YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==HYDROGEN SULFIDE== 1 AUTHOR Roth SH AUTHOR Skrajny B AUTHOR Reiffenstein RJ TITLE Alteration of the morphology and neurochemistry of the developing mammalian nervous system by hydrogen sulphide. SOURCE Clin Exp Pharmacol Physiol 1995 May;22(5):379-80 ABSTRACT 1. Hydrogen sulphide (H2S) is a broad spectrum toxicant that occurs widely in nature and is also released by a variety of industrial activities and processes. 2. The central nervous system (CNS) appears to be the major target organ. 3. There is great potential for insult or injury to the developing or immature CNS. 4. The risk of chronic or repeated exposures to low concentrations have not been well defined. 5. Exposure to low concentrations of H2S to time-pregnant rats from day 5 postcoitus until day 21 postnatal results in architectural modification of cerebellar Purkinje cells, alteration of putative amino acid neurotransmitters and changes in monoamine levels in the developing rat brain up to day 21 postnatal. 6. H2S-induced alterations in monoamine tissue levels observed in the developing rat brain return to control values if exposure is discontinued during development, that is, at day 21 postnatal. 3 AUTHOR Hannah RS AUTHOR Roth SH TITLE Chronic exposure to low concentrations of hydrogen sulfide produces abnormal growth in developing cerebellar Purkinje cells. SOURCE Neurosci Lett 1991 Jan 28;122(2):225-8 ABSTRACT Hydrogen sulfide (H2S) may produce deleterious effects on the developing central nervous system. The dendritic fields of developing cerebellar Purkinje cells were analyzed to determine the effects of chronic exposure to low concentrations of H2S during perinatal development. Treatment with two concentrations (20 and 50 ppm) of H2S produced severe alterations in the architecture and growth characteristics of the Purkinjec cell dendritic fields. The architectural modifications included longer branches, an increase in the vertex path length and variations in the number of branches in particular areas of the dendritic field. The treated cells also exhibited a nonsymmetrical growth pattern at a time when random terminal branching is normally occurring. These findings suggest that developing neurons exposed to low concentrations of H2S are at risk of severe deficits. 4 AUTHOR Hayden LJ AUTHOR Goeden H AUTHOR Roth SH TITLE Growth and development in the rat during sub-chronic exposure to low levels of hydrogen sulfide. SOURCE Toxicol Ind Health 1990 May-Jul;6(3-4):389-401 ABSTRACT The effects of low levels of hydrogen sulfide (H2S) on mammalian growth and development are unknown although it has long been postulated that H2S can inhibit critical developmental functions through the cleavage of disulfide bonds and chelation of essential metal ions. Gravid rat dams exposed to H2S (less than or equal to 75 PPM) from day 6 of gestation until day 21 postpartum (PP) demonstrated normal reproductive parameters until parturition. At parturition, however, delivery time was extended in a dose dependent manner with a maximum increase of 42% at 75 PPM. Maternal liver cholesterol content was elevated significantly on day 21 postpartum following exposure to 75 PPM H2S each day for 6 weeks. Pups which were exposed in utero and neonatally to day 21 postpartum developed with a subtle decrease in time of ear detachment and hair development and with no other observed change in growth and development through day 21 postpartum. 5 AUTHOR Hannah RS AUTHOR Bennington R AUTHOR Roth SH TITLE Low dose hydrogen sulfide and its effects on the dendritic arborization of developing cerebellar Purkinje cells. SOURCE Abstr Soc Neurosci 1989;15(2):1021 ABSTRACT Hydrogen sulfide (H2S) is an environmental pollutant which can produce severe effects on the adult CNS; however, little is known as to its effects on the developing CNS. Pregnant rats (Sprague-Dawley) were exposed to either 20 pmm or 50 pmm H2S for 7 hours per day in an environment chamber from Day 7 postcoitus until Day 21 postnatal. Controls were similarly treated including placement in an environmental chamber flushed with room air. On Day 21 postnatal, representative pups from each litter were euthanized, the cerebella removed and processed for Golgi staining. Ten complete Purkinje cells were selected from each group and analysed, using vertex analysis (Berry & Finn, Proc. R. Soc. Lond. B. 221:321, 1984). At both exposure concentrations, there was a significant increase in vertex path length suggesting an increased distance between each new generation of branches. New growth occurred toward the pial surface and internally but was restricted laterally. The treated cells exhibited an unusually high non-random growth pattern. In summary, both treatments produced significant growth changes in the dendritic arborization. 6 AUTHOR Saillenfait AM AUTHOR Bonnet P AUTHOR de Ceaurriz J TITLE Effects of inhalation exposure to carbon disulfide and its combination with hydrogen sulfide on embryonal and fetal development in rats. SOURCE Toxicol Lett 1989 Jul;48(1):57-66 ABSTRACT Pregnant rats were exposed to 0, 100, 200, 400 or 800 ppm of carbon disulfide (CS2), 100 ppm of hydrogen sulfide (H2S) alone or in combination with 400 and 800 ppm CS2, 6 h/d during days 6-20 of gestation. Maternal reproduction and fetal parameters were evaluated on gestational day 21. Treatment with 100 or 200 ppm CS2 or with 100 ppm H2S caused no maternal toxicity or adverse effects on the developing embryo or fetus. Exposure to 400 or 800 ppm CS2 resulted in a low incidence of club foot and in a significant reduction of maternal weight gain. Significant increases in unossified sternebrae occurred at 800 ppm CS2 and reduction of fetal body weight at 400 and 800 ppm CS2. The latter effect was enhanced by combination with 100 ppm H2S. These results support the conclusion that, at levels of exposure associated with maternal toxicity, CS2 leads to an increase in incidence of club foot and to fetal toxicity which is enhanced by simultaneous exposure to H2S. 1 AUTHOR Guidotti TL TITLE Hydrogen sulphide. SOURCE Occup Med (Oxf); VOL 46, ISS 5, 1996, P367-71 (REF: 45) ABSTRACT Hydrogen sulphide (H2S) is the primary chemical hazard in natural gas production in 'sour' gas fields. It is also a hazard in sewage treatment and manure-containment operations, construction in wetlands, pelt processing, certain types of pulp and paper production, and any situation in which organic material decays or inorganic sulphides exist under reducing conditions. H2S dissociates into free sulphide in the circulation. Sulphide binds to many macromolecules, among them cytochrome oxidase. Although this is undoubtedly an important mechanism of toxicity due to H2S, there may be others H2S provides little opportunity for escape at high concentrations because of the olfactory paralysis it causes, the steep exposure-response relationships, and the characteristically sudden loss of consciousness it can cause which is colloquially termed 'knockdown.' Other effects may include mucosal irritation, which is associated at lower concentrations with a keratoconjunctivitis called 'gas eye' and at higher concentrations with risk of pulmonary oedema. Chronic central nervous system sequelae may possibly follow repeated knockdowns: this is controversial and the primary effects of H2S may be confounded by anoxia or head trauma. Treatment is currently empirical, with a combination of nitrite and hyperbaric oxygen preferred. The treatment regimen is not ideal and carries some risk. 3 AUTHOR Snyder JW AUTHOR Safir EF AUTHOR Summerville GP AUTHOR Middleberg RA TITLE Occupational fatality and persistent neurological sequelae after mass exposure to hydrogen sulfide. SOURCE Am J Emerg Med; VOL 13, ISS 2, 1995, P199-203 (REF: 89) ABSTRACT Exposure to hydrogen sulfide (H2S) has been associated with death as well as survival following coma with or without hypoxic brain damage. The release of H2S at a beachfront construction site led to the emergency evaluation and treatment of 37 people, with six admissions and one death. At least one victim, who underwent extensive therapy with hyperbaric oxygen, developed persistent neurological sequelae. Despite increased awareness of the potentially life-threatening consequences of exposure to H2S, significant poisoning continues to occur, even in workplaces where the hazards are well-known and can be avoided. Recommended therapy includes nitrites, hyperbaric oxygen, and supportive care, but documentation of efficacy is lacking. Because patients with chronic neurological sequelae after acute H2S exposure continue to be reported, we suggest that any survivor of H2S poisoning who presents in coma or who manifests objectively verifiable evidence of neurotoxicity on physical examination or lab testing should undergo baseline and annual neurological and neuropsychological testing for at least five years. This approach could standardize and enhance our knowledge of, and ability to detect, the subtle but permanent alterations of central nervous system function that follow H2S exposure. 4 AUTHOR Guidotti TL TITLE Occupational exposure to hydrogen sulfide in the sour gas industry: some unresolved issues. SOURCE Int Arch Occup Environ Health; VOL 66, ISS 3, 1994, P153-60 (REF: 54) ABSTRACT Occupational exposure to hydrogen sulfide (H2S) and the medical management of H2S-associated toxicity remains a problem in the sour gas industry and some other industrial settings. The acute effects of exposure to H2S are well recognized, but accurate exposure-response data are limited to acutely lethal effects, even in animal studies. Odor followed by olfactory paralysis and keratoconjunctivitis are the characteristics effects of H2S at lower concentrations. H2S-induced acute central toxicity leading to reversible unconsciousness is a "knockdown"; it is controversial whether repeated or prolonged knockdowns are associated with chronic neurologic sequelae but the evidence is suggestive. Knockdowns can be acutely fatal as a consequence of respiratory paralysis and cellular anoxia. Pulmonary edema is also a well-recognized acute effect of H2S toxicity. Human studies of sublethal exposure with satisfactory exposure assessment are almost nonexistent. There are indications, poorly documented at present, of other chronic health problems associated with H2S exposure, including neurotoxicity, cardiac arrhythmia, and chronic eye irritation but apparently not cancer. Rigorous and comprehensive studies in the sour gas industry are difficult, in part because of confounding exposures and uncertain end points. 8 AUTHOR Reiffenstein RJ AUTHOR Hulbert WC AUTHOR Roth SH TITLE Toxicology of hydrogen sulfide. SOURCE Annu Rev Pharmacol Toxicol; VOL 32, 1992, P109-34 (REF: 114) ABSTRACT Significant progress has been made in determining the action of sulfide on the primary target organs. It is reasonably clear that sulfide causes both K(+)-channel-mediated hyperpolarization of neurons and potentiation of other inhibitory mechanisms. It is not clear whether these processes are similar to those that occur in anoxia. Changes in perinatal and adult brain neurotransmitter content and release may be related to clinical impairment of cognition. H2S exposures at concentrations below the current occupational limits cause physiological changes in pulmonary function, thus suggesting that asthmatics are at risk. Studies of fetal and neonatal brain tissue have shown an abnormal development, and the long-term consequences of these neuronal changes have not yet been assessed. Finally, new approaches to therapy are required, such as the use of agents that actively remove sulfide from its sites of action. This may prove more useful in preventing some of the long-term adverse sequelae than the use of nitrites and hyperbaric O2, although the latter should be used in cases of pulmonary edema. 17 AUTHOR Beauchamp RO Jr AUTHOR Bus JS AUTHOR Popp JA AUTHOR Boreiko CJ AUTHOR Andjelkovich DA TITLE A critical review of the literature on hydrogen sulfide toxicity. SOURCE Crit Rev Toxicol; VOL 13, ISS 1, 1984, P25-97 (REF: 196) ABSTRACT The information available on the biological activity of hydrogen sulfide has been examined for present status of critical results pertaining to the toxicity of hydrogen sulfide. This review of the literature is intended as an evaluative report rather than an annotated bibliography of all the source material examined on hydrogen sulfide. The information was selected as it might relate to potential toxic effects of hydrogen sulfide to man and summarized, noting information gaps that may require further investigation. Several recommendations are listed for possible consideration for either toxicological research or additional short- and long-term tests. Two bibliographies have been provided to assist in locating references considered in this report: (1) literature examined but not cited and (2) reference citations. The majority of the references in the first bibliography were considered peripheral information and less appropriate for inclusion in this report. You are now connected to the HSDB file. 1 - HSDB NAME OF SUBSTANCE HYDROGEN SULFIDE CAS REGISTRY NUMBER 7783-06-4 HUMAN TOXICITY EXCERPTS ... ACTS DIRECTLY UPON NERVOUS SYSTEM, RESULTING IN PARALYSIS OF RESP CENTER, & HAS PARALYZING EFFECT ON OLFACTORY SYSTEM. ... ACTION ... INFLUENCE/S/ LEVEL OF FERRIC HEMOGLOBIN ... WHICH CONTRIBUTES TO ASPHYXIATION. [Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 205] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS SYMPTOMATOLOGY: A. LOW TO MODERATELY HIGH VAPOR CONCENTRATIONS: 1. IRRITANT ACTIONS. EYES: PAINFUL CONJUNCTIVITIS, PHOTOPHOBIA, LACRIMATION, & CORNEAL OPACITY. RESP TRACT: RHINITIS WITH ANOSMIA, TRACHEOBRONCHITIS WITH PAIN AND COUGH, PULMONARY EDEMA WITH DYSPNEA, SOMETIMES LATE BRONCHOPNEUMONIA. SKIN: DIRECT CONTACT (AS SOLN) MAY PRODUCE ERYTHEMA & PAIN. B. VERY HIGH VAPOR CONCENTRATIONS: 1. SUDDEN COLLAPSE & UNCONSCIOUSNESS, WITH OR WITHOUT A WARNING CRY. 2. DEATH FROM PROMPT RESP PARALYSIS, USUALLY WITH TERMINAL ASPHYXIAL CONVULSION. 3. AFTER SUBLETHAL EXPOSURES COMA MAY DISAPPEAR PROMPTLY, BUT FULL RECOVERY IS USUALLY SLOW; THE PATIENT MAY HAVE A RESIDUAL COUGH, CARDIAC DILATATION, SLOW PULSE, PERIPHERAL ... /NEUROPATHY/, ALBUMINURIA AND SOME DEGREE OF AMNESIA OR OF PSYCHIC DISTURBANCE. RECOVERY IS EVENTUALLY COMPLETE IN MOST NONFATAL CASES. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984. III-200] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS A CASE OF POLYNEURITIS AND ENCEPHALOPATHY FROM 1 DAY EXPOSURE TO A CONCN INSUFFICIENT TO CAUSE LOSS OF CONSCIOUSNESS HAS BEEN REPORTED. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:, p. 318] American Conference of Governmental Industrial Hygienists, 1986., p. 318] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS ANALYSIS OF RETICULOCYTES FOR DELTA-AMINO-LEVULINIC ACID SYNTHASE (AMLEV SYNTHASE) AND HEME SYNTHASE ACTIVITY IN WORKERS IN PULP PRODUCTION WITH LOW-LEVEL HYDROGEN SULFIDE AND METHYLMERCAPTAN EXPOSURE SHOWED DECREASED ACTIVITIES. ERYTHROCYTE PROTOPORPHYRIN CONCENTRATION WAS BELOW THE CONTROL RANGE IN 7 CASES. LOW AMLEV SYNTHASE AND HEME SYNTHASE ACTIVITIES WERE FOUND IN 1 PATIENT WITH HYDROGEN SULFIDE INTOXICATION 1 WEEK AFTER THE EVENT. THE ACTIVITIES HAD RETURNED TO THE CONTROL LEVELS 2 MONTHS LATER, THOUGH ERYTHROCYTE PROTOPORPHYRIN REMAINED ABNORMALLY LOW. IN VITRO, HYDROGEN SULFIDE INHIBITED HEME SYNTHASE WITH AN APPARENT KI OF 3.4 MMOL/L. SULFIDE ANION INHIBITED AMLEV SYNTHASE ACTIVITY 85% AT 10 MMOL/L. [TENHUNEN P ET AL; CLIN SCI 64 (2): 187-91 (1983)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS SPONTANEOUS ABORTIONS WERE ANALYZED IN AN INDUSTRIAL COMMUNITY IN FINLAND IN WOMEN WHO WERE EMPLOYED IN RAYON TEXTILE JOBS AND PAPER PRODUCTS JOBS. AN INCREASED RATE OF SPONTANEOUS ABORTIONS WAS NOTED IN ALL SOCIOECONOMIC CLASSES IN AREAS WHERE THE MEAN ANNUAL LEVEL OF HYDROGEN SULFIDE EXCEEDED 4 UG/CU M. HOWEVER, THE DIFFERENCE (TOTAL RATES 7.6 AND 9.3, RESPECTIVELY) WAS NOT STATISTICALLY SIGNIFICANT. [HEMMINKI K, NIEMI ML; INT ARCH OCCUP ENVIRON HEALTH 51 (1): 55-63 (1982)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS HYDROGEN SULFIDE IS ASSOCIATED WITH DEATHS CAUSED BY FERMENTING MANURE. [MORSE DL ET AL; JAMA 25 (1): 63-4 (1981)] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS HYDROGEN SULFIDE CAN PENETRATE SKIN & CAUSE TOXICOSIS IN PEOPLE EXPOSED TO LARGE CONCN OVER LONG PERIOD ... SPEED OF ONSET OF ACUTE HYDROGEN SULFIDE POISONING & POTENCY OF HYDROGEN SULFIDE ARE ALMOST SAME AS FOR CYANIDE GAS ... [Jones, L.M., et al. Veterinary Pharmacology & Therapeutics. 4th ed. Ames: Iowa State University Press, 1977., p. 1161] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS POISONING WITH HYDROGEN SULFIDE ... HAS BEEN DESCRIBED FROM DRINKING CONTAMINATED WATER. [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 82] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Low concentrations of 20-150 ppm cause irritation of the eyes; slightly higher concentrations may cause irritation of the upper respiratory tract, and if exposure is prolonged, pulmonary edema may result. The irritant action has been explained on the basis that hydrogen sulfide combines with the alkali present in moist surface tissues to form sodium sulfide, a caustic. [Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 1552] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Lethal blood concentration: 0.092 mg %. [Winek, C.L. Drug and Chemical Blood-Level Data 1985. Pittsburgh, PA: Allied Fischer Scientific, 1985.] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS ... OF 174 EXPOSURES TO HYDROGEN SULFIDE IN A HEAVY WATER PLANT ... EYE IRRITATION WAS RELATIVELY UNCOMMON. MORE COMMON FINDINGS WERE NERVOUSNESS, COUGH, NAUSEA, HEADACHE & INSOMNIA. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:, p. 318] American Conference of Governmental Industrial Hygienists, 1986., p. 318] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS At a concentration of 150 ppm, the olfactory nerve is paralyzed. [USEPA; Health and Environmental Effects Profile for Hydrogen Sulfide p.118-8 (1980) ECAO-CIN-026A] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Hydrogen sulfide is an extremely hazardous gas which can be immediately life threatening at high concentrations (300 mg/cu m or 200 ppm). [NIOSH: Occupational Exposure to Hydrogen Sulfide p.79 (1977) DHEW (NIOSH) Publication # 77-158] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS 1400-2,800 mg/cu m inhalation <20 min number of subjects 342, hospitalization of 320, death of 22, residual nervous system damage in 4. [McCabe LC, Clayton GD; Arch Ind Hyg Occup Med (6): 199-213 (1952) as cited in NIOSH: Occupational Exposure to Hydrogen Sulfide; p.61 (l977) DHEW (NIOSH) Publication # 77-l58] **PEER REVIEWED** HUMAN TOXICITY EXCERPTS Concentrations of 20-50 ppm irritates the eyes. Inhalation of 500 ppm for 30 minutes produces headache, dizziness, excitement, staggering, and gastroenteric disorders followed in some cases by bronchitis or bronchial pneumonia. Concentrations above 600 ppm can be fatal within 30 minutes through respiratory paralyses. [Matheson; Guide to Safe Handling of Compressed Gases 2nd ED p.15 (1983)] **PEER REVIEWED**