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.

1) Do NOT induce emesis due to the corrosive nature of DMS and the potential for seizures.

1) MUCOSAL DECONTAMINATION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact 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. Patients should not be forced to drink after ingestion of an acid, nor should they be allowed to drink larger volumes since this may induce vomiting, and thereby re-exposure of the injured tissues to the corrosive acid. Dilution may only be helpful if performed in the first seconds to minutes after ingestion.
2) GASTRIC DECONTAMINATION: Ipecac contraindicated. Activated charcoal is not recommended as it may interfere with endoscopy and will not reduce injury to GI mucosa. Consider insertion of a small, flexible nasogastric or orogastric tube to suction gastric contents after recent large ingestion of a strong acid; the risk of further mucosal injury or iatrogenic esophageal perforation must be weighed against potential benefits of removing any remaining acid from the stomach.

1) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
2) Activated charcoal may interfere with endoscopic visualization of burns.

1) CAUSTIC INHALATION: Administer humidified oxygen, and remove from exposure. Monitor patient for respiratory distress; if a cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, and pneumonitis.
2) Patients with upper airway burns may develop significant edema abruptly; early intubation is advised.
3) Determine pulse oximetry and/or blood gases, obtain chest x-ray, perform endotracheal intubation and provide mechanical ventilation as clinically indicated.
4) Administer inhaled beta2-adrenergic agonists in patients with bronchospasm (National Heart,Lung,and Blood Institute, 2007). If acute lung injury develops, consider PEEP (Haas, 2011; Leaver & Evans, 2007; Stolbach & Hoffman, 2011).
5) Evaluate for esophageal, dermal and eye burns as indicated.
6) ENDOSCOPY: Because acid ingestion may cause severe gastric burns with relatively few initial signs and symptoms, endoscopic evaluation is recommended within 24 hours in any patient with a definite history of ingesting a strong acid, even if asymptomatic. If burns are found, follow 10 to 20 days later with a barium swallow.
7) PHARMACOLOGIC TREATMENT: The use of corticosteroids is controversial. Patients with first degree burns generally do well and rarely develop strictures. Corticosteroids are generally not beneficial in these patients. Some authors have advocated the use of corticosteroids for second degree, deep-partial thickness burns within 48 hours of ingestion in patients without gastrointestinal bleeding or evidence of perforation. However, no well-controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with second degree, superficial-partial thickness burns. Some authors have recommended steroids in patients with third degree burns. A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended. Antibiotics are indicated for suspected perforation or infection and in patients receiving corticosteroids.
8) SURGICAL OPTIONS: Initially, if severe esophageal burns are found a string may be placed in the stomach to facilitate later dilation. Insertion of a specialized nasogastric tube after confirmation of a circumferential burn may prevent strictures. Dilation is indicated after 2 to 4 weeks if strictures are confirmed; if unsuccessful, either colonic intraposition or gastric tube placement may be performed. Consider early laparotomy in patients with severe esophageal and/or gastric burns.

1) 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) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.

1) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

1) Laryngeal edema may necessitate airway management.

1) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

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).

1) CORNEAL BURNS - Roux et al (1977) and Littler & McConnell (1955) report chemical burns of the cornea and conjunctiva, epithelial corneal ulceration, and decreased visual acuity in workers following occupational exposures to DMS.

1) Onset of irritation is typically delayed for several hours after exposure to the pure material (Grant & Schuman, 1993; (Ip et al, 1989), but DMS which has been partially hydrolyzed to sulfuric acid will produce immediate acid burns, followed by delayed necrosis from methylation (Grant & Schuman, 1993).

1) INCIDENCE - In a retrospective series of 62 patients occupationally exposed to dimethyl sulfate, 30 (50%) developed photophobia (Wang et al, 1988).

1) Rhinorrhea and nasal inflammation were reported in 4 workers, with a latency period of 3 to 4 hours in 3 of them (Roux et al, 1977). Rhinorrhea was reported in a pipefitter after inhalation of vapor (Haswell, 1960). In one case report the rhinorrhea persisted for 72 hours (Rippey & Stallwood, 2005).
2) INCIDENCE - In a retrospective series of 62 patients occupationally exposed to dimethyl sulfate, 12 (21%) developed rhinorrhea and 12 (21%) developed nasal stuffiness (Wang et al, 1988).

1) Ingestion of an unknown quantity resulted in fatal glottal edema and severe local burns, necrosis and membranous mucosal detachment of the upper GI tract (Nida, 1947).
2) Mucosal burns and ulceration of the pharynx and larynx with red or whitish mucosa and purulent secretions, which were delayed for several hours, have been reported (Roux et al, 1977; Littler & McConnell, 1955). Tracheal perforation has resulted (Littler & McConnell, 1955).
3) Partial necrosis of the uvula, with some sloughing, was reported following DMS vapor inhalation (Haswell, 1960).

1) Death from severe DMS poisoning is due to circulatory failure (ACGIH, 1991; Huang et al, 1994).

1) In a group of 149 DMS-exposed Chinese workers, those with MILD poisoning had a 46.8% incidence of unspecified ECG abnormalities, those with MODERATE poisoning had a 56.8% incidence of ECG abnormalities, and there was a 100% incidence in patients with SEVERE poisoning (Huang et al, 1994).
2) In a retrospective series of 62 patients with inhalation exposure to DMS 90% of those patients with bronchopneumonia and pulmonary edema also showed signs of myocardial damage, evidenced on ECG as inverted or biphasic T waves and elevated or depressed ST segments. 39% of patients with peribronchitis had inverted T waves (Wang et al, 1988).

1) DMS causes severe inflammation of the bronchial mucosa, dyspnea, chest discomfort, and productive cough (Clayton & Clayton, 1994; Hathaway et al, 1996; Huang et al, 1994; Roux et al, 1977; Littler & McConnell, 1955).
2) INCIDENCE - Frothy and bloody sputum was reported in 7 out of 62 cases of moderate to severe DMS exposures. Bronchopneumonia developed in 6 of 62 cases and peribronchitis in 18 of 62 cases (Wang et al, 1988).

1) Necrosis of the tracheal mucosa has occurred (Roux et al, 1977; Nida, 1947). Tracheal perforation resulting in emphysema has occurred (Littler & McConnell, 1955; Nida, 1947).
2) Tracheobronchial stenosis was reported in a 35-year-old exposed to DMS vapors. Lung biopsy revealed erosion and granulated bronchiolar wall tissue (Kinoshita et al, 1992).

1) The onset of respiratory symptoms including pulmonary edema is typically delayed for up to 10 hours after exposure (Hathaway et al, 1996; Wang et al, 1988; Mohlau, 1920).
2) Fatalities following dimethyl sulfate poisoning have been due to either pulmonary edema or Adult Respiratory Distress Syndrome (ARDS) (Huang et al, 1994). Severe exposures resulting in ARDS have been successfully treated with steroids, antibiotics, bronchodilators, and postural drainage (Wang et al, 1988). Death from pulmonary edema may occur after 3 or 4 days (Lewis, 1996).
3) Non-cardiogenic pulmonary edema, with symptoms of central cyanosis and hypoxemia, occurring 12 hr following vapor exposure, developed in a 30-year-old male. FEV1 (L/min) on day 4 was 1.65, at 1 month it was 2.44, and at 10 months it was 3.3. Treatment with high-dose methylprednisolone markedly improved his symptomatology (Ip et al, 1989).
4) Pulmonary edema has occurred in several occupational exposures, with delays of 3 to 15 hours (Roux et al, 1977; Mohlau, 1920).

1) Oral ingestion has led to delayed glottal edema, resulting in asphyxiation and death (Nida, 1947). Pharyngo-laryngeal and bronchial obstruction may occur (Roux et al, 1977).
2) Nine hours after inhalation exposure to dimethyl sulfate, a patient developed hoarseness, a persistent harsh croup-like cough producing clear sputum, excessive salivation, throat and chest tightness, and dyspnea. Fiberoptic laryngoscopy revealed marked erythema of the false cords and arytenoids with a degree of laryngeal edema but a reasonable laryngeal inlet. He was preemptively intubated. Intravenous dexamethasone 8 mg every 8 hours was started. He was extubated the next day with good gas exchange. He returned to his normal work 4 weeks later and at 3 month follow-up was entirely asymptomatic (Rippey & Stallwood, 2005).

1) Cyanosis is a late finding in serious cases (Hathaway et al, 1996; Ip et al, 1989; Nida, 1947; Mohlau, 1920). Roux et al (1977) report two cases of cyanosis in occupational exposures.

1) Productive cough persisted for at least 3 months after acute exposure in one case (Ip et al, 1989). Roux et al (1977) report coughing as a second phase effect.
2) Dyspnea persisted for at least one month after acute respiratory failure from exposure to DMS vapor (Kinoshita et al, 1992). Persistent limitation of inspiratory capacity, with 25% reduction in lung capacity 2 months after inhalation of DMS vapors, occurred in a pipefitter (Haswell, 1960).

1) Mild to moderate impairment of ventilatory capacity was seen in 8 out of 62 cases of acute DMS intoxication after 2 to 12 years (Wang et al, 1988).

1) Headache and agitation are early signs of exposure, but may not appear for 10 hours (Hathaway et al, 1996; Roux et al, 1977). Migraine headache, as a delayed effect, was reported in an occupational exposure (Mohlau, 1920).

1) Delirium, as a delayed effect, was reported following vapor and dermal exposure to dimethyl sulfate (Mohlau, 1920).

1) Seizures, paralysis, and delirium progressing to coma have been reported in serious DMS poisonings (Clayton & Clayton, 1994).

1) Coma has been reported following severe toxic exposures (Clayton & Clayton, 1994; Mohlau, 1920).

1) Cerebral edema was a reported finding at autopsy in a death due to DMS exposure (Bartalini, 1957).

1) Nausea, vomiting, and/or diarrhea may occur (Hathaway et al, 1996; Roux et al, 1977).

1) Delayed hepatic injury with icterus and jaundice may occur (Clayton & Clayton, 1994; Hathaway et al, 1996). Death from liver damage may be delayed for several weeks (Lewis, 1996).

1) Impairments in liver function tests persisting for up to six years have been reported (ACGIH, 1991). Severely poisoned patients have developed elevated SGOT levels (Huang et al, 1994).

1) FATTY LIVER

1) Delayed kidney damage with albuminuria and hematuria may occur (Clayton & Clayton, 1994; Littler & McConnell, 1955). Serum BUN level of 32 mg% was reported in a pipefitter after inhalation of DMS vapors (Haswell, 1960). Death from kidney damage may be delayed for several weeks (Lewis, 1996).
2) Increased phosphates and sulfates were apparent in the urine of two workers exposed to vapors and liquid of dimethyl sulfate (Mohlau, 1920).

1) Renal failure secondary to shock has occurred in workers severely poisoned with dimethyl sulfate (Huang et al, 1994).

1) Dysuria can occur and may persist for 3 to 4 days following exposure (ACGIH, 1991; Hathaway et al, 1996).

1) Within 3 hours of direct contact with liquid DMS, swelling and redness of the genitalia occurred. 13 hours after exposure, blisters were noted on the penis and scrotum (Littler & McConnell, 1955).

1) RENAL FUNCTION ABNORMAL

1) As DMS may be metabolized to methanol (ACGIH, 1991), metabolic acidosis could theoretically occur, but has not been reported in human poisonings.

1) Elevated leukocyte counts have been reported in workers acutely poisoned with dimethyl sulfate (Huang et al, 1994; Haswell, 1960; Littler & McConnell, 1955). The frequency of leukocytosis appears to increase with severity of clinical symptoms (Wang et al, 1988).

1) LYMPHOCYTOSIS

1) DMS is very corrosive to intact skin, producing blister formation, ulceration, and necrosis, even with short-term contact (Clayton & Clayton, 1994; Lewis, 1996; Littler & McConnell, 1955). Skin exposure may vary from erythema to vesication, depending on the length of contact (Littler & McConnell, 1955).
2) Onset of dermal effects is typically delayed by several hours (Grant & Schuman, 1993).
3) Systemic poisoning may occur after absorption of DMS from even relatively minor dermal exposures (Littler & McConnell, 1955).

1) Profuse sweating and irritative erythema have been reported following exposures to DMS (Roux et al, 1977).

1) IRRITATION

1) LYMPHADENOPATHY

1) TRANSPLACENTAL CARCINOGEN - The offspring of pregnant rats given DMS IV at 20 mg/kg on day 15 of gestation developed squamous carcinomas of the nasal cavity or neurogenic tumors (Clayton & Clayton, 1994; Hathaway et al, 1996; ACGIH, 1991).

1) Preimplantation losses, embryotoxicity, and cardiovascular abnormalities occurred in fetal mice and rats exposed to 0.1 to 4 ppm throughout gestation (ACGIH, 1991; Hathaway et al, 1996; RTECS , 2000).

1) IARC Classification

1) One patient with oatcell bronchial carcinoma and DMS exposure for 15 years has been reported (ACGIH, 1991; Druckrey et al, 1966). The connection between the exposure and the tumor was inconclusive.

1) Data from epidemiologic studies of workers with exposure to air concentrations of DMS ranging from less than 0.2 ppm to greater than 1.0 ppm showed no excess incidence of respiratory tract cancers (ACGIH, 1991).

1) Animal studies have demonstrated lung carcinomas when exposed to high concentrations of DMS. It is theorized that DMS is a methylating agent of nucleic acids (Hathaway et al, 1996; Roux et al, 1977).

1) In rats, dimethyl sulfate was found to be an equivocal tumorigenic agent and carcinogenic by RTECS criteria with sense organs and special senses tumors, transplacental tumorigenesis, brain and coverings tumors, at the site of application, and lymphomas, including Hodgkin's disease (RTECS , 2000).
2) NASAL TUMORS occurred in rats exposed to 3 or 10 ppm DMS 1 hour/day, 5 days/week for 130 days (ACGIH, 1991; Druckrey et al, 1970). Squamous cell carcinomas of the nasal cavity developed in 3 of 15 surviving rats exposed to 10 ppm for 1 hour/day for 19 weeks; one animal each developed lymphosarcoma of the thorax and glioma of the cerebellum (Hathaway et al, 1996).
3) SARCOMA - DMS is carcinogenic in rats. Subcutaneous injections of very large amounts produced local sarcomas in 12 of 18 treated rats (ACGIH, 1991).
4) SQUAMOUS CARCINOMA - DMS has produced nasal cavity squamous carcinomas and neurogenic tumors in the offspring of pregnant rats administered the agent on day 15 of gestation (Hathaway et al, 1996).
5) In rats, dimethyl sulfate was found to be an equivocal tumorigenic agent and carcinogenic by RTECS criteria with sense organs and special senses tumors, transplacental tumorigenesis, brain and coverings tumors, tumors at the site of application, and lymphomas, including Hodgkin's disease (RTECS , 2000).
6) LUNG ADENOMAS were seen in mice exposed to 4 ppm for 4 hours/day, 5 days per week (Hathaway et al, 1996).
7) DMS was not carcinogenic in mice by the dermal route when applied at 0.1 mg in 0.01 mL acetone, 3 times/week for 475 days (HSDB , 2000).

1) Toxic serum DMS levels have not been established.
2) Baseline liver and renal functions should be monitored, especially in symptomatic patients. Serum electrolytes and CBC should also be monitored in patients with respiratory involvement.
3) As DMS may be metabolized to methanol (ACGIH, 1991), methanol serum levels should be obtained in severe cases. To date, however, there are no human case reports with measured methanol serum levels.

1) Monitor serum electrolytes, arterial pH, and blood gases, especially in patients with respiratory involvement (Hathway et al, 1991).

1) Baseline urinalysis should be obtained, as albuminuria and hematuria may occur.

1) Monitor pulmonary function tests.

A) The potential for delayed onset of serious toxicity mandates at least 12 hours of observation in a controlled setting. One reference recommends 72 hours of observation for all patients with significant exposure (Hathaway et al, 1996).

1) Rapid decontamination is paramount. Monitor respiration and airway status. Provide humidified oxygen to all patients with respiratory symptoms.

1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact 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).
2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).

1) Inducing emesis is CONTRAINDICATED due to the vesicant, corrosive nature of dimethyl sulfate.

1) There are no reports of activated charcoal use in patients poisoned with DMS, but theoretically it would adsorb the chemical. Activated charcoal may interfere with endoscopic visualization of burns.
2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
3) CHARCOAL DOSE

1) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
2) Laryngeal edema may necessitate airway management.

1) 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.

1) Rapid decontamination is necessary, but may not prevent systemic toxicity.
2) 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).

1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact 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).
2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).

1) Inducing emesis is CONTRAINDICATED due to the vesicant, corrosive nature of DMS and the potential for seizures.

1) There are no reports of activated charcoal use in patients poisoned with DMS, but theoretically it would adsorb the chemical. One source recommends saline catharsis in DMS poisoning (ITI, 1985). Activated charcoal may interfere with endoscopic visualization of burns.
2) CHARCOAL ADMINISTRATION
3) CHARCOAL DOSE

1) Gastric lavage is recommended by one source for gastric decontamination in oral exposures (ITI, 1985). Because of the potential for both systemic toxicity and mucosal damage from corrosive effects, passage of a nasogastric tube to suction gastric contents, followed by lavage, may be warranted after large ingestions.

1) As DMS is highly corrosive to skin, ingestion could produce a clinical picture similar to that of ingestion of strong acid. Baseline liver and renal function tests should be obtained. If albuminuria and hematuria occur, maintain good urine output to avoid renal failure.

1) Sucralfate may be useful in relieving symptomatology from acid induced injury. Efficacy in accelerating healing or preventing complications has not been proven.
2) Administration of sucralfate, 1 gram dissolved in 30 milliliters of water, four times a day, was used in a 25-year-old man with moderately severe gastric injury after ingestion of hydrochloric acid. No other therapy was given other than antibiotic. Within 48 hours, improvement in symptoms was noted, enabling progression to a liquid diet on the 3rd day. Strictures were not prevented, although nearly complete gastric mucosal healing occurred after 2 weeks. The patient received a gastrojejunostomy for pyloric stricture 6 weeks postingestion (Mittal et al, 1989).

1) Penner (1980) argues that following a large ingestion of strong acids, a nasogastric tube should be passed and suction performed in an attempt to remove as much acid as possible prior to cold water dilution which may result in an exothermic reaction and worsen the burn.
2) Many authorities oppose this procedure fearing esophageal or gastric perforation. Soft nasogastric or orogastric tube should only be passed within 90 minutes following the large ingestion of a strong acid.

1) The following recommendations are extrapolated from experience with ingestions of acids and/or alkaline corrosives.
2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible and perform endoscopy within the first 24 hours when indicated.
3) INDICATIONS: Most studies associating the presence or absence of gastrointestinal burns with signs and symptoms after caustic ingestion have involved primarily alkaline ingestions. Because acid ingestion may cause severe gastric injury with fewer associated initial signs and symptoms, endoscopic evaluation is recommended in any patient with a definite history of ingestion of a strong acid, even if asymptomatic.
4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.
5) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):
6) GRADING
7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.

1) The following recommendations are extrapolated from experience with ingestions of acids and/or alkaline corrosives.
2) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
3) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
4) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
5) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
6) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
7) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
8) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
9) STUDIES

1) In severe cases of gastrointestinal necrosis or perforation, emergent surgical consultation should be obtained. The need for gastric resection or laparotomy in the stable patient is controversial (Chodak & Passaro, 1978; Dilawari et al, 1984).
2) LAPAROTOMY/LAPAROSCOPY - Early laparotomy or laparoscopy should be considered in patients with endoscopic evidence of severe esophageal or gastric burns after acid ingestion to evaluate for the presence of transmural gastric or esophageal necrosis (Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993). Emergent laparotomy should be strongly considered in any patient with hypotension, altered mental status, or acidemia (Hovarth et al, 1991).
3) Observe for symptoms of gastric outlet obstruction, at which time parenteral fluids and/or hyperalimentation should be considered. Classically, this occurs at 3 weeks after ingestions.

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

1) SUMMARY
2) DOPAMINE
3) NOREPINEPHRINE
4) If hypotension is secondary to gastrointestinal bleeding, blood or blood products replacement therapy is the treatment of choice.

1) METHANOL - One source (ACGIH, 1991) mentions metabolism of DMS to methanol and sulfuric acid. As it cannot be determined from available literature whether DMS metabolism can produce serious methanol poisoning, a methanol component should be considered in substantial exposures.

1) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
2) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
3) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
4) Onset of symptoms may be delayed for up to 12 hours after respiratory exposure.

1) With severe dyspnea or hypoxemia, administer humidified oxygen until symptoms subside.

1) Evaluate for nasopharyngeal burns.

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

1) Baseline chest x-ray and arterial blood gases should be obtained.

1) Bronchospasm may be treated with inhaled bronchodilating agents.

1) Laryngeal and glottic edema may occur and necessitate airway management.

1) OPHTHALMOLOGIC CONSULT - Ophthalmologic consultation is recommended for all patients with persistent conjunctival irritation, corneal ulceration or opacification, decreased visual acuity, or impaired color vision.
2) VISUAL CHANGES - The possibility of a METHANOL POISONING component with ocular toxicity from DMS metabolism should be considered when visual changes other than conjunctival irritation or corneal opacification are present.

1) EVALUATION
2) IRRIGATION
3) MINOR INJURY
4) SEVERE INJURY
5) SURGICAL THERAPY

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).

1) DMS may cause significant dermal vesication and chemical burns which may be delayed in onset and should be treated as chemical burns.
2) APPLICATION
3) DEBRIDEMENT
4) TREATMENT
5) TETANUS PROPHYLAXIS

1) Serious systemic toxicity can occur after even minimal dermal exposure.

a) A chemist with dermal DMS exposure immediately flushed the exposed skin with water and neutralizing agents. Marked periorbital edema, tachycardia, bronchospasm, and rales appeared over the following 4 hours. Blisters appeared on exposed skin 13 hours after exposure.

a) ACUTE EFFECTS
b) CHRONIC EFFECTS

a) In two separate industrial accidents, 149 Chinese workers were exposed to dimethyl sulfate (Huang et al, 1994). Poisoning amongst these workers consisted of:
b) In workers with MILD POISONING, signs and symptoms consisted of:
c) In addition to signs/symptoms noted in workers with mild poisoning, those with MODERATE POISONING also had:
d) Workers with SEVERE POISONING also had:
e) The four fatal cases were complicated by fractures, soft tissue injuries, or extensive second degree chemical burns. Two died of pulmonary edema and shock, a third died of Adult Respiratory Distress Syndrome (ARDS), and the fourth died of massive gastric hemorrhage from a stress ulcer.

1) GENERAL

a) Adopted Value

1) Listed as: Dimethyl sulfate
2) REL:
3) IDLH:

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A3 ; Listed as: Dimethyl sulfate
2) EPA (U.S. Environmental Protection Agency, 2011): B2 ; Listed as: Dimethyl sulfate
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): 2A ; Listed as: Dimethyl sulfate
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Dimethyl sulfate
5) MAK (DFG, 2002): Category 2 ; Listed as: Dimethyl sulfate
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

1) Listed as: Dimethyl sulfate
2) Table Z-1 for Dimethyl sulfate:

1) LD50- (ORAL)MOUSE:
2) LD50- (INHALATION)RAT:
3) LD50- (ORAL)RAT:
4) LD50- (SUBCUTANEOUS)RAT:
5) TCLo- (INHALATION)RAT: