Thiomersal

greater than or equal to 100 mg/mL at 66 °F (NTP, 1992)

1 gram dissolves in about 8 ml of alcohol; practically insoluble in benzene and ether

1 gram dissolves in about 1 ml of water

Mercury((o-carboxyphenyl)thio)ethyl, sodium salt is a light cream-colored crystalline powder with a slight odor: pH (1% aqueous solution) 6.7. Slight odor. (NTP, 1992)

Light cream-colored crystalline powder with a slight odor; [CAMEO]

Danger

H300+H310+H330 (15.3%): Fatal if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P203, P260, P262, P264, P270, P271, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P318, P319, P320, P321, P330, P361+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 183 reports by companies from 25 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

Chemical: Mercurate(1-), ethyl(2-mercaptobenzoato(2-)-O,S)-, sodium

Thiomersal: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this class of compounds includes aphthous stomatitis, catarrhal gingivitis, nausea, liquid stools, pain, liver disorder, injury to the cardiovascular system and hematopoietic system, deafness and ataxia. Exposure may be fatal. Headache, paresthesia of the tongue, lips, fingers and toes, other non-specific dysfunctions, metallic taste, slight gastrointestinal disturbances, excessive flatus and diarrhea may occur. Acute poisoning may cause gastrointestinal irritation and renal failure. Earl signs of severe poisoning include fine tremors of extended hands, loss of side vision, slight loss of coordination in the eyes, speech, writing and gait, inability to stand or carry out voluntary movements, occasional muscle atrophy and flexure contractures, generalized myoclonic movements, difficulty understanding ordinary speech, irritability and bad temper progressing to mania, stupor, coma, mental retardation in children, skin irritation, blisters and dermatitis. Other symptoms include chorea, athetosis, tremors, convulsions, pain and numbness in the extremities, nephritis, salivation, loosening of the teeth, blue line on the gums, anxiety, mental depression, insomnia, hallucinations and central nervous system effects. Exposure may also cause irritation of the eyes, mucous membranes and upper respiratory tract.

Allergic contact dermatitis reported in a medical assistant (ophthalmology) and in veterinarians; [Kanerva, p. 1839] Thimerosal is metabolized to ethylmercury and thiosalicylate. [Rom, p. 992] See Mercury, aryl compounds and the linked diseases.

Permissible Exposure Limit: Table Z-2 8-hr Time Weighted Avg: 0.01 mg/cu m. /Organo (alkyl) mercury/

Permissible Exposure Limit: Table Z-2 Acceptable Ceiling Concentration: 0.04 mg/cu m. /Organo (alkyl) mercury/

MERCURY((O-CARBOXYPHENYL)THIO)ETHYL, SODIUM SALT is incompatible with strong oxidizing agents and strong bases. The oxidation of this compound is greatly accelerated by traces of copper ions. Incompatible with acids, iodine, heavy metal salts and many alkaloids. Can be absorbed by rubber caps. (NTP, 1992). Stable in air, but not sunlight. May discolor on exposure to light. Dilute aqueous solutions are fairly stable to heat but sensitive to light. Solutions are less stable to heat when acidic than when alkaline. Solutions are most stable to light at pH 5 to 7. Solutions are unstable to heat but not to light in the presence of copper, iron or zinc ions but not in the presence of calcium or magnesium ions.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Thimerosal (an organic mercury compound) is widely used in the pharmaceutical industry and hospitals. This study examines the removal of mercury (thimerosal and Hg (II)) from a pharmaceutical wastewater using F-400 granular activated carbon (GAC) at bench and pilot scales. Bench scale dynamic column tests are conducted with 30, 60, 90 and 120 min empty bed contact times (EBCTs). The pilot scale study is conducted using two GAC columns-in-series each of 30 min EBCT.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

0.1 [mg/m3], as Hg

8 hr Time Weighted Avg (TWA): 0.01 mg/cu m; 15 min Short Term Exposure Limit (STEL): 0.03 mg/cu m. Skin. /Mercury alkyl compounds, as Hg/

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

2 mg Hg/m3 (NIOSH, 2024)

2 mg/cu m (as Hg) /Mercury (organo) alkyl compounds (as Hg)/

Maximum mercury concentrations were blood 14 mg/L, serum 1.7 mg/L, urine 10.7 mg/L, and cerebrospinal fluid 0.025 mg/L /after an 83 mg/kg ingestion of thimerosal/. Mercury concentration in blood declined with two velocities: first with half-time 2.2 days, then with half-time 40.5 days. The decline of mercury concentration in blood, urinary mercury excretion, and renal mercury clearance were not substantially influenced by chelation therapy.

Mercury concentrations were determined in various tissues from 6 ... infants /exposed to topical applications of 0.1% thimerosalfor the treatment of exomphalos . Mean tissue concentrations in fresh samples of liver, kidney, spleen, and heart ranged from 5152 to 11,330 ppb, suggesting percutaneous absorption from repeated topical applications.

Selected as the 2002 American Contact Dermatitis Society Allergen of the Year; however, this publication notes that the prevalence of sensitization was presumed to be induced by vaccinations, because thimerosal was used as a preservative in vaccines up until 1999. Routine testing to thimerosal is no longer recommended and il is now the

Mercury mainly affects the nervous system. Exposure to high levels of metallic, inorganic, or organic mercury can permanently damage the brain, kidneys, and developing fetus. Effects on brain functioning may result in irritability, shyness, tremors, changes in vision or hearing, and memory problems. Acrodynia, a type of mercury poisoning in children, is characterized by pain and pink discoloration of the hands and feet. Mercury poisoning can also cause Hunter-Russell syndrome and Minamata disease. (L7)

High-affinity binding of the divalent mercuric ion to thiol or sulfhydryl groups of proteins is believed to be the major mechanism for the activity of mercury. Through alterations in intracellular thiol status, mercury can promote oxidative stress, lipid peroxidation, mitochondrial dysfunction, and changes in heme metabolism. Mercury is known to bind to microsomal and mitochondrial enzymes, resulting in cell injury and death. For example, mercury is known to inhibit aquaporins, halting water flow across the cell membrane. It also inhibits the protein LCK, which causes decreased T-cell signalling and immune system depression. Mercury is also believed to inhibit neuronal excitability by acting on the postsynaptic neuronal membrane. It also affects the nervous system by inhibiting protein kinase C and alkaline phosphatase, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Organic mercury exerts developmental effects by binding to tubulin, preventing microtubule assembly and causing mitotic inhibition. Mercury also produces an autoimmune response, likely by modification of major histocompatibility complex (MHC) class II molecules, self peptides, T-cell receptors, or cell-surface adhesion molecules. (L7, A8, A25, A26)

/HUMAN EXPOSURE STUDIES/ Ten of 13 infants exposed to topical applications of a thimerosal tincture 0.1% for the treatment of exomphalos died. The total number of applications ranged from 9 to 48. Mercury concentrations were determined in various tissues from 6 of the infants. Mean tissue concentrations in fresh samples of liver, kidney, spleen, and heart ranged from 5152 to 11,330 ppb, suggesting percutaneous absorption from repeated topical applications.

/HUMAN EXPOSURE STUDIES/ Mercury derivatives are frequent contact allergens and their cross-reactivity is not constant. Thimerosal is an organic mercurial used as an antiseptic and as a preservative in most vaccines. /The purpose of the study was / to evaluate cross-reactivity, exposure factors, and tolerance to vaccines containing thimerosal in patients sensitized to mercury derivatives.125 patients were recruited for the study, 72 women and girls and 53 boys and men, average age 18.7 years old, range 3 to 65, with positive patch tests to mercury derivatives and/or thimerosal; Interventions: All patients were studied by means of enquiry, patch tests, intradermal tests, and intramuscular challenge with thimerosal. A sensitization to thimerosal was observed in 57 patients. Twenty-four of these 125 patients presented a positive intradermal reaction. Ammoniated mercury seems to be a good marker of mercury sensitization eliciting positive reaction in 78% of all patients and merbromin in 66%. In most cases, (100/125) cross-reactivity was found among mercury derivatives. The intramuscular injection of thimerosal induced a mild local reaction in only 5 patients (4% of the total, 9% of thimerosal positive reactions). Childhood vaccinations, merbromin used as an antiseptic, broken thermometers, and the use of drops were the main sources of exposure. The majority of the patients showed positive tests to both organic and inorganic mercury derivatives. Vaccination with thimerosal is relatively safe, even for individuals with delayed type hypersensitivity to this chemical, since more than 90% of allergic patients tolerated intramuscular challenge tests with thimerosal. A simplified protocol of patch tests to study mercury derivatives is proposed. It would be advisable to restrict the use of mercurial antiseptics and mercury thermometers.

/SIGNS AND SYMPTOMS/ Common contact allergen. /from table/

/CASE REPORTS/ Six cases of severe mercury poisoning resulting in four deaths were reported following the intramuscular administration of chloramphenicol preserved with thimerosal. A manufacturing error resulted in each vial containing 510 mg of thimerosal instead of 0.51 mg per vial. Extensive tissue necrosis was noted at the site of injection in all patients. Fever, altered mental status, slurred speech, and ataxia were noted. On autopsy there was evidence of widespread degeneration and necrosis of the renal tubules. Elevated mercury concentrations were found in kidneys, livers, brain, and injection site tissues.

For more Human Toxicity Excerpts (Complete) data for THIMEROSAL (17 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ Maximum tolerated doses not associated with death of the animals were 20 mg thimerosal/kg (rabbits) and 45 mg/kg (rats).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The administration of thimerosal intranasally for 190 days was evaluated; no histopathological changes in the brain or kidney /were observed/.

/LABORATORY ANIMALS: Neurotoxicity/ The toxicity of ethyl- versus methylmercury in adult male and female rats administered 5 daily doses of equimolar concentrations of ethyl- or methylmercury by gavage. Ethylmercury, the mercury derivative found in thimerosal, /was/ less neurotoxic than methylmercury, the mercury derivative for which the various guidelines are based. /Ethyl mercury/

/LABORATORY ANIMALS: Neurotoxicity/ The effect of thimerosal, an organomercurial preservative in vaccines, on cerebellar neurons dissociated from 2-week-old rats was compared with those of methylmercury using a flow cytometer with appropriate fluorescent dyes. Thimerosal and methylmercury at concentrations ranging from 0.3 to 10 uM increased the intracellular concentration of Ca2+ ([Ca2+]i) in a concentration-dependent manner. The potency of 10 microM thimerosal to increase the [Ca2+]i was less than that of 10 uM methylmercury. Their effects on the [Ca2+]i were greatly attenuated, but not completely suppressed, under external Ca(2+)-free condition, suggesting a possibility that both agents increase membrane Ca2+ permeability and release Ca2+ from intracellular calcium stores. The effect of 10 uM thimerosal was not affected by simultaneous application of 30 uM L-cysteine whereas that of 10 uM methylmercury was significantly suppressed. The potency of thimerosal was similar to that of methylmercury in the presence of L-cysteine. Both agents at 1 uM or more similarly decreased the cellular content of glutathione in a concentration-dependent manner, suggesting an increase in oxidative stress. Results indicate that thimerosal exerts some cytotoxic actions on cerebellar granule neurons dissociated from 2-week-old rats and its potency is almost similar to that of methylmercury.

For more Non-Human Toxicity Excerpts (Complete) data for THIMEROSAL (9 total), please visit the HSDB record page.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and teat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with available water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Mercury and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient with severe pulmonary edema or respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Mercury and related compounds/

D - Dermatologicals

QD - Dermatologicals

Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties. Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish. Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury. Prior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first 6 months of life was 187.5 micrograms. In the most recently formulated vaccines, the maximum cumulative exposure during the first 6 months of life should now be less than 3 micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, however, only a trace remains after a chemical purification process. Note that the dose above is indicated for children 1-6 months of age is applicable only in the United States, and other countries may have varying indications.

Although its mechanism of action is not fully understood, thimerosal inhibits sulfhydryl-containing active site of various enzymes and binds to sulfhydryl compounds, including glutathione, cysteine, and sulfhydryl groups of proteins. In addition, thimerosal activates the InsP3 calcium channel on the endoplasmic reticular membrane, thereby triggering the release of intracellular calcium resulting in a calcium-induced calcium-influx of extracellular calcium. Therefore, thimerosal may induce or inhibit various cellular functions that are dependent on the signaling of calcium. Ethylmercury is metabolized to inorganic mercury more rapidly than methylmercury. This difference in metabolism may account for kidney pathology that can result from toxic quantities. Also, whereas the increase in oxidative stress and induction of apoptosis observed in vitro with large doses (405 μg/L to 101 mg/L) of thimerosal may explain its damaging neurological effects. The effects of low-dose ethylmercury are not completely understood to date. It is known, however, that the shorter half-life of ethylmercury (the metabolite of thimerosal) allows for very limited opportunities of ethylmercury derived from thimerosal in vaccines. Ethylmercury is a lipophilic cation that is capable of crossing the blood-brain barrier. The octanol/water partition coefficients of methyl and ethylmercury are 1.4 to 1.8, at intracellular pH and [Cl−], therefore, both organomercury compounds will primarily exist as intracellular lipophilic cations. It has been demonstrated that lipophilic cations accumulate inside mitochondria, in a Nernstian fashion, driven by the steady state membrane potential. As the typical mitochondrial membrane potential of astrocytes and neurons is between 140–170 mV, one would expect the concentration of these organomercury compounds within mitochondria to be approximately 1000 times greater than the cytosolic concentration.

A study was done to study the pharmacokinetics of Thimerosal in mice. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney. The the half-life of ethylmercury is 3–7 days in infants, with the half-life of intramuscular ethylmercury from thimerosal being 2.9-4.1 days. The half-life of ethylmercury in the blood also did not vary significant between age groups of infants, alongside the results that blood mercury levels before vaccination being similar in 2 month old and 6 month old infants suggests ethylmercury does not accumulate in the blood.

Ethylmercury (etHg) is derived from the metabolism of thimerosal (o-carboxyphenyl-thio-ethyl-sodium salt), which is the most widely used form of organic mercury.

Organic mercury is absorbed mainly by the gastrointestinal tract, then distributed throughout the body via the bloodstream. Organic mercury complexes with free cysteine and the cysteine and sulfhydryl groups on proteins such as haemoglobin. These complexes are able to mimic methionine and thus be transported throughout the body, including through the blood-brain barrier and placenta. Organic mercury is metabolized into inorganic mercury, which is eventually excreted in the urine and faeces. (T11)

2225PI3MOV

THIMEROSAL

Established Pharmacologic Class [EPC] - Standardized Chemical Allergen

Physiologic Effects [PE] - Increased Histamine Release

Physiologic Effects [PE] - Cell-mediated Immunity

Chemical Structure [CS] - Allergens

Less than 0.01% of an ingested dose is absorbed from the GI tract (rat study).

Gastrointestinal tract.

266 L in one study

The high concentrations of mercury identified in stool samples suggest that ethylmercury may be eliminated through the gastrointestinal tract.

Mercury concentrations were measured in the aqueous humor and excised corneal buttons of nine patients undergoing keratoplasty. A contact lens stored for several weeks in a solution containing thimerosal was applied to one eye for 4 hours. After 4 hours the lens was removed and mercury concentrations were determined in aqueous humor, corneal buttons, and the contact lens itself. Markedly elevated levels of mercury were determined in both aqueous humor and corneal buttons of subjects as compared to controls; however, there was little residual mercury on the contact lens after 4 hours.The mercury content in the corneal buttons of subjects ranged from 0.6 to 14 ng per tissue. The mercury content in samples of aqueous humor from subjects ranged from 20 to 46 ng/mL.

Ten of 13 infants exposed to topical applications of a thimerosal tincture 0.1% for the treatment of exomphalos died. The total number of applications ranged from 9 to 48. Mercury concentrations were determined in various tissues from 6 of the infants. Mean tissue concentrations in fresh samples of liver, kidney, spleen, and heart ranged from 5152 to 11,330 ppb, suggesting percutaneous absorption from repeated topical applications.

Use is diminishing as a preservative in eye drops, vaccines, and cleaners for contact lenses; [Kanerva, p. 1839] Used in vaccines until 1999 at a concentration of 25 ug per 0.5 ml dose of several common vaccines; [Rom, p. 992] Has been removed from US-licensed vaccines for children under 7 years--either thimerosal-free or contain only trace amounts (<0.5 ug Hg/dose) with the exception of some inactivated influenza vaccines. [Goldfrank, p. 812]

Using Disinfectants or Biocides [Category: Clean]

For thimerosal (USEPA/OPP Pesticide Code: 078901) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

An ophthalmic preservative, a topical anti-infective

Fungicide for cotton seed treatment.

Pharmaceutic aid (preservative)

Drugs and other preparations containing thimerosal /as a preservative/: Crotalidae (Wyeth) antivenin; Diphtheria - tetanus toxoid; Gammar (gamma immune globulin); Lactrodectus mactans antivenin; Micrurus fulvius antivenin; Neosporin (triple antibiotic) ophthalmic solution; Ocufren (flurbiprofen) ophthalmic solution; Pneumovax-23 (pneumococcal) vaccine; Rabies immune globulin /From table/

Thimerosal contains approximately 49% mercury /by molecular weight calculation/.