Hydrogen Sulphide General Information Key Points Fire Very flammable Reacts with metals, metal oxides and strong oxidising agents. Heating may cause violent combustion Emits toxic fumes of sulphur oxides when heated to decomposition In the event of a fire involving hydrogen sulphide, use fine water spray and gas tight kit with breathing apparatus Health Toxic by inhalation Very toxic Inhalation of high concentrations may lead to collapse, inability to breathe and death within minutes. Following single or repeated exposure to high concentrations a range of effects on the nervous and cardiovascular system may occur. Skin exposure causes skin discolouration, pain, itching, skin redness and local frostbite if exposed to liquefied hydrogen sulphide gas Eye effects may be delayed and include irritation, inflammation, tearing, sensitivity to light and conjunctivitis Environment Dangerous for the environment Inform Environment Agency of substantial incidents Prepared by the Toxicology Department CRCE, PHE 2009 Version 1 HYDROGEN SULPHIDE – GENERAL INFORMATION Background Hydrogen sulphide is a colourless, flammable gas with a characteristic odour of rotten eggs. It is produced both naturally and through human activity. Hydrogen sulphide is one of the key compounds in the natural cycle of sulphur in the environment. It is produced during the decay of plant and animal protein and it occurs in volcanic gases. Some natural gas fields and geothermally active areas have found significant concentrations of hydrogen sulphide. Skin exposure may also occur, which may cause discolouration, pain, itching, redness of skin and local frostbite. Eye exposure may cause irritation, inflammation, tearing, sensitivity to light and conjunctivitis. Hydrogen sulphide is usually produced as an undesirable by-product, such as in the production of coke from sulphur-containing coal, the refining of sulphur-containing crude oils and from producing wood pulp. However in some processes it is an important reagent or intermediate such as in the manufacture of sulphuric acid, inorganic sulphides and as an agricultural disinfectant. Exposure to hydrogen sulphide usually occurs as a result of an accidental spill or leak during transportation, manufacturing or disposal. Occupational exposure may occur in oil, gas and petrochemical industries. Hydrogen sulphide is a gas therefore it is most likely to be breathed in. Skin and eye contact may also occur. The nervous system and cardiovascular system are most affected by hydrogen sulphide, leading to a range of symptoms. Single exposures to high concentrations may rapidly cause breathing difficulties and death. General Information: Page 2 of 3 HYDROGEN SULPHIDE – GENERAL INFORMATION Frequently Asked Questions What is hydrogen sulphide? Hydrogen sulphide is a colourless, flammable gas with a characteristic odour of rotten eggs. How does hydrogen sulphide get into the environment? Hydrogen sulphide occurs both naturally and through human activity. It may be released from a number of human activities such as production of coke from sulphur-containing coal, the refining of sulphur-containing crude oils and from producing wood pulp. How will I be exposed to hydrogen sulphide? You may be exposed to hydrogen sulphide by breathing it in, or skin and eye contact. If there is hydrogen sulphide in the environment will I have any adverse health effects? The presence of hydrogen sulphide 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 it in, or by skin and eye 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 in which you are exposed, the duration of exposure, the form of the chemical and if you were exposed to any other chemicals. Health effects following inhalation of high concentrations of hydrogen sulphide may include collapse, inability to breathe and death within minutes. A range of effects on the nervous and cardiovascular system may occur following single or repeated exposures to high hydrogen sulphide concentrations. Skin discolouration, pain, itching, skin redness and local frostbite may occur if skin is exposed to compressed hydrogen sulphide liquid. Eye exposure may cause irritation, inflammation, tearing, sensitivity to light and conjunctivitis. Can hydrogen sulphide cause cancer? There is no evidence to suggest that exposure to hydrogen sulphide would cause cancer in humans. Does hydrogen sulphide affect children or damage the unborn child? Children will be affected by hydrogen sulphide in the same way as adults, however because hydrogen sulphide is heavier than air and children are shorter than adults, children may be exposed to higher concentrations than adults. There is no evidence to suggest that exposure to hydrogen sulphide can affect the health of the unborn child. What should I do if I am exposed to hydrogen sulphide? It is very unlikely that the general population will be exposed to a level of hydrogen sulphide high enough to cause adverse health effects. This document has been created by the PHE Centre for Radiation, Chemical and Environmental Hazards. The information contained in this document is correct at the time of its publication. General Information: Page 3 of 3 Hydrogen Sulphide Incident Management Key Points Fire Very flammable Incompatible with metals and strong oxidising agentsEmits toxic fumes of sulphur oxides when heated to decomposition In the event of a fire involving hydrogen sulphide, use fine water spray and gas tight kit with breathing apparatus Health Toxic by inhalation Prolonged inhalation causes respiratory tract irritation and systemic effects including vomiting, diarrhoea, headache,s dizziness, drowsiness, tachycardia and convulsionsInhalation of high concentrations leads rapidly to collapse, respiratory paralysis, coma cardiac arrhythmias and death Eye exposure causes pain, blepharospasm, lacrimation, conjunctivitis and photophobia Dermal contact can result in itching, pain, redness and skin discolouration Environment Acute hazard to the aquatic environment Inform Environment Agency of substantial incidents Prepared by the Toxicology Department CRCE, PHE 02/2013 Version 2 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Hazard Identification Standard (UK) Dangerous Goods Emergency Action Codes(a) UN 1053 EAC 2WE APP A(cf) Hydrogen sulphide Use fine water spray. 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. There may be a public safety hazard outside the immediate area of the incident**. Gas-tight chemical protective suit with breathing apparatus. Liquefied flammable gas with a boiling point below -20 oC. Class 2.3 Toxic gases Sub risks 2.1 Flammable gases 263 Toxic gas, flammable Hazards HIN UN – United Nations number; EAC – Emergency Action Code; APP – Additional Personal Protection; HIN - Hazard Identification Number *Liquid-tight chemical protective clothing (BS 8428) in combination with self-contained open circuit positive pressure compressed air breathing apparatus (BS EN 137). ** People should stay indoors with windows and doors closed, ignition sources should be eliminated and ventilation stopped. Non-essential personnel should move at least 250 m away from the incident. a Dangerous Goods Emergency Action Code List 2011. National Chemical Emergency Centre (NCEC). The Stationary Office, London. Incident Management: Page 2 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Chemical Hazard Information and Packaging for Supply Classification(a) Classification Risk phrases Safety phrases F+ Very flammable T+ Very toxic N Dangerous for the environment R12 Extremely flammable R26 Very toxic by inhalation R50 Very toxic to aquatic organisms S1/2 Keep locked up and out of the reach of children S9 Keep container in a well-ventilated place S16 Keep away from sources of ignition - No smoking S36 Wear suitable protective clothing S38 S45 S61 In case of insufficient ventilation wear suitable respiratory equipment In case of accident or if you feel unwell seek medical advice immediately (show the label where possible) Avoid release to the environment. Refer to special instructions/safety data sheet 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 02/2013) Incident Management: Page 3 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Globally Harmonised System of Classification and Labelling of Chemicals * (GHS)(a) Flam. Gas 1 Flammable gas, category 1 Press. Gas Gas under pressure Hazard Class and Category Hazard Statement Acute Tox. 2 Acute toxicity (inhalation), category 2 Aquatic Acute 1 Acute hazard to the aquatic environment H220 Extremely flammable gas. H330 Fatal if inhaled. H400 Very toxic to aquatic life. Signal DANGER Words * Implemented in the EU on 20 January 2009. 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 02/2013) Incident Management: Page 4 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Physicochemical Properties CAS number 7783-06-4 Molecular weight 34.0 Empirical formula H2S Common synonyms H2S, hydrosulphuric acid, sulphur hydride, dihydrogen monosulphide State at room temperature Gas Volatility Vapour pressure = 20 atm (at 25.5 oC) Specific gravity 1.19 (air = 1) Flammability Highly flammable Lower explosive limit 4.3 % Upper explosive limit 46 % Reaction or degradation products 0.5 g 100 ml-1 water at 20 oC. Soluble in water. Water solutions of hydrogen sulphide are not stable; absorbed oxygen leads to the formation of elemental sulphur and such solutions rapidly become turbid. Soluble in glycerol, alcohol, gasoline, crude oil, and kerosene May form explosive mixture with air. It may easily be ignited by sparks, flames or heat. Note wide explosive limits. Incompatible with metals and strong oxidizing agents.. Heating may cause violent combustion or explosion. Attacks many metals and some plastics. The substance decomposes on burning producing toxic gases (sulphur oxides). Odour Strong odour of rotten eggs Water solubility Reactivity S Structure H H (a,b,c) Table references a Hydrogen sulphide (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 (accessed 02/2013). b International Programme on Chemical Safety (IPCS): Hydrogen sulphide. International Chemical Safety Card: 0165,.2000, WHO: Geneva. c The Merck Index (14th Edition). Entry 4800:Hydrogen sulphide, 2006. Incident Management: Page 5 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Threshold Toxicity Values EXPOSURE VIA INHALATION ppm mg m-3 10 - 20 15 - 30 50 - 100 SIGNS AND SYMPTOMS REFERENCES Threshold for eye irritation a 70 – 140 Serious eye damage a 150 - 250 210 - 350 Loss of olfactory sense a 320 - 530 450 - 750 530 - 1000 750 - 1400 1000 - 2000 1400 - 2800 Pulmonary oedema with risk of death Strong CNS stimulation, hyperpnoea followed by respiratory arrest Immediate collapse with paralysis of respiration a a a a 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 6 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Published Emergency Response Guidelines Emergency Response Planning Guideline (ERPG) Values(a) ERPG-1* ERPG-2** ERPG-3*** Listed value (ppm) 0.1 30 100 Calculated value (mg m-3) 0.14 41.72 139.06 * 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. Acute Exposure Guideline Levels (AEGLs) (b) AEGL-1† AEGL-2†† AEGL-3††† 10 min 0.75 41 76 30 min 0.60 32 59 ppm 60 min 0.51 27 50 4 hr 0.36 20 37 8 hr 0.33 17 31 † 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_tab le-only.pdf (accessed 01/2013). b U.S. Environmental Protection Agency. Acute Exposure Guideline Levels, http://www.epa.gov/oppt/aegl/pubs/chemlist.htm (accessed 01/2013). Incident Management: Page 7 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Exposure Standards, Guidelines or Regulations Occupational Standards LTEL(8 hour reference period): 5 ppm (7 mg m-3) WEL(a) STEL(15 min reference period):10 ppm (14 mg m-3) Public Health Guidelines DRINKING WATER QUALITY GUIDELINE(b) It is unlikely that a person could consume a harmful dose of hydrogen sulphide from drinking-water; hence, a health-based guideline value has not been derived for this compound. Taste and odour threshold estimated to be between: 0.05 and 0.1 mg L-1 AIR QUALITY GUIDELINE (c) SOIL GUIDELINE VALUE AND HEALTH CRITERIA VALUES 0.15 mg m-3 with an averaging time of 24 hours. Concentrations should not be allowed to exceed 7 μg m-3 with a 30-minute averaging period Data not available 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 01/2013) 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 8 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT Health Effects Major Route of Exposure(a) Toxic by inhalation Immediate Signs or Symptoms of Acute Exposure(a) Prolonged inhalation exposure causes respiratory tract irritation, with rhinitis, pharyngitis, bronchitis, dyspnoea and pulmonary oedema. Systemic effects include vomiting, diarrhoea, headache, nystagmus, dizziness, agitation, drowsiness, tremor, muscular weakness, convulsions, tachycardia and hypotension. Inhalation of high concentrations leads rapidly to collapse, respiratory paralysis, cyanosis, convulsions, coma, cardiac arrhythmias and death within minutes. Eye exposure causes pain, blepharospasm, lacrimation, conjunctivitis, palpebral oedema and photophobia. Dermal contact can result in pain, itching, redness and skin discolouration may occur. Exposure to the compressed liquid may cause frostbite injury. TOXBASE - http://www.toxbase.org (accessed 02/2013) a TOXBASE: Hydrogen sulphide, 2012. Incident Management: Page 9 of 11 HYDROGEN SULPHIDE – 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) Decontamination not necessary as it is gas. Removing patient's clothing and washing the skin with water and a mild detergent may reduce the risk of odour related complaints in healthcare personnel, but this is not a priority if dealing with a critically ill patient. If the skin has been exposed to compressed liquid treat frostbite injury conventionally. Other measures as indicated by the patient's clinical condition. Ocular Exposure(a) 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 sca 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 and those whose symptoms do not resolve rapidly should be referred for urgent ophthalmological assessment. Inhalation(a) Maintain a clear airway and ensure adequate ventilation. Remove from exposure and give oxygen in as high a concentration as possible, if necessary via an endotracheal tube. Monitor pulse, blood pressure, oxygen saturation and cardiac rhythm. Perform a 12 lead ECG. If the patient has clinical features of bronchospasm treat conventionally with nebulised bronchodilators and steroids. Apply other supportive measures as indicated by the patient’s clinical condition Ingestion Not applicable TOXBASE - http://www.toxbase.org (accessed 02/2013) a TOXBASE: Hydrogen sulphide, 2012. Incident Management: Page 10 of 11 HYDROGEN SULPHIDE – INCIDENT MANAGEMENT This document from the PHE Centre for Radiation, Chemical and Environmental Hazards reflects understanding and evaluation of the current scientific evidence as presented and referenced in this document. Incident Management: Page 11 of 11 Hydrogen Sulphide Toxicological Overview Key Points Kinetics and metabolism Hydrogen sulphide is a gas that is rapidly absorbed by the lungs into the bloodstream. It is widely distributed throughout the body. Metabolism of hydrogen sulphide occurs by oxidation, methylation or reaction with metalloproteins and the principal product is sulphate. Hydrogen sulphide is excreted rapidly from the body in the form of sulphate in urine. Health effects of acute exposure The major route of exposure is by inhalation. Acute inhalation exposure to high concentrations may result in effects on the respiratory, neurological, ocular and cardiovascular systems. Exposure to low concentrations may result in irritation to the mucous membranes of the eyes and respiratory tract. Following acute ocular exposure, eye irritation, with keratoconjunctivitis, punctate corneal erosion, blepharospasm, lacrimation and photophobia may occur. Dermal exposure may result in discolouration, pain, itching, erythema (redness of skin) and local frostbite. Health effects of chronic exposure Limited data suggest that effects from repeated exposure are similar to those for acute exposure, with respiratory, neurological and ocular effects at high concentrations. There are no adequate data on chronic toxicity/carcinogenicity. Prepared by the Toxicology Department CRCE, PHE 2011 Version 2 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Toxicological Overview Summary of Health Effects Hydrogen sulphide is a gas and, therefore, inhalation is the most relevant route of exposure to humans [1]. Acute inhalation exposure to low concentrations of hydrogen sulphide may result in irritation to the mucous membranes of the eye and respiratory tract. Acute exposure to high concentrations of hydrogen sulphide results in depression of the nervous system, loss of consciousness and respiratory paralysis. Other health effects have been reported, the most sensitive being the respiratory, neurological and ocular system [1, 2]. Data on the effects in humans following repeated exposure are limited and difficult to interpret because of co-exposure to other chemicals. There is some limited evidence to suggest an association with spontaneous abortions, but the effects seen were small and confounded by exposure to other chemicals, therefore no conclusions could be drawn. Studies in experimental animals exposed to high concentrations of hydrogen sulphide via inhalation have resulted in respiratory and cardiovascular effects. The most sensitive target organ in animals following acute inhalation exposure was the respiratory tract [2]. No chronic studies have been reported in experimental animals exposed to hydrogen sulphide. Hydrogen sulphide is not considered to be mutagenic or a reproductive or developmental toxicant. There are inadequate data on the carcinogenicity of hydrogen sulphide in humans or experimental animals. Hydrogen sulphide is not listed as a carcinogen by the International Agency for Research on Cancer (IARC) [3]. Toxicological Overview: Page 2 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Kinetics and Metabolism The primary route of hydrogen sulphide exposure is via inhalation and to a lesser extent via dermal and ocular absorption [1, 2]. It is unlikely that oral exposure occurs since hydrogen sulphide is a gas. Hydrogen sulphide is absorbed rapidly through the lungs into the bloodstream and distributed widely throughout the body [1, 2]. Absorption of hydrogen sulphide occurs to a lesser extent through the gastrointestinal tract and intact skin. Metabolism of hydrogen sulphide occurs via three pathways: oxidation, methylation and reaction with metalloproteins or disulphide-containing proteins, the latter being the principal mechanism [1]. The mechanism of action of hydrogen sulphide is thought to be direct inhibition of cellular enzymes, such as cytochrome c oxidase, which is involved in cellular oxidative processes and energy production. Such enzyme inhibition leads to disruption of the electron transport chain and impairs oxidative metabolism, leading to anaerobic metabolism, decreased ATP production and generation of lactic acid [1, 2]. The major detoxication pathway for hydrogen sulphide in humans is via oxidation in the liver [1]. Hydrogen sulphide is rapidly eliminated from the body in the form of sulphate in urine, with peak levels around 15 hours after exposure [2]. It may also be excreted unchanged in exhaled air and, in faeces and flatus. Sources and Route of Human Exposure Hydrogen sulphide is produced both naturally and through human activity. Most endogenous production results from the metabolism of sulphydryl-containing amino acids, e.g. cysteine, by bacterium in the intestinal tract and mouth. It is also produced in the brain and smooth muscle [1]. Exposure to hydrogen sulphide may occur via inhalation, dermal or ocular routes [1]. Hydrogen sulphide is a gas and therefore, inhalation exposure is the most relevant route to humans [2]. In the UK and EU, long-term exposure limits (LTEL) for hydrogen sulphide is 7 mg/m3 (8hour time weighted average (TWA) exposure reference period) [4, 5]. The short-term exposure limit in the UK (STEL) is 14 mg/m3 (15-minute reference period) [4]. The World Health Organization (WHO) has not set a health-based guideline value in drinking water. The presence of hydrogen sulphide in drinking water is easily detected by odour or taste and hence, although oral toxicity data are lacking, it is unlikely that a person could consume a harmful dose of hydrogen sulphide from drinking water [6] . Toxicological Overview: Page 3 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Health Effects of Acute / Single Exposure Human Data Inhalation Exposure to concentrations of about 700 mg/m3 (500 ppm) hydrogen sulphide and above may be fatal. Respiratory failure was the most common cause of death, but a wide range of health effects have been reported following exposure to high concentrations including respiratory, neurological and cardiovascular effects [1, 2]. Neurological effects at high exposure have included nausea, headache, delirium, disturbed equilibrium, poor memory, neurobehavioral changes, olfactory paralysis, loss of consciousness, tremors and convulsions. In those surviving exposure to high concentrations some of the neurological effects may be permanent or persistent. Cardiac irregularities including arrhythmias as well as hypertension have been reported [1, 2]. No adverse cardiovascular effects were seen in healthy volunteers exposed to 7 or 14 mg/m3 (5 and 10 ppm) for 30 minutes of submaximal exercise, nor were any changes seen in pulmonary function tests in separate studies when healthy volunteers were exposed to 14 mg/m3 (10 ppm) for 15 minutes. However, asthmatics were more sensitive, with bronchoconstriction and headache being observed after exposure to 2.8 mg/m3 (2 ppm). hydrogen sulphide concentration. This was considered the Lowest Observed Adverse Effect Level (LOAEL) [1]. Although the odour threshold has been reported to be around 0.011 mg/m3 (0.008 ppm) in naïve subjects, olfactory paralysis occurs at greater than about 140 mg/m3 (100 ppm). The loss of odour perception makes hydrogen sulphide especially dangerous since a few breaths at around 700 mg/m3 (500 ppm) is lethal [1]. Table 1 outlines the health effects associated with various concentrations of hydrogen sulphide. Table 1 – Human health effects of hydrogen sulphide at various concentrations [1]. mg/m3 0.011 2.8 5.0 7 or 14 ppm 0.008 2 4 5 or 10 5-29 28 >140 >560 ≥700 4-21 20 >100 >402 ≥502 Exposure via Inhalation Signs and symptoms Odour threshold Bronchial constriction in asthmatic individuals Increased eye complaints Increased blood lactate concentration, decreased skeletal muscle citrate synthase activity, decreased oxygen uptake Eye irritation Fatigue, loss of appetite, headache, irritability, poor memory, dizziness Olfactory paralysis Respiratory distress Death Ingestion No data could be located regarding the human health effects following acute oral exposure to hydrogen sulphide, but exposure by this route is unlikely. Toxicological Overview: Page 4 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Dermal / ocular exposure Acute exposure of six men to hydrogen sulphide resulted in facial peeling in one man exposed to probable concentrations of 11-22 mg/m3 (8-16 ppm) [1, 2]. Exposure to hydrogen sulphide gas does not induce any appreciable absorption through intact skin in humans [7]. Hydrogen sulphide gas is an eye irritant, with keratoconjunctivitis, punctate corneal erosion, blepharospasm, lacrimation, and photophobia having developed in individuals exposed briefly to high concentrations (concentration not specified) [1, 2]. There have been reports of severe damage to eye tissues following exposure to hydrogen sulphide concentrations of >70 mg/m3 (50 ppm) for 1 hour or more [1]. In a separate study, workers exposed to hydrogen sulphide at concentrations of 15-29 mg/m3 (11-21 ppm) for 6-7 hours reported eye irritation. A LOAEL of 15 mg/m3 could be identified from these observations. Delayed effects following an acute exposure In individuals surviving exposure to high levels of hydrogen sulphide the neurological effects may be permanent or persistent. Animal and In-Vitro Data Inhalation The mortality rate induced by hydrogen sulphide in experimental animals is dependent on the species, strain and concentration to which they are exposed. Table 2 outlines the effect hydrogen sulphide has on mortality in experimental animals. Table 2 – Effects on mortality following exposure to hydrogen sulphide in experimental animals [1, 2] Species Strain Sex Number Mouse CB20 Male 30 Hydrogen sulphide concentration mg/m3 (ppm) 139 (100) Mouse NMR1 Female 20 139 (100) Mouse Not specified Not specified Not specified Male 6 1006 (722) 6 2609 (1872) 10 minutes 5 2307 (1655) 3 minutes Rat Not specified Not specified SpragueDawley F-344 2 hours/day (1-4 days) 50 minutes F-344 Male 697-976 (500700) ≤558 (≤400) 4 hours Rat Rat Wistar albino Japanese white Male Not specified Not specified 10 1115 (800) 12 minutes 697-1394 (500-1000) 30 minutes Mouse Rat Rabbit Not specified 5 Exposure time Effect 2 hours No mortality No mortality Mortality (100%) Mortality (100%) Mortality (100%) Mortality (100%) No mortality Mortality (100%) Mortality (100%) 4 hours Several studies have been carried out in F344 rats and various parameters reported. Following exposure to 0, 70, 279 and 558 mg/m3 (0, 50, 200 or 400 ppm) hydrogen sulphide for 4 hours, cytochrome c oxidase activity in lung mitochondria was significantly decreased Toxicological Overview: Page 5 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW at all concentrations, with activity only returning to normal levels within 24 hours in animals exposed to <279 mg/m3 (200 ppm) hydrogen sulphide. The viability of pulmonary alveolar macrophages decreased in the lung lavage fluid of rats exposed to the highest concentration and a complete abolition of Zymosan-induced stimulation of respiratory rates of pulmonary alveolar macrophages was observed in rats exposed to the two highest concentrations. A NOAEL of 70 mg/m3 could be identified from this study. In the same study, cellularity of nasal lavage fluid increased at all concentrations and enzyme activity, indicative of pulmonary epithelium toxicity, increased in rats administered the highest two doses of hydrogen sulphide. A LOAEL of 14 mg/m3 was derived [2]. Male F344 rats were also exposed to hydrogen sulphide at doses of 0, 116 or 612 mg/m3 (0, 83 and 439 ppm) or 0, 523 or 556 mg/m3 (0, 375 and 399 ppm) for 4 hours. Mild perivascular oedema was observed in rats exposed to 116 mg/m3 hydrogen sulphide whereas pulmonary oedema was evident at higher concentrations, as well as effects on bronchiolar epithelium and alveoli and a decrease in the number of viable pulmonary alveolar macrophage cells [2]. Male Wistar rats were exposed to 0 or 105 mg/m3 (0 and 75 ppm) hydrogen sulphide for 1 hour, resulting in a decrease in heart rate and slight pulmonary congestion. Conversely, Wistar rats (sex not specified) exposed to 140-279 mg/m3 (100-200 ppm) for 1 hour showed increased heart and respiratory rates, as well as changes in a number of histological and biochemical parameters in the respiratory tissues and fluids [1, 2]. Rabbits and rats (sex and strain not specified) exposed to 100 mg/m3 (72 ppm) hydrogen sulphide for 1.5 hours or 1115 mg/m3 (800 ppm) for 20 minutes were found to lose consciousness [2]. Ingestion No data could be located regarding the health effects following acute oral exposure to hydrogen sulphide in experimental animals. Dermal / ocular exposure F344 rats (sex not specified) were exposed to 0, 279 or 558 mg/m3 (0, 200 and 400 ppm) hydrogen sulphide for 4 hours [2]. Epiphora (watery eye) was observed in rats exposed to the highest concentration. A NOAEL of 279 mg/m3 was derived from this study. Toxicological Overview: Page 6 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Health Effects of Chronic / Repeated Exposure Human Data Inhalation Repeated exposure to hydrogen sulphide by inhalation has resulted in fatigue, poor memory, dizziness and irritability [1]. Individuals were exposed via inhalation to hydrogen sulphide at <10, 10-30 or >30 µg/m3 (<0.007, 0.007-0.02 and 0.02 ppm) for an unknown period of time at a pulp mill [2]. At the highest exposure level, a significant increase in nausea was reported. Both nasal (i.e. stuffy or runny nose) and pharyngeal irritation increased in a dose-dependent manner. However, the interpretation of these findings should be treated with caution since the presence of multiple sulphur compounds complicates the results. Ingestion No data could be located regarding the human health effects following repeated oral exposure to hydrogen sulphide, but such exposure is unlikely. Dermal / ocular exposure There has been one report of dermal penetration of hydrogen sulphide resulting in toxicosis in humans exposed to large concentrations (concentration not specified) over a long exposure period [8]. No further details were available. A significantly higher prevalence of eye complaints has been reported in workers repeatedly exposed to hydrogen sulphide levels above 5 mg/m3 (3.7 ppm) compared to unexposed workers [1]. Genotoxicity No data could be located regarding genotoxicity in humans following chronic exposure to hydrogen sulphide. Carcinogenicity Hydrogen sulphide is not listed as a carcinogen by the International Agency for Research on Cancer (IARC) [3]. No data are available to assess the carcinogenicity of hydrogen sulphide in humans. Reproductive and developmental toxicity Women living in areas with hydrogen sulphide concentrations exceeding 4 mg/m3 (2.85 ppm) were found to have a non-statistically significant rise in the incidence of spontaneous abortions [2]. However, these findings were confounded by the presence of other chemicals also being detected in the same areas. In a separate study, women who were employed in to work with rayon textile and paper products showed a statistically significant increase in the rate of spontaneous abortions [1]. This was also observed in those women whose husbands/partners worked in rayon textile or chemical processing jobs. Furthermore, areas in which annual levels of hydrogen sulphide was >4 µg/m3 (>0.03 ppm), a rise in the number of spontaneous abortions was observed. Toxicological Overview: Page 7 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW However, this was not statistically significant. It is important to note here that the chemicals detected at these places of employment included sulphur dioxide, hydrogen sulphide and carbon disulphide, the latter compound being a recognised reproductive toxicant. Animal and In-Vitro Data Inhalation One 90 day repeat dose toxicity study in rats and mice was conducted to modern protocol and conforms to Good Laboratory Practice principles [1]. Male and female F344 rats, Sprague-Dawley rats or B6C3F1 mice were exposed via inhalation to hydrogen sulphide at time-weighted average concentrations of 0, 14, 42 or 112 mg/m3 (0, 10, 30 and 80 ppm) for 6 hours/day, 5 days/week for 90 days. No treatment-related changes in histopathological or haematological parameters were observed nor were any changes in renal function. A significant decrease in body weight was evident in the Sprague-Dawley rats and B6C3F1 mice exposed to the highest concentration of hydrogen sulphide whereas no changes were noted in F344 rats. Absolute brain weights were decreased in male Sprague-Dawley rats exposed to the highest concentration of hydrogen sulphide, but there was no change to neurological function or neuropathology. Similarly, neurological function and neuropathology was not altered in F344 rats or B6C3F1 mice. A NOAEL of 42 mg/m3 was identified from this study based on decreased body weights. The only effect observed at autopsy in the mice was minimal to mild irritation of the nasal mucosa at the highest dose. No pathological effects were seen at any dose level in the rat [2]. Male Sprague-Dawley rats exposed to 0 or 70 mg/m3 (0 and 50 ppm) did not exhibit any neurotoxic effects [2]. Guinea pigs (strain and sex not specified) were exposed daily to 0 or 28 mg/m3 hydrogen sulphide (0 and 20 ppm) for 1 hour/day for 11 days. Fatigue, somnolence, dizziness and eye irritation were reported, with decreased cerebral hemisphere and brain stem total lipids and phospholipids at autopsy [2]. Ingestion There were limited data available on the ingestion of hydrogen sulphide in animals. Pigs (strain and sex not specified) were fed hydrogen sulphide at a dose of 0 or 6.7 mg/kg bw/day for 105 days. Body weight gain was decreased in treated animals compared to controls [2]. Adult pigs (strain and sex not specified) were fed hydrogen sulphide at a dose of 15 mg/kg bw/day for a few days. Diarrhoeic digestive disorder was observed. In a repeat study using younger pigs that weighed less, no diarrheic disorder was noted [2]. Genotoxicity Hydrogen sulphide gas was not mutagenic in the Ames test employing Salmonella typhimurium strains TA97, TA98 or TA100, with or without a metabolic activation system [1, 2]. No other data were available. Carcinogenicity No data could be located regarding the carcinogenicity of hydrogen sulphide in experimental animals. Toxicological Overview: Page 8 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW Reproductive and developmental toxicity Female Sprague-Dawley rats were exposed to hydrogen sulphide concentrations of 0, 14, 42 or 112 mg/m3 (0, 10, 30 and 80 ppm) for 6 hours/day, 7 days/week for 2 weeks prior to, and during the 2 week mating period, and on gestational days 0-19. The male animals were exposed to similar level for 70 days up to and including the mating period. No significant changes in gestation length, fertility, number of females with live pups, litter size or number of implants per female were observed. Furthermore, sperm count and morphology were not altered in the exposed males during this study. No significant alterations in the incidence of structural anomalies were found in the offspring. Continued exposure of offspring on postnatal days 5-18 did not show any developmental delays, performance on developmental neurobehavioral tests or brain histopathology. A reproductive and developmental NOAEL of 42 mg/m3 was identified [2]. Sprague-Dawley rat dams were exposed to hydrogen sulphide concentrations of 0, 28, 70 or 110 mg/m3 (0, 20, 50 and 75 ppm) for 7 hours/day from gestation day 1 through to postnatal day 21. A significant decrease in time for pinna detachment and hair growth was reported, but no other changes in development landmarks including incisor eruption, eyelid opening and surface righting, were noted. The LOAEL for developmental effect was 28 mg/m3 [1, 2]. Pregnant Sprague-Dawley rats were exposed to 0, 140 or 210 mg/m3 hydrogen sulphide (0, 100 and 150 ppm) on gestation days 6-20. Decreased body weight gain was observed at the highest concentration. No external fetal abnormalities were observed, but a significant, though slight, decrease in fetal body weight was noted. No developmental effects were reported [1, 2]. Toxicological Overview: Page 9 of 10 HYDROGEN SULPHIDE – TOXICOLOGICAL OVERVIEW References 1. International Programme on Chemical Safety (IPCS), Hydrogen Sulfide. Concise International Chemical Assessment Document 53. 2003, WHO: Geneva. 2. Agency for Toxic Substances and Disease Registry (ATSDR), Toxicological Profile for Hydrogen Sulfide. 2006, US Department of Health and Human Services: Atlanta, US. 3. International Agency for Research on Cancer (IARC), Overall Evaluations of Carcinogenicity to Humans, in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 2009, IARC: Lyon. 4. Health and Safety Executive (HSE), EH40/2005 Workplace Exposure Limits. 2005. 5. Scientific Committee on Occupational Exposure Limits (SCOEL), Hydrogen Sulphide - Occupational Exposure Limits and Biological Limit Values. 2007, European Union. 6. World Health Organization (WHO), Guidelines for Drinking-Water Quality: Third edition. Vol 1. Recommendations. 2006, WHO: Geneva. 7. International Programme on Chemical Safety (IPCS), Hydrogen sulphide. Environmental Health Criteria 19. 1981, WHO: Geneva. 8. Hazardous Substances Data Base (HSDB), Hydrogen sulphide., in Hazardous Substances Data Base. 1988. This document from the PHE 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