TOXICOLOGICAL PROFILE FOR
 

TETRYL
 

(2,4,6-Trinitrophenyl-N-methylnitramine)
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

June 1995 
TETRYL ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by 

the Agency for Toxic Substances and Disease Registry. 
TETRYL iii 

UPDATE STATEMENT 

Toxicological profiles are revised and republished as necessary, but no less than once every three 

years. For information regarding the update status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology/Toxicology Information Branch
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 



TETRYL vii 

CONTRIBUTORS
 

CHEMICAL MANAGERS (S)/AUTHOR (S):
 

Carolyn Harper, Ph.D
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Fernando Llados, Ph.D.
 

Research Triangle Institute, Research Triangle Park, NC
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:
 

1.	 Green Border Review. Green Border review assures consistency with ATSDR policy. 

2.	 Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and 

classifying end points. 

3.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific minimal risk levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

4.	 Quality Assurance Review. The Quality Assurance Branch assures that consistency across 

profiles is maintained, identifies any significant problems in format or content, and establishes 

that Guidance has been followed. 

TETRYL ix 

PEER REVIEW
 

A peer review panel was assembled for tetryl. The panel consisted of the following members: 

1. Dr. Tim Borges, Technical Information Analyst, Oak Ridge National Laboratories, Oak Ridge, 

Tennessee; 

2. Dr. Lawrence Holland, Private Consultant, Los Alamos, New Mexico; and 

3. Dr. Theodore Mill, SRI International, Menlo Park, California. 

These experts collectively have knowledge of tetryl’s physical and chemical properties, toxicokinetics, 

key health end points, mechanisms of action, human and animal exposure, and quantification of risk to 

humans. All reviewers were selected in conformity with the conditions for peer review specified in 

Section 104(i)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, 

as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the 

peer reviewers’ comments and determined which comments will be included in the profile. A listing 

of the peer reviewers’ comments not incorporated in the profile, with a brief explanation of the 

rationale for their exclusion, exists as part of the administrative record for this compound. A list of 

databases reviewed and a list of unpublished documents cited are also included in the administrative 

record. 

The citation of the peer review panel should not be understood to imply its approval of the profile’s 

final content. The responsibility for the content of this profile lies with the ATSDR. 









TETRYL 1 

1. PUBLIC HEALTH STATEMENT
 

This Statement was prepared to give you information about tetryl and to emphasize the 

human health effects that may result from exposure to it. The Environmental Protection 

Agency (EPA) has identified 1,397 hazardous waste sites as the most serious in the nation. 

These sites make up the National Priorities List (NPL) and are the sites targeted for long-term 

federal clean-up activities. Tetryl has been found in at least 12 of the sites on the NPL. 

However, the number of NPL sites evaluated for tetryl is not known. As EPA evaluates more 

sites, the number of sites at which tetryl is found may increase. This information is important 

because exposure to tetryl may cause harmful health effects and because these sites are 

potential or actual sources of human exposure to tetryl. 

When a substance is released from a large area, such as an industrial plant, or from a 

container, such as a drum or bottle, it enters the environment. This release does not always 

lead to exposure. You can be exposed to a substance only when you come in contact with it. 

You may be exposed by breathing, eating, or drinking substances containing the substance or 

by skin contact with it. 

If you are exposed to a substance such as tetryl, many factors will determine whether harmful 

health effects will occur and what the type and severity of those health effects will be. These 

factors include the dose (how much), the duration (how long), the route or pathway by which 

you are exposed (breathing, eating, drinking, or skin contact), the other chemicals to which 

you are exposed, and your individual characteristics such as age, gender, nutritional status, 

family traits, life-style, and state of health. 

1.1 WHAT IS TETRYL? 

Tetryl is a synthetic substance that was used to make explosives, mostly during World War I 

and World War II. It is no longer manufactured or used in the United States. The chemical 

name for tetryl is N-methyl-N,2,4,6-tetranitroaniline. Other commonly used names are 

2,4,6-trinitrophenyl-N-methylnitramine, nitramine, tetralite, and tetril. Stocks of tetryl are 
TETRYL 2 

1.PUBLIC HEALTH STATEMENT
 

found in storage at military installations and are being destroyed by the Department of 

Defense. Tetryl was frequently manufactured as pellets or powder. Under certain 

manufacturing conditions, it could exist in the air as a dust. Tetryl is a yellow, crystal-like 

solid at room temperature. It dissolves slightly in water. It can also dissolve in other liquids, 

including benzene, alcohol, and acetone. At temperatures of 369 °F (187 °C) or higher, tetryl 

will explode. Tetryl has no odor, but some of its manufactured forms may have odors due to 

the presence of other chemicals. In addition, high concentrations of tetryl dust have an 

irritating effect on the nose that produces a sensation that might seem to be an odor. See 

Chapters 3 and 4 for more information on what tetryl is and how it is used. 

1.2 WHAT HAPPENS TO TETRYL WHEN IT ENTERS THE ENVIRONMENT? 

Tetryl may be released to the air, water, and soil when old stores of the explosive are 

destroyed by exploding or burning. However, tetryl has not been measured in air during any 

of these activities. Tetryl that was manufactured or stored at military installations, like Army 

ammunition plants, may still be present in the soil and water at or around these sites. Tetryl 

is not likely to evaporate into air from water or soil surfaces. However, tetryl may be present 

in air associated with dust from these sites. Tetryl appears to break-down rapidly in some 

soils. Picric acid, is one of the break down products of tetryl in soil. Tetryl probably does 

not easily travel from soil to groundwater. Erosion of soil from contaminated sites may 

release tetryl to nearby surface water. Once it is in the water, tetryl may dissolve or associate 

with small particles of suspended solids, sediments, or organic debris. Some of these 

particles will settle to the bottom. Tetryl breaks down rapidly in sunlit rivers and lakes but 

much more slowly in groundwater. It is not known whether tetryl will build up in fish, 

plants, or land animals. See Chapters 4 and 5 for more information on tetryl in the 

environment. 

1.3 HOW MIGHT I BE EXPOSED TO TETRYL? 

Most people are not exposed to tetryl because contamination is localized around military 

installations where it was manufactured, used, or stored. Tetryl can move through soil and 
TETRYL 3 

1.PUBLIC HEALTH STATEMENT
 

enter underground water. If you live at or near one of these installations with tetryl 

contamination, you may be exposed to tetryl by drinking contaminated well water. You may 

also be exposed to tetryl by skin contact with contaminated soil or water. Workers who were 

previously involved in the processes of making, using, packing, or loading tetryl were 

probably exposed to tetryl by breathing contaminated dust and through skin contact. Workers 

currently involved in the clean-up, disposal, and destruction of tetryl may also be exposed by 

these routes. We do not know how many workers are exposed to tetryl. 

Tetryl has been found in soil and water at some military installations, such as Army 

ammunition plants, and in underground water at one site located near a military installation. 

See Chapter 5 for more information on exposure to tetryl. 

1.4 HOW CAN TETRYL ENTER AND LEAVE MY BODY? 

Tetryl can enter your body if you breathe it in the air, drink it in water, or get it on your skin. 

We do not know the extent to which tetryl enters your body by these routes. Based on 

limited information from animal studies, tetryl probably leaves your body in urine after being 

broken down to other substances. See Chapter 2 for more information on how tetryl enters 

and leaves your body. 

1.5 HOW CAN TETRYL AFFECT MY HEALTH? 

Most of the information on the health effects of tetryl is from studies on workers employed in 

military facilities during World War I and World War II. These workers were involved in the 

production, use, packing, or loading of tetryl. The levels of tetryl in air at these facilities 

were often not measured. Many workers who breathed tetryl-laden dust complained of 

coughs, fatigue, headaches, eye irritation, lack of appetite, nosebleeds, nausea, and/or 

vomiting. Most workers who routinely handled tetryl powder and pellets in munitions 

factories developed a distinct yellow staining of the hands, neck, and hair. Workers with this 

staining were sometimes referred to as “canaries.” Many workers who had skin contact with 

tetryl dust or compounds containing tetryl also developed skin rashes (dermatitis). The rashes 
TETRYL 4 

1. PUBLIC HEALTH STATEMENT
 

ranged from mild to severe and symptoms often included reddening, itching, swelling, and 

peeling of skin. Most of these health effects usually developed within a few days to a few 

weeks after exposure to tetryl. Some workers were more sensitive to tetryl exposure and 

developed allergies to tetryl. These often included severe asthma-like reactions that 

sometimes required medical attention or hospitalization. Workers who developed allergies to 

tetryl had reactions within a few hours after being exposed again to tetryl. Many of these 

workers were moved to work areas where there was no tetryl. Little is known about the 

longer term health effects in workers exposed to tetryl. 

There is no information on health effects in humans exposed to drinking water contaminated 

with tetryl. Rabbits fed high doses of tetryl every day for 6 to 9 months developed 

degenerative lesions of the liver and kidney. Decreased blood-clotting capability and changes 

in the spleen were also noted. We do not know if tetryl causes cancer or birth defects, or if it 

affects reproduction in humans or animals. The Department of Health and Human Services, 

the International Agency for Research on Cancer, and the Environmental Protection Agency 

have not classified the carcinogenicity of tetryl. For more information on health effects, see 

Chapter 2. 

1.6 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO TETRYL? 

During World War I and World War II, most workers who routinely handled tetryl powder 

and pellets in munitions factories developed a distinct yellow staining of the skin. Many 

workers also developed skin rashes. These workers were exposed to high concentrations of 

tetryl dust in the air and by direct contact with the explosives. There are no medical tests to 

show if you have been specifically exposed to tetryl. However, if the breakdown products of 

tetryl found in the urine of animals exposed to tetryl were also present in the urine of exposed 

humans, these breakdown products could be used to indicate exposure to tetryl or similar 

substances. The symptoms caused by exposure to tetryl can also occur for many other 

reasons; therefore, they cannot be used as proof of tetryl exposure. Refer to Chapters 2 and 6 

for more information. 
TETRYL 5 

1. PUBLIC HEALTH STATEMENT
 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government has developed standards and guidelines to protect people from the 

health effects of tetryl. The Department of Transportation has many regulations for the 

transportation of explosives such as tetryl. Although tetryl is no longer being manufactured 

or used, the Occupational Safety and Health Administration (OSHA) has set a regulatory level 

for tetryl in the workplace. The maximum allowable amount of tetryl in workroom air during 

an 8-hour workday, 40-hour workweek, is 1.5 milligrams of tetryl per cubic meter of air 

(mg/m3

). This level may apply to workers engaged in destruction of tetryl explosives and 

those who work in locations where tetryl is stored. The National Institute for Occupational 

Safety and Health recommends that workers not be exposed to air containing more than 

1.5 mg/m3

 during a 10-Hour workday. For more information on federal and state 

recommendations, see Chapter 7. 

1.8 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department or: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road NE, E-29
 

Atlanta, Georgia 30333
 

(404) 639-6000 

This agency can also provide you with information on the location of the nearest occupational 

and environmental health clinic. These clinics specialize in the recognition, evaluation, and 

treatment of illness resulting from exposure to hazardous substances. 

TETRYL 7 

2. HEALTH EFFECTS
 

2.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective of the toxicology of tetryl. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public 

health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposureinhalation, 

oral, and dermal-and then by health effect-death, systemic, immunological/lymphoreticular, neurological, 

developmental, reproductive, genotoxic, and carcinogenic effects. These data are discussed in terms of three 

exposure periods-acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). 

The existing database on tetryl is quite limited. Most of the information on health effects comes from 

case studies and reports on the health of workers employed in tetryl munitions plants during World 

War I and World War II. The levels of tetryl to which these workers were exposed were generally not 

reported. Few data exist from animal studies with tetryl. None of the data located were reliable 

enough to determine levels of significant exposure (LSE). Because of this, estimates of levels posing 

minimal risk to humans (Minimal Risk Levels, or MRLs) could not be derived. 

2.2.1 Inhalation Exposure 

The only studies located regarding health effects in humans after inhalation exposure to tetryl were 

case studies and other reports of workers exposed to tetryl dusts in manufacturing plants during World 

War I and World War II. Little information was available regarding the number of people exposed or 
TETRYL 8 

2. HEALTH EFFECTS
 

the duration and level of exposure. Since exposure was to the tetryl-laden dusts, the effects could 

have been caused by inhalation, direct skin contact, or by swallowing. The dermal effects noted in 

these studies were most likely caused by direct skin contact and are described in Section 2.2.3. It is 

unknown whether the other effects were caused by inhaling or by swallowing tetryl; therefore, in this 

profile, it is assumed that the primary route of exposure was inhalation. 

One study, which investigated skin and anaphylactic reactions of guinea pigs sensitized by inhalation 

of tetryl smoke (Gel1 1944), is discussed below. No other health effects were studied in animals. 

2.2.1.l Death 

Only two studies reporting death in humans were located. One study reports about two men who died 

approximately 3-5 years after exposure to tetryl dusts in a manufacturing plant (Hardy and Maloof 

1950). Air samples taken in 1942, the only period for which exposure data were provided, ranged 

from 1 to 18 mg/m3

. The period of exposure for the 2 men ranged from 1 to 4 years. Both men 

complained of general symptoms, such as cough, fatigue, and weight loss, during and after the time 

they worked with tetryl. In both cases, death was attributed to liver failure, but the specific cause of 

the liver failure was difficult to determine. In one case, the liver failure was considered to be due to 

advanced hepatitis or cirrhosis, but rheumatic heart disease was also present. In the other case, 

symptoms were consistent with chemically-induced cirrhosis. A hepatoma that was observed at 

autopsy was considered a possible result of the cirrhosis. Neither subject had a history of excessive 

alcohol intake. One woman employed for approximately 2 years in a munitions factory in England 

died following clinical symptoms of toxic jaundice (Troup 1946). Autopsy revealed atrophy of the 

liver with distortion of the upper parts of the liver. Work subsequent to leaving the munitions factory 

and prior to death involved handling of closed containers of chlorinated naphthalenes. None of these 

deaths can be unequivocally attributed to tetryl; the possibility of complicating medical conditions 

and/or exposure to other toxic chemicals could also have been contributing factors in the deaths. 

One of eight guinea pigs exposed to a tetryl smoke died of an anaphylactic reaction when later 

challenged with a picrylgelatin antigen which had a structure similar to suspected tetryl metabolites 

(Gel1 1944). 
TETRYL 9 

2. HEALTH EFFECTS
 

2.2.1.2 Systemic Effects 

No studies were available regarding cardiovascular, musculoskeletal, renal, dermal or ocular effects in 

humans after inhalation exposure to tetryl. Dermal effects, presumably from direct skin contact, are 

described in Section 2.2.3.2. No studies were located regarding systemic effects in animals after 

inhalation exposure to tetryl. The systemic effects that have been observed after inhalation exposure 

in humans are described below. 

Respiratory Effects. Workers exposed to tetryl dusts often complained of throat and nasal 

irritation consisting of dryness, burning, sneezing, nosebleeds, and coughing (Bergman 1952; Cripps 

1917; Eddy 1943; Fischer and Murdock 1946; Hardy and Maloof 1950; McConnell et al. 1946; 

Murray et al. 1944; Probst et al. 1944; Smith 1916; Witkowski et al. 1942). In susceptible individuals, 

these symptoms were reported to occur within a few hours to a few weeks (Probst et al. 1944; 

Witkowski et al. 1942). Coughing generally occurred during exposure to tetryl but also occurred at 

night in some workers. In most cases, the symptoms disappeared within a few days after removal 

from tetryl exposure (Hardy and Maloof 1950; Probst et al. 1944; Witkowski et al. 1942). The throat 

and nasal symptoms were probably due to the irritating effect of inhaled dust particles on mucosal 

membranes (McConnell et al. 1946; Probst et al. 1944; Witkowski et al. 1942). 

Two workers developed an asthma-like condition within a few weeks of being exposed to tetryl (Eddy 

1943). Asthma-like symptoms (severe spasmodic coughing and wheezing) were reported in 6 of 

11 workers involved in the manufacture of tetryl explosives (Hardy and Maloof 1950). Similar 

symptoms have been reported by other investigators (Cripps 1917; Smith 1916). Some workers 

complained of difficulty breathing after leaving the workplace (Cripps 1917). One of 11 workers in a 

munitions factory was diagnosed as having emphysema and fibrosis of the lungs several years after 

leaving the manufacturing plant, but the disease in this worker could not be clearly linked to tetryl 

exposure (Hardy and Maloof 1950). X-ray examinations revealed no evidence of lung damage in 

4,000 workers exposed to tetryl (Hatch and Probst 1945). The authors attributed this to the large size 

of the airborne particles of tetryl in their facility. No pulmonary pathology was observed in chest 

X-rays of approximately 981 workers employed in a shell loading plant, although these subjects were 

exhibiting respiratory symptoms (cough, nasal and throat irritation, epistaxis) believed to be associated 

with tetryl exposure (Fisher and Murdock 1946). X-ray examinations of about 800-900 workers 
TETRYL 10 

2. HEALTH EFFECTS
 

employed in the tetryl area of a manufacturing plant revealed no pulmonary conditions att’ributable to 

tetryl powder (Probst et al. 1944). 

Gastrointestinal Effects. Workers exposed to unspecified levels of tetryl dusts in the workplace 

for unspecified durations occasionally complained of nausea, vomiting, or abdominal cramps (Bergman 

1952; Cripps 1917; Fischer and Murdock 1946; Hardy and Maloof 1950; Hilton and Swanston 1941; 

Murray et al. 1944; Troup 1946; Witkowski et al. 1942). These effects may have been due to direct 

gastric irritation from swallowing tetryl-laden dusts. These effects generally occurred within the first 

two weeks of exposure and, according to some reports, were more common in workers who had not 

eaten adequately (Bergman 1952; Witkowski et al. 1942). No other information was available. 

Hematological Effects. There are a few studies that examined hematological effects in workers 

exposed to tetryl dusts. Examinations of an unspecified number of operators engaged in the making 

and cleaning of tetryl pellets revealed many cases of slight leukocytosis and increased levels of 

lymphocytes (incidences not reported) and two cases of decreased red blood cells (Cripps 1917). 

Other symptoms exhibited by the subjects and the total number of subjects involved in the study were 

not specified. Three of 37 workers exposed to tetryl had slight variations in the size of red corpuscles, 

and an additional three had an increase in polymorphonuclear white blood cells when blood films were 

examined (Ruxton 1917). The author did not consider these changes to be related to tetryl exposure. 

Slight decreases in hemoglobin concentration and white blood cell counts were also reported in 

exposed workers (number exposed and exposure details not reported) who complained of loss of 

appetite, slight nausea, malaise, and sleeplessness (Brabham 1943). A later study of 800-900 workers 

reported that incidences of leukocytosis and leukopenia were not related to type or duration of tetryl 

exposure, symptoms, or complaints (Probst et al. 1944). The 4% incidence of anemia found in the 

study was considered to be within normal limits by the autnors, although no control values were used 

for comparison. Moderate secondary anemia was diagnosed in a small number of workers exhibiting 

tetryl dermatitis (<l% of 3,807 cases), but this incidence did not differ from that found in tetryl 

workers exhibiting symptoms other than dermatitis (<1% of 1,962 cases) or from that found in 

unexposed workers (Fischer and Murdock 1946). Anemia was diagnosed in a female tetryl operator 

following nine days of hospitalization for treatment of a severe tetryl-induced dermatitis (Witkowski et 

al. 1942). These authors stated that anemia was a common effect of tetryl exposure in munitions 

plants but presented no incidence data. An increased incidence of anemia was not observed in 

workers employed at Picatinny Arsenal (Dover, New Jersey) during 1941-1950 (size of the study 
TETRYL 11 

2. HEALTH EFFECTS
 

population was not reported) (Bergman 1952). These studies are limited by the lack of control groups 

and/or values, incomplete hematological data, possible concomitant exposure to other chemicals, and 

the subjective nature of the reports. None of the studies examined changes in blood-clotting ability. 

The limitations and the differences in end points examined in the studies make it difficult to determine 

which hematological effects are most likely to occur in humans. There is no conclusive evidence to 

associate anemia with exposure to tetryl. 

Hepatic Effects. Liver failure was reported in two of thirteen workers who died several years 

following exposure to tetryl dust in a plant that manufactured explosives (Hardy and Maloof 1950). In 

one case, the liver showed signs of advanced hepatitis or cirrhosis on autopsy. No history of excessive 

alcohol intake was noted, but evidence of rheumatic heart disease was present. The second subject 

had cirrhosis of the liver, and a hepatoma was found at autopsy. The authors considered the findings 

to be consistent with repeated chemical intoxication leading to cirrhosis and development of hepatoma. 

No history of excessive alcohol intake was noted in this subject. Jaundice, possibly toxic in origin, 

was reported in two women who worked in a munitions factory in England (Troup 1946). The total 

number of people exposed to tetryl in this factory was estimated to be about 5,000. In both cases, the 

period of exposure was slightly less than 2 years. In one of the subjects, excess urobilinogen, urobilin, 

and bile pigment were found in the urine. In the second case, which resulted in death, atrophy of the 

liver and distortion of the upper parts of the liver were found at autopsy. Subsequent to her 

employment as a tetryl worker, the subject was employed in a factory in which she handled closed 

containers of chlorinated naphthalene. In a third study, workers exposed over a 35-month period to 

tetryl dusts showed no evidence of liver injury, but details regarding the tests conducted were not 

provided (McConnell et al. 1946). 

Body Weight Effects. Weight loss was reported in three workers exposed to tetryl for 14 years 

during the manufacture of explosives (Hardy and Maloof 1950). Anorexia was reported in three of 

eight workers similarly exposed to tetryl for a year or more (Hardy and Maloof 1950). Anorexia and 

weight loss have been reported by other authors as well (Brabham 1943; Fischer and Murdock 1946; 

Troup 1946; Witkowski et al. 1942) and may affect as many as 10% of exposed workers (Witkowski 

et al. 1942). Any role of tetryl in causing these effects could not be determined because details of 

exposure, past medical histories, and exposure to other chemicals were not reported. 
TETRYL 12 

2. HEALTH EFFECTS
 

2.2.1.3 Immunological and Lymphoreticular Effects 

No studies which specifically examined immunologic end points in humans exposed to tetryl were 

located. However, asthma-like symptoms (severe spasmodic coughing, wheezing, and difficulty 

breathing) and a reaction similar to hay fever observed in susceptible individuals exposed during the 

manufacture of tetryl-containing explosives indicate that an immunologic response may occur 

following inhalation of tetryl-contaminated dust (Cripps 1917; Eddy 1943; Smith 1916). Although the 

respiratory effects have generally been attributed to the local irritative properties of tetryl dust 

(Bergman 1952; Cripps 1917; McConnell et al. 1946), in some cases the symptoms seemed to be 

associated with hypersensitivity to tetryl (Fischer and Murdock 1946; Probst et al. 1944). Acute 

asthma-like attacks have been controlled by administration of adrenalin (Eddy 1943). In one study, 

sympathomimetic drugs (e.g., ephedrine or amphetamine sulfate) were reported to control the 

respiratory effects associated with tetryl exposure better than an antihistamine (Bain and Thomson 

1954). In the absence of definitive immunologic studies, it is difficult to determine the specific role of 

the immune system in tetryl toxicity. 

Eight guinea pigs were exposed to a particulate smoke of tetryl made by blowing air over a 

10% solution of tetryl in acetone (Gel1 1944). The estimated tetryl concentration in the exposure 

chamber was about 400 mg/m3

 and the animals were exposed 30 minutes per day for 6 days out of 14. 

Total absorption was estimated to be about 7-10 mg per animal. Six of the guinea pigs developed 

anaphylactic sensitivity to picrylgelatin antigen (Gel1 1944). Picrylgelatin was chosen as the antigen 

because prior testing with different possible metabolites of tetryl (picric acid among them) and protein 

analogs of tetryl and its metabolites indicated that the 2,4,6-trinitrophenylamino group (present in both 

tetryl and picric acid) was the primary antigenic determinant in the immune response to tetryl. 

Induced tetryl sensitivity in females exposed by inhalation was tested using an in vitro challenge 

method, and three of four responded positively in this test. Three of four males exposed to tetryl 

vapors and challenged with an intravenous dose of the antigen showed signs of anaphylaxis. In one, 

the reaction was severe enough to cause death. The experiment was limited by the use of whole-body 

animal exposure, the use of only a small number of exposed animals and the absence of a control 

group, the use of acetone as the solvent in the generation of the tetryl smoke, and the imprecise 

methods used to generate and measure the tetryl smoke. The overall evidence indicates that inhaled 

tetryl may initiate an immune response. 
TETRYL 13 

2. HEALTH EFFECTS
 

2.2.1.4 Neurological Effects 

Workers exposed to unspecified levels of tetryl dusts for unspecified durations occasionally
 

complained of increased irritability, headaches, nausea, vomiting, fatigue, or insomnia (Bergman 1952,
 

Brabham 1943; Cripps 1917; Hardy and Maloof 1950; Murray et al. 1944; Witkowski et al. 1942).
 

No other information was available.
 

2.2.1.5 Reproductive Effects 

Only two reports were located that discussed possible effects of tetryl on the reproductive system. 

Two women employed in a plant that manufactured explosives containing tetryl during World War II 

(concentrations of tetryl dust and exposure duration were not given) reported increased durations 

between menstrual cycles and amenorrhea (Hardy and Maloof 1950). In contrast, decreased intervals 

between menstrual cycles and/or increased duration of flow were reported in women who worked with 

tetryl powder or pellets (Cripps 1917). The total population examined and the incidence within this 

population were not reported; however, of 30 individual cases discussed, four individuals reported 

excessive menstruation. It is not possible to draw conclusions regarding the effect of tetryl on the 

menstrual cycle because these reports described opposite effects, had few subjects, failed to describe 

pertinent health histories or exposure to other chemicals, and provided few details. No other data on 

effects to the reproductive system were located. 

No studies were located regarding the following health effects in animals or humans after inhalation 

exposure to tetryl: 

2.2.1.6 Developmental Effects 

2.2.1.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.1.8 Cancer 
TETRYL 14 

2. HEALTH EFFECTS
 

2.2.2 Oral Exposure 

No studies were located regarding effects in humans after exposure to tetryl in food or drinking water. 

However, workers exposed to tetryl dusts in the air may have swallowed some of the larger particles. 

Because the primary exposure route for these workers was considered to be inhalation, these studies 

were discussed in Section 2.2.1. 

A limited number of studies in animals exposed to tetryl via the oral route were located. These 

describe the acute effects of tetryl on rats (Parmeggiani et al. 1956) and rabbits (Wells et al. 1920), the 

effects in rabbits administered tetryl by gavage for 2 months (Guarino and Zambrano 1957) or 

6-9 months (Daniele 1964; Fati and Daniele 1965), and the carcinogenicity of tetryl in rats treated by 

gavage for 30 days (Griswold et al. 1968). 

2.2.2.1 Death 

Groups of rats administered 1 or 2 g/kg/day by gavage died between 10 and 18 days after dosing 

started (Parmeggiani et al. 1956); the specific cause of death was not provided. Rabbits given 

1,000 mg/kg/day in milk by gavage died after l-3 doses (Wells et al. 1920). This study was limited 

by the lack of a control group, use of only a single exposure concentration, and absence of 

microscopic data. No other details were provided. An additional study in rabbits reported that the 

mean survival time of 20 rabbits treated orally with 25 mg/kg/day was 2 months (Guarino and 

Zambrano 1957). No controls were used and no information was provided regarding the cause of 

death. 

2.2.2.2 Systemic Effects 

No studies were located regarding musculoskeletal, or ocular effects in animals after oral exposure to 

tetryl. The systemic effects that have been observed in animals after oral exposure are described 

below. 

Respiratory Effects. Edema of the lungs and bronchi were observed in rabbits treated orally with 

l-3 doses of 1,000 mg/kg (Wells et al. 1920). This dose level was lethal and no other dose level was 

tested. Rabbits treated with daily doses of 25 mg/kg/day for up to 3 months exhibited gross and 
TETRYL 15 

2. HEALTH EFFECTS
 

microscopic signs of congestion in their lungs (Guarino and Zambrano 1957). In contrast, no.gross or 

histological alterations were observed in the lungs of 12 rabbits treated orally with doses of 

125 mg/kg/day for 6-9 months (Fati and Daniele 1965). In both studies, a control group was not used 

and no other dose level was tested. No other respiratory end points were assessed. The reason for the 

discrepancy between the results from Guarino and Zambrano (1957) and those from Fati and Daniele 

(1965) is unknown. Dyspnea was reported in rats treated orally with 1 or 2 g/kg/day; these doses 

killed the rats in 10-18 days (Parmeggiani et al. 1956). 

Cardiovascular Effects. No gross or histological alterations were noticed in the hearts of rabbits 

treated orally with doses of 125 mg/kg/day for 6-9 months (Fati and Daniele 1965). A control group 

was not used, and no other dose level was tested. No other cardiovascular end points were monitored. 

No gross alterations, and no significant histological alterations were observed in rats treated with 

25 mg/kg/day for up to 3 months (Guarino and Zambrano 1957), but moderate vascular congestion 

was noted. This study did not examine a control group and only one dose level was tested. 

Gastrointestinal Effects. No gross or histological alterations were seen in the gastrointestinal 

mucosa of rabbits treated orally with 25 mg/kg/day for up to 3 months (Guarino and Zambrano 1957) 

or with 125 mg/kg/day for 6-9 months (Fati and Daniele 1965). Neither study used a control group 

and in both studies only one dose level was tested. No further details were provided. 

Hematological Effects. Administration of 125 mg/kg/day to 12 rabbits for 120 days resulted in 

some statistically significant changes in blood parameters compared to controls (3 rabbits) (Daniele 

1964). These changes, which suggested a coagulation disorder, were inconsistent and showed no 

increase in severity with time. The small numbers of animals used and the inconsistent results make i 

difficult to unequivocally attribute the observed effects to tetryl exposure. Accumulation of hematic 

pigments in the spleen was noted in rabbits administered a lethal dose of 1,000 mg/kg/day for 

l-3 doses (Wells et al. 1920) and rabbits administered 125 mg/kg/day for 6 months (Fati and Daniele 

1965). 

Hepatic Effects. The cytoplasm of the hepatocytes of rats that received 1 or 2 g/kg/day by gavage 

(death occurred in 10-18 days) had a granular appearance and the nuclei were polymorphous and 

pyknotic (Parmeggiani et al. 1956); frequent activation of Kupffer cells was also observed. Rabbits 

that received 1,000 mg/kg/day for l-3 days had normal livers at necropsy. No other relevant 
TETRYL 16 

2. HEALTH EFFECTS
 

information was provided (Wells et al. 1920). The livers of rabbits treated with 25 mg/kg/day (a dose 

that was lethal to 18 of 20 rabbits) for up to 3 months were congested and yellowish in color (Guarino 

and Zambrano 1957). Microscopic examination revealed swelling of the epithelium, fatty infiltration, 

and necrotic foci. Similar observations were made in the livers of 12 rabbits administered 

125 mg/kg/day for 6 months (Fati and Daniele 1965). In 4 of the rabbits treated for an additional 

3 months, there was congestion of the liver. Microscopic examination revealed more severe damage 

of the hepatocytes than was observed at 6 months, including necrosis and hyperplasia of the Kuppfer 

cells. These studies in rabbits were limited by the small number of animals used in the treated groups, 

the absence of a control group, and by the use of only one dose level. 

Renal Effects. Rats that received 1 or 2 g/kg/day (death occurred in 10-18 days) had frank kidney 

lesions which included swollen tubular epithelium, unrecognizable cytoplasmic structures, pyknotic 

nuclei, and obliterated tubular lumen (Parmeggiani et al. 1956). Rabbits that received 

1,000 mg/kg/day for l-3 days had swelling and degeneration of the epithelium of the kidneys. No 

other relevant information (e.g., number of animals and whether or not controls were used) was 

provided (We& et al. 1920). Rabbits treated with 25 mg/kg/day for up to 3 months (this dose killed 

18 of 20 rabbits before 3 months) showed renal congestion, lesions to the parenchymal tissue, and 

swelling and vacuolar degeneration of the convoluted tubules (Guarino and Zambrano 1957). Three of 

4 rabbits administered 125 mg/kg/day for 9 months had slight congestion of the kidneys with cloudy 

swelling and vacuolar degeneration of the convoluted tubules on microscopic examination (Fati and 

Daniele 1965). Six rabbits treated similarly, but for only 6 months, showed no signs of toxicity; this 

is in conflict with the results of Guarino and Zambrano (1957), but no explanation is apparent from 

data presented in these studies. The studies in rabbits were limited by the absence of a control group, 

and by the use of only one dose. 

Dermal Effects. The only information regarding dermal effects after oral administration of tetryl to 

animals is that rats treated with 1 or 2 g/kg/day by gavage exhibited rough coat and a yellow 

pigmentation in the nose, ears, and tail (Parmeggiani et al. 1956). These dose levels caused death in 

10-18 days. 

Body Weight Effects. Rats that received 1 or 2 g/kg/day by gavage experienced a steady and 

significant body weight loss accompanied by anorexia until death occurred 10-18 days after dosing 

began (Parmeggiani et al. 1956). No further information was available. 
TETRYL 17 

2. HEALTH EFFECTS
 

2.2.2.3 Immunological and Lymphoreticular Effects 

Rats given 2 g/kg/day by gavage for up to 18 days had moderate hemosiderosis in the spleen and also 

exhibited atrophy of lymphatic follicles (Parmeggiani et al. 1956). It should be mentioned, however, 

that 2 g/kg/day was a lethal dose. In rabbits treated with 25 mg/kg/day for up to 3 months the spleen 

generally appeared congested with free erythrocytes in the splenic sinuses (Guarino and Zambrano 

1957). Similar results were observed in rabbits given 125 mg/kg/day for 6 months (Fati and Daniele 

1965). In some cases, atrophy of the lymph nodes and moderate splenic hemosiderosis were found. 

The study was limited by the small number of animals used in the treated groups, the absence of a 

control group, the use of only one dose, and the failure to report the incidence of effects. 

2.2.2.4 Neurological Effects 

The only information located regarding neurological effects in animals following oral exposure to 

tetryl is that rats treated with 1 or 2 g/kg/day by gavage had paralysis of the hind limbs, sometimes 

front limbs, and suffered tonic-clonic convulsions before death occurred lo-18 days after dosing began 

(Parmeggiani et al. 1956). Because the dose levels used were relatively high and lethal, the effects 

observed may represent general signs of deterioration that preceded death. 

No studies were located regarding the following health effects in animals after oral exposure to tetryl: 

2.2.2.5 Reproductive Effects 

2.2.2.6 Developmental Effects 

2.2.2.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.2.8 Cancer 

One study was located regarding cancer in rats following treatment with tetryl (Griswold et al. 1968). 

Twenty female Sprague-Dawley rats received 40 mg tetryl by gavage every 3 days for 30 days for a 
TETRYL 18 

2.HEALTH EFFECTS
 

total dose of 400 mg of tetryl. The rats were examined for up to 9 months from initiation of 

exposure. Statistical analyses were not performed on the data from this study which was designed to 

survey the carcinogenicity of a large number of chemicals. Carcinomas, fibroadenomas, and 

hyperplasia were found in the mammary tissues of 5 of 132 control rats and in 1 of 19 of the tetryltreated 

rats. No stomach tumors were found in the controls, but an adenoma was found in 1 of 19 of 

the tetryl-treated rats. Several design limitations rendered the study inadequate to evaluate the 

carcinogenicity of tetryl. Limitations included an insufficient number of animals used, only females 

were tested, an insufficient follow-up period, and the use of only a single dose. 

2.2.3 Dermal Exposure 

Several studies are available regarding health effects in humans exposed to tetryl in munitions 

manufacturing plants. In most studies, the number of workers or the duration and level of exposure 

were not provided. These studies were conducted during World War I and World War II when tetryl 

was being manufactured in large quantities. The workers were exposed by both dermal and inhalation 

routes, and it is possible that some of the dusts were swallowed. The toxic effects, other than dermal 

and ocular effects, are described in Section 2.2.1, Inhalation Exposure. 

One study, which showed no sensitization reactions in guinea pigs following dermal application of 

tetryl (Gel1 1944), is discussed below. No other health effects were studied in animals. 

2.2.3.1 Death 

No studies were located regarding death in humans or animals following dermal exposure to tetryl. 

2.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, or renal effects in humans or animals after dermal exposure to tetryl. The 

systemic effects that have been observed after dermal exposure are described below. 
TETRYL 19 

2. HEALTH EFFECTS
 

Dermal Effects. Workers handling tetryl powder often developed a yellow staining on the hands, 

face, and hair (Bergman 1952; Cripps 1917; Hilton and Swanston 1941; Murray et al. 1944; Probst et 

al. 1944; Smith 1916). The terms “canary” or “tetryl blonde” were frequently used to describe the 

affected workers. Staining occurred in most workers and was not indicative of systemic effects or 

dermatitis. Discoloration was due to surface reactions and deepened with continued exposure. Persons 

with oily skin or those who perspired profusely were usually more susceptible to discoloration 

(Bergman 1952; Cripps 1917). Fading of the color occurred once workers were removed from the 

contaminated areas, but it often took several months before skin color returned to normal (Bergman 

1952). Workers exposed to unspecified levels of tetryl dusts often complained of dermatitis (Bergman 

1952; Cripps 1917; Fischer and Murdock 1946; Hilton and Swanston 1941; McConnell et al. 1946; 

Murray et al. 1944; Parmeggiani et al. 1956; Probst et al. 1944; Ruxton 1917; Schwartz 1944; Smith 

1916; Witkowski et al. 1942). The dermatitis ranged from mild to severe and was characterized by 

itching or burning, redness, papular eruptions, and facial edema particularly on the eyelids, nasal folds, 

cheeks, forehead, and neck. Exfoliation usually occurred after the edema subsided. Dermatitis 

generally affected areas with more sebaceous glands, and persons with oily skin were generally more 

frequently and seriously affected (Cripps 1917; Fischer and Murdock 1946; Murray et al. 1944; 

Schwartz 194.4). The effects began within a few days to a few weeks of initial exposure to tetryl. 

Estimates of workers exposed to tetryl affected by dermatitis varied greatly. Figures such as 6% of 

20,451 (Bergman 1952), 19% of 5,000 (Witkowski et al. 1942), 30% of 6,364 (Schwartz 1944), and 

32% (number of exposed workers not reported) (Ruxton 1917) have been reported. Some workers 

were reported to become tolerant to continued exposure to tetryl and no longer exhibited dermatitis 

(Bergman 1952; Fischer and Murdock 1946; Schwartz 1944). Other workers, however, became 

sensitized by exposure and developed a rash whenever they were reexposed to even very small 

amounts of the substance (Bergman 1952; Cripps 1917; Probst et al. 1944). Hair loss has also been 

reported (Bergman 1952; Cripps 1917; Hardy and Maloof 1950; Smith 1916). 

No studies were located regarding death in animals following dermal exposure to tetryl. 

Ocular Effects. Conjunctivitis has been observed in workers exposed to tetryl (Brabham 1943; 

Hilton and Swanston 1941; Ruxton 1917; Troup 1946). It may have resulted from direct contact of 

airborne tetryl particles with the conjunctiva or from rubbing the eyes. According to the reports, the 

response varied from mild to marked conjunctivitis with purulent secretion followed by irido-cyclitis 

and keratitis. 
TETRYL 20

2. HEALTH EFFECTS 

No studies were located regarding death in animals following dermal exposure to tetryl. 

2.2.3.3 Immunological and Lymphoreticular Effects 

Reports of workers involved in the manufacture of tetryl during World War I and World War II 

described hypersensitivity-like reactions (dermatitis, facial edema, asthma) in some workers upon 

reexposure to even small amounts of tetryl (Bergman 1952; Cripps 1917; McConnell et al. 1946; 

Murray et al. 1944; Probst et al. 1944). In one case, dermatitis developed in a woman who had 

worked 4 months in an ammunition factory manufacturing 2,4,6-trinitrotoluene (TNT), tetryl, and 

hexahydro-1,3,5-trinitro-1,3,5triazine (RDX). Patch testing with 0.05-0.5% tetryl in petroleum 

ointment produced a positive response (Goh 1984). The response was negative when similar 

concentrations in olive oil or acetone were tested. Patch testing on 20 controls with 0.1% tetryl in 

petroleum ointment was negative. Although it was clear that the vehicle played a role in the 

manifestation of the response, no apparent explanation was offered regarding the mechanism involved. 

Only 3 out of approximately 200 workers employed in charging boosters with tetryl showed a positive 

response to the patch application of pure tetryl (Parmeggiani et al. 1956). A study in which 

individuals exhibiting symptoms of tetryl dermatitis were treated with an antihistamine lends support 

to an immune response in tetryl dermatitis (Bain and Thomson 1954). Twenty-six of 28 men given 

the antihistaminic treatment were able to continue work with tetryl compared to only 4 of 16 who 

received standard topical treatments. Problems with this study include bias in assignment of subjects 

to treatment groups, lack of a placebo control group, and inconsistent treatment in both experimental 

and control groups. 

Limited information in animals was available. No sensitization occurred when guinea pigs had 

unspecified amounts of tetryl applied to normal or burned skin (Gel1 1944). A positive reaction to 

dermal challenge was observed when the tetryl was initially administered intravenously or by 

subcutaneous implantation of a tetryl pellet. In contrast, negative results were obtained in rats to 

which a compress of tetryl solution was applied 10 days after repeated intracutaneous inoculations of 

1% tetrylin propylene glycol (Parmeggiani et al. 1956). 
TETRYL 21 

2. HEALTH EFFECTS
 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to tetryl: 

2.2.3.4 Neurological Effects 

2.2.3.5 Reproductive Effects 

2.2.3.6 Developmental Effects 

2.2.3.7 Genotoxic Effects 

Genotoxicity studies are discussed in Section 2.4. 

2.2.3.8 Cancer 

2.3 TOXICOKINETICS 

Data regarding the toxicokinetics of tetryl in humans are limited to information from cases of 

occupational exposure by the inhalation and dermal routes. These data provide qualitative evidence 

that tetryl may be absorbed in humans by these routes. There are no data regarding oral absorption of 

tetryl in humans. There is qualitative evidence that tetryl is absorbed when administered to animals by 

the oral route, but there is no information regarding absorption after inhalation or dermal exposure. 

The mechanism by which tetryl or its metabolites are transported to the tissues is unknown. There are 

no data regarding distribution patterns for tetryl or putative metabolites in humans or animals. No 

information is available regarding the metabolism of tetryl in humans. In animal studies, limited data 

suggest the existence of nitro reduction and sulfoconjugation reactions. There is no information on 

how tetryl or its metabolites might be excreted in humans. Urinary excretion of possible metabolites 

was reported in animals. The mechanism of tetryl toxicity is not known. 
TETRYL 22 

2. HEALTH EFFECTS
 

2.3.1 Absorption 

2.3.1.1 Inhalation Exposure 

Workers exposed to tetryl-laden dusts, primarily by the inhalation and dermal routes, occasionally 

complained of systemic effects such as nausea, vomiting, and headaches, indicating possible absorption 

from the respiratory tract into the bloodstream (Cripps 1917; Hardy and Maloof 1950; Hilton and 

Swanston 1941; Ruxton 1917; Troup 1946; Witkowski et al. 1942). No information is available on 

rates or extent of exposure. No animal data are available. 

2.3.1.2 Oral Exposure 

No human data are available regarding absorption after oral exposure. Studies in rats (Griswold et al. 

1968; Parmeggiani et al. 1956) and rabbits (Daniele 1964; Fati and Daniele 1965; Guarino and 

Zambrano 1957; Wells et al. 1920) showed adverse health effects following gavage exposure, 

indicating that gastrointestinal absorption occurs. In addition, appearance of picramic acid, a 

metabolite of tetryl, in the urine of rabbits fed the chemical provides evidence that tetryl is absorbed 

following ingestion (Zambrano and Mandovano 1956). No information is available on rates or extent 

of absorption. 

2.3.1.3 Dermal Exposure 

Workers exposed to tetryl dusts, primarily by the inhalation and dermal routes, occasionally 

complained of systemic effects such as nausea, vomiting, and headaches, indicating possible absorption 

through the skin (Cripps 1917; Hardy and Maloof 1950; Hilton and Swanston 1941; Ruxton 1917; 

Troup 1946; Witkowski et al. 1942). No information is available on rates or extent of exposure. No 

animal data are available. 

2.3.2 Distribution 

No information is available regarding the distribution of tetryl in humans. In animals, however, the 

appearance of liver and kidney damage following oral exposure to tetryl (Fati and Daniele 1965) 

implies that tetryl (or its metabolites) is distributed to these organs. 
TETRYL 23 

2. HEALTH EFFECTS
 

2.3.3 Metabolism 

No information is available regarding the metabolism of tetryl in humans. Seven rabbits orally 

administered 36 mg/kg/day (range of 32.3-40.0 mg/kg/day) for up to 30 days excreted picramic acid 

in their urine (Zambrano and Mandovano 1956). Picramic acid was not detected in the urine of two 

control rabbits (the detection limit was 0.05 mg/L). In addition, the ratio of sulfoconjugates to total 

sulfates increased with duration of treatment in the treated rabbits, but not in the controls. These data 

support the hypothesis that tetryl is metabolized to pick acid by removal of the methylnitramine 

complex, and further metabolized to picramic acid by reduction of a nitro group (Zambrano and 

Mandovano 1956). The increased sulfoconjugates may be caused by conjugation of picramic acid to 

sulfates. No further data on the metabolic pathway for tetryl were located. 

2.3.4 Excretion 

2.3.4.1 Inhalation Exposure 

No information is available regarding the excretion of tetryl in humans or animals following inhalation 

exposure. 

2.3.4.2 Oral Exposure 

No human data are available regarding excretion after oral exposure. Seven rabbits administered 

100 mg tetryl daily for up to 30 days excreted picramic acid in their urine (Zambrano and Mandovano 

1956). No picramic acid was detected in the urine of two control rabbits. Urinary excretion of 

sulfoconjugates was also increased in the treated rabbits. 

2.3.4.3 Dermal Exposure 

No information is available regarding the excretion of tetryl in humans or animals following dermal 

exposure. 
TETRYL 24 

2. HEALTH EFFECTS
 

2.3.5 Mechanisms of Action 

No information was located regarding the mechanism by which tetryl enters the blood stream from the 

lungs, skin, or gastrointestinal tract, the mechanism by which tetryl is transported in the blood stream, 

or the mechanism of toxicity for tetryl. Earlier studies suggested that the cause of tetryl-induced 

dermatitis, which is the most common and widely studied adverse effect, may be both physical (direct 

irritation by sharp tetryl crystals) and chemical (by reacting with components of the skin) (Ruxton 

1917). The chemical hypothesis was later advanced by others as well (Bain and Thompson 1954; 

Brownlie and Cumming 1946). Bain and Thompson (1954) specifically suggested that histamine 

release may result from a tetryl-induced sensitization reaction or from direct tetryl-induced release 

from mast cells. 

The chemical structure of tetryl suggests that tetryl, like many amino and nitro aromatic compounds, 

has the potential to induce the formation of methemoglobin in red blood cells, which could lead to 

cyanosis and eventually death (Beard and Noe 1981). Methemoglobin results from iron in the ferrous 

state being oxidized to the ferric state. Methemoglobin is unable to reversibly combine with oxygen 

and carbon dioxide. This causes a shift in the oxygen dissociation curve which tends to prevent the 

transfer of oxygen from the blood to the tissues. The many occupational studies did not report 

increased incidence of methemoglobinemia or secondary anemia among the exposed workers. This 

may indicate either that the response was not observed or that it was not tested appropriately. No 

further information was located regarding the mechanism of tetryl toxicity. 

2.4 RELEVANCE TO PUBLIC HEALTH 

To help public health officials and others address the needs of persons living or working near 

hazardous waste sites, this section evaluates and interprets the significance of existing toxicity data 

with regard to human health. Because no reliable levels of exposure have been reported for human or 

animal studies, no MRLs were calculated for tetryl for any route or duration of exposure. Most of the 

human studies were from the time periods of World War I or World War II and often did not provide 

adequate information on number of people exposed, duration and levels of exposure, incidence of 

effects, and coexposure to other chemicals, and were deficient in clinical investigations. In spite of 

these limitations, the general effects (skin discoloration, dermatitis, coughing, sneezing, epistaxis, 
TETRYL 25 

2. HEALTH EFFECTS
 

headache, dizziness, nausea and vomiting, and epigastric pain) have been consistently reported and 

attributed to tetryl exposure. 

Very little information was located regarding health effects in humans or animals following exposure 

to tetryl by the inhalation, oral, or dermal routes. In reports of workers exposed while manufacturing 

munitions during World War I and World War II, the route of exposure was not well defined, but 

because exposure was primarily to tetryl-laden dusts, the main route of exposure is considered to have 

been inhalation. In most of these studies, the exposure concentration was not known, the duration of 

exposure was not well defined, and concomitant exposure to other chemicals was likely. Based on 

these reports, it is possible that inhalation exposure to tetryl may cause respiratory problems 

(nosebleeds, coughs, and difficulty breathing), gastrointestinal disturbances (nausea, vomiting, and 

abdominal cramps), weight loss and anorexia, and neurological effects (irritability, headaches, nausea, 

vomiting, fatigue, and insomnia). Mild to severe dermatitis (redness, itching, discoloration) affecting 

the eyes, eyelids, nasal folds, cheeks, neck, and hands has been linked to dermal exposure to tetryl. In 

addition to the dermatitis, skin discoloration, conjunctivitis, and hair loss have also been attributed to 

direct contact with tetryl-laden dust or tetryl-containing compounds. In most cases, workers became 

tolerant to exposure within a few weeks. However, some individuals became sensitized and developed 

a rash in response to recontact with even small amounts of the compound. Animals administered 

tetryl orally showed adverse effects of the liver, kidneys, and spleen. 

Although most human exposure to tetryl was believed to have occurred by inhalation, this is not 

considered the most likely route of exposure for populations living near tetryl-contaminated waste 

sites. The low vapor pressure of tetryl makes partitioning of the compound to the atmosphere 

unlikely. Tetryl does partition to soil and water and has been detected in these media in and around 

sites where tetryl was manufactured, used, stored, or disposed. The most likely route of exposure for 

populations living near sites contaminated with tetryl is ingestion of contaminated drinking water. 

Dermal contact with contaminated water or soil is a possible secondary route. 
TETRYL 26 

2. HEALTH EFFECTS
 

Minimal Risk Levels for Tetryl. 

Inhalation MRLS. 

No MRLs have been derived for inhalation exposure to tetryl because human and animal data for all 

durations are insufficient or lacking. Insufficiencies in the human inhalation data include mixedchemical 

and unquantified exposures. The animal inhalation database is limited to one early study by 

Gel1 (1944). 

Oral MRLs. 

No MRLs have been derived for oral exposure to tetryl because of lack of human data and insufficient 

animal data. The few animal studies available (Daniele 1964; Fati and Daniele 1965; Guarino and 

Zambrano 1957; Parmeggiani et al. 1956; Wells et al. 1920) suffer from severe limitations such as 

small number of animals, lack of control groups, and use of only one dose level. 

Death. The only reports of death in humans are case studies of two workers who died of liver 

failure 3 or 5 years after exposure to tetryl dust in a manufacturing plant (Hardy and Maloof 1950). 

Although cirrhosis was reported in both cases, neither worker had a history of excessive alcohol 

intake. These men worked with tetryl for l-4 years and were exposed primarily by inhalation of 

tetryl-laden dust. Limited air monitoring, conducted in 1942, reported concentrations of tetryl ranging 

from 1 to 18 mg/m3

 (Hardy and Maloof 1950). These deaths, however, cannot be unequivocally 

attributed to tetryl; complicating medical conditions and/or coexposure to other toxic chemicals could 

be contributing factors in the deaths. Available animal data report death in rats following gavage with 

1 or 2 g/kg/day for about 2 weeks (Parmeggiani, et al. 1956), in rabbits following gavage with 

1,000 mg/kg/day for l-3 days and 25 mg/kg/day for about 2 months (Guarino and Zambrano 1957) 

and in dogs following subcutaneous injection of 100 mg/kg/day for 5 days (Wells et al. 1920). 

Systemic Effects. 

Respiratory Effects. Respiratory symptoms, consisting of nasal and throat irritation, sneezing, 

epistaxis, coughing, wheezing, and difficulty breathing, have been associated with exposure of workers 

to tetryl-laden dust (Cripps 1917; Eddy 1943; Fischer and Murdock 1946; Hardy and Maloof 1950; 
TETRYL 27 

2. HEALTH EFFECTS
 

McConnell et al. 1946; Murray et al. 1944; Probst et al. 1944; Smith 1916; Witkowski et al. 1942). 

Some individuals were especially susceptible to exposure and developed symptoms similar to hay fever 

or asthma (Cripps 1917; Eddy 1943; Fischer and Murdock 1946; Hardy and Maloof 1950; McConnell 

et al. 1946; Probst et al. 1944; Smith 1916). Most authors attribute these symptoms to the irritating 

nature of the tetryl particles; however, a hypersensitivity reaction is suggested in some severe cases 

(Bergman 1952; Cripps 1917; Fischer and Murdock 1946; McConnell et al. 1946; Probst et al. 1944). 

It is clear from the epidemiological data that the respiratory system is a target organ for inhaled tetryl 

in humans. Lethal oral doses of tetryl induced lung congestion in rabbits (Guarino and Zambrano 

1957) and dyspnea in rats (Parmeggiani et al. 1956). 

Gastrointestinal Effects. Workers inhaling tetryl dusts during the manufacture of tetryl-containing 

explosives complained of abdominal pain, nausea, and vomiting (Bergman 1952; Cripps 1917; Fischer 

and Murdock 1946; Hardy and Maloof 1950; Hilton and Swanston 1941; Troup 1946; Witkowski et 

al. 1942). While the primary route of exposure for these populations is considered to be inhalation, it 

is possible that some of the tetryl-laden dusts were swallowed. Swallowing of tetryl may be the result 

of direct contamination of the mouth and pharynx and secondary exposure from tetryl that is coughed 

up and then swallowed. Not all workers exposed to the chemical exhibited these symptoms, 

suggesting that there are individuals who are susceptible to the gastrointestinal effects of tetryl. In 

some studies, gastrointestinal effects appeared to be more common in workers who had not eaten 

adequately prior to beginning their workshift (Bergman 1952; Witkowski et al. 1942). These data 

suggest that the gastrointestinal tract may be a target organ for tetryl toxicity, although the route of 

exposure and circumstances under which this toxicity may be exhibited are unclear. 

Hematological Effects. Some studies have reported mild blood effects in workers exposed to tetrylladen 

dust and tetryl-containing compounds during the manufacture of explosives (Bergman 1952; 

Brabham 1943; Cripps 1917; Fischer and Murdock 1946; Probst et al. 1944; Ruxton 1917; Witkowski 

et al. 1942). These’effects included slight leukocytosis, increased lymphocytes, and slight anemia. 

Most authors did not find these effects to be associated with tetryl exposure as the incidence was 

comparable to that found in control subjects (Bergman 1952; Fischer and Murdock 1946; Probst et al. 

1944; Ruxton 1917). However, picric acid, a suspected metabolite of tetryl (Gel1 1944; Zambrano and 

Mandovano 1956), has been suggested to cause destruction of red blood cells (Army 1987d), and 

could be involved in the anemia observed in some exposed workers. In addition, changes suggestive 

of a coagulation disorder and hemosiderin deposition in the spleen were observed in rabbits 
TETRYL 28 

2. HEALTH EFFECTS
 

administered 125 mg/kg/day for 6 months (Daniele 1964; Fati and Daniele 1965). It is not possible to 

determine from these data if the hematopoietic system and/or the blood are targets of tetryl toxicity. 

Hepatic Effects. There are only isolated reports of workers exhibiting liver effects following exposure 

to tetryl-containing compounds during employment in plants manufacturing explosives. The deaths of 

two men who died several years after exposure were attributed to liver failure (Hardy and Maloof 

1950); however, there was no conclusive evidence that exposure to tetryl was a contributing factor. 

Two women who worked in factories that manufactured tetryl explosives were hospitalized with 

jaundice and one died (Troup 1946). While liver pathology was noted in three of these cases and 

functional indications of liver damage were found in the fourth, the hepatic symptoms could not be 

unequivocally attributed to their exposure to tetryl. In contrast with the results reported by Troup 

(1946), McConnell et al. (1946) found no evidence of liver injury in workers exposed to tetryl dusts 

over a 35-month period; however, no information was provided regarding the tests that were 

conducted. Rabbits administered 25 mg/kg/day for up to 3 months (Guarino and Zambrano 1957) or 

125 mg/kg/day for 6-9 months had liver damage ranging from mild (swollen hepatocytes, cytoplasmic 

changes) to severe (hyperplasia and necrosis) (Fati and Daniele 1965). Dogs administered 

100 mg/kg/day subcutaneously for 5 days had liver lesions consisting of necrosis and fatty 

degeneration (Wells et al. 1920). The animal data suggest that the liver may be a target organ for 

tetryl toxicity; however, the small number of cases of liver effects reported in humans makes it 

difficult to determine if it is a target organ in humans. No epidemiological studies of hepatic function 

in exposed workers exist to support or refute the case for hepatic toxicity in humans. However, picric 

acid, a suspected metabolite of tetryl (Gel1 1944; Zambrano and Mandovano 1956), has been 

associated with functional and clinical indications of liver impairment (elevated bilirubin and 

urobilinogen and jaundice) following inhalation or oral exposure of humans (Army 1987d). 

Renal Effects. The limited data on renal effects of tetryl shows pathological changes (swelling and 

degeneration) in the kidneys of rabbits orally administered 1,000 mg/kg/day for l-3 days, 

25 mg/kg/day for 3 months or 125 mg/kg/day for 9 months (Fati and Daniele 1965; Guarino and 

Zambrano 1957; Wells et al. 1920). Dogs given subcutaneous doses of 100 mg/kg/day for 5 days also 

exhibited kidney damage (swelling of the tubular epithelium with albuminuria and fatty deposits and 

necrosis) (Wells et al. 1920). Rats that received 1 or 2 g/kg/day for about 2 weeks also had signs of 

kidney damage (Parmeggiani et al. 1956). No supporting data in humans were located, but picric acid, 

a possible metabolite of tetryl (Gel1 1944; Zambrano and Mandovano 1956), produced hematuria in 
TETRYL 29 

2. HEALTH EFFECTS
 

humans following ingestion (Army 1987d). It cannot be determined with certainty from these data if 

the kidneys are a target of tetryl toxicity in humans. 

Dermal Effects. The most common effects (e.g., skin discoloration and dermatitis) observed in 

workers exposed to tetryl-laden dust were believed to have been caused by dermal exposure to the 

compound. Workers that handled tetryl in manufacturing plants frequently developed a yellow 

staining of the hands, face, and hair (Bergman 1952; Brabham 1943; Cripps 1917; Hilton and 

Swanston 1941; Murray et al. 1944; Probst et al. 1944; Smith 1916). The terms “canary” and “tetryl 

blond” were often used to describe .workers who developed this staining. This discoloration was not 

indicative of systemic effects or dermatitis. Fading of the color occurred once workers were removed 

from the tetryl areas, but it often took several months for skin color to return to normal (Bergman 

1952). Dermatitis was also commonly observed in workers exposed to tetryl dusts in the workplace 

(Bergman 1952; Cripps 1917; Fischer and Murdock 1946; Hilton and Swanston 1941; McConnell et 

al. 1946; Murray et al. 1944; Probst et al. 1944; Ruxton 1917; Schwartz 1944; Smith 1916; Troup 

1946; Witkowski et al. 1942). Dermatitis ranged from mild to severe and was characterized by 

itching, burning, redness, papular eruptions, and facial edema. The most severe cases sometimes 

required hospitalization. Dermatitis generally affected the areas with more sebaceous glands, such as 

the eyelids, nasal folds, cheeks, forehead, and neck, and persons with oily skin were generally more 

frequently and seriously affected (Cripps 1917; Fischer and Murdock 1946; Murray et al. 1944; 

Schwartz 1944). The reported incidence of dermatitis among exposed workers ranged from 6% to 

32% (Bergman 1952; Ruxton 1917; Schwartz 1944; Witkowski et al. 1942). Some workers became 

tolerant to tetryl (Bergman 1952; Fischer and Murdock 1946; Schwartz 1944), while other workers 

were hypersensitive and developed a rash whenever reexposed to even very small amounts of tetryl 

(Bergman 1952; Brabham 1943; Cripps 1917; Probst et al. 1944). The levels of exposure that caused 

this dermatitis were not reported, but onset of symptoms generally occurred within a few days to a few 

weeks of initial exposure. 

Ocular Effects. Conjunctivitis has been reported in workers exposed to tetryl dusts (Brabham 1943; 

Hilton and Swanston 1941; Ruxton 1917; Troup 1946). This condition results from either direct 

exposure to airborne tetryl particles or from rubbing of the eyes. Reports of conjunctivitis were less 

frequent than reports of dermatitis. 
TETRYL 30 

2. HEALTH EFFECTS
 

Body Weight Effects. Weight loss and anorexia have been reported in some workers exposed to tetryl 

(Brabham 1943; Fisher and Murdock 1946; Hardy and Maloof 1950; Troup 1946; Witkowski et al. 

1942) and may have affected as many as 10% of the exposed workers (Witkowski et al. 1942). The 

role of tetryl in causing these effects could not be determined because of the lack of details of 

exposure. 

Immunological and Lymphoreticular Effects. Dermatitis and symptoms similar to hay fever 

and asthma have been observed in susceptible individuals exposed to tetryl-laden dust (Bergman 1952; 

Cripps 1917; Eddy 1943; Goh 1984; Smith 1916). Some workers exhibited severe reactions that 

recurred upon reexposure to even small amounts of the chemical. The hypersensitivity observed in 

these workers indicates that exposure to tetryl may initiate an allergic immune response in some 

people. The successful use of epinephrine to control asthma-like respiratory symptoms (spasmodic 

cough, restricted breathing) (Bergman 1952; Eddy 1943) and antihistamines to control dermatitis (Bain 

and Thomson 1954) also suggests that these effects are an allergic reaction to tetryl. In addition, patch 

testing on a woman who worked around tetryl and developed dermatitis produced a positive response 

when concentrations of tetryl ≥ 0.05% in petroleum ointment were used (Goh 1984). A study in 

guinea pigs supports the case for an immune involvement in the observed respiratory effects (Gel1 

1944). The anaphylactic reaction observed in these animals on challenge with a picrylgelatin antigen 

following initial sensitization via inhalation of a tetryl smoke is indicative of an allergic response to a 

metabolite-protein analog of tetryl. These studies implicated the N,2,4,6-trinitrophenylamino group as 

the primary antigenic determinant in the immune response to tetryl. Results from an in vitro study 

showed tetryl bound to egg albumin and amino acids when incubated together for 14 days at 37.5 oC 

in a neutral or acid solution (Brownlie and Cumming 1946). The authors suggested that similar 

binding of tetryl to skin protein generated a product that elicited an immune response resulting in 

dermatitis. Together, these data indicate that tetryl elicits an immune response in susceptible 

individuals. 

Neurological Effects. Epidemiological data show that workers exposed to tetryl during the 

manufacture of explosives in the workplace occasionally developed irritability, headaches, fatigue, and 

insomnia (Bergman 1952; Cripps 1917; Hardy and Maloof 1950). These effects suggest that tetryl 

may affect the nervous system. However, these symptoms have many other possible origins (e.g., loss 

of sleep could be caused by the intense itching of dermatitis or respiratory difficulties and could result 

in irritability and headaches) and cannot be unequivocally attributed to a direct effect of tetryl on the 
TETRYL 31 

2. HEALTH EFFECTS
 

nervous system. Possible neurological effects have also been observed following dermal application of 

picric acid in humans and oral administration of picric acid to cats and mice (Army 1987d). Picric 

acid is a suspected metabolite of tetryl (Gel1 1944; Zambrano and Mandovano 1956). In the absence 

of more definitive studies, it is difficult to determine the nature of the neurologic response observed in 

exposed workers. 

Reproductive Effects. Only two reports were located that discussed possible effects of tetryl on 

the reproductive system (Cripps 1917; Hardy and Maloof 1950). Both described changes in the 

menstrual cycle in a small number of female workers employed in tetryl munitions factories. It should 

be noted that some women had diminished menstrual flow, while others had increased bleeding. 

However, these studies have a number of limitations: very few women were studied, other medical 

history was not provided, possible exposures to other substances were not accounted for, and controls 

were not used. No animal data were available for any route of exposure. 

Developmental Effects. No information was available regarding developmental effects in humans 

or animals after inhalation, oral, or dermal exposure to tetryl. 

Genotoxic Effects. No studies were available regarding the genotoxicity of tetryl in either humans 

or animals. Bacterial and fungal assays for gene mutations, deoxyribonucleic acid (DNA) damage, 

gene conversion, and recombination comprise the available information for tetryl genotoxicity. Tetryl 

was shown to induce gene mutations in Salmonella typhimurium strains TA1535 (Whong et al. 1980a), 

TAlOO (Kawai et al. 1987; McGregor et al. 1980; Whong et al. 1980a), TA1537, TA1538 (McGregor 

et al. 1980), and TA98 (Kawai et al. 1987). In all cases in which the S. typhimurium studies were 

performed with and without metabolic activation, the absence of metabolic activators produced 

stronger positive results (Kawai et al. 1987; McGregor et al. 1980; Whong et al. 1980a). One possible 

conclusion is that the mutagenicity of tetryl is direct; that is, metabolic breakdown of tetryl may not be 

required to produce gene mutations (Whong et al. 1980a). However, all these S. typhimurium strains 

possess nitroreductase activity (Ames et al. 1979), suggesting that bacterial nitroreductase activity may 

directly activate tetryl to a mutagen. Two strains of the fungus Neurospora crassa were also tested for 

gene mutations following treatment with tetryl. Strain N23 was positive for gene mutations while 

strain 12-9-17 was not. N. crussu 12-9-17 is used to detect frameshift mutations. These results 

suggest that tetryl is a base-pair substitution mutagen (Whong et al. 1980a). In contrast, the positive 

results observed in the S. typhimurium strains TA1537, TA1538, and TA98 suggest that tetryl is a 
TETRYL 32 

2. HEALTH EFFECTS 

frameshift mutagen (Kawai et al. 1987; McGregor et al. 1980). Escherichia coli was used to test for 

tetryl-induced DNA damage. Positive results were observed both with and without metabolic 

activation (McGregor et al. 1980). The effects of tetryl on mitotic gene conversion were investigated 

using Saccharomyces cerevisiae D4. As the dose of tetryl increased, the number of conversions at the 

ade+ and trp+ loci increased. Metabolic activation was not used in this study (Whong et al, 1980a). 

In another experiment, S. cerevisiae D5 was used to test the effects of tetryl on mitotic recombination. 

With metabolic activation, the numbers of recombinants were not significantly increased. However, 

when metabolic activators were not used, the number of recombinants and other genetic aberrations 

did significantly increase (McGregor et al. 1980). Together, these in vitro studies support the 

hypothesis that tetryl is a direct-acting genotoxin. Refer to Table 2-l for a further summary of these 

results. 

Cancer. No information is available regarding cancer in humans exposed to tetryl. The only 

animal carcinogenicity study found that 1 of 19 female rats treated orally with 40 mg of tetryl every 

3 days for 30 days developed stomach adenomas (Griswold et al. 1968); males were not tested. The 

lack of human data and the limitations of the single animal study (small numbers of animals, 

insufficient duration of exposure and follow-up, use of only a single dose, and lack of statistical 

analyses) do not permit an assessment of the potential carcinogenicity of tetryl. 

2.5 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They 

have been classified as markers of exposure, markers of effect, and markers of susceptibility 

(NAS/NRC 1989). 

A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction 

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a 

compartment of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally 

the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. 

However, several factors can confound the use and interpretation of biomarkers of exposure. The 

body burden of a substance may be the result of exposures from more than one source. The substance 

being measured may be a metabolite of another xenobiotic substance (e.g., high urinary levels of 

phenol can result from exposure to several different aromatic compounds). Depending on the 

TETRYL 34 

2. HEALTH EFFECTS
 

properties of the substance (e.g., biologic half-life) and environmental conditions (e.g., duration and 

route of exposure), the substance and all of its metabolites may have left the body by the time biologic 

samples can be taken. It may be difficult to identify individuals exposed to hazardous substances that 

are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc, 

and selenium). Biomarkers of exposure to tetryl are discussed in Section 25.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within 

an organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals 

of tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital 

epithelial cells), as well as physiologic signs of dysfunction such as increased blood pressure or 

decreased lung capacity. Note that these markers are often not substance specific. They also may not 

be directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of 

effects caused by tetryl are discussed in Section 2.5.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism’s 

ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an 

intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed 

dose, biologically effective dose, or target tissue response. If biomarkers of susceptibility exist, they 

are discussed in Section 2.7, Populations That Are Unusually Susceptible. 

2.5.1 Biomarkers Used to Identify or Quantify Exposure to Tetryl 

Picric acid and picramic acid have been identified as possible metabolites of tetryl exposure 

(Zambrano and Mandovano 1956). Picramic acid has been detected in rabbits fed 

32.3-40.0 mg/kg/day for up to 30 days. The concentrations of picramic acid in the urine of these 

animals were estimated to be between 0.05 and 0.33 Mg/L; however, the calorimetric assay used to 

detect the metabolite was only semiquantitative. Picric acid could not be detected in the treated 

animals, possibly because of the high detection limit of the calorimetric assay used (1 mg/L). 

Sulfoconjugates were also detected in the urine and were found to increase with duration of exposure. 

These would only be useful biomarkers of exposure if they could be identified and quantitated. No 

other biomarkers to identify or quantify exposure to tetryl were located. No studies have been 
TETRYL 35 

2. HEALTH EFFECTS
 

designed to identify interactions between tetryl (or its metabolites) and target molecules or cells within 

exposed humans or animals. 

2.5.2 Biomarkers Used to Characterize Effects Caused by Tetryl 

Many of the potential effects of tetryl exposure are very general (headaches, coughs, nausea, or 

dermatitis) and can be associated with numerous other chemically or biologically induced disease 

states. These factors limit the use of these effects as biomarkers for tetryl. Dermatitis is more specific 

to tetryl exposure, although other nitro compounds-mercury fulminate, ammonium picrate, and picric 

acid-may also produce this effect (Army 1987d; Goh 1984; Schwartz 1944). Persons exhibiting 

dermatitis of unknown origin and with possible exposure to tetryl (e.g., through proximity to a 

hazardous waste site, explosives storage area, or site of demolition activity) could be suspected of 

exhibiting signs of tetryl toxicity. Patch testing with tetryl could be used to determine if sensitivity to 

tetryl was exhibited in these individuals. No specific biomarkers are known. 

For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on 

biomarkers for neurological effects see OTA (1990). 

2.6 INTERACTIONS WITH OTHER CHEMICALS 

No information was located regarding interactions between tetryl and other chemicals in humans or 

animals. There are no known chemicals that influence the toxicity of tetryl in the body. 

2.7 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to tetryl than will most persons 

exposed to the same level of tetryl in the environment. Reasons include genetic make-up, 

developmental stage, health and nutritional status, and chemical exposure history. These parameters 

result in decreased function of the detoxification and excretory processes (mainly hepatic and renal) or 

the pre-existing compromised function of target organs. For these reasons we expect the elderly with 

declining organ function and the youngest of the population with immature and developing organs will 

generally be more vulnerable to toxic substances than healthy adults. Populations who are at greater 
TETRYL 36 

2. HEALTH EFFECTS
 

risk due to their unusually high exposure are discussed in Section 5.6, Populations With Potentially 

High Exposure. 

Some people who developed dermatitis following exposure to tetryl dusts in the workplace became 

hypersensitive to subsequent exposure to even very small amounts of tetryl (Bergman 1952; Brabham 

1943; Cripps 1917; McConnell et al. 1946; Probst et al. 1944). Those with oily or sweaty skin were 

more susceptible to dermatitis than those with dry skin (Bergman 1952; Cripps 1917). Some workers 

were especially sensitive to irritation of the respiratory tract and developed symptoms similar to hay 

fever and/or severe, asthma-like coughs (Bergman 1952; Cripps 1917; Eddy 1943; Fischer and 

Murdock 1946; Hardy and Maloof 1950; McConnell et al. 1946; Probst et al. 1944; Smith 1916). 

There are no other populations that are known to be unusually susceptible to the toxic effects of tetryl. 

2.8 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects 

of exposure to tetryl. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to tetryl. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 

for medical advice. 

2.8.1 Reducing Peak Absorption Following Exposure 

Current information about reducing absorption of tetryl is limited. People who are exposed by 

inhaling tetryl dusts should be removed from the site of exposure and allowed to breathe fresh air 

(Mackison et al. 1978). In cases where tetryl has been swallowed, large amounts of water should be 

administered and, if the person is conscious, vomiting should be induced (HSDB 1994). Exposed 

areas of the skin should be treated by washing the affected areas with soap and water. Washing with 

soap containing sodium sulfite has been recommended because it will turn a purple color until the 

tetryl is washed away (Bergman 1952; Schwartz 1944). 

2.8.2 Reducing Body Burden 

There are no known specific methods for reducing tetryl body burden. 
TETRYL 37 

2. HEALTH EFFECTS
 

2.8.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanism of tetryl toxicity is not completely understood. The primary response to tetryl 

exposure is dermatitis and irritation of mucous membranes in general (see Section 2.2). These 

responses, which appear to have an immunological component, have been successfully treated with 

epinephrine and antihistamines (Bain and Thompson 1954; Bergman 1952; Eddy 1943). Although not 

widely reported, secondary anemia has been observed after exposure to tetryl (Brabham 1943; 

Witkowski et al. 1942). Although no concrete evidence exists, secondary anemia may have resulted 

from increased formation of methemoglobin, a common response to exposure to amino and nitro 

aromatic compounds (Beard and Noe 1981). Ferrous sulfate was used to treat secondary anemia in 

exposed workers (Brabham 1943; Witkowski et al. 1942). It is possible that other antidotes used to 

treat methemoglobinemia and/or anemia, such as methylene blue, will also be effective after tetryl 

exposure (Beard and Noe 1981). Calamine lotion and zinc oxide ointments and lotions have been 

used to treat tetryl dermatitis (Bain and Thompson 1954; Bergman 1952; Cripps 1917; Eddy 1943; 

Ruxton 1917; Smith 1916; Troup 1946; Witkowski et al. 1942). Aluminum acetate or boric acid 

dressings also have been used to treat dermatitis and eye irritation (Bergman 1952; Brabham 1943; 

Eddy 1943; Schwartz 1944; Troup 1946; Witkowski et al. 1942). 

2.9 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of tetryl is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure 

the initiation of a program of research designed to determine the health effects (and techniques for 

developing methods to determine such health effects) of tetryl. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that, if met, 

would reduce or eliminate the uncertainties of human health assessment. This definition should not be 

interpreted to mean that all data needs discussed in this section must be filled. In the future, the 

identified data needs will ‘be evaluated and prioritized, and a substance-specific research agenda may 

be proposed. 
TETRYL 38 

2. HEALTH EFFECTS
 

2.9.1 Existing Information on Health Effects of Tetryl 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

tetryl are summarized in Figure 2-l. The purpose of this figure is to illustrate the existing information 

concerning the health effects of tetryl. Each dot in the figure indicates that one or more studies 

provide information associated with that particular effect. The dot does not imply anything about the 

quality of the study or studies. Gaps in this figure should not be interpreted as “data needs.” A data 

need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data Needs Related to 

Toxicological Profiles (ATSDR 1989), is substance-specific information necessary to conduct 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature. 

Information on the health effects of tetryl is limited. The information on humans consists of a number 

of studies on workers exposed to tetryl dusts in the workplace during World War I and World War II. 

The reported effects were general, and limited information was provided on duration or levels of 

exposure. The workers were most likely exposed primarily by the inhalation route, although they 

probably had some direct skin contact and may have swallowed some of the dusts. The dermal effects 

(skin discoloration, dermatitis) observed in workers were attributed to dermal exposure; other effects 

(respiratory, gastrointestinal, neurological, etc.) were believed to be due to inhalation exposure. One 

animal study gave information on the possible immunological effects following inhalation exposure. 

There are no human studies on the effects of tetryl ingested in the drinking water. There are only a 

few animal studies in which tetryl was administered by the oral route. These provide data on effects 

of acute- and intermediate-duration exposure in a small number of rabbits and rats, and data on cancer 

effects following intermediate-duration exposure of rats. The one dermal study in animals gives 

information on possible adverse immunological effects. There are no studies in humans or animals 

regarding developmental or genotoxic effects after inhalation, oral, or dermal exposure. 

2.9.2 Identification of Data Needs 

Although most human exposure to tetryl was believed to have occurred by inhalation, this is not 

considered the most likely route of exposure for populations living near tetryl-contaminated waste 

sites. The low vapor pressure of tetryl makes partitioning of the compound to the atmosphere 

unlikely. Tetryl does partition to soil and water and has been detected in these media in and around 

TETRYL 40 

2. HEALTH EFFECTS
 

sites where tetryl was manufactured, used, stored, or disposed of. The most likely route of exposure 

for populations living near sites contaminated with tetryl is ingestion of contaminated drinking water. 

Dermal contact with contaminated water or soil is a possible secondary route. Exposed populations 

need to be better identified and the extent of exposure quantitated. 

Acute-Duration Exposure. Studies in workers exposed to tetryl indicate that the target organ 

following acute dermal exposure is the skin (Bergman 1952; Brabham 1943; Cripps 1917; Hilton and 

Swanston 1941; McConnell et al. 1946; Murray et al. 1944; Probst et al. 1944; Schwartz 1944; Smith 

1916; Troup 1946; Witkowski et al. 1942). Dermal and ocular effects (yellow staining, dermatitis, 

hair loss, conjunctivitis) were generally observed within a few days to a few weeks of initial exposure. 

The incidence of dermatitis among exposed workers ranged from 6% to 32% (Bergman 1952; Ruxton 

1917; Schwartz 1944; Witkowski et al. 1942). Humans exposed primarily by inhalation have 

exhibited respiratory (irritation, coughs, epistaxis), gastrointestinal (stomach cramps, nausea, vomiting), 

and neurological (irritability, headaches, nausea, vomiting, fatigue, insomnia) effects (Bergman 1952; 

Cripps 1917; Eddy 1943; Fischer and Murdock 1946; Hardy and Maloof 1950; Hilton and Swanston 

1941; McConnell et al. 1946; Murray et al. 1944; Probst et al. 1944; Ruxton 1917; Smith 1916; Troup 

1946; Witkowski et al. 1942). The target organs following acute oral exposure in humans are not 

known, but animals exposed by gavage have developed adverse hepatic and renal effects (Parmeggiani 

et al. 1956; Wells et al. 1920). Methodological problems with these studies, such as lack of control 

animals, lack of supporting histopathological data, and/or lack of exposure data, prevent their use in 

development of acute-duration MRLs. No pharmacokinetic data were available. Acute-duration 

studies in animals following oral or dermal exposure would help define target organs and levels of 

exposure that may be harmful to populations near hazardous waste sites. 

Intermediate-Duration Exposure. Studies of workers exposed to tetryl indicate that the skin is 

most likely the target organ following dermal exposure for an intermediate duration (Bergman 1952; 

Brabham 1943; Cripps 1917; Hilton and Swanston 1941; McConnell et al. 1946; Murray et al. 1944; 

Probst et al. 1944; Schwartz 1944; Smith 1916; Troup 1946; Witkowski et al. 1942). Dermal and 

ocular effects (yellow staining, dermatitis, hair loss, conjunctivitis) were generally observed within a 

few days to a few weeks of initial exposure. Staining was observed in most workers who were 

routinely exposed to tetryl. The incidence of dermatitis among exposed workers ranged from 6% to 

32% (Bergman 1952; Ruxton 1917; Schwartz 1944; Witkowski et al. 1942). Workers exposed 

primarily by inhalation for unspecified periods of time have exhibited respiratory (irritation, coughs, 
TETRYL 41 

2. HEALTH EFFECTS
 

epistaxis), gastrointestinal (stomach cramps, nausea, vomiting), anorexia and weight loss, and 

neurological (irritability, headaches, nausea, vomiting, fatigue, insomnia) effects (Bergman 1952; 

Brabham 1943; Cripps 1917; Eddy 1943; Fischer and Murdock 1946; Hardy and Maloof 1950; Hilton 

and Swanston 1941; McConnell et al. 1946; Murray et al. 1944; Probst et al. 1944; Ruxton 1917; 

Smith 1916; Troup 1946; Witkowski et al. 1942). Menstrual irregularities have also been reported in 

some women workers exposed to tetryl for intermediate and chronic durations (Cripps 1917; Hardy 

and Maloof 1950). Most of these studies failed to provide adequate information on duration or levels 

of exposure. No human data are available regarding effects following intermediate-duration oral 

exposure, although this is considered the most likely route of exposure for people living near tetryl contaminated 

hazardous waste sites. Intermediate-duration oral studies in rabbits have shown liver and 

kidney lesions, hemosiderin deposition in the spleen, and, possibly, reduced blood-clotting (Daniele 

1964; Fati and Daniele 1965; Guarino and Zambrano 1957). No studies are available regarding effects 

in animals following intermediate-duration inhalation or dermal exposure. The data are insufficient to 

develop any intermediate-duration MRLs. No pharmacokinetic data were available. Intermediateduration 

studies of humans or animals following oral and dermal exposures would help define target 

organs and levels of exposure that may be harmful to populations near hazardous waste sites. 

Chronic-Duration Exposure and Cancer. There are several studies that describe health effects 

in persons exposed to tetryl in the workplace (Bergman 1952; Brabham 1943; Cripps 1917; Hilton and 

Swanston 1941; McConnell et al. 1946; Murray et al. 1944; Probst et al. 1944; Schwartz 1944; Smith 

1916; Troup 1946; Witkowski et al. 1942). However, levels and durations of exposures were often not 

defined. The exposure route was considered to be primarily inhalation. The target organs of humans 

exposed for chronic periods are not known, but the effects appear to be similar as those observed for 

acute- and intermediate-duration exposures. No information on chronic oral exposure via drinking 

water was available for humans, although this is a likely route of exposure. No chronic animal studies 

were available. Because exposure levels were not determined in human studies, no chronic MRLs 

were developed. Chronic-duration studies in animals following oral exposure are needed since 

contamination through drinking water is the major route of concern for populations living around 

tetryl-contaminated sites. Such studies would help define target organs of effect and would be useful 

in developing MRLs in order to protect the health of people living near these sites. There were no 

suitable studies for evaluating the risks of cancer from tetryl. No human data were available, and the 

only animal data were from an oral study that was limited by a short exposure duration (30 days), a 

short post-exposure monitoring period (up to 9 months), and small group size (19 rats) (Griswold et al. 
TETRYL 42 

2. HEALTH EFFECTS
 

1968). Chronic-duration oral studies in a sufficient number of animals would need to be conducted to 

determine if humans living near hazardous waste sites have an increased risk of cancer from exposure 

to tetryl. Dermal studies may also be useful if absorption via this route is found to be significant. 

Genotoxicity. There were no available human or animal studies regarding the genotoxicity of 

tetryl. In vitro studies suggest that tetryl is a direct-acting genotoxin for certain strains of S. 

typhimurium, E. coli, S. cerevisiae, and N. crassa (Kawai et al. 1987; McGregor et al. 1980; Whong et 

al. 1980a). These data suggest a potential for genotoxic effects that requires further evaluation. In 

vivo animal studies and epidemiological studies of tetryl-exposed workers and/or Army personnel 

would be especially useful for evaluating the genotoxicity of tetryl in humans. 

Reproductive Toxicity. Information regarding reproductive effects in humans comes primarily 

from two studies that indicated that a small number of women workers exposed to unspecified levels 

of tetryl dusts in factories developed menstrual irregularities (Cripps 1917; Hardy and Maloof 1950). 

The probable route of exposure for these women was inhalation of tetryl-laden dusts. It is not clear 

that exposure to tetryl caused these irregularities. No other information for humans or animals was 

available. In order to assure that humans living near tetryl-containing hazardous waste sites are not 

adversely affected by this substance, oral animal reproductivity studies would need to be performed, 

since the most likely route of exposure for humans is through contaminated drinking water. Dermal 

studies may be useful if dermal absorption is found to be significant. 

Developmental Toxicity. No information was available regarding developmental effects in 

humans or animals following exposure to tetryl by any route. In order to assure that humans living 

near hazardous waste sites containing tetryl are not adversely affected by this substance, oral studies 

examining developmental end points would need to be performed in animals. If dermal absorption 

proves to be significant, dermal studies in animals that examine developmental end points may also be 

relevant. 

Immunotoxicity. The information located regarding immunological effects in animals and humans 

following exposure to tetryl is limited. Some workers exposed to tetryl developed hypersensitivity-like 

reactions (dermatitis, facial edema, asthma) (Bergman 1952; Cripps 1917; McConnell et al. 1946; 

Murray et al. 1944; Probst et al. 1944). Amelioration of these effects by epinephrine and 

antihistaminic treatment suggest that they were due to an immunological effect (Bain and Thomson 
TETRYL 43 

2. HEALTH EFFECTS
 

1954; Bergman 1952; Eddy 1943). In addition, a positive reaction to a skin patch test was observed in 

a worker who had developed dermatitis (Goh 1984). Limited animal data also suggest that tetryl is 

allergenic (Gel1 1944). However, unequivocal data demonstrating the immune system to be a target 

for tetryl are not available. Further studies examining potential antibody formation in response to 

tetryl and the determination of the type of hypersensitivity reaction would be useful in defining 

possible immunological effects for people exposed to tetryl at hazardous waste sites. 

Neurotoxicity. The only available information regarding neurotoxicity of workers exposed to tetryl 

dusts, primarily via inhalation, were occasional irritability, headaches, nausea, vomiting, fatigue, and 

insomnia (Bergman 1952; Brabham 1943; Cripps 1917; Hardy and Maloof 1950; Hilton and Swanston 

1941; Murray et al. 1944; Smith 1916; Witkowski et al. 1942). No other data in humans or animals 

were available. Because the effects noted in workers were minor and relatively nonspecific, it is not 

likely that the nervous system was a target of toxicity. Further studies in animals would be useful in 

understanding the neurotoxicity of tetryl. 

Epidemiological and Human Dosimetry Studies. Although there are several studies reporting 

health effects in groups of people exposed in the workplace (Bergman 1952; Hilton and Swanston 

1941; Probst et al. 1944; Schwartz 1944; Troup 1946; Witkowski et al. 1942), most of these studies 

were missing critical data on incidences, exposure concentration, and exposure durations. In several 

cases, control populations were not well defined or were absent. Because tetryl was manufactured 

primarily during World Wars I and II, it is unlikely that a suitable population can be identified that is 

currently exposed to measurable amounts of tetryl. However, retrospective cohort mortality studies of ’ 

exposed workers would be useful in assessing possible causes of death in workers previously 

employed in tetryl manufacturing plants. There are currently no techniques for measuring tetryl in 

human tissues or body fluids. Therefore, dosimetry studies of populations living near hazardous waste 

sites cannot be conducted until appropriate analytical methods are developed. 

Biomarkers of Exposure and Effect. 

Exposure. Picramic acid has been detected in the urine of rabbits fed tetryl (Zambrano and 

Mandovano 1956). No other studies suggested possible biomarkers of exposure to tetryl. Further 

information on the metabolism of tetryl and excretion of metabolites is needed to establish biomarkers 
TETRYL 44 

2. HEALTH EFFECTS
 

of exposure for tetryl. This information is needed so that medical surveillance of potentially exposed 

populations can be conducted. 

Effect. There are no specific biomarkers for the effects of tetryl. The toxic effects of tetryl, such as 

headaches, coughs, nausea, and dermatitis, are too general to be used to characterize exposure to this 

substance. Patch tests can be conducted in individuals who appear to be sensitive to tetryl (i.e., those 

who exhibit hypersensitivity-like reactions). Further studies are necessary to determine which types of 

biomarkers can be used to indicate effects caused by tetryl. 

Absorption, Distribution, Metabolism, and Excretion. One study was available that 

investigated the metabolism of tetryl in rabbits (Zambrano and Mandovano 1956). This experiment 

showed that ingested tetryl was absorbed and metabolized and that picramic acid was excreted in the 

urine. Systemic effects in humans following exposure to tetryl dust support that the chemical is 

absorbed by humans. Further studies on the toxicokinetics of tetryl following oral or dermal exposure 

would help determine the relative importance of these two routes of exposure for populations located 

near tetryl-contaminated waste sites. These would also help to determine the most important route to 

use in studies examining the health effects of tetryl exposure. 

Comparative Toxicokinetics. One study in rabbits fed tetryl showed that the chemical is 

absorbed and metabolized (Zambrano and Mandovano 1956). Picramic acid was detected in the urine 

of these animals. Since there were no other studies available, the toxicokinetics cannot be compared. 

The best animal models for studying the health effects of the chemical are not known. Further studies 

would be useful to determine if the target organs are likely to be the same in humans and animals. 

Methods for Reducing Toxic Effects. Limited information is available on treatments to 

alleviate the symptoms of tetryl exposure. These include treatment of the dermatitis with calamine 

lotion and/or zinc oxide preparations, treatment of dermatitis and ocular irritation with aluminum 

acetate or boric acid compresses, and treatment of hypersensitivity-like symptoms (including severe 

dermatitis and asthma-like symptoms) with epinephrine or antihistamines (Bain and Thomson 1954; 

Bergman 1952; Cripps 1917; Eddy 1943; Ruxton 1917; Smith 1916; Troup 1946; Witkowski et al. 

1942). The data on the pharmacokinetics of tetryl are also limited (Zambrano and Mandavana 1956). 

In order to develop mitigating agents, further studies are needed on its kinetics and mechanisms of 

action. 
TETRYL 45 

2. HEALTH EFFECTS 

2.9.3 Ongoing Studies
 

There are no known ongoing studies on the health effects of tetryl.
 
TETRYL 47 

3. CHEMICAL AND PHYSICAL INFORMATION 

3.1 CHEMICAL IDENTITY
 

Information regarding the chemical identity of tetryl is located in Table 3-l.
 

3.2 PHYSICAL AND CHEMICAL PROPERTIES
 

Information regarding the physical and chemical properties of tetryl is located in Table 3-2.
 



TETRYL 51 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
 

4.1 PRODUCTION 

Tetryl has been produced in a batch process by dissolving dimethylaniline in an excess of concentrated 

sulfuric acid at 20-30 oC to give dimethylaniline sulfate (Kirk-Othmer 1980). The solution was 

nitrated with a mixture of nitric and sulfuric acids to produce 2,4-dinitrodimethylaniline and eventually 

crude tetryl. The crude product was filtered, washed with water, and dissolved in acetone. The 

acetone was evaporated and the product filtered to yield purified tetryl. In a second production 

process 2,4- or 2,6-dinitrochlorobenzene was reacted with methylamine to form dinitrophenyl 

methylamine, which was nitrated to form tetryl (Gibbs and Popolato 1980). 

Tetryl is not produced commercially in the United States (Army 1984c, 1989b; HSDB 1994). Prior 

production was limited to Army ammunition plants such as Joliet Army Ammunition Plant (Illinois), 

which produced tetryl until 1973 (HSDB 1994). Data on past production volumes for tetryl are not 

available. Other Army ammunition plants that have handled tetryl include Alabama (Alabama), 

Anniston (Alabama), Crane (Indiana), Fort Wingate (New Mexico), Hawthorne (Nevada), Letterkenny 

(Pennsylvania), Lexington (Kentucky), Louisiana (Louisiana), McAlester (Oklahoma), Milan 

(Tennessee), Navajo (Arizona), Pine Bluff (Arkansas), Pueblo (Colorado), Red River (Texas), Savanna 

(Illinois), Seneca (New York), Sierra (California), Tooele (Utah), and Umatilla (Oregon) (Army 1986a, 

1986b). 

Because tetryl releases are not required to be reported under SARA Section 313, there are no data on 

tetryl in the Toxics Release Inventory (TRI 1993). 

4.2 IMPORT/EXPORT 

Current import and export data for tetryl are not available. 

4.3 USE 

The primary use of tetryl from 1916-1979 was as a common component of military explosives 

(Jenkins and Walsh 1994). It has been largely replaced by RDX in modem explosive formulations 
TETRYL 52 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
 

(Army 1984c, 1989b; Gibbs and Popolato 1980; Jenkins and Walsh 1994). Tetryl was used as an 

explosive in detonators and primers, as a detonating agent for other less sensitive high explosives, and 

as a booster charge for military devices (HSDB 1994; Sax and Lewis 1987). As a component in 

binary explosives, tetryl was used with 2,4,6-trinitrotoluene (TNT) to form tetrytols (80% tetryl, 20% 

TNT) that were used as a base charge in detonators (Army 1986b; Gibbs and Popolato 1980). Tetryl 

has also been used as a chemical indicator in the pH range between 10.8 (colorless) and 13.0 (redbrown) 

(Merck 1989). 

4.4 DISPOSAL 

Beginning in 1963, the U.S. Navy loaded munitions on obsolete liberty ships and sank them at 

selected oceanic sites (CEQ 1970; Hoffsommer and Rosen 1972). Tetryl was one of the most 

common and abundant explosives dumped in this manner (Hoffsommer and Rosen 1972), but ocean 

dumping has not been used since 1970 (CEQ 1970). Waste waters from tetryl manufacture were 

passed to holding lagoons for primary settling of solid materials before being released to rivers and 

streams (Harvey et al. 1993). Tetryl is completely deactivated into nonexplosive, water-soluble 

products by the action of sodium sulfite, and this reaction was used for the disposal of waste material 

(Bergman 1952). The deactivation was accomplished by adding the explosive to an aqueous solution 

containing 13% by weight of hydrated sodium sulfite. By-products, such as those created during the 

manufacture of tetryl, were openly burned or detonated at many Army ammunition plants. As much 

as 80% of waste munitions and propellants that have been disposed of in recent years have been 

incinerated (Army 1986d). 

Wastes containing tetryl have been incinerated by grinding and spraying the ground material with 

water to form a slurry. The types of incineration that have been used to destroy waste munitions such 

as tetryl include rotary kiln incineration, fluidized bed incineration, and pyrolitic incineration (Army 

1986d). The primary disadvantage of open burning or incineration is that explosive contaminants are 

often released into the air, water, and soils (Army 1986b). Wastes generated in the manufacturing of 

tetryl are classified as EPA hazardous wastes and any stored tetryl or tetryl-containing wastes from 

hazardous waste sites must be disposed according to EPA regulations (EPA 1990b). For more 

information on hazardous waste regulations that apply to tetryl, see Chapter 7. 
TETRYL 53 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
 

Over 90% of tetryl wastes found in soils were transformed to non-carbon dioxide products in testing 

composts using substances such as hay-horse feed and sewage sludge-wood shavings (Army 1986a). 

The chemical has been destroyed from contaminated lagoon sediments using aqueous thermal 

decomposition (heating under pressure to 200-250 oC in an aqueous medium) (Army 1985). Tetryl 

waste munitions have also been removed from waste waters by activated carbon columns (Army 

1986b, 1987a). Once carbon columns were saturated with the explosive, they were traditionally 

destroyed by open burning. Since this practice is no longer allowed in many areas, other alternatives 

of disposing of spent carbons, such as thermal reactivation for reuse, oxidative incineration and burial, 

or thermal deactivation and carbon burial, have been investigated (Army 1987a). A method for 

removing tetryl from contaminated waste water and lagoons using a chemical reaction with a 

surfactant containing a quaternary ammonia group under basic conditions (pH 1l-l1.5) followed by 

filtration to remove the precipitate has been tested (Army 1984c). 

TETRYL 55 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Tetryl is a synthetic compound that does not occur naturally. It was once widely used as a military 

explosive but is no longer manufactured or used in the United States (see Chapter 4). Effluents and 

emissions from Army ammunition plants were responsible for the release of tetryl into the 

environment. When released to the atmosphere, tetryl is expected to react and undergo transformation 

with sunlight and it will be removed from the atmosphere by wet and dry deposition. When released 

to water, tetryl is subjected to hydrolysis and photolysis, but photolysis will be more important in 

surface water. Hydrolysis and photolysis products include picrate ion, N-methylpicramide, 

methylnitramine, nitrite ion, and nitrate ion. Tetryl is not mobile in soil and leaching into groundwater 

is not likely. Biodegradation studies suggest that tetryl may undergo biotransformation under certain 

environmental conditions. 

The general population is not likely to be exposed to tetryl. During World War I and World War II, 

occupational exposure to tetryl was confined to workers in munition plants. For these workers, 

exposure occurred primarily by inhalation of tetryl-laden dusts, although some dermal and oral 

exposure probably occurred. Current exposure to tetryl is likely limited to areas around military 

installations, such as Army ammunition plants, where it was manufactured, converted to munitions, 

packed, loaded, or released through the demilitarization of antiquated munitions. The probable route 

of exposure for populations living near contaminated facilities or waste sites is ingestion of 

contaminated drinking water. Dermal exposure via contaminated water and soil may also occur. 

Occupational exposure to tetryl may occur in workers handling tetryl at Army ammunition plants 

during disposal operations. 

Tetryl has been identified in 12 of the 1,397 hazardous waste sites on the NPL (HazDat 1994). The 

frequency of these sites within the United States can be seen in Figure 5-1. 

5.2 RELEASES TO THE ENVIRONMENT 

Since tetryl releases are not required to be reported under SARA Section 3 13, there are no data on 

tettyl in the Toxics Release Inventory (TRI 1993). 

TETRYL 57 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.2.1 Air 

No data were located regarding releases of tetryl to air. A report on emissions from the Joliet Army 

Ammunition Plant (Joliet, Illinois), based on samples of effluent gases taken in 1967, showed only 

nitrogen oxides and sulfuric acid mist released to the air from the bubble tower and fume recovery 

facilities of tetryl manufacturing operations (Army 1976). Because tetryl is no longer manufactured or 

used in the United States, releases from these sources no longer occur. It is possible that some tetryl 

could be released to air during detonation, open-air burning, or incineration of the explosive during 

disposal operations (Army 1976, 1986b, 1986d). The by-products that have been reported to be 

produced when these methods are used include carbon monoxide, carbon dioxide, nitrogen oxides, 

nitrogen, water, and particulate carbon. The reported releases did not include tetryl, but it is unclear if 

tetryl was included in the analyses. 

5.2.2 Water 

Tetryl was released to water in waste discharge effluents from Army ammunition plants or through 

leaching from contaminated soil deposits. For example, the Joliet Army Ammunition Plant (Joliet, 

Illinois) produced tetryl until July 1973, releasing it via waste water into drainage ditches. Waste 

water streams discharged into drainage ditches typically containing 400,000-600,000 μg/L tetryl, 

corresponding to a daily discharge of 769 pounds from the tetryl nitration and refining houses (Army 

1976). Even after production of tetryl at the Army ammunition plant ceased, tetryl releases to surface 

water and groundwaters were still possible via runoff and leaching from contaminated soils at the plant 

site (Army 1974, 1976). A 1988 survey showed tetryl was present at a concentration of 67 μg/L in a 

sample from a groundwater monitoring well installed in an area where highest soil contamination had 

been detected in 1981. However, tetryl was not detected in surface water, groundwater and sediment 

samples taken from other areas during 1981-1988 (detection limit of 1.8-100 μg/L for surface water 

and 2.86 μg/L for sediment) (Army 1990b). A monitoring study conducted at the ammunition plant 

during 19851986, detected tetryl in several groundwater samples at concentrations of 67 μg/L in the 

tetryl production area, 34.5 μg/L in the TNT production area, and 13.7 μg/L in a waste water area 

(Army 1990b). The other possible sources of water contamination with tetryl are from runoff and 

leaching of the material at dump sites containing tetryl and at sites of demilitarization activities. No 

specific data on these potential sources were located. 
TETRYL 58 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.2.3 Soil 

Tetryl was released to the soil in waste-discharge effluents from the manufacture of tetryl at Army 

ammunition plants and as a result of its use as an explosive (Army 1981b). Because tetryl is no 

longer manufactured or used in the United States (Army 1984c, 1989b), new releases from 

manufacturing sources will not occur. However, contamination from past releases may still exist. In 

addition, tetryl may be released to soil from demolition landfills or during demilitarization operations 

(open detonation or open burning) (Army 1981b, 1986b). Tetryl was detected at concentrations of 

<1,000 μg/gram in 4.8% of soil samples taken from open-burning grounds at selected military 

installations; none of the samples contained >1,000 μg tetryl/gram of soil (Army 1986b). In a 1981 

survey of contamination at the Joliet Army Ammunition Plant (Joliet, Illinois), tetryl was found in two 

of five surface soil samples. Measured levels were 38,500 μg/gram in the surface soil near the tetryl 

production area and at a concentration 23.5 μg/gram in a location removed from this area. Tetryl was 

not detected in five soil core samples taken from the same area in 1988 (detection limit of 

1.86μg/gram) (Army 1990b). No other specific data on releases to soil were located. 

5.3 ENVIRONMENTAL FATE 

5.3.1 Transport and Partitioning 

Neat tetryl is chemically stable and only slightly hygroscopic. It has remained stable for as long as 

20 years during storage at ordinary temperatures (Bergman 1952). Although nitrated compounds are 

expected to exist in both the vapor phase and particulate form (Eisenreich et al. 1981), based on a 

vapor pressure of 4x10-10 mmHg (Army 1987d), it is unlikely that tetryl will partition to air. It is 

possible that tetryl might exist in the air as a particulate under certain conditions (i.e., following 

detonation or open-air burning), although no data were located. Tetryl present in the air as particulate 

would likely be deposited to land and water through wet and dry deposition. Tetryl is slightly soluble 

in water (75 mg/L in 20 oC fresh water; 26 mg/L in 25 oC salt water) (Army 1987d; Hoffsommer and 

Rosen 1973) but is soluble in alcohol, ether, benzene, acetone, and glacial acetic acid (Merck 1989). 

The calculated Henry’s law constant for tetryl is 2.0x10-12 atm-m3

/mol (Army 1987d). Based on this 

value of Henry’s law constant, tetryl is considered essentially nonvolatile (Lyman et al. 1982); 

therefore, volatilization is not expected to be an important fate process. 
TETRYL 59 

5. POTENTIAL FOR HUMAN EXPOSURE
 

The mobility of tetryl through soil may be determined based on its Koc value. A Koc value of 406 has 

been calculated for tetryl based on a water solubility of 75 mg/L (HSDB 1994); however, a Koc of 

1,357-2,948 was estimated for tetryl based on measured water-soil partition coefficients (Army 1979, 

1987d). The higher measured value may result from the binding of tetryl and its decomposition 

products to humic matter in soil (Army 1987d; Bongiovanni et al. 1984; Harvey et al. 1992). These 

higher Koc values suggest that tetryl is slightly mobile in soil (Swarm et al. 1983); therefore, tetryl is 

not expected to leach substantially into groundwater, particularly if the soil has a high organic content. 

Monitoring studies have indicated that the movement of tetryl through soil to groundwater may be 

influenced by other factors. These factors include its rapid hydrolysis in soil which may, in some 

cases, prevent tetryl reaching the underlying groundwater (Kayser and Burlinson 1988). Alternatively, 

the presence of other solvents at contamination sites may increase the mobility of tetryl through the 

soil (Army 1974, 1990b). Tetryl has been detected in water collected in seepage holes and 

groundwater monitoring wells dug at contaminated soil sites, indicating some leaching does occur 

(Army 1974, 1990b). 

The logarithm of the n-octanol/water partition coefficient (log Kow) is a useful preliminary indicator of 

potential bioaccumulation of a compound. The log Kow for tetryl was calculated to be 2.4 (Army 

1987d), indicating a low potential for bioaccumulation. The bioconcentration factor (BCF) for tetryl 

was calculated to be 54 from a recommended regression-derived equation (HSDB 1994; Lyman et al. 

1982). This BCF value does not suggest a potential for significant bioconcentration in aquatic 

organisms (HSDB 1994). Using an alternate regression-derived equation, a BCF of 15 was calculated 

(Army 1987d), which supports the low bioaccumulation potential of tetryl. However, the estimated 

BCF value based on Kow is highly uncertain since it does not adequately take in account the 

interaction of tetryl with protein and other compounds present in fish tissues. Partition coefficients for 

plant/soil and beef fat/diet of 1 and 3.7x10-3, respectively, were also calculated (Army 1987d). 

However, during attempts to develop a method of analyzing for tetryl in biological tissues (animal 

plasma, kidney, muscle/fat, and liver, as well as plant stems), tetryl could not be extracted from the 

samples even when intentionally spiked (Army 1981a). The authors concluded that tetryl was 

irreversibly adsorbed to macromolecules in the plant and animal tissues by binding of the 

methylnitroamino group (Army 1981a). The impact of macromolecular binding on the 

bioconcentration of tetryl in aquatic and terrestrial organisms is not known. No experimental 

bioconcentration data were located. 
TETRYL 60 

5. POTENTIAL FOR HUMAN EXPOSURE
 

In a plant uptake study with bush bean plants maintained on tetryl-amended hydroponic cultures for 

exposure periods of up to 7 days, all but a small amount (3%) of tetryl was rapidly converted to polar 

metabolites. The majority of the tetryl metabolites (89% to 96%) were located within the root tissues. 

An intermediate amount of metabolites (3%-7%) was found in the stem tissues; the leaf tissues 

contained the smallest quantity (1%-4%) (Harvey et al. 1993). 

Picric acid, one of the breakdown products of tetryl, is soluble in water and is expected to leach 

through soil to groundwater in substantial amounts (Army 1987d). It is expected to dissociate in 

water, especially when present in low concentrations. Picric acid may also form complexes with metal 

ions in soil, causing some of the chemical to remain bound (Army 1987d). Picric acid that is bound 

to soil may- be transformed via photolysis if present at the soil surface (Army 1987d). 

5.3.2 Transformation and Degradation 

5.3.2.1 Air 

Tetryl (vapor phase) in the air may react with photochemically formed hydroxyl radicals. The half-life 

for this reaction was estimated to be >> 10 days assuming a normal atmospheric concentration of 

5x105 hydroxyl radicals per cm3

 and a gas phase reaction rate of << 1x10-12cm3/molecule-second 

(Atkinson 1987; HSDB 1994). However, because tetryl has a very low vapor pressure and Henry’s 

law constant (see Table 3-2), only a small amount of tetryl is expected to exist in the atmosphere in 

the vapor phase (Eisenreich et al. 1981) and be available for transformation via reaction with hydroxyl 

radicals. In the atmosphere, tetryl is expected to be more prevalent in the particulate form. The 

hydroxyl radical reaction rate for particulate tetryl would be much slower than the vapor phase 

reaction rate. Therefore, the transformation of tetryl in air due to reaction with OH radicals may not 

be important. No data were located on direct photolysis of tetryl in the atmosphere, but tetryl is 

expected to undergo direct photolytic degradation in the atmosphere because it undergoes this reaction 

in water (Army 1984d). Based on a pure water photolysis half-life of 20-40 hours for TNT, a 

structurally similar compound (Mabey et al. 1983), it is likely that photolysis will dominate the 

degradative fate of tetryl in air. 
TETRYL 61 

5. POTENTIAL FOR HUMAN EXPOSURE
 

5.3.2.2 Water 

If released to water, tetryl may be degraded by hydrolysis. Based on experimentally-derived pH 

(range of 4-9) versus rate profiles for tetryl at 40, 72, and 85 oC and a range of activation energies, 

the hydrolysis half-life of tetryl at 20 oC and pH 6.8 was crudely estimated to be 302 ± 76 days. 

Since the estimated half-life has a maximum uncertainty factor of 3, the hydrolysis half-life at 20 oC! 

and pH 6.8 may be as high as 900 days. The hydrolysis rate is expected to increase with increasing 

temperature and pH (Navy 1984b). Hydrolysis products include picrate ion, N-methylpicramide, 

methylnitramine, nitrite ion, and nitrate ion. In the dark and under buffered, alkaline conditions 

(pH 9), methylnitramine formation dominated (66%); picrate ion (28%), nitrite (4.1%), nitrate (3.1%), 

and N-methylpicramide (4.1%) were also formed. Under laboratory light and more acidic conditions 

(pH 4-6), N-methylpicramide (41%) and nitrate (35.2%) were the major products; picrate ion (3.9%), 

nitrite (9.4%), and methylnitramine (0.01%) were also formed (Navy 1984b). In sea water at 25 oC 

and pH 8.1, 88% of initial tetryl hydrolyzed in 101 days, yielding picric acid as a hydrolysis product. 

This hydrolysis rate corresponds to a first-order half-life of 33 days (Hoffsommer and Rosen 1973; 

HSDB 1994). 

Under ambient lighting conditions and pH 6, the photolysis rate has been observed to be at least an 

order of magnitude faster than hydrolysis, with a hydrolysis half-life of approximately 302 days (Navy 

1984b). After 20 minutes of incubation in the light, more than 95% of the initial concentration of 

tetryl (l-20 mg/L) had reacted, but only 3.2% had reacted in the dark. Therefore, photolysis may be 

the dominant degradation process in sunlit water (Navy 1984b). The photolysis study of a structurally 

similar compound (TNT) conducted by Mabey et al. (1983) tends to confirm this conclusion. The 

major detectable photolytic product of tetryl in aqueous solution was reported to be N-methylpicramide 

(Navy 1984b). 

Insufficient data are available to predict the relative importance of biodegradation in water. 

5.3.2.3 Soil 

Based on effects observed in water (Navy 1984b), tetryl released to soil is expected to be susceptible 

to slow hydrolysis in acidic and neutral soils and to relatively rapid hydrolysis in highly alkaline soils 

(HSDB 1994). Samples of water collected from lysimeters containing tetryl-contaminated soil 
TETRYL 62 

5. POTENTIAL FOR HUMAN EXPOSURE
 

indicated that the major transformation products were picric acid (5-14%) and other polar, watersoluble 

decomposition products; no tetryl was detected in the water, or in the soil at the end of the 

study, suggesting complete hydrolysis (Kayser and Burlinson 1988; Navy 1982). The specific reaction 

leading to these products was not determined. Because tetryl is subject to photolysis in water, it may 

be susceptible to photolysis on sunlit soil surfaces (HSDB 1994). 

Data from composting experiments suggest that biodegradation of tetryl may occur under some 

conditions (Army 1986a). When tetryl-contaminated sediment was added to hay-horse feed or sewage 

sludge-wood chip compost, 90% of the tetryl was removed after 44 days. A first-order half-life of 1.2 

weeks was calculated for tetryl in a manure-hay-sawdust compost. In a biodegradation study with two 

types of soils (silt-loam and sandy loam), tetryl was found to undergo rapid biotransformation via two 

principal pathways (Harvey et al. 1992). The principal product of biodegradation was identified as N-methyl-2,4,6­

trinitroaniline. Aminodinitrophenylmethylnitramine and other unidentified polar 

metabolites were identified as secondary biodegradation products. Mineralization of tetryl to carbon 

dioxide accounted for 9% of total degradation over a 60-day incubation period. However, the authors 

did not provide conclusive evidence that the primary degradation product N-methyl-2,4,6-trinitroaniline 

was not an artifact of methanolic Soxhlet extraction of soil. This may cast doubt on the validity of the 

conclusions of this soil biodegradation study (Jenkins and Walsh 1994). 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

5.4.1 Air 

No data were located regarding the levels of tetryl in air. 

5.4.2 Water 

Seepage water collected in a hole dug at the Joliet Army Ammunition Plant (Joliet, Illinois) in August 

1973 contained tetryl at a concentration of 44,000 μg/L (Army 1974, 1990b). Later surveys conducted 

between 1985 and 1986 showed tetryl was present in groundwater samples taken from monitoring 

wells around the plant site; it was detected at 67 μg/L in a sample from the tetryl production area, at 

34.5 μg/L in samples from the TNT production area, and at 13.7 μg/L in a waste water area (Army 

1990b). The groundwater beneath the tetryl manufacturing area of the Alabama Army Ammunition 
TETRYL 63 

5. POTENTIAL FOR HUMAN EXPOSURE
 

Plant (Talladega County, Alabama) contained 72.8 μg/L tetryl (ATSDR 1987). Tetryl has been 

detected in groundwater beneath artificial leaching pits located at the Louisiana Army Ammunition 

Plant at concentrations ranging from 1.4 to 53 μg /L (Army 1988). 

No tetryl was detected (detection limit of 20 μg /L) in samples from 44 groundwater sites, 23 surface 

water sites, or 5 treatment lagoons located at the Milan Army Ammunition Plant in Tennessee (Army 

1980). In addition, sediment samples from the 5 lagoons did not show tetryl to be present (detection 

limit of 90 μg /L). Tetryl was detected in groundwater samples taken at the Iowa Army Ammunition 

Plant at a maximum concentration of 49 μg /L; it did not exceed the level of detection (2.9 μg /L) in 

any surface water samples (Army 1982c). 

Sea water samples taken in 1971 from two munitions dumping areas (at depths of 0-20 meters above 

the bottom and at the centers of the dumping areas) located in the Pacific Ocean (85 miles west of 

Cape Flattery, Washington) and the Atlantic Ocean (172 miles south-southeast of Charleston, South 

Carolina) were analyzed for tetryl (Navy 1972). No tetryl was found in any of the samples examined 

(detection limit of 20 ng/L). 

5.4.3 Soil 

Analysis of surface soil collected from the Joliet Army Ammunition Plant (Illinois) from 1973 to 1981 

showed tetryl levels ranging from 23.5 to 84,400 μg /gram. Analysis of subsurface soil detected levels 

of 1,450-84,400 μg /gram tetryl. It was estimated that the soil at the Joliet Army Ammunition Plant 

(Illinois) contained approximately 31,000 pounds of tetryl in August 1973, less than 1 month after 

tetryl production had been terminated (Army 1974, 1990b). In a 1981 survey of contamination at the 

Joliet Army Ammunition Plant (Joliet, Illinois), tetryl was found in 2 of 5 samples from the tetryl 

production area at levels of 23.5-38,500 μg /gram in an old drainage ditch and in a location removed 

from the ditch, but none was detected in 5 soil samples taken from the same area in 1988 (detection 

limit of 2.86 μg /gram) (Army 1990b). One of 49 surface soil samples collected from 11 sites at the 

Milan Army Ammunition Plant (Milan, Tennessee) contained approximately 1.8 μg /gram of tetryl 

(Army 1980). 

At the Louisiana Army Ammunition Plant (a shell manufacturing and explosives loading, assembly, 

and packing facility near Shreveport, Louisiana), waste waters were trucked to and discharged into on­
TETRYL 64 

5. POTENTIAL FOR HUMAN EXPOSURE
 

site artificial leaching pits from 1951 to 1980 (Army 1986a, 1988). Tetryl in surface soil samples 

taken from the lagoons in 1984 ranged from below detectable levels (detection limit of 0.3 μg /grarn) to 

42,217 μg /gram, while tetryl concentrations in the underlying soil cores ranged from below the 

detection limit to 7,113 μg /gram. 

At the Alabama Army Ammunition Plant, tetryl was measured in the soil of the tetryl manufacturing 

area (13,600 μg /gram) and in the flashing ground (for flash burning of equipment and demolition 

materials to remove explosive residues) (6,620 ppm) (ATSDR 1987). At the same site, tetryl levels 

were also reported as <257-6,624 ppb in the flashing ground, >500 ppb in the rifle powder flashing 

area, and 554 ppb in the demolition landfill (Army 1981b). In the tetryl manufacturing area, a 

crystalline material suspected of being tetryl was visible in the soil. 

Tetryl was detected in sediment samples taken at the Iowa Army Ammunition Plant at a maximum 

concentration of 33 μg /gram (Army 1982c). However, all soil samples were below the level of 

detection (2 μg /gram). 

Ocean floor sediment samples taken in 1971 from two munitions dumping areas located in the Pacific 

Ocean (85 miles west of Cape Flattery, Washington) and the Atlantic Ocean (172 miles southsoutheast 

of Charleston, South Carolina) were analyzed for tetryl (Navy 1972). No tetryl was found in 

any of the sediment samples analyzed (no detection limit reported). 

5.4.4 Other Environmental Media 

Samples from ocean floor fauna (rat tail fish and sea cucumbers) taken in 1971 from two munitions 

dumping areas located in the Pacific Ocean (85 miles west of Cape Flattery, Washington) and the 

Atlantic Ocean (172 miles south-southeast of Charleston, South Carolina) were analyzed for tetryl 

(Navy 1972). No tetryl was found in any of the fauna samples analyzed (detection limit of 740 ppt). 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population is not likely to be exposed to tetryl. Exposure to tetryl is likely to be limited 

to areas around military installations, such as Army ammunition plants (where tetryl was manufactured 

and converted to munitions), around storage and waste sites, and around sites of demilitarization and 
TETRYL 65 

5. POTENTIAL FOR HUMAN EXPOSURE
 

disposal operations. The most likely route of exposure for populations living near these areas is 

ingestion of contaminated drinking water: However, no data regarding estimated daily intakes of tetryl 

through drinking water were found for such populations. Inhalation of contaminated particulate matter 

produced during incineration, open-air burning, and detonation of tetryl-containing waste material is a 

possible route of exposure. However, since no monitoring data were located regarding levels of tetryl 

in air, the extent of exposure by this route is not known. Dermal contact with contaminated soil is 

also a possible route of exposure. However, no data concerning extent of absorption following dermal 

contact with tetryl-contaminated soil were located. 

Inhalation, dermal, and some oral exposure to tetryl has occurred in workers involved in production 

and use of tetryl compounds. In the past, workers in munitions plants were exposed to tetryl dust 

released into workroom air (Cripps 1917; Hardy and Maloof 1950; Hilton and Swanston 1941; Probst 

et al. 1944; Troup 1946; Witkowski et al. 1942). In one study, air samples taken in 1942 from a small 

powder house where exploder bags were loaded with weighted tetryl, stemmed, tied, and inspected had 

tetryl levels ranging from 1 to 18 mg/m3

 (Hardy and Maloof 1950). Workers in these plants were 

exposed via inhalation of the tetryl dust and by dermal contact with the tetryl powder and pellets. 

Today, workers engaged in demilitarization operations involving detonation, open-burning, or 

incineration of tetryl explosives are likely to be exposed to tetryl. The extent of exposure in these 

workers has not been adequately determined. 

5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Workers who were involved in the production and use of tetryl at Army ammunition plants were 

exposed to tetryl. Persons living near military installations, such as Army ammunition plants, may be 

exposed to tetryl from ingestion of drinking water or contact with soil contaminated by past 

manufacture and use. Persons involved in demilitarization operations or in the clean-up of 

contaminated sites may be exposed to high levels of tetryl. 

5.7 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of tetryl is available. Where adequate information is not 
TETRYL 66 

5. POTENTIAL FOR HUMAN EXPOSURE
 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of 

research designed to determine the health effects (and techniques for developing methods to determine 

such health effects) of tetryl. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that, if met, 

would reduce or eliminate the uncertainties of human health assessment. This definition should not be 

interpreted to mean that all data needs discussed in this section must be filled. In the future, the 

identified data needs will be evaluated and prioritized, and a substance-specific research agenda may 

be proposed. 

5.7.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of tetryl as shown in 

Table 3-2 are not sufficiently characterized to permit estimation of its environmental fate (Army 

1987d; HSDB 1994; Navy 1984b). It would be helpful to develop experimental Kow and Koc data for 

tetryl. 

Production, Import/Export, Use, and Release and Disposal. Tetryl is no longer produced in 

the United States (Army 1984c, 1989b). Production in the United States was limited to Army 

ammunition plants such as the Joliet Army Ammunition Plant (Illinois), which produced tetryl until 

1973 (HSDB 1994). Several other Army ammunition plants that have handled tetryl in the past 

include Anniston (Alabama), Crane (Indiana), Fort Wingate (New Mexico), Hawthorne (Nevada), 

Letterkenny (Pennsylvania), Lexington (Kentucky), Louisiana (Louisiana), McAlester (Oklahoma), 

Milan (Tennessee), Navajo (Arizona), Pine Bluff (Arkansas), Pueblo (Colorado), Red River (Texas), 

Savanna (Illinois), Seneca (New York), Sierra (California), Tooele (Utah), and Umatilla (Oregon) 

(Army 1986a, 1986b). Past production and import/export data for tetryl were not available. Tetryl has 

primarily been used as an explosive (Gibbs and Popolato 1980; HSDB 1994), although it has also been 

used as a chemical indicator in the pH range between 10.8 and 13.0 (Merck 1989). Tetryl was 

primarily released to soil, surface water, and groundwater around military installations, such as Army 

ammunition plants (Army 1974, 1981b, 1987b, 1988; ATSDR 1987), and contamination still remains 

in some of these areas. Current releases probably occur at waste sites where tetryl is stored and at 

sites of demilitarization activities. More data on possible releases from these sources are needed in 
TETRYL 67 

5. POTENTIAL FOR HUMAN EXPOSURE
 

order to better determine populations at risk of exposure to tetryl. Data on the most commonly used 

disposal methods are sufficient (Army 1986b, 1986d, 1987a); however, more data on amounts of tetryl 

being disposed of and on alternative disposal methods would be useful. Wastes generated in the 

manufacturing of tetryl are classified as EPA hazardous wastes and must be disposed of according to 

EPA regulations (EPA 1990b). 

Environmental Fate. Tetryl released to the environment partitions mainly to water and soil (Army 

1987d; Lyman et al. 1982; Navy 1984b). Tetryl is transported in soil, surface water, and, rarely, in 

groundwater (Army 1987d; Swann et al. 1983). Because of its very low vapor pressure, it is unlikely 

to partition to air (Army 1987d). No data were located regarding atmospheric transport of tetryl. 

Experimental data are needed regarding photolysis of tetryl in the atmosphere so that the relative 

contributions of photochemical degradation can be determined. Photolysis and hydrolysis are the 

primary mechanisms that degrade tetryl in water (HSDB 1994). It would be helpful to develop 

reliable data for photoreaction, hydrolysis and biodegradation rates of tetryl in natural water, and 

biodegradation rates of tetryl in natural soils. 

Data on the rates of biodegradation, photolysis and hydrolysis of tetryl in natural waters and the rate 

of biodegradation of tetryl in natural soil would help to estimate more accurately the persistence of 

tetryl in the environment. Additional data on the nature and fate of transformation products of tetryl 

in air, water, and soil are also needed. 

Bioavailability from Environmental Media. Indirect evidence for absorption of tetryl is 

provided by the adverse health effects observed in exposed workers (Cripps 1917; Hardy and Maloof 

1950; Hilton and Swanston 1941; Troup 1946; Witkowski et al. 1942). However, the relative 

contribution by the three possible routes (inhalation, oral, and dermal) is not known. Rabbits fed tetryl 

excreted picramic acid, a metabolite of tetryl, in their urine, showing that tetryl is absorbed following 

ingestion (Zambrano and Mandovano 1956). The oral and dermal routes of exposure, in particular, 

may be of concern to humans because of the potential for tetryl to contaminate drinking water and 

soil. Information regarding absorption of tetryl following ingestion of contaminated drinking water 

and dermal contact with contaminated water or soil would be useful in characterizing the 

bioavailability of tetryl from these media. 
TETRYL 68 

5. POTENTIAL FOR HUMAN EXPOSURE
 

Food Chain Bioaccumulation. Since tetryl is likely to be bound strongly to fish tissues, the
 

estimated BCF values based on Kow (Army 1987d; HSDB 1994; Lyman et al. 1982) is likely to be
 

questionable. Therefore, it would be useful to develop experimental data for BCF in aquatic
 

organisms. Based on estimated plant-soil and beef fat-diet partition coefficients, bioaccumulation in
 

plants and animals is expected to be low (Army 1987d). However, data exist to suggest that tetryl
 

may bind to macromolecules in plant and animal tissues (Army 1981a), implying that bioconcentration
 

is possible. No experimental data were located that would support either possibility. Experimental
 

data are needed regarding the biomagnification potential of tetryl in both aquatic and terrestrial food
 

chains. Primary emphasis needs to be given to development of a method that will enable tetryl to be
 

extracted from plants and animal tissue. Metabolism data could also provide useful information that
 

would help in determining the potential for bioaccumulation within organisms.
 

Exposure Levels in Environmental Media. Tetryl has been detected in seepage water,
 

groundwater, and surface and subsurface soil at military installations (Army 1980, 1981b, 1986a, 1988,
 

1990b; ATSDR 1987; HazDat 1994). More data are needed regarding levels of tetryl in surface water,
 

groundwater, soil, and air in and around these sites. Quantitative information is needed to assess the
 

potential for human exposure and to better identify exposed populations.
 

Exposure Levels in Humans. Biomarkers for exposure to tetryl, especially metabolic products
 

need to be identified so that biological monitoring studies can be conducted. Data are needed both for
 

occupationally exposed populations and for populations living in the vicinity of Army ammunition
 

plants and hazardous waste sites. These data would aid in evaluating the extent of human exposure.
 

Exposure Registries. No exposure registries for tetryl were located. This substance is not
 

currently one of the compounds for which a subregistry has been established in the National Exposure
 

Registry. The substance will be considered in the future when chemical selection is made for
 

subregistries to be established. The information that is amassed in the National Exposure Registry
 

facilitates the epidemiological research needed to assess adverse health outcomes that may be related
 

to the exposure to this substance.
 

5.7.2 Ongoing Studies 

No ongoing studies on tetryl were located. 
TETRYL 69 

6. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting and/or 

measuring and monitoring tetryl in environmental media and in biological samples. The intent is not 

to provide an exhaustive list of analytical methods that could be used to detect and quantify tetryl. 

Rather, the intention is to identify well-established methods that are used as the standard methods of 

analysis. Many of the analytical methods used to detect tetryl in environmental samples are the 

methods approved by federal organizations such as EPA and the National Institute for Occupational 

Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by 

groups such as the Association of Official Analytical Chemists (AOAC) and the American Public 

Health Association (APHA). Additionally, analytical methods are included that refine previously used 

methods to obtain lower detection limits, and/or to improve accuracy and precision. 

6.1 BIOLOGICAL SAMPLES 

No analytical methods specifically used for the determination of tetryl in biological fluids and tissues 

were located. One attempt to develop a method for detecting tetryl in animal tissues using highperformance 

liquid chromatography (HPLC) with ultraviolet (UV) detection was unsuccessful because 

of suspected metabolism and binding of the parent compound and/or metabolites to macromolecules 

(Army 1981a). However, methods were located for the detection of the tetryl metabolites, picric acid 

and picramic acid, in urine and for the analysis of tetryl in hand swabs. Table 6-l is a summary of 

methods used to determine tetryl metabolites in urine and tetryl in hand swabs. 

Methods to detect picric acid and picramic acid in rabbit urine using calorimetric assays have been 

reported (Zambrano and Mandovano 1956). The detection limits were in the sub- to low ppm range, 

but no information on recovery or precision was given. 

Methods for the analysis of tetryl in hand swabs are used in forensics, but they could also be used to 

determine if dermal exposure of workers has occurred. The methods that have been used for the 

determination of trace amounts of tetryl on hands include high resolution gas chromatography (HRGC) 

with electron capture detection (ECD) or thermal energy analyzer (TEA), or HPLC with TEA or 

electrochemical detection (ED) (Douse 1982, 1985; Fine et al. 1983, 1984; Lloyd 1983a, 1983b). 

Thin-layer chromatography (TLC) has also been tested, but because of the large amounts of sample 

TETRYL 71 

6. ANALYTICAL METHODS
 

required for the analysis, it is useful only as a confirmatory test (Douse 1982). Both HPLC and 

HRGC can rapidly separate tetryl from other explosive compounds, but HPLC has the advantage of 

being run at ambient temperature. This decreases temperature-related breakdown of the analyte and 

yields higher recoveries. The type of detector seems to be the most important factor in determining 

which of the reported methods is most useful in the analysis of tetryl in hand swabs. ECD appears to 

be less sensitive (ng amounts) than either TEA or electrochemical detection using pendant mercury 

drop electrode (PMDE) (pg amounts) (Douse 1982; Fine et al. 1983; Lloyd 1983a, 1983b). In 

addition, a clean-up step using ECD is usually required to prevent matrix interference (Douse 1982, 

1985). Both TEA and PMDE appear to have greater selectivity than ECD, and because of the 

selectivity of the detector, a clean-up step was not required (Fine et al. 1983; Lloyd 1983b). Both 

TEA and PMDE methods are rapid, selective, and have high precision (Fine et al. 1983; Lloyd 1983b). 

6.2 ENVIRONMENTAL SAMPLES 

A variety of methods have been described for the detection of tetryl in environmental samples, 

including air, fresh water and sea water, soil, sediment, ocean floor fauna, and explosives. Table 6-2 

is a summary of several representative methods for determining tetryl in environmental media. 

A single method of analyzing tetryl in air was located (NIOSH 1977). The method utilized 

spectrophotometric analysis. Air samples were collected on a cellulose membrane filter and then 

extracted with N,N-diethylethanolamine. 

The primary analytical methods for determining tetryl in water are gas chromatography (GC), 

GC/ECD, HRGC/ECD, HPLC/ED, HPLCKJV, and mass spectrometry (MS) (Army 1981c, 1984c, 

1986c, 1988, 1989a; Belkin et al. 1985; Feltes and Levsen 1989; Hoffsommer and Rosen 1972; Yinon 

and Laschever 1982). These methods have been used to determine tetryl in sea water, well water, 

surface water, groundwater, and drinking water. Both GC and HPLC methods have been applied to 

the analysis of tetryl. One drawback with GC analysis is that thermally labile chemicals, such as 

tetryl, are subject to a significant amount of heating. This introduces the likelihood of partial 

degradation (Army 1986c). Liquid chromatographic methods, by contrast, do not volatilize the 

sample; therefore, thermal degradation was not a complication (Army 1986c). Following concentration 

of samples by liquid-liquid extraction or by solid phase extraction with C-18 adsorbents, HPLCAJV 

method can attain a detection limit of 0.05 ppb for tetryl in water samples (Levsen et al. 1993). 



TETRYL 75 

6. ANALYTICAL METHODS
 

GC/ECD has been used to analyze tetryl in sea water with sensitivity in the ppt range (Hoffsommer 

and Rosen 1972). Recovery of tetryl was adequate (70%) (Hoffsommer and Rosen 1972). The 

sensitivity of the HRGC/ECD method for analysis of tetryl in drinking water was in the low ppb range 

(Belkin et al. 1985). The sample preparation was simple and yielded recoveries of 100% (Belkin et al. 

1985). Precision was very good, as shown by the relative standard deviation (RSD) range of 5.4- 7.5% 

for tetryl (Belkin et al. 1985). 

Tetryl has also been measured in well water and surface water by HPLC/ED, using a gold-mercury 

electrode (Army 1986c). The technique provides a higher degree of selectivity than either UV or 

ECD. Sensitivity is in the low ppb range, but precision was not reported. Tetryl was best recovered 

using the Amberlite XAD-4® resin. A limitation with this method was that tetryl was not stable in 

acetone; therefore, the acetone eluates from the resin must be analyzed as quickly as possible (Army 

1986c). Reversed-phase HPLC/UV is a highly selective technique that yields excellent recovery 

(Army 1988; Feltes and Levsen 1989). It can be used as an alternative method to gas chromatography 

(Feltes and Levsen 1989). Sensitivity was in the ppb-to-ppt range, and the precision was acceptable 

(<5-21% RSD) (Army 1988; Feltes and Levsen 1989). Tetryl was found to be unstable in a 

methanol-water matrix if left for an extended period of time, but was stable in a water-acetonitrile 

matrix. Therefore, dilution with acetonitrile prior to filtration was recommended (Army 1988). Tetryl 

has also been analyzed in groundwater by HPLC using UV and photo-conductivity (PC) in tandem 

(HPLC/UV/PC) (Army 1989a). This method allowed a solid sorbent cartridge to be used to collect the 

sample, which improved selectivity (Army 1989a), The serial use of the detectors effectively 

differentiated tetryl from other explosives and from contaminants in the solid sorbent cartridge. 

Sensitivity was in the low ppb range. Of all the explosives studied, tetryl was the only compound that 

showed evidence of chemical decomposition. Harsh conditions during the Hayesep-R® treatment were 

reflected in reduced recoveries (62-82%) and precision (7-47% RSD) (Army 1989a). To prevent 

negative baseline drift and random spikes in the PC, only highly purified water must be used and the 

eluent must be exhaustively degassed. 

Other methods that have been used to determine tetryl in water are MS and immunoassays (Krogsrud 

and Lang 1990; Yinon and Laschever 1982). MS with chemical ionization (CIMS) permits direct 

injection of the water sample into the analytical instrument, but sensitivity was substantially less (ppm 

range) than with GC/ECD (ppt range) (Yinon and Laschever 1982). However, its selectivity makes it 

a good method for screening samples for further analysis (Yinon and Laschever 1982). A method has 
TETRYL 76 

6. ANALYTICAL METHODS
 

been developed for the analysis of tetryl in water using monoclonal antibodies (Krogsrud and Lang 

1990). Because the detection limit achieved by the tetryl immunoassay was significantly higher 

(2 ppm) than that obtainable by more conventional methods such as HPLC, the assay will more likely 

be used as a field screen rather than a quantitative laboratory method (Krogsrud and Lang 1990). 

Tetryl can be analyzed in soil using HPLC/UV (Army 1987b, 1990a; Bauer et al. 1990; Bongiovanni 

et al. 1984; Jenkins et al. 1989). It has also been qualitatively analyzed using HPLCAJV, GCYECD, 

and GC/MS (Army 1980, 1981c). The preparation steps for HPLC analysis generally involved drying, 

grinding, homogenizing, and extracting with acetonitrile in an ultrasonic bath (Army 1987b; Bauer et 

al. 1990; Bongiovanni et al. 1984; Jenkins et al. 1989). The method was rapid and selective and 

generally gave high recoveries from complex samples (Army 1987b; Bongiovanni et al. 1984; Jenkins 

et al. 1989). Supercritical carbon dioxide extraction also provides high recovery (Engelhardt et al. 

1993). The lower recovery (≈70%) and precision (≈18% RSD) that were found in some laboratories 

were attributed to thermal degradation of tetryl (Bauer et al. 1990). The problem was corrected when 

the sonic bath temperatures were maintained near ambient levels (Bauer et al. 1990). Similarly, tetryl 

is not stable during methanolic Soxhlet extraction (Jenkins and Walsh 1994). Sensitivity in the low 

ppm to low ppb range has been reported and precision was excellent (0.1-6% RSD) (Army 1987b; 

Bauer et al. 1990; Bongiovanni et al. 1984; Jenkins et al. 1989). 

GC/ECD has been used to measure tetryl in ocean floor sediment and fauna (Navy 1972). Preparation 

steps generally involved homogenization and extraction with benzene, filtering, clean-up with TLC, 

and concentration. The sensitivity for detecting tetryl in ocean floor fauna using this method was 

estimated to be in the ppt range. Precision and accuracy were not reported (Navy 1972). 

An attempt to develop an HPLC/UV method for detecting tetryl in plant stems was unsuccessful 

because of binding of the compound to macromolecules in the tissue (Army 1981a). A methodology 

based on solvent extraction of plant tissues followed by silica gel fractionation and HPLCKJV 

detection was used for the determination of tetryl in plant tissues (Harvey et al. 1993). This method 

allowed 82.7% recovery of tetryl from fortified bush bean leaves. 

Several methods have been used to detect and measure tetryl in explosive materials or mixtures and in 

debris from explosions. The most common separation procedures used are HPLC and HRGC. These 

methods have been paired with TEA, UV, ECD, and MS (Army 1988; Douse 1981; Fine et al. 1984; 
TETRYL 77 

6. ANALYTICAL METHODS
 

Strobe1 and Tontarski 1983; Tamiri and Zitrin 1986). Several of the methods used were similar to 

those used to analyze for tetryl in hand swabs. The identification of tetryl in explosive debris usually 

involves extracting the debris with a suitable polar solvent such as acetone or methanol. TEA was 

very selective for nitroso compounds and nitramines (e.g., tetryl) and when paired with either HPLC or 

HRGC gave excellent selectivity, precision (2.6% RSD when paired with HRGC), and high sensitivity 

(low pg) (Fine et al. 1984). Because of the selectivity of this technique, there was no need for sample 

clean-up before analysis (Fine et al. 1984). The use of a dual column clean-up technique using both 

polar and nonpolar sorbents gave excellent recovery (96%) with HPLC/UV (Strobel and Tontarski 

1983). Sensitivity and precision were not reported (Strobe1 and Tontarski 1983). With HPLC, tetryl 

elutes very near TNT, but a separation of TNT and tetryl may be achieved using a methanol/water 

(50/50) mobile phase (Army 1977). The level of sensitivity for the HPLC/UV method permits a lower 

limit of detection in the ppb range (Army 1977). The sensitivity of ECD was comparable to TEA (pg 

amounts) and precision was very good (5% RSD) (Douse 1981). A sophisticated method linking 

HPLC, thermospray (TSP), and MS (with both positive and negative chemical ionization) has also 

been proposed as a sensitive (low pg range) and selective method for detecting tetryl in explosives and 

explosive debris (Berberich et al. 1988). Other methods include photochemical decomposition, 

followed by ion-pair chromatography with electrochemical detection (Engelhardt et al. 1993) and 

micellar electrokinetic capillary chromatography (Kleiboehmer et al. 1993). 

HRGC/MS has been used to identify tetryl in explosive debris (Tamiri and Zitrin 1986). Tetryl was 

reported to decompose by hydrolysis during the analysis, but its decomposition product, 

N-methylpicramide, was well defined and served as evidence for the presence of tetryl (Tamiri and 

Zitrin 1986). The authors of this report concluded that the hydrolysis of tetryl during the GC analysis 

could take place at the injector, which was held at relatively high temperatures (Tamiri and Zitrin 

1986). MS can be used by itself for the identification of tetryl and its decomposition products, picric 

acid and 2,4,6-trinitroanisol, generated by laser irradiation (Bhasu et al. 1991). Chemical ionization 

mass spectrometry (CIMS) has also been successfully used to identify tetryl (Zitrin and Yinon 1976). 

Other methods that have been used to determine tetryl in explosive material and debris from 

explosions are thin layer chromatography (TLC), supercritical fluid chromatography (SFC)AJV, and 

nuclear magnetic resonance (NMR) spectrometry (Griest et al. 1989; Margalit et al. 1986; Parker et al. 

1975). TLC has been used to confirm the presence of tetryl in explosive residues using various 

solvent systems (Parker et al. 1975). The TLC method is suited to the analysis of bomb scene 
TETRYL 78 

6. ANALYTICAL METHODS
 

residues (Parker et al. 1975). SFC is complementary to GC and HPLC because of its ability to 

mobilize compounds not readily chromatographed by GC and because it can be interfaced with 

GC-like ionization detectors and mass spectroscopy more easily than can HPLC (Greist et al. 1989). 

The precision for the standard solutions was very good (2.8% RSD) with sensitivity in the low-ppm 

range (Griest et al. 1989). However, more work is needed to improve the mobile phase and column 

packing material before samples in complex matrices can be analyzed by this method. NMR 

spectrometry has also been applied to the analysis of explosive samples (Margalit et al. 1986). For 

unexploded samples, NMR was found to be a simple, fast, and reliable method, allowing for 

identification of mixtures without preseparation. Some of the postexplosion samples, which required 

sample preparation, were also successfully analyzed by NMR. Although sensitivity problems still 

exist, NMR shows promise for the difficult field of postexplosion analysis (Margalit et al. 1986). 

6.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with 

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of tetryl is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of 

research designed to determine the health effects (and techniques for developing methods to determine 

such health effects) of tetryl. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that, if met, 

would reduce or eliminate the uncertainties of human health assessment. This definition should not be 

interpreted to mean that all data needs discussed in this section must be filled. In the future, the 

identified data needs will be evaluated and prioritized, and a substance-specific research agenda may 

be proposed. 

6.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Methods have been 

developed for detecting tetryl metabolites (picric and picramic acid) in urine (Zambrano and 

Mandovano 1956) and analyzing hand swabs for explosives (Douse 1982; Fine et al. 1984; Lloyd 
TETRYL 79 

6. ANALYTICAL METHODS
 

1983b), including tetryl. The calorimetric assays for tetryl metabolites in urine have been used only in 

animal studies and lack sensitivity. In addition, they are only semiquantitative, and no data on 

recovery or precision were provided. Analysis methods for tetryl in hand swabs have been used 

primarily in forensics and not on workers or the general population. No methods for measuring tetryl 

or its metabolites in the tissues, fluids, or excreta of humans or animals were located. One attempt to 

develop a method failed because of suspected binding of tetryl to macromolecules in the animal tissue 

(Army 1981a). There are no known sensitive biomarkers of exposure or effect for tetryl. More 

sensitive methods for analyzing tetryl metabolites in urine are needed in order to assess the utility of 

urinary metabolites in monitoring human exposure. Development of a method for extracting tetryl and 

metabolites from biological samples are needed so that important information on tetryl metabolism and 

bioconcentration can be obtained and so that biomarkers of tetryl exposure can be better defined. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. One spectrophotometric method for detecting tetryl in air was located (NIOSH 1977). 

Methods exist to detect and quantify tetryl and/or its degradation products in water (Army 1986c, 

1988, 1989a; Belkin et al. 1985; Feltes and Levsen 1989; Hoffsommer and Rosen 1972; Yinon and 

Laschever 1982), soil and sediments (Army 1987b, 1990a; Bauer et al. 1990; Bongiovanni et al. 1984; 

Jenkins et al. 1989; Navy 1972), ocean floor fauna (Navy 1972), and explosive materials and debris 

from explosions (Army 1988; Douse 1981; Fine et al. 1984; Griest et al. 1989; Strobe1 and Tontarski 

1983; Tamiri and Zitrin 1986). These methods are relatively sensitive, selective, and reliable, and can 

be used to detect low levels of the compound in the environment (specifically water and soil). The 

most sensitive and selective methods for detecting tetryl in water and soil are HPLC-based with 

detection by UV and ECD (Army 1986c, 1987b, 1988, 1989a; Bongiovanni et al. 1984; Feltes and 

Levsen 1989; Lyter 1983). However, precision data are needed to assess the reproducibility of these 

methods. Methods are needed to detect and measure tetryl in fish, plants, and other aquatic and 

terrestrial organisms. One attempt to develop an HPLC/UV method for determining tetryl in plant 

tissue was unsuccessful because of binding of the compound to macromolecules in the plant tissue 

(Army 1981a). A method reportedly used to determine tetryl in ocean floor fauna did not give 

recovery data (Navy 1972). A reliable, well-characterized method for extracting and measuring tetryl 

in biological tissue is needed in order to investigate bioaccumulation in aquatic and terrestrial species. 

The most sensitive and selective methods for detecting tetryl in explosive materials and debris from 

explosions are HPLC/TEA and HPLC/ECD (Army 1977; Douse 1981; Fine et al. 1984). Recovery 

and precision data are needed in order to adequately assess the reproducibility of these methods. 
TETRYL 80 

6. ANALYTICAL METHODS 

Improvements that have been made in current methods and the improvements proposed for newer 

methods (Griest et al. 1989; Krogsrud and Lang 1990) will be useful in monitoring environmental 

contamination from manufacture and disposal of tetryl and in forensics. 

6.3.2 Ongoing Studies
 

No ongoing analytical methods studies were located.
 
TETRYL 81 

7. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding tetryl in air, water, and other 

media are summarized in Table 7- 1. 

ATSDR has not derived MRLs for tetryl because of the lack of reliable human or animal studies 

which identify levels of exposure associated with adverse health effects. In addition, EPA has not 

verified a reference dose (RfD) for oral exposure or a reference concentration (RfC) for inhalation 

exposure to tetryl. 

The transportation of explosives including tetryl must be in accordance with the Department of 

Transportation hazardous material regulations (49 CFR 171-190) and the motor carrier safety 

regulations (49 CFR 390-398). Numerous states have established regulations on explosives for air 

quality control, solid waste disposal, storage, manufacture, and use. 





TETRYL 87 

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*Cited in text 
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Disease Control, National Institute for Occupational Safety and Health, 3:S225-1. 

*NIOSH. 1990. Pocket guide to chemical hazards. Washington, D.C.: U.S. Department of Health 

and Human Services, Public Health Service, Centers for Disease Control, National Institute for 

Occupational Safety and Health, U.S. Government Printing Office, 212-213. 

Noro L. 1941. Untersuchungen uber die trotyl-, tetryl- und knallquecksilber- vergiftungen bei den 

arbeiten der munitionsfabriken Finnlands. Acta Med Stand 120:1-95. (German) 

*NREPC. 1986. Proposed regulation. Frankfort, KY: Department for Environmental Protection, 

Natural Resources and Environmental Protection Cabinet. 401 KAR 63:022. 

*OSHA. 1989a. Occupational safety and health standards: Toxic and hazardous substances. U.S. 

Department of Labor, Occupational Safety and Health Administration. Code of Federal Regulations. 

29 CFR 1910.1000. 

*OSHA. 1989b. Air contaminants. U.S. Department of Labor, Occupational Safety and Health 

Administration. Federal Register 54:2920-2960. 

*OTA. 1990. Neurotoxicity: Identifying and controlling poisons of the nervous system. Office of 

Technology Assessment, Washington, DC. OTA-BA-438. 

*Parker RG, McOwen JM, Cherolis JA. 1975. Analysis of explosives and explosive residues: Part 2. 

Thin layer chromatography. J Forensci Sci 20:254-256. 

*Parmeggiani L, Bartalini E, Sassi C, et al. 1956. Tetryl occupational diseases: Experimental 

investigation and prevention. Med Lavoro 47:293-3 13. [Italian] 

Parmeggiani L, ed. 1983. Encyclopedia of occupational health and safety. Geneva, Switzerland: 

International Labour Office, 2165-2166. 
TETRYL 98 

8. REFERENCES
 

Pesce-Rodriquez RA, Fifer RA. 1990. Photoacoustic FTIR investigation of a nitramine propellant
 

system [Abstract]. In: 41st Pittsburgh Conference and Exposition on analytical chemistry and applied
 

spectroscopy, Pittsburgh, PA, March 5-9, 1990. Aberdeen Proving Ground, MD: U.S. Army Ballistic
 

Research Laboratory, 5-9.
 

Petrosyan VA, Frolovskii VA. 1989. Electrochemical generation of n-nitramine ions upon the
 

reduction of n-nitramines. Bulletin of the Academy of Sciences of the USSR Division of Chemical
 

Science 382439.
 

*Probst EW, Mund MH, Lewis LD. 1944. Effects of tetryl. JAMA 126:424-427.
 

Roth M, Murphy JM Jr. 1978. Correlation of oxygen demand and total organic carbon tests on
 

wastewaters from ammunition plants. Proc Ind Waste Conf 32:674-688.
 

*Ruxton WL. 1917. An investigation into the cause and prevention of industrial diseases due to
 

tetryl. Br J Dermatol 29:18-29.
 

*Sax NI, Lewis RJ Sr. 1987. Hawley’s condensed chemical dictionary. 11th edition. New York,
 

NY: Van Nostrand Reinhold Co., 1141.
 

Sax NI, Lewis RJ Sr. 1989. Dangerous properties of industrial materials. 7th edition, volume III.
 

New York, NY: Van Nostrand Reinhold Co.
 

*Schwartz L. 1944. Dermatitis from explosives. JAMA 125:186-190.
 

Seidell A. 1941. Solubilities of organic compounds. New York, NY: Van Nostrand Reinhold Co.
 

Selavka CM, Krull IS. 1986. Liquid chromatography with photolysis - electrochemical detection for
 

nitro-based high explosives and water gel formulation sensitizers. J Energetic Material 4:273-303.
 

Silver ALL. 1938. The treatment and prevention of industrial diseases in filling factories. J R Army
 

Med Corps 71:87-96.
 

*Smith E. 1916. The prevention, symptoms, and treatment of tetryl dermatitis. Br Med J 1:618.
 

Solomonovici A. 1986. Identification of explosives in Soviet weapons. J Energetic Material
 

4:315-324.
 

*Strobe1 RA, Tontarski RE. 1983. Organic solvent extracts of explosive debris: Clean-up procedures
 

using bonded phase sorbents. In: Proceedings of the International Symposium on the analysis and
 

detection of explosives, FBI Academy, Quantico, VA, March 29-31, 1983. Washington, DC: U.S.
 

Department of Justice, Federal Bureau of Investigation, 67-70.
 

Sullivan RJ, Watson GW. 1983. Sampling of explosives with multiple, portable preconcentrating
 

cartridges. In: Proceedings of the International Symposium on the analysis and detection of
 

explosives, FBI Academy, Quantico, VA, March 29-31, 1983. Washington, DC: U.S. Department of
 

Justice, Federal Bureau of Investigation, 431-440.
 
TETRYL 99 

8. REFERENCES
 

*Swarm RL, Laskowski DA, McCall PJ, et al. 1983. A rapid method for the estimation of the 

environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio, 

and water solubility. Residue Reviews 85:16-28. 

*Tamiri T, Zitrin S. 1986. Capillary column gas chromatography/mass spectrometry of explosives. 

Journal of Energetic Material 4:215-237. 

*TRI. 1993. Toxic Chemical Release Inventory. National Library of Medicine, National Toxicology 

Information Program, Bethesda, MD. 

*Troup HB. 1946. Clinical effects of tetryl (CE powder). Br J Ind Med 3:20-21. 

Urbanski T. 1983. Chemistry and technology of explosives. Volume 3. New York, NY: Pergamon 

Press, 40-62. 

Volk F. 1977. [Study on the fumes produced by the detonation of various explosives.] Explosifs 

30:72-80. (German) 

*Wells HG, Lewis JH, Sansum WD, et al. 1920. Observations of the toxicity of 

tetranitromethylaniline (tetryl), tetranitroxylene (T.N.X), tetranitraniline (T.N.A), 

dinitrodichlorobenzene (parazol), and metanitraniline. Journal of Industrial Hygiene 2: 247-252. 

Whong WZ, Edwards GS. 1984. Genotoxic activity of nitroaromatic explosives and related 

compounds in Salmonella typhimurium. Mutat Res 136:209-215. 

*Whong WZ, Speciner ND, Edwards GS. 1980a. Mutagenic activity of tetryl, a nitroaromatic 

explosive, in 3 microbial test systems. Toxicol Lett (Amst) 5:11-18. 

Whong WZ, Speciner ND, Edwards GS. 1980b. Mutagenicity of polynitroaromatic explosives in 

microbial test systems. Proc Am Assoc Cancer Res 21:195. 

Williams RT, Ziegenfuss PS, Mohrman GB, et al. 1989. Composting of explosives and propellant 

contaminated sediments. Hazard Ind Waste 21:599-611. 

*Witkowski LJ, Fischer CN, Murdock HD. 1942. Industrial illness due to tetryl. JAMA 

i19:1406-1409. 

Yinon J. 1983. Analysis of explosives by LC/MS. In: Proceedings of the International Symposium 

on the analysis and detection of explosives, FBI Academy, Quantico, VA, March 29-31, 1983. 

Washington, DC: U.S. Department of Justice, Federal Bureau of Investigation, 227-234. 

*Yinon J, Laschever M. 1982. Direct-injection chemical ionization mass spectrometry of explosives 

in water. European Journal of Mass Spectrometry in Biochemistry, Medicine, and Environmental 

Research 2:101-104. 

Yoshida M, Sunaga M, Hara I. 1990. Selenium status in workers handling aromatic nitro-amino 

compounds in a chemical factory. J Toxicol Environ Health 31: l-10. 
TETRYL 100 

8. REFERENCES 

*Zambrano A, Mandovano S. 1956. Urinary excretion of picric acid, picramic acid, and of 

sulfoconjugation products in experimental tetryl poisoning. Folia Med. (Naples) 39: 162-171. (Italian) 

*Zitrin S, Yinon J. 1976. Chemical ionization mass spectrometry of explosives. Advances in Mass 

Spectrometry in Biochemistry and Medicine 1:369-381. 
TETRYL 101 

9. GLOSSARY
 

Acute Exposure - Exposure to a chemical for a duration of 14 days or less, as specified in the
 

Toxicological Profiles.
 

Adsorption Coefficient (KOC) - The ratio of the amount of a chemical adsorbed per unit weight of
 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.
 

Adsorption Ratio (Kd) - The amount of a chemical adsorbed by a sediment or soil (i.e., the solid
 

phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid
 

phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per
 

gram of soil or sediment.
 

Bioconcentration Factor (BCF) - The quotient of the concentration of a chemical in aquatic
 

organisms at a specific time or during a discrete time period of exposure divided by the concentration
 

in the surrounding water at the same time or during the same period.
 

Cancer Effect Level (CEL) - The lowest dose of chemical in a study, or group of studies, that
 

produces significant increases in the incidence of cancer (or tumors) between the exposed population
 

and its appropriate control.
 

Carcinogen - A chemical capable of inducing cancer.
 

Ceiling Value - A concentration of a substance that should not be exceeded, even instantaneously.
 

Chronic Exposure - Exposure to a chemical for 365 days or more, as specified in the Toxicological
 

Profiles.
 

Developmental Toxicity - The occurrence of adverse effects on the developing organism that may
 

result from exposure to a chemical prior to conception (either parent), during prenatal development, or
 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any
 

point in the life span of the organism.
 

Embryotoxicity and Fetotoxicity - Any toxic effect on the conceptus as a result of prenatal
 

exposure to a chemical; the distinguishing feature between the two terms is the stage of development
 

during which the insult occurred. The terms, as used here, include malformations and variations,
 

altered growth, and in utero death.
 

EPA Health Advisory - An estimate of acceptable drinking water levels for a chemical substance
 

based on health effects information. A health advisory is not a legally enforceable federal standard,
 

but serves as technical guidance to assist federal, state, and local officials.
 

Immediately Dangerous to Life or Health (IDLH) - The maximum environmental concentration of
 

a contaminant from which one could escape within 30 min without any escape-impairing symptoms or
 

irreversible health effects.
 

Intermediate Exposure - Exposure to a chemical for a duration of 15-364 days, as specified in the
 

Toxicological Profiles.
 
TETRYL 102 

9. GLOSSARY
 

Immunologic Toxicity - The occurrence of adverse effects on the immune system that may result 

from exposure to environmental agents such as chemicals. 

In Vitro - Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo - Occurring within the living organism. 

Lethal Concentratiorq(LO) (LCLO) - The lowest concentration of a chemical in air which has been 

reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50) - A calculated concentration of a chemical in air to which exposure 

for a specific length of time is expected to cause death in 50% of a defined experimental animal 

population. 

Lethal Dose(LO) (LD(LO) - The lowest dose of a chemical introduced by a route other than inhalation 

that is expected to have caused death in humans or animals. 

Lethal Dose(50) (LD(50) ) - The dose of a chemical which has been calculated to cause death in 50% 

of a defined experimental animal population. 

Lethal Time(50) (LT(50) ) - A calculated period of time within which a specific concentration of a 

chemical is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL) - The lowest dose of chemical in a study, or 

group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Malformations - Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level - An estimate of daily human exposure to a dose of a chemical that is likely to 

be without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. 

Mutagen - A substance that causes mutations. A mutation is a change in the genetic material in a 

body cell. Mutations can lead to birth defects, miscarriages, or cancer. 

Neurotoxicity - The occurrence of adverse effects on the nervous system following exposure to 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL) - The dose of chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen 

between the exposed population and its appropriate control. Effects may be produced at this dose, but 

they are not considered to be adverse. 

Octanol-Water Partition Coefficient (KOW) - The equilibrium ratio of the concentrations of a 

chemical in n-octanol and water, in dilute solution. 

Permissible Exposure Limit (PEL) - An allowable exposure level in workplace air averaged over 

an 8-hour shift. 
TETRYL 103 

9. GLOSSARY
 

q1* - The upper-bound estimate of the low-dose slope of the dose-response curve as determined by 

the multistage procedure. The ql* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for food, and 

pg/m3

 for air). 

Reference Dose (RfD) - An estimate (with uncertainty spanning perhaps an order of magnitude) of 

the daily exposure of the human population to a potential hazard that is likely to be without risk of 

deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from animal 

and human studies) by a consistent application of uncertainty factors that reflect various types of data 

used to estimate RfDs and an additional modifying factor, which is based on a professional judgment 

of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as 

cancer. 

Reportable Quantity (RQ) - The quantity of a hazardous substance that is considered reportable 

under CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an 

amount established by regulation either under CERCLA or under Sect. 3 11 of the Clean Water Act. 

Quantities are measured over a 24-hour period. 

Reproductive Toxicity - The occurrence of adverse effects on the reproductive system that may 

result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the 

related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual 

behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the 

integrity of this system. 

Short-Term Exposure Limit (STEL) - The maximum concentration to which workers can be 

exposed for up to 15 min continually. No more than four excursions are allowed per day, and there 

must be at least 60 min between exposure periods. The daily TLV-TWA may not be exceeded. 

Target Organ Toxicity - This term covers a broad range of adverse effects on target orgatis or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen - A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV) - A concentration of a substance to which most workers can be 

exposed without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. 

Time-Weighted Average (TWA) - An allowable exposure concentration averaged over a normal 8­

hour workday or 40-hour workweek. 

Toxic Dose (TD50) - A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Uncertainty Factor (UF) - A factor used in operationally deriving the RfD from experimental data. 

UFs are intended to account for (1) the variation in sensitivity among the members of the human 

population, (2) the uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in 

extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the 

uncertainty in using LOAEL data rather than NOAEL data. Usually each of these factors is set equal 

to 10. 

A-l

APPENDIX A 

USER’S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects smnrnary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it 

would still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence 

that will direct the reader to chapters in the profile that will provide more information on the given 

topic. 

Chapter 2 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (2-1, 2-2, and 2-3) and figures (2-l and 2-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed 

at increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer endpoints, and EPA’s estimated range associated with an 

upper-bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and 

figures for a quick review of the health effects and to locate data for a specific exposure scenario. The 

LSE tables and figures should always be used in conjunction with the text. All entries in these tables 

and figures represent studies that provide reliable, quantitative estimates of No-Observed-AdverseEffect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels 

(CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 2-l and Figure 2-l are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See LSE Table 2-1 

(1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The 

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and 

dermal (LSE Table 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 2-l) and oral (LSE Figure 2-2) routes. Not all substances will have data on each 

route of exposure and will not therefore have all five of the tables and figures, 
A-2 

APPENDIX A 

(2)	 Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15-364 days), 

and chronic (365 days or more) are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference 

to health effects occurring from a known length of exposure, locate the applicable exposure 

period within the LSE table and figure. 

(3)	 Health Effect The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the “System” column of the LSE table (see key number 

18). 

(4)	 Key to Figure Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the 2 ” 18r” data points in Figure 2-l). 

(5)	 Species The test species, whether animal or human, are identified in this column. Section 2.4, 

“Relevance to Public Health,” covers the relevance of animal data to human toxicity and Section 

2.3, “Toxicokinetics,” contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAFLs and LOAELs from 

different studies. In this case (key number lS), rats were exposed to toxaphene via inhalation for 

6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the dosing 

regimen refer to the appropriate sections of the text or the original reference paper, i.e., Nitschke 

et al. 1981. 

(7)	 System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. 

“Other” refers to any systemic effect (e.g., a decrease in body weight) not covered in these 

systems. In the example of key number 18, 1 systemic effect (respiratory) was investigated. 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which 

no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 

3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation 

MRL of 0.005 ppm (see footnote “b”). 

(9)	 LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the 

study that caused a harmful health effect. LOAELs have been classified into “Less Serious” and 

“Serious” effects. These distinctions help readers identify the levels of exposure at which 

adverse health effects first appear and the gradation of effects with increasing dose. A brief 

description of the specific endpoint used to quantify the adverse effect accompanies the LOAEL. 

The respiratory effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 

ppm. MRLs are not derived from Serious LOAELs. 

(10) Reference The complete reference citation is given in chapter 8 of the profile. 
A-3 

APPENDIX A 

(11) CEL	 A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report

doses not causing measurable cancer increases. 

(12) Footnotes	 Explanations of abbreviations or reference notes for data in the LSE tables are found

in the footnotes. Footnote "c" indicates the NOAEL of 3 ppm in key number 18 was used to

derive an MRL of 0.0006 ppm. 

LEGEND 

See Figure 2-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the

reader quickly compare health effects according to exposure concentrations for particular exposure

periods. 

(13) Exposure Period	 The same exposure periods appear as in the LSE table. In this example, health

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14) Health Effect	 These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15) Levels of Exposure	 concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the 

log scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is 

reported in mg/kg/day. 

(16) NOAEL	 In this example, 18r NOAEL is the critical endpoint for which an intermediate

inhalation exposure MRL is based. As you can see from the LSE figure key, the open-circle

symbol indicates to a NOAEL for the test species-rat. The key number 18 corresponds to the

entry in the LSE table. The dashed descending arrow indicates the extrapolation from the

exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.0006 ppm (see footnote "c"

in the LSE table). 

(17) CEL	 Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The 

diamond symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 

corresponds to the entry in the LSE table. 

(18) Estimated Upper-Bound Human Cancer Risk Levels	 This is the range associated with the

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are 

derived from the EPA's Human Health Assessment Group's upper-bound estimates of the slope

of the cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. 


A-6 

APPENDIX A
 

Chapter 2 (Section 2.4) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based on evaluations of 

existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to 

present interpretive, weight-of-evidence discussions for human health endpoints by addressing the 

following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous

 waste sites? 

The section covers endpoints in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data 

are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In 

vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this section. If data are located in the scientific literature, a table of genotoxicity 

information is included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer endpoints (if 

derived) and the endpoints from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to 

public health are identified in the Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). 

These MRLs are not meant to support regulatory action; but to acquaint health professionals with 

exposure levels at which adverse health effects are not expected to occur in humans. They should 

help physicians and public health officials determine the safety of a community living near a chemical 

emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs 

are based largely on toxicological studies in animals and on reports of human occupational exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. 

Chapter 2.4, “Relevance to Public Health,” contains basic information known about the substance. 

Other sections such as 2.6, “Interactions with Other Substances,” and 2.7, “Populations that are 

Unusually Susceptible” provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 
A-7 

APPENDIX A 

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is 

available for all potential systemic, neurological, and developmental effects. If this information and 

reliable quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the 

most sensitive species (when information from multiple species is available) with the highest NOAEL 

that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty 

factor (UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for 

human variability to protect sensitive subpopulations (people who are most susceptible to the health 

effects caused by the substance) and for interspecies variability (extrapolation from animals to 

humans). In deriving an MRL, these individual uncertainty factors are multiplied together. The 

product is then divided into the inhalation concentration or oral dosage selected from the study. 

Uncertainty factors used in developing a substance-specific MRL are provided in the footnotes of the 

LSE Tables.