce or twice daily

• Debride once weekly with file/sand Debride once weekly with file/sand paper/pumice stonepaper/pumice stone

• No masking of areaNo masking of area

• Review at 4 weeksReview at 4 weeks