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THIOGLYCOLATES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Thioglycolates are salts of thioglycolic acid, usually encountered as sodium or ammonium thioglycolates. These agents are most commonly used in the cold-waving of hair.

Specific Substances

    A) SYNONYMS FOR THE GROUP
    1) Ammonium thioglycolate
    2) Calcium thioglycolate
    3) Mercaptoacetic Acid
    4) Sodium thioglycolate
    5) Thioglycolic Acid
    6) Thioglycollic Acid
    7) CAS 68-11-1 (thioglycolic acid)

Available Forms Sources

    A) FORMS
    1) Thioglycolic acid is a liquid with a strong and unpleasant odor. It is readily oxidized by air (Budavari, 1996).
    B) SOURCES
    1) Thioglycolic acid is prepared by the action of sodium sulfhydrate on sodium chloroacetate. It is also prepared by electrolysis of dithioglycollic acid (from sodium sulfide and sodium chloroacetate) (Budavari, 1996).
    C) USES
    1) Thioglycolates are most typically used as sodium, ammonium, or calcium thioglycolates, which are commonly employed in the permanent or cold-waving solution of hair. In these preparations, there is no free thioglycolic acid. Concentrations of the salt forms generally range from 5.5% to 7%. The pH is mildly alkaline, commonly pH 9.5, and is less dangerous to mucous membranes than is free thioglycolic acid (Grant & Schuman, 1993; Brunner, 1952).
    a) They penetrate hair easily and reduce disulfide cross linkages to form free -SH (Lehman, 1949).
    b) Once the hair is put in its "set" position, an oxidizer converts the -SH to S-S cross linkages. The two most common salts used are the ammonium and sodium (Brunner, 1952).
    2) Depilatories usually contain the calcium salt in a 2.5% to 4.0% solution. pH is 10 to 12.5. Below pH 10 the procedure becomes too lengthy for hair removal, and at greater than pH 12.5, products are too alkaline and may cause skin damage (Barry, 1972) Webber, 1967).
    3) Thioglycolates are also sensitive reagents for iron, molybdenum, silver, and tin (Budavari, 1996)
    4) The sodium salt of thioglycolic acid has been used in bacteriology for the preparation of thioglycolate media (Budavari, 1996).
    5) Thioglycolic acid is often used in preparations where the pH has been adjusted from 9 to 12.5, by adding alkaline agents (Barry, 1972).
    6) Thioglycolates have also been used in industry for dehairing hides, processing wool and as an iron indicator (Reiss & Gerstl, 1946).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Various dermal reactions have been noted with the use of thioglycolate containing depilatories or cold-wave (hair-waving) solutions. Many of these are the result of misuse, overuse, or sensitization to the ingredients of these products.
    a) Alkaline irritation and burns may result from increased concentration or prolonged exposure times. Direct systemic effects due to dermal use have not been seen.
    2) Toxic effects from ingestions would most likely be due to the high alkalinity of these products. Significant corrosive injury is unlikely to occur from substances with a pH less than 11. If the pH is greater than 11 in the ingested product, refer to the "Corrosives-Alkaline" management.
    0.2.4) HEENT
    A) WITH POISONING/EXPOSURE
    1) Instillation of thioglycolates into rabbit eyes produced mild conjunctival irritation. Thioglycolate containing products may be significantly alkaline and result in ocular damage.
    2) Second degree scalp burns have been reported in 6 black children.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) CNS depression, seizures, and paralysis were seen in animal experiments, but not in human exposures.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Exposures to thioglycolates for 90 days produced severe cutaneous reaction in animals tested. Acute exposures also caused reactions, but these were much less severe.
    2) Both primary dermatitis and allergic dermatitis have been reported in beauty salon operators. Casual home use is unlikely to cause serious reactions.
    0.2.16) ENDOCRINE
    A) WITH POISONING/EXPOSURE
    1) Hypoglycemia was seen in animals fatally poisoned with thioglycolates. The maximum effect occurred 4 to 6 hours postadministration.

Laboratory Monitoring

    A) No abnormalities in blood chemistry, morphology, or liver function was seen in 72 factory workers exposed daily to wave solutions containing thioglycolates. Severe hypoglycemia has been seen in animals, and may need to be evaluated in human overdose cases.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) EMESIS - Because of the risk of alkaline irritation and the apparent low systemic toxicity, emesis and activated charcoal are not recommended for thioglycolate containing solutions.
    C) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Toxic serum/blood concentrations have not been established. Dogs given 2 g developed no symptoms, while 5 g produced vomiting.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Various dermal reactions have been noted with the use of thioglycolate containing depilatories or cold-wave (hair-waving) solutions. Many of these are the result of misuse, overuse, or sensitization to the ingredients of these products.
    a) Alkaline irritation and burns may result from increased concentration or prolonged exposure times. Direct systemic effects due to dermal use have not been seen.
    2) Toxic effects from ingestions would most likely be due to the high alkalinity of these products. Significant corrosive injury is unlikely to occur from substances with a pH less than 11. If the pH is greater than 11 in the ingested product, refer to the "Corrosives-Alkaline" management.

Heent

    3.4.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Instillation of thioglycolates into rabbit eyes produced mild conjunctival irritation. Thioglycolate containing products may be significantly alkaline and result in ocular damage.
    2) Second degree scalp burns have been reported in 6 black children.
    3.4.2) HEAD
    A) WITH POISONING/EXPOSURE
    1) SCALP BURNS - Second degree burns of the scalp have been reported in 6 black children associated with permanent wave treatment containing glyceryl thioglycolate and thioglycolic acid (Fischer & Caurdy-Bess, 1990).
    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) IRRITATION - The salts of thioglycolic acid are generally found at mild pH's of 9.5, and are far less dangerous to the eye than is free thioglycolic acid (Grant & Schuman, 1993).
    a) Instillation of thioglycolates into rabbit eyes showed mildly transient conjunctival irritation with no sequelae (Brunner, 1952). Thioglycolate containing products may be significantly alkaline, and result in ocular damage if exposure times are prolonged.
    b) Grant & Schuman (1993) reported that continuous drops of ammonium thioglycolate (pH 7) for 15 seconds to rabbit eyes resulted in no damage. When the pH was adjusted to pH 9, small hemorrhages in the nictitating membrane and loss of small patches of epithelium from the cornea occurred, which spontaneously returned to normal in 2 days.
    2) CASE REPORT - Obstructed or veiled vision was reported on the second day following eye splash of a cold-wave product. On the third day the cornea was stippled with fine round dots and the conjunctiva was hyperemic. Corneal turbidity progressively worsened with reduction in vision over the next few days. Vision improved over the next 8 months, although corneal clouding was still evident (Grant & Schuman, 1993). The authors suggest this reaction may have been due to free thioglycolic acid.
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) ALLERGIC RHINITIS - Schwartz et al (1990) reported cases of occupationally exposed hairdressers who had increased nasal airway resistance.

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) CNS depression, seizures, and paralysis were seen in animal experiments, but not in human exposures.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) CNS depression was seen in several animal species tested (Freeman et al, 1956B).
    2) SEIZURES
    a) Seizures were seen in most animal species tested with thioglycolates (Freeman et al, 1956B).
    3) PARALYSIS
    a) Paralysis was seen in rabbits fatally poisoned (Reiss & Gerstl, 1946).

Gastrointestinal

    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTROINTESTINAL DISORDER
    a) Increased peristalsis was seen in several animal species studied (Freeman et al, 1956B).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) ABNORMAL LIVER FUNCTION
    1) WITH POISONING/EXPOSURE
    a) Cotter (1946) found liver function abnormalities in patients with prolonged exposure, but the result of this experiment has not been repeated.

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) DISORDER OF MENSTRUATION
    1) WITH POISONING/EXPOSURE
    a) In a study evaluating the effect of long-term exposure to permanent-waving solution (PWS) containing thioglycolic acid on menstruation, the frequency of any abnormality of menstruation was significantly higher in study cases (57 female hairdressers exposed to PWS) than in controls (64 female school teachers); 22.81% vs 9.38%, respectively; p value 0.043. However, the occurrence of menstrual cycle disorder, menstrual period disorder and dysmenorrhea did not differ significantly (Gan et al, 2003).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMATOLOGY FINDING
    1) WITH POISONING/EXPOSURE
    a) LACK OF EFFECT
    1) CASE SERIES - No abnormalities in blood chemistry morphology or liver function was seen in 72 factory workers exposed daily to wave solutions containing thioglycolates (Behrman et al, 1949).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Exposures to thioglycolates for 90 days produced severe cutaneous reaction in animals tested. Acute exposures also caused reactions, but these were much less severe.
    2) Both primary dermatitis and allergic dermatitis have been reported in beauty salon operators. Casual home use is unlikely to cause serious reactions.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Both primary irritant dermatitis and allergic eczematous dermatitis have been reported (Brunner, 1952; Fisher, 1989) in beauty operators. Casual home use is unlikely to cause serious reactions.
    b) Transient erythema of intact skin was all that was noted in several studies which attempted to document thioglycolate's irritant nature (McNally & Scull, 1948; Brunner, 1952).
    c) Glycerol monothioglycolate (GMTG) used for acid permanent waving has been associated with contact dermatitis in hairdressers (Burry, 1985; Morrison & Storrs, 1988; Tosti et al, 1988).
    B) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Sensitization was seen in animals tested with chronic thioglycerol exposure (Lehman, 1949) but human sensitization potential, especially with the ammonium salt, is low (Brunner, 1952).
    C) CHEMICAL BURN
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES - Fischer & Caurdy-Bess (1990) reported seeing 6 black children with second degree burns of the scalp associated with Jheri Redding Nucleics Natural Conditioning Perm containing glyceryl thioglycolate and thioglycolic acid.
    1) Four of these children had the permanent wave treatment applied in the home and two at a beauty shop.
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN ULCERATION
    a) Thioglycolic acid (84% and less) injected subcutaneously produced large, severe, slow to heal skin ulcers in rabbits and rats (McCord et al, 1947). Buffered thioglycolic acid produced mild ulceration in a similar experiment (McCord et al, 1947). Sodium thioglycolate (4.75%) produced no ulceration (McCord et al, 1947).
    2) DERMATITIS
    a) Exposures to thioglycolates for 90 days produced severe cutaneous reactions in animals tested. Acute exposures also caused reactions, but they were less severe (Lehman, 1949).

Endocrine

    3.16.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Hypoglycemia was seen in animals fatally poisoned with thioglycolates. The maximum effect occurred 4 to 6 hours postadministration.
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) THYROID DISORDER
    a) Thyroid hyperplasia was seen in animals chronically poisoned (Lehman, 1949).
    2) HYPOGLYCEMIA
    a) Hypoglycemia was seen in rabbits, rats, and dogs fatally poisoned with thioglycolates (Freeman et al, 1956B; Freeman & Rosenthal, 1952). The maximum effect occurred 4 to 6 hours post-administration. One mM/kg dropped blood sugar from an average of 129 mg% to 68 mg% (Freeman et al, 1956B).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS5421-46-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    B) IARC Carcinogenicity Ratings for CAS814-71-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    C) IARC Carcinogenicity Ratings for CAS367-51-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    D) IARC Carcinogenicity Ratings for CAS68-11-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No abnormalities in blood chemistry, morphology, or liver function was seen in 72 factory workers exposed daily to wave solutions containing thioglycolates. Severe hypoglycemia has been seen in animals, and may need to be evaluated in human overdose cases.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) No abnormalities in blood chemistry morphology or liver function was seen in 72 factory workers exposed daily to wave solutions containing thioglycolates (Behrman et al, 1949). Cotter (1946) found liver function abnormalities in patients with prolonged exposure, but the result of this experiment has not been repeated. Severe hypoglycemia has been seen in animals (Freeman & Rosenthal, 1952).
    4.1.4) OTHER
    A) OTHER
    1) DERMAL
    a) Patients positive on dermal patch test to glyceryl monothioglycolate may rarely cross-react to ammonium thioglycolate (Fisher, 1989).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No abnormalities in blood chemistry, morphology, or liver function was seen in 72 factory workers exposed daily to wave solutions containing thioglycolates. Severe hypoglycemia has been seen in animals, and may need to be evaluated in human overdose cases.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Toxicity from these products would be expected to be primarily secondary to mucosal irritation or burns rather than systemic absorption. Emesis and activated charcoal are NOT recommended.
    B) DILUTION -
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    6.5.2) PREVENTION OF ABSORPTION
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) ACTIVATED CHARCOAL
    1) Toxicity from these products would be expected to be primarily from mucosal irritation or burns rather than systemic absorption. Activated charcoal is NOT recommended as it may obscure endoscopy results and is not expected to prevent toxicity.
    C) EMESIS/NOT RECOMMENDED
    1) Because of the risk of alkaline irritation, and the apparent low systemic toxicity, emesis is not recommended for thioglycolate containing solutions. Should aggressive decontamination be necessary due to other components in the solution or product, other methods such as activated charcoal should be used.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Cases involving human, oral exposure to thioglycolate containing solutions are rare. Most of the products which contain thioglycolates have enough alkalinity added to produce alkaline irritation.
    2) First aid treatment should be directed at dilution and observation for oral or esophageal burns.
    3) Systemic manifestations might include seizures, CNS depression, or hypoglycemia, but these have not been reported in human cases.
    B) SUPPORT
    1) CNS and respiratory depression has been reported in animal models, but not yet in humans. Aggressive supportive care may be necessary should these occur in a human overdose.
    C) BURN
    1) There are insufficient numbers of human cases to evaluate the potential for creating alkaline burns. Practitioners should consider the possibility of such burns, and the necessity for esophagoscopy on an individual basis until more information is available.
    D) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    E) HYPOGLYCEMIA
    1) Hypoglycemia has only been seen in animal models, but it is theoretically possible in humans as well. If hypoglycemia is severe, immediately administer an intravenous bolus (50 milliliters) of 50 percent dextrose over a period of 2 to 3 minutes. If necessary, continuous intravenous infusion of 10 percent dextrose and water may be started.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Abstracts

Case Reports

    A) ADVERSE EFFECTS
    1) Reports in the literature of ingested cold wave solution components containing thioglycolates are rare. The extent to which these components are irritating or caustic is difficult to determine from the currently available literature.
    2) Cold wave solutions usually come in several components. Thioglycolates are in that component which is intended to straighten the hair and break the S-S bonds. Wetting agents, perfumes, detergents, and alkaline are often included in the same component.
    a) Symptoms seen after an ingestion will be a result of the combined effect of these agents, and therefore could include nausea, vomiting, irritation/burns, and diarrhea as well as the effects listed above for thioglycolates.
    3) The second component of a hair wave solution is a neutralizer or fixer, which may contain borates, bromates, acids, or peroxides which have toxicities separate from that of the thioglycolate containing component.
    4) DEPILATORIES - Contain thioglycolates at a higher concentration, and work at a more alkaline pH. The potential for alkaline burns, rather than just irritation, is greater with depilatories than with cold wave solutions. Again, the extent of burns to be expected is difficult to evaluate based on current literature.

Range Of Toxicity

Summary

    A) Toxic serum/blood concentrations have not been established. Dogs given 2 g developed no symptoms, while 5 g produced vomiting.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Dogs given 2 grams (approximately 182 milligrams/kilogram) over 2 days developed no symptoms. Five grams (455 milligrams/kilogram orally) caused vomiting (Brunner, 1952).
    2) Thiodiglycolic acid and the oxidation product dithioglycolic acid were tested and found to be less toxic than thioglycolates themselves (Lehman, 1949).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The amount of hydrogen sulfide produced from decomposition of either thioglycolic acid or thioglycolates is insufficient to produce systemic poisoning (McCord, 1946).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Have not been established.

Workplace Standards

    A) ACGIH TLV Values for CAS5421-46-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) ACGIH TLV Values for CAS814-71-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    C) ACGIH TLV Values for CAS367-51-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    D) ACGIH TLV Values for CAS68-11-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Thioglycolic acid
    a) TLV:
    1) TLV-TWA: 1 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Skin
    3) Definitions:
    a) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s): Eye and skin irr
    d) Molecular Weight: 92.12
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    b) Under Study
    1) Thioglycolic acid
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight:
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    E) NIOSH REL and IDLH Values for CAS5421-46-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    F) NIOSH REL and IDLH Values for CAS814-71-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    G) NIOSH REL and IDLH Values for CAS367-51-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    H) NIOSH REL and IDLH Values for CAS68-11-1 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Thioglycolic acid
    2) REL:
    a) TWA: 1 ppm (4 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: [skin]
    1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.
    f) Note(s):
    3) IDLH: Not Listed

    I) Carcinogenicity Ratings for CAS5421-46-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    J) Carcinogenicity Ratings for CAS814-71-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    K) Carcinogenicity Ratings for CAS367-51-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    L) Carcinogenicity Ratings for CAS68-11-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Thioglycolic acid
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Thioglycolic acid
    3) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    4) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    5) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Thioglycolic acid
    6) MAK (DFG, 2002): Not Listed
    7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    M) OSHA PEL Values for CAS5421-46-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    N) OSHA PEL Values for CAS814-71-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    O) OSHA PEL Values for CAS367-51-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    P) OSHA PEL Values for CAS68-11-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) SODIUM THIOGLYCOLATE
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 148 mg/kg (Freeman & Rosenthal, 1952)
    b) 390 mg/kg -- with 25% dextrose added (Freeman & Rosenthal, 1952)
    B) THIOGLYCOLIC ACID
    1) LD50- (ORAL)MOUSE:
    a) 242 mg/kg (RTECS, 2000)
    2) LD50- (SKIN)MOUSE:
    a) 47 mg/kg (RTECS, 2000)
    3) LD50- (ORAL)RAT:
    a) 0.15 mL/kg (Barry, 1972)
    b) 114 mg/kg (RTECS, 2000)

Pharmacology Toxicology

Toxicologic Mechanism

    A) In thioglycolate-treated animals, the adverse effects are primarily due to thioglycolate-ion, not the thioether (Lehman, 1949) or its oxidation products (thiodiglycolate-ion). Thioglycolate causes increased catabolism of proteins in glucose, followed by glycogenolysis of liver glycogen (Freeman et al, 1956B).
    B) OTHER -
    1) The hair is composed of primarily protein which is susceptible to alkali and keratolytic activity. Therefore, most cold wave solutions contain an alkali (usually ammonia) which brings the pH to 9 to 9.5. The alkali makes the hair plastic by breaking cystine and other bonds.
    2) Thioglycolic acid dissolves hair at pH 11.0; at pH 9 to 9.5 there is keratolysis, but at a slower rate. The extent of change varies by concentration, pH, and length of exposure (Lehman, 1949).
    3) Surface active agents are used to distribute the solvent and various dyes, emulsifiers, perfumes and creaming agents are added to the manufacturer's specifications.
    4) Weakly acidic or oxidizing agents such as peroxides, citric acids, bromates, or borates, are usually employed as neutralizers to counteract the effect of the thioglycolates (Lehman, 1949).

Physicochemical

Physical Characteristics

    A) THIOGLYCOLIC ACID: Unpleasant odor, sometimes resembling hydrogen sulfide (Budavari, 1996); colorless liquid (McCord, 1946)
    B) SODIUM THIOGLYCOLATE: Hydroscopic crystals
    C) CALCIUM THIOGLYCOLATE: Hydroscopic crystals

Molecular Weight

    A) THIOGLYCOLIC ACID: 92.12 (Budavari, 1996) SODIUM THIOGLYCOLATE: 114.1 (Budavari, 1996) CALCIUM THIOGLYCOLATE: 130.19 (Budavari, 1996)

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