Formaldehyde General information Key Points Fire
Formaldehyde General information Key Points Fire Flammable Reactive with strong oxidising agents, bases and acrylonitrile Emits toxic fumes of carbon monoxide and carbon dioxide when heated to decomposition; and hydrogen gas on reaction with strong bases In the event of a fire involving formaldehyde, use alcohol resistant foam, or normal foam if not available, and liquid tight protective clothing with breathing apparatus Health Due to its gaseous nature, inhalation and eye exposure are most likely Possible carcinogen, toxic and corrosive Inhalation of formaldehyde can lead to irritation of the nose, mouth and throat. In severe cases, respiratory distress and swelling of the larynx and lungs may occur Ingestion of formaldehyde can cause burns and ulcers in the stomach or intestines in the early stages after ingestion. Chest or abdominal pain, sickness, diarrhoea and haemorrhages in the stomach or intestines may also result. Other clinical features include rapid breathing, yellowish discolouration of the skin, blood in the urine and kidney failure Exposure of the eyes to formaldehyde causes immediate stinging and burning with spasm of the eyelids and tearing. High concentrations may cause burns to the cornea Skin contact with concentrated formaldehyde gas can cause burns to the skin Environment Avoid release into the environment Inform Environment Agency of substantial incidents Prepared by J C Wakefield CHAPD HQ, HPA 2008 Version 1 FORMALDEHYDE – GENERAL INFORMATION Background Formaldehyde is a colourless, corrosive, flammable gas with a pungent, suffocating odour. Formaldehyde may be present in the environment from either natural or industrial sources. spasm of the eyelids and tearing. Exposure to high concentrations may cause burns to the cornea. Exposure of the skin to formaldehyde causes irritation with burns to the skin. Formaldehyde is produced in large quantities industrially. It is predominantly used commercially as a solution in water at concentrations in the range of 25 – 56 % formaldehyde. Formaldehyde is a common constituent used in the manufacture of many complex materials. It is used in the production of resin polymers for permanent adhesives such as those used in fibreboard, particle board, plywood and carpeting. It is also used in foam insulation and as paper and textile finishing treatments. Formaldehyde at approximately 5% in a solution with water is used as a disinfectant and fumigant in hospitals, ships, dwellings and animal handling facilities, as it is effective in killing most bacteria, viruses and fungi. Ingestion of formaldehyde solutions can cause burns and ulcers to the gastrointestinal tract in the early stages after ingestion. Formaldehyde ingestion may also cause chest or abdominal pain, nausea, vomiting, diarrhoea and gastrointestinal tract haemorrhage. Other clinical features can include rapid breathing, yellowish discolouration of the skin, blood in the urine and kidney failure. Formaldehyde is produced in the atmosphere due to the degradation of methane by sunlight. It is also released during the combustion of organic materials, and as such may be present in smoke from wood fires, automobile emissions and tobacco smoke. Small quantities of formaldehyde may also be produced as a product of metabolism by most organisms. Formaldehyde is very toxic to humans. The most common routes of exposure to formaldehyde gas are either inhalation or skin contact. However, solutions containing formaldehyde may also be toxic following ingestion. Repeated or prolonged skin contact with solutions of formaldehyde can give rise to skin sensitisation (allergic contact dermatitis) in some individuals, with symptoms such as redness, itching, rash and swelling of the skin. Children exposed to formaldehyde would be expected to display similar effects to those seen in exposed adults. Exposure to formaldehyde during pregnancy is not expected to cause damage to the unborn child at doses which do not cause adverse effects to the mother. Formaldehyde has been classified by the International Agency for Research on Cancer as carcinogenic to humans. It produces nasal tumours following prolonged exposure by inhalation to levels producing chronic irritant effects. Inhalation of formaldehyde gas will cause irritation to the nose, mouth and throat and in severe cases may cause respiratory distress and swelling of the larynx and lungs. Inhalation of formaldehyde may cause the onset of asthma in sensitive individuals. Exposure of the eyes to vapour or splashes of formaldehyde solutions causes irritation with immediate stinging and burning, with General information: Page 2 of 5 FORMALDEHYDE – GENERAL INFORMATION Production and Uses Key Points Formaldehyde can occur naturally in the environment and is also produced industrially Formaldehyde is mainly used commercially as a solution in water It is commonly used in the manufacture of resin polymers to produce permanent adhesives, foam insulation and paper and textile finishing treatments It is used as a disinfectant and fumigant in hospitals, ships, dwellings and animal handling facilities. Formaldehyde is also used to fix tissues for histology and pathology Formaldehyde can occur naturally in the environment as it is produced from the breakdown of methane by sunlight. Small quantities of formaldehyde may be produced as a product of metabolism by most organisms including humans. Formaldehyde is also released during the combustion of organic materials, and as such may be present in smoke from wood fires, automobile emissions and tobacco smoke. Formaldehyde is also produced in large quantities industrially. It is predominantly used commercially as a solution in water at concentrations in the range of 25 – 56 % formaldehyde. Formaldehyde is a common constituent used in the manufacture of many complex materials. It is used in the production of polymers such as urea formaldehyde resin, phenolic resins and melamine resin. A common use of these resins is in permanent adhesives such as those used in fibreboard, particle board, plywood and carpeting. They are also used in foam insulation and as paper and textile finishing treatments. Formaldehyde at approximately 5% in a solution with water is used as a disinfectant and fumigant in hospitals, ships, dwellings and animal handling facilities, as it is effective in killing most bacteria, viruses and fungi. A solution of approximately 37% formaldehyde is commonly known as formalin and is used as a tissue fixative for histology and pathology. General information: Page 3 of 5 FORMALDEHYDE – GENERAL INFORMATION Frequently Asked Questions What is formaldehyde? Formaldehyde is a colourless, corrosive, flammable gas with a pungent, suffocating odour. It may be present in the environment from either natural sources or it may be produced industrially. The main use of formaldehyde is in the production of resins for permanent adhesives used in fibreboard, particle board, plywood and carpeting. Formaldehyde has also been used as a disinfectant and fumigant. How does formaldehyde get into the environment? Formaldehyde can occur naturally in the environment from the breakdown of methane by sunlight. Formaldehyde is also released during the combustion of organic materials, and as such may be present in smoke from wood fires, automobile emissions and tobacco smoke. As formaldehyde is used industrially it may also enter the environment from workplaces where it is manufactured or used. How will I be exposed to formaldehyde? The greatest potential for exposure to formaldehyde is in occupations where it is manufactured or used. Anyone working with formaldehyde is at risk of inhaling the vapours if there is insufficient ventilation or if adequate protective equipment is not used. People working with formaldehyde are also at risk of getting splashes of it on their skin if they are not adequately protected. Ingestion of significant amounts of formaldehyde is not a common route of occupational exposure. As formaldehyde may also be present naturally in the environment, individuals may come into contact with very low levels of formaldehyde in air. If there is formaldehyde in the environment will I have any adverse health effects? The presence of formaldehyde in the environment does not always lead to exposure. Clearly, in order for it to cause any adverse health effects you must come into contact with it. You may be exposed by breathing, eating, or drinking the substance or by skin contact. Following exposure to any chemical, the adverse health effects you may encounter depend on several factors, including the amount to which you are exposed (dose), the way you are exposed, the duration of exposure, the form of the chemical and if you were exposed to any other chemicals. Inhalation of formaldehyde gas will cause irritation to the nose, mouth and throat and in severe cases may cause respiratory distress and swelling of the larynx and lungs. Inhalation of formaldehyde may cause the onset of asthma in sensitive individuals. Exposure of the eyes to vapour or splashes of formaldehyde solutions causes irritation with immediate stinging and burning, with spasm of the eyelids and tearing. Exposure to high concentrations may cause burns to the cornea. Exposure of the skin to formaldehyde causes irritation with burns to the skin. Ingestion of formaldehyde solutions can cause burns and ulcers to the gastrointestinal tract in the early stages after ingestion. Formaldehyde ingestion may also cause chest or abdominal pain, nausea, vomiting, diarrhoea and gastrointestinal tract haemorrhage. Other clinical features can include rapid breathing, yellowish discolouration of the skin, blood in the urine and kidney failure. General information: Page 4 of 5 FORMALDEHYDE – GENERAL INFORMATION Can formaldehyde cause cancer? Formaldehyde is known to be a cancer causing substance and has been classified by the International Agency for Research on Cancer as carcinogenic to humans. It may produce nasal cancer following repeated exposure via inhalation to levels that produce chronic irritation. Exposure to lower levels for shorter periods is not considered to present any carcinogenic risk. Does formaldehyde affect children or damage the unborn child? Children will be affected by formaldehyde in the same way as adults. However, the effects seen in children may potentially be more severe. Exposure of a pregnant mother to formaldehyde is not expected to cause damage to the unborn child at amounts below that which cause significant health effects to the mother. What should I do if I am exposed to formaldehyde? It is very unlikely that the general population will be exposed to a level of formaldehyde high enough to cause adverse health effects. This document from the HPA Centre for Radiation, Chemical and Environmental Hazards reflects understanding and evaluation of the current scientific evidence as presented and referenced in this document. General information: Page 5 of 5 Formaldehyde Incident management Key Points Fire Flammable Reactive with strong oxidising agents, bases and acrylonitrile Emits toxic fumes of carbon monoxide and carbon dioxide when heated to decomposition; and hydrogen gas on reaction with strong bases In the event of a fire involving formaldehyde, use alcohol resistant foam, or normal foam if not available, and liquid tight protective clothing with breathing apparatus Health Due to its gaseous nature, inhalation and ocular exposure are most likely Inhalation of formaldehyde can lead to irritation of the mucous membranes and respiratory tract. In severe cases laryngeal and pulmonary oedema, pneumonitis and acute respiratory distress syndrome may occur. Ingestion of concentrated formaldehyde solutions can cause burns and ulceration to the GI tract. Common features are a burning sensation in the mouth and throat, chest or abdominal pain, nausea, vomiting, diarrhoea and GI haemorrhage. Dermal exposure to formaldehyde solutions may cause skin irritation Formaldehyde is irritating to the eyes Environment Avoid release into the environment Inform Environment Agency of substantial incidents CRCE HQ, HPA 03/2012 Version 2 FORMALDEHYDE – INCIDENT MANAGEMENT Hazard Identification Standard (UK) Dangerous Goods Emergency Action Codes(a) 1198 Formaldehyde solution, flammable EAC ●2W Use alcohol resistant foam but, if not available, fine water spray can be used. Wear liquid-tight chemical protective clothing in combination with breathing apparatus*. Danger that the substance can be violently or explosively reactive. Spillages and decontamination run-off should be prevented from entering drains and watercourses. APP A(fl) Gas-tight chemical protective suit with breathing apparatus ** UN Class 3 Flammable liquid Sub risks 8 Corrosive substance Hazards HIN 38 UN 2209 EAC ●2X APP - Class 8 Sub risks - Flammable liquid (flash point between 23oC and 60oC inclusive), slightly corrosive or self-heating liquid, corrosive Formaldehyde solution, with not less than 25 % formaldehyde Use alcohol resistant foam but, if not available, fine water spray can be used. Wear liquid-tight chemical protective clothing in combination with breathing apparatus*. Spillages and decontamination run-off should be prevented from entering drains and watercourses. Corrosive substance Hazards HIN 80 Corrosive or slightly corrosive substance UN – United Nations number; EAC – Emergency Action Code; APP – Additional Personal Protection; HIN - Hazard Identification Number a Dangerous Goods Emergency Action Code List 2011. National Chemical Emergency Centre (NCEC). The Stationary Office, London. Incident management: Page 2 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT *Liquid-tight chemical protective clothing (BS 8428or EN 14605) in combination with selfcontained open circuit positive pressure compressed air breathing apparatus (BS EN 137). ** Gas-tight chemical protective clothing conforming to BS EN 943 part 2 in combination with self-contained open circuit positive pressure compressed air breathing apparatus to BS EN 137. Incident management: Page 3 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Chemical Hazard Information and Packaging for Supply Classification(a) Carc. Cat 3 Classification T Toxic C Corrosive R23/24/25 Toxic by inhalation, in contact with skin and if swallowed R34 Causes burns R40 Limited evidence of a carcinogenic effect R43 May cause sensitisation by skin contact S1/2 Keep locked up and out of the reach of children Risk phrases S26 Safety phrases Category 3 carcinogen S36/37/39 S45 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice Wear suitable protective clothing, gloves and eye/face protection In case of accident or if you feel unwell seek medical advice immediately (show the label where possible) Use only in well-ventilated areas S51 Specific concentration limits Concentration Classification C ≥25 % T; R23/24/25 5 % ≤ C < 25 % Xn; R20/21/22 C ≥25 % C; R34 5 % ≤ C < 25 % Xi; R36/37/38 C ≥ 0,2 % R43 a Annex VI to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures- Table 3.2. http://esis.jrc.ec.europa.eu/index.php?PGM=cla (accessed 03/2012) Incident management: Page 4 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Globally Harmonised System of Classification and Labelling of Chemicals ) (GHS)(a Carc. 2 Carcinogenicity, category 2 Acute Tox. 3 Acute toxicity, category 3 Skin Corr. 1B Skin corrosion, category 1B Skin Sens. 1 Skin sensitizer, category 1 Hazard Class and Category Hazard Statement Signal Words H351 Suspected of causing cancer H331 Toxic if inhaled H311 Toxic in contact with skin H301 Toxic if swallowed H314 Causes severe skin burns and eye damage H317 May cause an allergic skin reaction DANGER Implemented in the EU on 20 January 2009. Specific concentration limits Concentration Hazard Class and Category C ≥ 25 % Skin Corr. 1B Hazard Statement H314 Causes severe skin burns and eye a Annex VI to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures- Table 3.1. http://esis.jrc.ec.europa.eu/index.php?PGM=cla (accessed 03/2012) Incident management: Page 5 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT damage 5 % ≤ C < 25 % Skin Irrit. 2 H315 Causes skin irritation 5 % ≤ C < 25 % Eye Irrit. 2 H319 Causes serious eye irritation C≥5% STOT SE 3 H335 May cause respiratory irritation C ≥ 0,2 % Skin Sens. 1 H317 May cause an allergic skin reaction Incident management: Page 6 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Physicochemical Properties CAS number 50-00-0 Molecular weight 30 Empirical formula CH2O Common synonyms Methanal; Methylene glycol; Oxomethane; Methylene oxide; Methyl aldehyde State at room temperature Gas Volatility Vapour pressure 3,890 mm Hg at 25°C Specific gravity 1.1 at 25°C (air = 1) Flammability Flammable Lower explosive limit 7.0% Upper explosive limit 73.0% Water solubility Soluble in water at 25°C Reactivity Reactive. Formaldehyde can react violently with strong oxidising agents, causing risk of fire and explosion. Reacts with strong bases, producing hydrogen gas which is flammable. Reacts violently with acrylonitrile Reaction or degradation products Releases toxic fumes of carbon monoxide and carbon dioxide when heated to decomposition. Produces hydrogen gas on reaction with strong bases Odour Pungent, suffocating Structure References (a,b,c) Formaldehyde (HAZARDTEXT® Hazard Management). In: Klasco RK (Ed): TOMES® System, Thomson Micromedex, Greenwood Village, Colorado, USA. (electronic version). RightAnswer.com, Inc., Midland, MI, USA, Available at: http://www.rightanswerknowledge.com/data/dt/dt149.htm (accessed 01/2012). b The Merck Index (14th Edition). Entry 4235: Formaldehyde, 2006. c The Dictionary of Substances and their Effects. Ed. S Gangolli. Second Edition, Volume 4, 1999. a Incident management: Page 7 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Threshold Toxicity Values EXPOSURE VIA INHALATION ppm mg m-3 0.05 0.06 0.08 – 2.5 0.1 - 3 >5 >6 SIGNS AND SYMPTOMS Slight eye irritation a Throat and upper respiratory tract irritation a Lower airway and pulmonary irritation a a International Programme on Chemical Safety, Environmental Health Criteria 89: Formaldehyde, 1989. Incident management: Page 8 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Published Emergency Response Guidelines Emergency Response Planning Guideline (ERPG) Values(a) ERPG-1* ERPG-2** ERPG-3*** Listed value (ppm) 1 10 40 Calculated value (mg m-3) 1.2 12 48 * Maximum airborne concentration below which it is believed that nearly all individuals could be exposed for up to 1 hr without experiencing other than mild transient adverse health effects or perceiving a clearly defined, objectionable odour. ** Maximum airborne concentration below which it is believed that nearly all individuals could be exposed for up to 1 hr without experiencing or developing irreversible or other serious health effects or symptoms which could impair an individual's ability to take protective action. *** Maximum airborne concentration below which it is believed that nearly all individuals could be exposed for up to 1 hr without experiencing or developing life-threatening health effects. Interim Acute Exposure Guideline Levels (AEGLs)(b) AEGL-1† AEGL-2†† AEGL-3††† 10 min 0.9 14 100 30 min 0.9 14 70 ppm 60 min 0.9 14 56 4 hr 0.9 14 35 8 hr 0.9 14 35 † The level of the chemical in air at or above which the general population could experience notable discomfort. †† The level of the chemical in air at or above which there may be irreversible or other serious longlasting effects or impaired ability to escape. ††† The level of the chemical in air at or above which the general population could experience lifethreatening health effects or death. a American Industrial Hygiene Association (AIHA). 2011 Emergency Response Planning Guideline Values. http://www.aiha.org/insideaiha/GuidelineDevelopment/ERPG/Documents/2011erpgweelhandbook_tabl e-only.pdf (accessed 03/2012). b U.S. Environmental Protection Agency. Acute Exposure Guideline Levels, http://www.epa.gov/oppt/aegl/pubs/chemlist.htm (accessed 03/2012). Incident management: Page 9 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Exposure Standards, Guidelines or Regulations Occupational standards LTEL(8 hour reference period): 2 ppm (2.5 mg m-3) WEL(a) http://www.hse.gov.uk/ STEL(15 min reference period): 2 ppm (2.5 mg m-3) Public health guidelines DRINKING WATER QUALITY GUIDELINE(b) http://www.who.int/en/ No formal guideline value specified AIR QUALITY GUIDELINE(c) http://www.who.int/en/ 0.1 mg m-3 as a 30 minute average SOIL GUIDELINE VALUE AND HEALTH CRITERIA VALUES No guideline value specified WEL – Workplace exposure limit; LTEL - Long-term exposure limit; STEL – Short-term exposure limit a EH40/2005 Workplace Exposure Limits (second edition, published 2011). http://www.hse.gov.uk/pubns/priced/eh40.pdf (accessed 01/2012) b Guidelines for Drinking-Water Quality, Fourth Edition. WHO, Geneva. 2011. c Air Quality Guidelines for Europe. World Health Organization Regional Office for Europe, Copenhagen WHO Regional Publications, European Series, No. 91, Second Edition, 2000. Incident management: Page 10 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Health Effects Major route of exposure(a-b) Due to its gaseous nature, inhalation is the most likely route of exposure. Exposure to formaldehyde solutions may occur via ingestion and skin or eye contact. Immediate Signs or Symptoms of Acute Exposure(b-e) b c Inhalation of formaldehyde causes irritation of the mucous membranes and respiratory tract. Sore throat, rhinitis, nasal irritation, bronchospasm and breathlessness are common In severe cases, laryngeal and pulmonary oedema, pneumonitis and acute respiratory distress syndrome may occur. Ingestion of concentrated formaldehyde solutions can cause burns and ulceration to the GI tract. Common features are a burning sensation in the mouth and throat, chest or abdominal pain, nausea, vomiting, diarrhoea and GI haemorrhage. The most severe damage is found in the stomach; perforation has been reported. Rarely, free fluid has been demonstrated in the abdomen in the absence of obvious perforation. Hypotension and shock are common. Restlessness, drowsiness, coma and convulsions may also occur. Respiratory failure occasionally secondary to acute respiratory distress syndrome may also complicate severe poisoning. Death from circulatory collapse may occur in severe cases. Other clinical features include metabolic acidosis, disseminated intravascular coagulation, jaundice, proteinuria, albuminuria, haematuria, hyperglycaemia , minor increase in transaminase activity and methaemoglobinaemia. Dermal contact with solutions of formaldehyde may produce skin irritation. Sensitisation caused by dermal contact has been reported frequently. In some individuals, formaldehyde can react with proteins in the epidermis, producing haptenprotein complexes that are capable of sensitising T lymphocytes so that subsequent exposures result in allergic contact dermatitis through a type IV hypersensitivity reaction. Formaldehyde is irritating to the eyes. TOXBASE - http://www.toxbase.org (accessed 01/2012) a TOXBASE: Formaldehyde, 2011 b TOXBASE: Formalin and formaldehyde solutions- ingestion, 2011 c TOXBASE: Formaldehyde – Inhalation, 2011 d TOXBASE: Formalin and formaldehyde solutions – skin contact, 2011. e TOXBASE: Formalin and formaldehyde solutions – eye contact, 2011. Incident management: Page 11 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Decontamination and First Aid Important Notes Ambulance staff, paramedics and emergency department staff treating chemicallycontaminated casualties should be equipped with Department of Health approved, gas-tight (Respirex) decontamination suits based on EN466:1995, EN12941:1998 and prEN943-1:2001, where appropriate. Decontamination should be performed using local protocols in designated areas such as a decontamination cubicle with adequate ventilation. Dermal exposure(a) Remove patient from exposure. Do NOT apply neutralising chemicals as heat produced during neutralization reactions may cause thermal burns and increase injury. Contaminated clothing and any particulate matter adherent to skin should be removed and the patient washed with copious amounts of water under low pressure for at least 10-15 minutes, or until pH of skin is normal (pH of the skin is 4.5 – 6 although it may be closer to 7 in children, or after irrigation). The earlier irrigation begins, the greater the benefit. Pay special attention to skin folds, fingernails and ears. Recheck pH of affected areas after a period of 15-20 minutes and repeat irrigation if abnormal. Burns with strong solutions may require irrigation for several hours or more. Once the pH is normal and stabilised, treat as per a thermal injury. Burns totalling more than 15% of body surface area in adults (>10% in children) will require standard fluid resuscitation as for thermal burns. Moderate/severe chemical burns should be reviewed by a burns specialist. Excision or skin grafting may be required. Other measures as indicated by the patient's clinical condition Ocular exposure(b) Remove patient from exposure. Remove contact lenses if present and immediately irrigate the affected eye thoroughly with water or 0.9% saline for at least 10-15 minutes. Continue until the conjunctival sac pH is normal (7.5 - 8.0), retest after 20 minutes and use further irrigation if necessary.. Any particles lodged in the conjunctival recesses should be removed. Patients with corneal damage or those whose symptoms do not resolve rapidly should be referred for urgent ophthalmological assessment. Inhalation(c) Remove patient from exposure. Ensure a clear airway and adequate ventilation. Give high-flow oxygen through a tight-fitting mask. Apply other supportive measures as indicated by the patient’s clinical condition. TOXBASE - http://www.toxbase.org (accessed 01/2012) a TOXBASE: Skin decontamination – corrosives, 2010. b TOXBASE: Chemicals splashed or sprayed into the eyes, 2007. c TOXBASE: Formaldehyde – Inhalation, 2011 Incident management: Page 12 of 13 FORMALDEHYDE – INCIDENT MANAGEMENT Ingestion(a) Ensure a clear airway and adequate ventilation. There is no role for either gastric lavage or activated charcoal. Look for evidence of burns in the mouth and throat and watch for features of GI haemorrhage. Monitor pulse, blood pressure and urine output. Apply other supportive measures as indicated by the patient’s clinical condition. This document from the HPA Centre for Radiation, Chemical and Environmental Hazards reflects understanding and evaluation of the current scientific evidence as presented and referenced in this document. TOXBASE - http://www.toxbase.org (accessed 01/2012) a TOXBASE: Formalin and formaldehyde solutions- ingestion, 2011 Incident management: Page 13 of 13 Formaldehyde Toxicological overview Key Points Kinetics and metabolism Formaldehyde is readily absorbed following inhalation and ingestion, but poorly absorbed following dermal exposure Formaldehyde is rapidly metabolised at the initial site of contact into formate prior to reaching the systemic circulation Negligible amounts of inhaled or ingested formaldehyde reach the systemic circulation It is eliminated either by urinary excretion as formic acid or exhaled as carbon dioxide Health effects of acute exposure Acute inhalation exposure to formaldehyde results in irritation and burning of the mucous membranes of the nose, mouth and upper respiratory tract Severe inhalation may cause weakness, headache, nausea, vomiting, pneumonia, dyspnoea, wheezing, coughing, laryngeal and pulmonary oedema, bronchospasm, respiratory depression, laryngeal spasm, CNS depression, convulsions and coma Acute ingestion will cause irritation, ulceration, burns and haemorrhage to the gastrointestinal tract, as well as metabolic acidosis, tachypnoea, jaundice and acute renal failure Formaldehyde is corrosive and can cause irritation and burns to the skin and irritation of the eyes. Ocular exposure may result in permanent vision alterations or blindness Health effects of chronic exposure Chronic exposure to formaldehyde causes irritation of the mucous membranes tract as observed following acute exposure and may be associated with temporarily decreased lung function Chronic dermal exposure can lead to skin irritation and may cause skin sensitisation (allergic contact dermatitis) Formaldehyde is a human carcinogen Prepared by J C Wakefield CHAPD HQ, HPA 2008 Version 1 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Toxicological Overview Summary of Health Effects Formaldehyde is readily absorbed from the respiratory tract following inhalation, and from the gastrointestinal tract following ingestion, but is poorly absorbed following dermal exposure [1, 2]. Ingestion of formaldehyde is not a common route of exposure to formaldehyde in humans and much of the data relating to the adverse effects of oral ingestion are from case reports of acute poisoning incidents [1]. The predominant effects following an acute inhalation exposure to formaldehyde is irritation and burning of the mucous membranes of the nose, mouth and upper respiratory tract [2]. Some adverse effects following acute exposure to large amounts of formaldehyde may include weakness, headache, nausea, vomiting, pneumonia, dyspnoea, wheezing, coughing, laryngeal and pulmonary oedema, bronchospasm, laryngeal spasm, respiratory depression, obstructive tracheo-bronchitis, central nervous system depression, convulsions and coma [2, 3]. The onset of pulmonary oedema may be delayed for 24-48 hours post exposure and may be fatal [3, 4]. Acute ingestion of formaldehyde will lead to irritation and burns of the mouth and throat and burns and ulceration of the gastrointestinal tract, chest or abdominal pain, nausea, vomiting, diarrhoea, gastrointestinal haemorrhage and renal failure [2, 5]. Formaldehyde is corrosive and can cause irritation and burns to the skin and irritation of the eyes [1-3]. Ocular exposure to formaldehyde may result in permanent alterations to vision or blindness [6]. Repeated or prolonged occupational exposure to formaldehyde causes irritation of the mucous membranes tract similar to that observed following acute exposure [1]. Occupational exposure to formaldehyde vapour has been associated with temporary reversible decreases in lung function [3]. Repeated or prolonged dermal exposure to splashes of solutions containing formaldehyde can lead to skin irritation and may also cause skin sensitisation (allergic contact dermatitis) [2]. Formaldehyde is not considered to be a reproductive or developmental toxicant at exposures below those which result in significant maternal toxicity [7]. The International Agency for Research on Cancer has evaluated that there is sufficient evidence for the carcinogenicity of formaldehyde both in humans and in experimental animals. Formaldehyde is therefore considered to be carcinogenic to humans (group 1) [7]. Toxicological overview: Page 2 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Kinetics and metabolism Formaldehyde is readily absorbed from the respiratory tract following inhalation, and from the gastrointestinal tract following ingestion, but is poorly absorbed following dermal exposure [1, 2]. Studies involving human volunteers and experimental animals have demonstrated that inhalation exposure to formaldehyde resulted in only local absorption in the upper respiratory tract, with any absorbed formaldehyde rapidly undergoing metabolism prior to reaching the systemic circulation [1]. Formaldehyde is metabolised at the initial site of contact into formate, by formaldehyde dehydrogenase [1]. Formaldehyde is naturally a metabolic intermediate produced in all cells during the metabolism of serine, glycine, methionine and choline [1]. Neither formaldehyde or its metabolites accumulate in any of the body tissues to any appreciable extent. However, the elimination of formate is slower than its formation from formaldehyde [2]. Formaldehyde is eliminated mainly by urinary excretion as formic acid or exhaled as carbon dioxide [1-3]. Sources and route of human exposure The major source of exposure to exogenous formaldehyde is from occupational exposure, since it is produced and used in large quantities industrially. Formaldehyde is used in the manufacture of many permanent adhesives such as those used to produce plywood, fibreboard, particle board and carpet adhesives [1-3]. Small amounts of formaldehyde may be released into the environment by off-gassing from such materials [2, 3]. Formaldehyde in solutions of approximately 5% in water is also used as a disinfectant and fumigant in hospitals [1-3]. Small amounts of formaldehyde occur naturally in the environment and may also be present in the emissions from the combustion of organic materials such as wood and tobacco smoke, and automobile emissions [1-3]. However, the amounts of formaldehyde present from such sources are likely to be smaller than may be found in an occupational setting [2]. In occupational settings the level of formaldehyde in the air should be controlled to the occupational exposure standard (2 ppm in the UK) by adequate ventilation, if this cannot be achieved breathing protection should be used [4]. Adequate personal protective equipment is also recommended to protect against skin contact from splashes of formaldehyde solutions [4]. The major routes of occupational exposure to formaldehyde are by inhalation of vapour or by dermal contact with splashes of formaldehyde solutions. However, ingestion of formaldehyde is not a significant occupational hazard [1-3]. Toxicological overview: Page 3 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Health Effects of Acute / Single Exposure Human Data General toxicity Formaldehyde is toxic by inhalation and ingestion. Formaldehyde is also a severe irritant to the skin, eyes, mouth, nose and upper respiratory tract [1-4]. Inhalation The predominant effects following an acute inhalation exposure to formaldehyde is irritation and burning of the mucous membranes of the nose, mouth and upper respiratory tract [2]. Acute inhalation exposure to large amounts of formaldehyde may also give rise to weakness, headache, nausea, vomiting, pneumonia, dyspnoea, wheezing, coughing, laryngeal and pulmonary oedema, bronchospasm, laryngeal spasm, respiratory depression, obstructive tracheo-bronchitis, central nervous system depression, convulsions and coma [2, 3]. Inhalation of significant amounts of formaldehyde may be fatal due to the onset of pulmonary oedema or respiratory failure [2]. Ingestion Acute ingestion of solutions of formaldehyde is not likely to be a significant route of occupational exposure. Much of the data relating to the adverse effects of oral ingestion of formaldehyde in humans are from case reports of acute poisoning incidents [1]. Acute ingestion of formaldehyde will lead to irritation and burns of the mouth and throat and burns and ulceration of the gastrointestinal tract, chest or abdominal pain, nausea, vomiting, diarrhoea and gastrointestinal haemorrhage [2, 5]. Formaldehyde ingestion may also result in metabolic acidosis, tachypnoea, jaundice, proteinuria, haematuria and acute renal failure [5]. Dermal / ocular exposure Exposure to either gaseous formaldehyde or splashes of solutions containing formaldehyde are corrosive and can cause irritation and burns to the skin and irritation of the eyes [1-3]. Ocular exposure to formaldehyde may result in permanent alterations to vision or blindness [6]. Delayed effects following an acute exposure Following an acute inhalation exposure of formaldehyde, the onset of pulmonary oedema which may be delayed for 24 to 48 hours post-exposure [3, 4]. Toxicological overview: Page 4 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Animal and In-Vitro Data General toxicity The acute toxicity of formaldehyde in experimental animals appears similar to that observed in humans, with local irritation being the most common adverse effect [1, 2]. Inhalation The LC50 for formaldehyde in rats following a 4-hour exposure is 578 mg m-3 (471 ppm), whilst in mice the 4-hour LC50 is 497 mg m-3 (405 ppm) [2]. Mice exposed to formaldehyde by inhalation at 0.6 mg m-3 (0.5 ppm) developed irritation of the eyes, nose and throat [2]. Severe irritation and damage to the epithelium of the nasal cavity has been observed in rats exposed to formaldehyde at concentrations above 2-6 ppm (2.5 – 7.4 mg m-3) [1, 3]. Ingestion The oral LD50 for formaldehyde in rats is 800 mg kg-1 body weight [2]. However, there is little data available relating to the adverse health effects of formaldehyde in experimental animals following acute oral exposure [1, 2]. Dermal / Ocular Solutions of formaldehyde have been shown to produce mild to moderate skin irritation following a 4-hour application of a 37% solution [6]. Formaldehyde has been shown to be an eye irritant in rabbits [2]. Toxicological overview: Page 5 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Health Effects of Chronic / Repeated Exposure Human Data Inhalation Repeated or prolonged inhalation exposure to formaldehyde as may be experienced in occupational settings causes irritation of the mucous membranes of the eyes, nose, mouth and upper respiratory tract similar to that observed following acute exposure [1]. Occupational exposure to formaldehyde vapour has been associated with temporary reversible decreases in lung function [3]. Chronic inhalation of formaldehyde does not lead to respiratory sensitisation but can cause symptoms of asthma in susceptible individuals due to respiratory irritation [3]. Dermal / Ocular Repeated or prolonged dermal exposure to splashes of solutions containing formaldehyde can lead to skin irritation or allergic contact dermatitis and may also cause skin sensitisation [2]. Following sensitisation dermal contact with small amounts of formaldehyde will give rise to outbreaks of dermatitis which may spread from the hand and arms to the body and face [6]. Genotoxicity There is some evidence to suggest that formaldehyde may be genotoxic in humans. Studies of workers occupationally exposed to formaldehyde showed increases in DNA-protein crosslinks compared to non-exposed individuals [1, 7]. Another study of workers exposed to formaldehyde showed significant increases in chromosomal aberrations and chromosomal breakage compared to unexposed controls. However, in the same study, no differences were observed in the incidences of sister chromatid exchange and unscheduled DNA synthesis and repair [1]. The Committee on Mutagenicity (COM) considered a number of biomonitoring studies of genotoxicity in workers exposed to formaldehyde in a variety of occupations. They concluded that there was no convincing evidence regarding direct systemic mutagenic effects of formaldehyde from the available biomonitoring studies. They suggested that a secondary mechanism might be involved, with regard to the genotoxic effects documented in peripheral blood lymphocytes, in the biomonitoring studies reviewed [8]. The COM concluded that there was no reason to consider that direct systemic mutagenicity would be involved in the mechanism of formaldehyde-induced systemic mutagenicity. For occupational and environmental exposure to formaldehyde, the pattern of metabolism and distribution indicates that a threshold level for in vivo systemic mutagenicity is likely [8]. Carcinogenicity The International Agency for Research on Cancer (IARC) has evaluated that there is sufficient evidence for the carcinogenicity of formaldehyde in humans, and has therefore concluded that formaldehyde is carcinogenic to humans (group 1) [7]. Toxicological overview: Page 6 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Occupational exposure of workers to formaldehyde has been associated with a significant increase in mortality due to nasopharyngeal cancers compared with the US national population [7]. The results from the largest and most informative cohort of industrial workers in the USA, supported by largely positive findings from other studies, provide sufficient evidence that formaldehyde causes nasopharyngeal cancer in humans. There was only limited epidemiological evidence that formaldehyde causes sinonasal cancer in humans [7]. There is strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to formaldehyde. Increased risk for leukaemia has consistently been observed in studies of professional workers and in 2 of 3 of the most relevant studies of industrial workers. These findings fall slightly short of being fully persuasive because of some limitations in the findings from the cohorts of industrial and garment workers in the USA and because they conflict with the non-positive findings from the British cohort of industrial workers [7]. Reproductive and developmental toxicity There have been relatively few studies investigating the reproductive and developmental toxicity of formaldehyde. One study noted an increased incidence of menstrual disorders, anaemia, toxaemia and low birth weight of offspring in female workers exposed to ureaformaldehyde [2]. Of these studies there is insufficient evidence to determine whether formaldehyde causes reproductive toxicity, due to limitations such as small sample sizes, no information of confounding factors, self-reporting and a lack of information regarding concurrent exposure to other potentially harmful compounds [2, 3]. Formaldehyde is not expected to cause reproductive or developmental toxicity at exposures below maternally toxic doses [7]. Animal and In-Vitro Data Inhalation The chronic toxicity of formaldehyde has been investigated in male rats exposed by wholebody inhalation to concentrations up to 15 ppm (18.4 mg m-3) for 6 hours day-1, 5 days week-1 for 6 weeks. At doses above 6 ppm (7.4 mg m-3), a dose dependent increase in lesions of the nasal passages was observed, in addition to a significant increase in cell proliferation in the nasal cavity [3]. Mice exposed to formaldehyde by inhalation at concentrations up to 40 ppm (49.1 mg m3) for 6 hours day-1, 5 days week-1 for 13 weeks displayed a marked reduction in body weight, laboured breathing, listlessness, hunched posture and loss of coordination at concentrations of 20 ppm (24.6 mg m-3) and above. In this study, damage to the trachea and larynx were also noted at 20 and 40 ppm formaldehyde [3]. Ingestion Male and female Wistar rats exposed to formaldehyde in drinking water for up to 2 years displayed a significant reduction in body weight compared to the controls at 82 mg kg-1 body weight day-1 for the males and 109 mg kg-1 body weight day-1 in the females. The body weight reduction was associated with a decrease in food and water intake, with terminal weights approximately 10 – 15% lower than the control animals [1, 6]. In this study, gastrointestinal lesions including papillomatous hyperplasia and hyperkeratosis, chronic atrophic gastritis, focal ulceration in the forestomach and hyperplasia in the glandular stomach were first observed at the same concentrations after 53 weeks [1]. An increase in Toxicological overview: Page 7 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW renal papillary necrosis was also observed in this study in both male and female rats at 82 mg kg-1 and 109 mg kg-1, respectively, which in the female rats was also accompanied by a relative increase in kidney weight [1]. Dermal Hairless mice dermally exposed to 0.2 ml of a 10% aqueous solution of formaldehyde, 2 times week-1 for 60 weeks, developed epidermal hyperplasia and some mice developed cutaneous ulcers [1, 6]. Studies in guinea pigs, using the guinea pig maximisation test and the Beuhler test, and in mice using the local lymph node assay, have confirmed that repeated dermal exposure to formaldehyde causes skin sensitisation [1, 6]. Genotoxicity The potential of formaldehyde to induce genetic mutations has been extensively studied in vitro in the Ames test using strains of Salmonella typhimurium both with and without metabolic activation with liver S9 fraction. Both positive and negative results have been obtained [2, 3, 6]. Formaldehyde has been found to be positive for mutations in many mammalian culture systems in the absence of metabolic activation. An increase in sister chromatid exchanges was reported in cultured human lymphocytes treated with formaldehyde [2]. Positive results have also been obtained for unscheduled DNA synthesis and chromosomal aberrations in the absence of metabolic activation [2, 3]. These data suggest that formaldehyde does possess significant direct acting mutagenic potential in vitro. In-vivo studies in rats and monkeys exposed to formaldehyde by inhalation at 6 ppm (7.4 mg m-3) have reported positive results for DNA-protein cross-links in the nasal mucosa [3, 7]. Positive results for chromosomal aberrations have also been obtained in lung cells of rats exposed to 15 ppm (18.4 mg m-3) formaldehyde by inhalation [3]. Studies of the potential for formaldehyde to induce sister chromatid exchange in the bone marrow of mice exposed by inhalation have however, proved to be inconclusive. These studies suggest that formaldehyde has direct acting mutagenic potential in vivo. The available in-vivo tests for mutagenicity using the well established bone marrow assays for chromosome aberrations or micronuclei induction, using either the inhalation or the intraperitoneal route were predominantly negative [2, 7, 8]. They also considered the reported positives for a dominant lethal effect in in-vivo germ cell assays using this endpoint and concluded that it was unlikely that the effects resulted from a systemic mutagenic effect of formaldehyde [8]. The mode of action regarding the induction of nasopharyngeal tumours in rats following inhalation is consistent with formation of formaldehyde DNA protein cross links with a similar dose-response to the formation of nasal tumours, with consequent marked local effects on cytotoxicity, cell proliferation and local site of contact mutagenic events being key elements. The magnitude of the formaldehyde induced local site of contact proliferation was emphasised [8]. Overall, formaldehyde has been investigated for its genotoxic potential using both in-vitro and in-vivo studies. Based on these results, formaldehyde is considered to be mutagenic at the site of contact. Toxicological overview: Page 8 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW Carcinogenicity Evidence of the carcinogenicity of formaldehyde was observed in several studies of rats exposed by inhalation, particularly by the induction of squamous cell carcinomas in the nasal cavities [7]. Similar studies in hamsters showed no evidence of carcinogenicity, and studies in mice either showed no effect, or were inadequate to allow evaluation [3, 7]. Studies in rats exposed to formaldehyde in drinking water have also shown evidence of carcinogenicity. A study in male rats demonstrated an increase in forestomach papillomas. A further study in both male and females rats showed an increase in gastrointestinal leiomyosarcomas, particularly in the females, whilst another study identified an increased incidence in the male rats of malignant tumours, lymphomas, leukaemias and testicular interstitial-cell adenomas [7]. Overall, IARC has concluded that there is sufficient evidence for the carcinogenicity of formaldehyde in experimental animals [7]. Reproductive and developmental toxicity Studies of the reproductive and developmental toxicity of formaldehyde in rats, mice, rabbits and dogs following inhalation, ingestion or dermal exposure have not identified any embryotoxic, fetotoxic or teratogenic effects at doses below those causing significant maternal toxicity [2, 6, 7]. Therefore formaldehyde is not considered to be a reproductive or developmental toxicant. Toxicological overview: Page 9 of 10 FORMALDEHYDE – TOXICOLOGICAL OVERVIEW References [1] Agency for Toxic Substances and Disease Registry (ATSDR) (1999). Toxicological Profile for Formaldehyde. US department of Health and Human Services. Atlanta, US. [2] International Programme on Chemical Safety (IPCS) (1989). Formaldehyde. Environmental Health Criteria 89. WHO. Geneva. [3] Canadian Centre for Occupational Formaldehyde gas, Cheminfo. [4] International Programme on Chemical Safety (IPCS) (2004). Formaldehyde. International Chemical Safety Card: 0275. WHO. Geneva. [5] National Poisons Information Service (NPIS) (2002). Formaldehyde. TOXBASE®. [6] Canadian Centre for Occupational Formaldehyde solutions, Cheminfo. [7] International Agency for the Research on Cancer (IARC) (2004). Formaldehyde. Vol 88. IARC. Lyon. [8] Committee on Mutagenicity (COM) (2007). Formaldehyde: Evidence for Systemic Mutagenicity. COM/07/S5. Health Health and and Safety Safety (CCOHS) (CCOHS) (2004). (2004). This document from the HPA Centre for Radiation, Chemical and Environmental Hazards reflects understanding and evaluation of the current scientific evidence as presented and referenced in this document. Toxicological overview: Page 10 of 10
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