Diethylsulfat

Hazardous Air Pollutants (HAPs)

Toxic Gases & Vapors -> Other Toxic Gases & Vapors

Carcinogens

log Kow= 1.14

1.14

1.14

Peppermint odor

Faint ethereal odor

1.1803 at 68 °F (USCG, 1999) - Denser than water; will sink

1.172 g/cu cm @ 25 °C

Relative density (water = 1): 1.2

1.172 @25 °C

Miscible in alcohol and ether.

In water, 7,000 mg/l @ 20 °C

Solubility in water: reaction

220 °F (USCG, 1999)

104 °C

220 °F (CLOSED CUP)

104 °C c.c.

409 °F at 760 mmHg (USCG, 1999)

209.5 °C with decomposition

208 °C @760 [mm Hg]

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P270, P271, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P321, P330, P362+P364, P363, P405, and P501 (click each P-code to see the statement)

Danger

H302 (99.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P262, P264, P264+P265, P270, P271, P273, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P321, P330, P361+P364, P362+P364, P363, P403+P233, P405, and P501 (click each P-code to see the statement)

Chemical: Sulfuric acid, diethyl ester

Hazard Traits - Carcinogenicity; Genotoxicity

Sulfuric acid, diethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Sulfuric acid, diethyl ester are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 26-04-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/24081

Substance: Diethyl sulphate

Diethyl sulphate: HSNO Approval: HSR002968 Approved with controls

Special Hazards of Combustion Products: Highly toxic fumes contaning sulfur oxides may be generated along with thermal decomposition products such as ethyl ether and ethylene. Sulfuric acid may be produced in the presence of moisture.

· Combustible material: may burn but does not ignite readily.

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

May be fatal if inhaled, swallowed or absorbed through skin. Inhalation causes nausea and vomiting. Causes burns to skin and eyes. Ingestion may cause nausea, vomiting abdominal pain and collapse. (USCG, 1999)

· Highly toxic, may be fatal if inhaled, ingested or absorbed through skin.

Diethyl sulfate is used as an ethylating agent and as a chemical intermediate. No information is available on the acute (short-term), chronic (long-term), reproductive, or developmental effects of diethyl sulfate in humans. In an epidemiological study, an excess mortality rate from laryngeal cancer was associated with occupational exposure to high concentrations of diethyl sulfate. In one study, rats orally exposed to diethyl sulfate developed tumors in the forestomach. EPA has not classified diethyl sulfate with respect to potential carcinogenicity. The International Agency for Research on Cancer (IARC) has classified diethyl sulfate as a Group 2A, probable human carcinogen.

A skin, eye, and respiratory tract irritant; May cause pulmonary edema; [ICSC] May cause severe burns to eyes and skin; [HSDB] May be fatal by ingestion, inhalation, and skin absorption; [CAMEO] Germ cell mutagens that have shown to increase the mutant frequency in the progeny of exposed mammals. [MAK] Decomposes in water and releases sulfuric acid; A corrosive substance that can cause injury to the skin, eyes, and respiratory tract; Inhalation may cause chemical pneumonitis; May be absorbed through skin; [MSDSonline]

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Diethyl sulfate (64-67-5) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s070diet.pdf]

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest. Half-upright position. Refer immediately for medical attention.

Remove contaminated clothes. Rinse skin with plenty of water or shower for at least 15 minutes. Refer immediately for medical attention.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Do NOT induce vomiting. Give nothing to drink. Refer immediately for medical attention.

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

INHHALATION: Remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen.

General First Aid:

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Store in a cool, dry, well-ventilated location. Separate from bases, oxidizing materials, water and air.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

Stop or control the leak, if this can be done without undue risk. Use water spray to cool & disperse vapors, & protect personnel. Approach release from upwind. Absorb in noncombustible material for proper disposal. Prompt cleanup and removal are necessary.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for DIETHYLSULFATE (6 total), please visit the HSDB record page.

Personal protection: complete protective clothing including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

TERRESTRIAL FATE: Based upon the hydrolysis of diethylsulfate in aqueous environments(1), diethylsulfate is expected to hydrolyze in moist soils(SRC). Volatilization from soil surfaces and adsorption to soil are not expected to be important processes because of hydrolysis(SRC).

AQUATIC FATE: If released to water, diethylsulfate is expected to hydrolyze rapidly(SRC). A hydrolysis rate constant of 1.15X10-4/sec at 25 °C(1) translates to a half-life of 1.7 hours at pH 7(SRC). The rate of hydrolysis will increase in both acidic and basic waters as the reaction is catalyzed under these conditions(2). Volatilization from water surfaces, adsorption to suspended solids and sediments, biodegradation, and bioconcentration are not expected to be important fate processes in aquatic systems because of hydrolysis(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethylsulfate, which has a vapor pressure of 0.212 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase diethylsulfate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-lives for this reaction in air is estimated to be about 9 days(SRC), calculated from its rate constant of 1.8X10-12 cu cm/molecule-sec at 25 °C(3). Diethylsulfate also reacts rapidly with water in the atmosphere, with an estimated half-life of <1 day(3).

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

/PLANTS/ Diethyl sulfate induced unscheduled DNA synthesis in pollen of petunia hybrida. It induced chromosomal aberrations in meiotic cells and chlorophyll mutations in rice, ring chromosomes in Allium sativum root tips and anaphase and telophase aberrations in Papaver somniferum root meristemic cells.

Cough. Sore throat. Laboured breathing. Shortness of breath. Symptoms may be delayed.

Redness. Pain. Serious skin burns.

Redness. Pain. Severe burns.

Burns in mouth and throat. Burning sensation behind the breastbone. Abdominal pain. Shock or collapse.

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

The dermal carcinogenicity of diethyl sulfate was evaluated in a group of 40 C3H/HeJ male mice painted 3 times/week for their lifespan on the skin of the back, with undiluted diethyl sulfate at an average dose of 0.0074 g/mouse/application. A negative control group of 40 animals was exposed to 0.0126 g acetone/mouse/application in the same manner as the treated group. All the treated mice were dead after 23 months of the study, 11 after 18 months, and 27 after one year. The first skin neoplasm was observed after 12 months of treatment, with a total of 21 animals developing malignant skin neoplasms. The total cancer incidence was 87.5% and the median latent periods for appearance of neoplasms and cancer were 15.7 and 16.2 months, respectively. No skin tumors were observed in the control group.

The mutagenicity of diethyl sulfate was evaluated in the Chinese Hamster Ovary (CHO) Mutation test, both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on the results of preliminary toxicity determinations, diethyl sulfate, diluted with DMSO, was tested for mutagenicity at ranges of concentrations of 2.5-40x10(-3)% and 5-80x10(-3)% (v/v in DMSO) in the presence and absence of activation, respectively. All concentrations of diethyl sulfate tested caused a positive response in the tests both with and without activation.

The ability of diethyl sulfate to induce sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells was evaluated in the absence of added metabolic activation. Based on preliminary toxicity tests, diethyl sulfate, diluted with DMSO, was tested at concentrations of 0, 0.00125, 0.0025, 0.0050, 0.010 or 0.020 % (v/v). A total of 15 cells/dose level were examined in all but the highest dose level tested since this dose level was toxic to the cells. There were statistically significant increases observed in the numbers of SCE/cell and SCE/chromosome relative to negative controls at concentrations of 0.0050 and 0.010% (p < 0.001, Student's t-test). A positive dose-response relationship was observed.

The ability of diethyl sulfate to cause an increase in unscheduled DNA synthesis in rat liver cells was evaluated. Based on preliminary toxicity tests, diethyl sulfate, diluted in DMSO, was tested at concentrations of 0, 0.0001, 0.001, 0.003, 0.010, 0.030 or 0.100% (v/v). Cells were treated with test article for 2 hrs. Statistically significant increases in DNA synthesis relative to negative controls were observed at all tested concentrations using both values for radioactivity incorporation into either nuclei or DNA (p < 0.05 for concentrations of 0.001 and 0.100% and p < 0.001 for the remaining concentrations). A linear dose-response pattern was not observed although the cumulative responses observed over a wide range of concentrations suggested a significant biological effect.

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Diethyl sulfate is produced, as an intermediate or a final product, by process units covered under this subpart.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Diethyl sulfate is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

ETHYLMERCAPTURIC ACID WAS IDENTIFIED AS A URINARY METABOLITE OF SC, IP, OR ORAL DIETHYL SULFATE, ALSO ISOLATED FROM URINE WAS THE DICYCLOHEXYLAMMONIUM SALT IN 2.4% YIELD.

After male CFE albino rats were administered 1 ml of a 5% (v/v) solution of diethyl sulfate in arachis oil by gavage or by intraperitoneal or subcutaneous injection, ethylmercapturic acid and a sulfoxide were identified as metabolites.

Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.

Diethyl sulfate is primarily used as an ethylating agent, and also as an accelerator in the sulfation of ethylene and in some sulfonations. Diethyl sulfate is also a chemical intermediate for ethyl derivatives of phenols, amines, and thiols, and as an alkylating agent.

Used mainly to make dyes; Also used as an ethylating agent (pigment production), a finishing agent (textile manufacturing), a dye-set agent (carbonless paper), and an accelerator (sulfation of ethylene); Also used in agricultural chemicals, household products, pharmaceuticals, and cosmetics; [HSDB]

Pulp and Paper Processing [Category: Industry]

Chiefly as an ethylating agent; as an accelerator in the sulfation of ethylene; in some sulfonations.

Chemical intermediate for ethyl derivatives of phenols, amines, and thiols and as an alkylating agent.

The principal uses are as an intermediate in dye manufacture, as an ethylating agent in pigment production, as a finishing agent in textile manufacture and as a dye-set agent in carbonless paper. Smaller applications are in agricultural chemicals, in household products, in the pharmaceutical and cosmetic industries, as a laboratory reagent, as an accelerator in the sulfation of ethylene and in some sulfonation processes.

2023: 2,500,000 - <4,000,000 lb

(1972) PROBABLY GREATER THAN 4.5X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

GRADES: TECHNICAL

Diethyl sulfate is available as a technical grade product that contains 99.5% active ingredient or as a laboratory chemical with a purity of 95% to >98%.

Not Known or Reasonably Ascertainable

Sulfuric acid, diethyl ester: ACTIVE

Method of purification: rectification in vacuo.

...Could be used as a mutagenic agent to produce a new variety of barley called Luther; however, no evidence was found that it is presently being used commercially for this purpose.