Possible Long-Term Health Effects of Short-Term Exposure To Chemical Agents, Volume 2 Cholinesterase Reactivators, Psychochemicals and Irritants and Vesicants (1984) / Chapter Skim
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4. Irritants and Vesicants
4. Irritants and Vesicants
Pages 101-255
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From page 101... ...
Mustard gas and irritant chemical agents, the latter often called harassing agents, were introduced to the battlefield in World War I to confuse, harass, and disable enemy troops. Since the 1920s, irritants have been used as riot-control agents by civil authorities.
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From page 103... ...
No such systematic investigation has been conducted of any of the agents reviewed in this chapter, except possibly mustard gas. In the case of any agent for which a risk assessment is desires with respect to past human exposure or that continues to be used for riot control or relates purposes, it seems desirable to use a battery of tents, such as those recommended in the National Research Council report on chemical environmental mutagens.4 Under the sponsorship of the National Cancer Institute and the National T Toxicology Program, two chronic tests of CN and CS administered by inhalation are unter way.
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177 p. MUSTARD GAS CHARACTERI STICS Mustard gas (H)
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From page 105... ...
Over several years, Auerbach and her colleagues found that mustard gas causes genetic alterations ranging from gene mutations to chromosomal breaks asked rearrangements. ~ lDhe mechanism of mutagenesis by sulfur mustard (and other mustarda)
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From page 106... ...
Nevertheless, the possibility that sulfur mustard is a human ge.,u cell mutagen cannot be disregarded, part icularly because it is mutagenic in diverse assays, including tests for germ cell mutations in Drosophila and dominant lethals in mice; moreover, other directacting alkylating agents are known to induce mutations63 ant chromosomal alterations 1 in mammalian germ cells. Pathogen IS iS of Skin bee ions Vogt et al.72 recently studied the pathogenesis of lesions caused by the appl ices ion of H to the skin of guinea pigs and rabbi to; their methods inc luded l ight and e lee tron microscopy, h i s to-106
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This expectation in borne out by carcinogenicity tests in experimental animals and by data from human exposures. The International Agency for Research on Cancer classifies sulfur mustard a.
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From page 108... ...
The concentration of mustard gas78 may have reached 50-70 mg/m3, as determined by bioassay. The bioassay involved exposure of unprotected birds in the work areas that resul-108—
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From page 109... ...
involving the respiratory tract (Table 4-21.
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TABLE 4-2 Characteristics of Male Mustard-Gas Workers Who Died from Cancer (1955-1967) a Case ___ Interval f ram Exposure Employment Age at Durat ion, to Death, Death, Site of yr ma ~ ma yr Neoplasm Histolo~ Type 3 7 2 22 4 62 Pharynx Undif ferent iated 4 5 3 22 0 40 Pharynx Squamou ~ ce 1 ~ 5 8 0 24 5 57 Paranasal ~ inus Squamous ce 11 6 4 11 23 2 44 Paranasal sinus Squamous cell 7 7 5 28 1 65 Paranasal ~ inus Squamous ce 11 10 ~ 0 16 10 62 Larynx Squamous cell 11 10 0 19 2 52 Larynx Squamous cell 12 12 10 22 11 58 Larynx Squamous cell 13 7 11 20 10 58 Larynx Squamous ce 11 15 8 0 25 5 48 Larynx Squamous cell 16 7 0 23 4 59 Trachea Squamous ce 11 18 1 4 10 1 1 30 Bronchu ~ Squamou ~ c e 11 21 6 1 23 1 62 Bronchus Squamous ce 11 22 ~ 1 17 4 62 Lung Squamous cell 23 2 0 33 0 54 Bronchus Undifferentiated 24 17 0 27 0 54 Bronchus Undifferentiated 26 16 4 27 10 61 Bronchus Undifferentiated 27 4 10 17 9 61 Bronchus Squamous cell 29 2 2 19 3 58 Bronchus Undifferentiated 30 ~ 5 22 5 63 Bronchus Undif ferent fated 32 5 ~ 20 ~ 50 Bronchus Undifferentiated 38 7 11 27 7 74 Lung Squamous cell 40 2 0 27 6 55 Bronchus Squamous ce 11 43 0 3 26 1 47 Lung Undif ferent iated 44 7 3 29 0 63 Bronchus Squamous ce 11 __ —^ a Data from Wada _ alms -1 10
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From page 111... ...
Most important, these long-ter~ sequel ae ~ except the malignancies ~ generally const ituted extensions or continuations of acute probe ems experienced during exposure to H; they did not sudden1 y appear years af ter exposure. MEDICAL EFFECTS Immediate Ef fects An unprotected person exposed to H vapor will suffer simultaneously from skin burns, eye injury, and irritation of the respiratory tract.
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From page 112... ...
died as a result of expocell~ in the spleen, thyme, and other lymphatic organs; depletion of hematopoietic cells of the bone marrow; necrosis and desquamation of epithellum in the small intestine; acute ulceration of the duodenum; membranous ~ aryngotracheobronchitis; and pulmonary edema , congestion, and patchy emphysema that may be complicated by bronchopneumonia or other evidence of pulmonary infection. 2, 7 Postmortem examinations of persons who sure to H have shown depletion of lymphoid - and The acute effects of H were observed ire three children, as well as in the rescuer and attending medical and nursing personnel, after they were injured by the accidental explosion of a 40-yr-old mustardgas shell.29 Two children died within 4 h after experiencing congestion and swelling of the eyes, continuous vomiting, edema of the skin, pulmonary edema, pain, and shock.
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From page 113... ...
Cullumbine, 15 describing the action of an experimental droplet on human skin, said, "The first macroscopic sign of the action of mustard gas appears under temperate climatic conditions about two hours later" (after application)
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TABLE 4-3 Effects of Various Concentrat ions of Mustard Gas on Humansa Concent rat ion .
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Mann43 examined the records of 84 men described as suf fering from "delayed mustard gas keratitis." This group had been created at the Contact Lenses Clinic at Moorfields, England. The eye in juries were described as "typical mustard gas scars with corneal degenerat ion.
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From page 117... ...
Redrawn from Mann.28 Hughes32 reviewed mainly British and European reports and cited official British data estimating that 75-90: of mustard gas canualties had some degree of ocular injury. A rough estimate, based on information reported by Case and Lea, 13 indicates a little over 100, 000 cases of eye injury.
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From page 118... ...
23 Berghoff9 noted that, whereas a single exposure to mustard gas primarily affects the respiratory tree acutely, long-term (5 mo) effects of such exposure most notably involved the skin ant eyes, although as many as 30% of gas victims also appeared to manifest chronic bronchitis.
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Systemic E f fees ~ Lohe4t reviewed the literature ant came to highly disputed conclusions. The panel felt that information was misquoted, distorted, scientifically inaccurate, or politically flavored, because authors hold strong personal views opposing chemical warfare.
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From page 120... ...
Mustard gas in c irculat ion 1 Body gene ra 1 ly Shock Leukopenia Gastrointestinal ef fects Nervous e f fee ts - ~ Increased Rapidly capi 1 lary permeabil ity or Some de lay Epithe 1 ial loosening 1 Ve 8 icat ion FIGURE 4-2 Phys iologic processes that occur af ter mustard-gas contaminat ion o f skin. exposures at 150 mg/m3 are generally lethal for man.
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From page 121... ...
Case and Leal3 concluded that chronic bronchitis 'rom H led to cancer of the lung ant pleura, but thee H was not a d irect care inogen. Beebe, 8 like Cane and Lea, set up three groups: mustard gas casualties, pneumonia cases, and those with leg wounded the latter two series excluded any who might possibly have had contact with H
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From page 123... ...
TABLE 4-7 Observed and Expected Deaths, by Roster and Times Series ant No. Deaths Period Observed Expec ted Mortal ity Rat lo Mus lard-gas 1919-1929 122 163 - O
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36 EFFECTS ON HUMAN SUBJECTS AT EDGEWOOD Between 1955 and 1965, 147 human subjects underwent exposure to H at Edgewoo~i. One hundred sixteen masked subjects had aerosol chamber exposures to test the ef festiveness of various protective garments.
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so a: :^ ~ o 0 o - ~ ~~ 1 L
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One sub ject, whose total Ct was 17, 700 mg min/m3, was hospital ized 5 d after his last exposure because of diffuse Erythema and bullae.44 In 1957, two sub jects hat three daily aerosol exposures of 499, 1, 000, and 2, 031 mg minims . No leak.
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Mustard gas is not only a vesicant, but also a systemic poison. Its a :ute effects have been demonstrated in bone marrow, intestinal tract, and respiratory tract.
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From page 128... ...
Delayed keratitis due to mustard gas (dichlorodiethyl sulfide burns)
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From page 129... ...
IN Chemical Warfare Agents, and Related Chemical Problems, 2 vol. ~ Summary Technical Report of Division 9, National Defense Research Committee)
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Collective intoxi cation caused by the explosion of a mustard gas shell. Trans let ion o f Ann.
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Chemical Warfare Laboratories. Army Chemical Center, Hd.
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Edgewood Arsenal, Md. Technical Report CRDLR 3225.
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Edgewood Arsenal, Md. Technical Report EATR 4031.
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t., and Mackintosh, J.M. Mustard gas poisoning.
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On the late in juries fol lowing occupat tonal inhalation of mustard gas, with special references to carcinoma of the respiratory tract. Acts Pathol.
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From page 136... ...
ogic reactions to CS in the dog. A spray containing CS at 25 ~g/L caused an increase in blood pressure, tachycardia, and changes in respiratory pattern.
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From page 137... ...
Data were presented only on strain TA100 in the absence of metabolic activation; the data on a negative control, a positive control, and eight concentrat ions of CS supported the authors ' conclusion of nonautagenicity. Although the result would be more convincing if data were available on all strains and on tests with metabolic activation, it is noteworthy that the negative data presented were on the same strait.
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From page 138... ...
Aerosol exposures were at 6, 20, and 60 mg/m3 for 5 min on days 6-15 of pregnancy in rats and days 6-~8 of pregnancy in rabbits. Control aerosols consisted of water or suspensions of Neosil ~ silica dust)
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From page 139... ...
On balance, one can conclude only that under the candle ions of this study CS did not exhibit eeratogenic or fetotoxic activity. Care Erogenic Sty The National Toxicology Program in the United States performed a subchronic study of CS to generate data on the maximal ly tolerated dose (~)
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They cone luded that no cumulat ive or systemic injuries follow long exposures at low concentrations.
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0 · c~ ~ ~ ol o ~ c~ ~ ~ ~ ~ .~- ~ ~ - - - - L ~ _ ~ O O O ~ .
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3 Range ~ c over re su 1 ts f rom var i ous au thor ~ . b LCtso, values for exposures at high concentration for short duration.
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TABLE 4-12 Exposures of Monkeys to CS at High ce ~ sa 3 10 32 Average Duration of Concentration, Ct. Exposure, min mg/m3 m~:min/m3 .
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From page 144... ...
LCtso values were estimated as follows: LCtso, me min/m3 R Spec ie ~ Mean ante Guinea pig 35 x l~ 25-45 x 10 Rabb i ~ 63 x 103 50-80 x 10 Rat 68 x 103 61-77 x 10 Mouse 76 x 103 61-119 x 103 The experiment was repeated, but with a mean CS concentrat ion of about 38.3 mg/m3 and longer exposure times ~ 5-35 h)
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From page 145... ...
, they estimated the following: Spec ies Guinea pig Rabbit Rat Mouse Mean LCt 50, ma. min/m3 67 e 2 x 103 54~l x 103 88 e 5 x 10 50 ~ O x 103 lithe chie f variable appears to have been the change from grenadegenerated CS to pure CS, but there were also differences in exposure times and concentrations.
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Rengstorff33 measured the effects of CS in a wind tunnel on visual acuity of 10 young human volunteers with 20-20 vi~ion -- six with CS at 0.
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From page 147... ...
Threshold concentrations of CS were also measured in the rabbit sod guinea pig with blepharospasm as the criterion o f ocular response. CS at various concentrations was dispensed into the eyes and onto the tongue in O.Ol-ml droplets.
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From page 148... ...
Recovery usually occurs within 30 min after exposure ceases.3 The effects inc lude a burning, pricking, or peppery seneat ion in the eyes, nose, mouth, throat, and skin; lacrimation, rhinorrhea, and salivation; blepharospa~m and injection of the conjunctival and margins of the eye1 ice; photophobia lasting up to ~ h in 10X of sub jects; tightness of the chest assoc fated with gripping pain, breathholding, dyspnea, coughing, and sneezing; erythema ant occasionally vesiculation of exposed skin; and nausea, Toni t ing, headache, and apprehension.3, 19~20~28 Moisture worsens the skin effects. tt ,22 Tolerance to CS may develop from repeated exposures at low concentrations, 20 but it is reduces by hyperventilation, as well as by increased environmental temperature and humid ity.
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From page 149... ...
19 A causal relationship between exposure to CS and asthmas ic attacks has not been establ ished, but irritant CS smoke may predispose susceptible persons to asthmatic attacks.3, 19, 20 Similarly, persons with pre-exi~ting chronic bronchitis may have superimposed acute bronchi" is or bronchopneumonia after exposure to CS.3,20 Expe r imene al Human Echo sure ~ In some experiments, volunteers were exposed to CS aerosols through gasmasks arranged for air-agent passage in and out. Typically, men were exposed in a large wind tunnel in which CS concentrat;.on, air ~peed, and temperature were controlled.
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cm on O 00 1 In e ~ o o ~ x c A: Ant o ~ 0 · - C ~ 0 · lo C ~ .
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TABLE 4-15 Munition (M7A3) Inhalation Toxicitya Exposure Ct.
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From page 152... ...
Small particles had a predominantly respiratory e f feet, whereas large part ic les had predominant ly ocular e f fects (Tables 4-16 ant 4-17~. Gutentag _ al.17 showed that CS, either dry or in solution, produced erythema and vesicles in the skin of human subjects.
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From page 153... ...
of subjects exposed to CS. Reprinted with permission from Punte et al.32 - 1 90 100 Subjects in Groups I and II immediately developed erythema, which persisted up to 30 min after exposure and left no after-effecta; all subjects reported a stinging sensation soon after the exposure began.
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From page 154... ...
The control drenches with water alone caused a ~cransitory rise in blood pressure, but the effect of the 0.005: CS spray was a mean rise of 31 + 2.7 ~ He systolic and 19 + 2 ~ Hg diastolic. It took an average of about 6.3 min for the pressure to decrease to nearly normal -- close to the time it took for skin sensation to end.
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From page 155... ...
78 men, merely asked to remain in the wind tunnel as long as possible b. 35 men, no motivation 30 men, same as a -1 55ICts3, mg/m 3.0, 4.7 0~1, 0~07 0~3, 0~2
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From page 156... ...
Sensit ization Guinea pig tests indicated that CS had a potent ial for produc ins hymn skin irritation and sensitizatlon.38~39 Fisher,l4 discussing tear gases and their effect on human skin, remarked that CS is a sensitizer and a primary irritant capable of causing first- and second-degree burns and even ulcers if not washed off the skin. In experimentally sensitized sub jects, CS elicited a akin response in one of Ale when tested at O.IX, but none reacted at 0.
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From page 157... ...
reported case histories of Il men who developed contact dermatitis after exposures to CS from 2 ~ to 2 mot There appeared to be a wide range of sensitization potential, greater in white then in black workers. Five men developed hypersensitivity after repeated esposures.
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From page 158... ...
We believe that it must be accepted in principle that exposure to CS may precipitate an acute asthmatic attack, but we found no evidence that such attacks differed in kind or degrees from those attributable to natural causes and-, in the cases that we either saw or heard of, we were unable to exclude the possibility that the attacks in mid-August were due to such causes. We must accept the possibility that exposure to CS of a patient with chronic bronchitis and emphysema may result in an acute bronchitis being superimposed on the chronic condition.
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From page 159... ...
To that end, the effects of any such agent should be appropriately invest igated, not only in respect of the healthy persons against whom it may be directed, but also in relation to the possible effects on the young, the elderly and those with impaired health, who may inadvertently be exposed to the agent in question. It is primarily for this reason that we have recommended and it has already been agreed by the Home Secretary that our membership should be expanded and the evidence in regard to CS assessed in the widest possible way.
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From page 160... ...
A primary concern was for adverse reactions in people with respiratory diseases, such as chronic bronchitis and asthma. Although exposure to CS had exacerbated effects in patients with chronic bronchitis, a follownp visit showed that they had returned to their preriot health status.
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From page 161... ...
It concluded that in the open air it would be impossible for a healthy human to receive a lethal dose, because even light grinds disperee CS and the burning time is short for cartilages ~10-15 s) and grenades (25 a)
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From page 162... ...
LONG-1~ERM FOLLOWUP Mar rs _ a1~26 exposed 300 mice, 200 rats, and 200 guinea pig89 all males, to CS at high, medium, ami low concentrations in aerosol form 1 in/d, S d/^ for 120 Be The aerosols were generated from pure CS and had a mass median diameter of 3-4 use Mice were exposed 55 times (ll wish, lance and guinea pigs, 120 times (24 wk)
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From page 163... ...
For 1,073 subjects, there was some type of aerosol CS exposure, IS0 subjects had skin applications, 82 Subjects had both skin applications and aerosol exposures, and 31 underwent CS application to their eyes. Earlier subjects underwent up to 10 CS exposures in the wind tunnel on different days, but later experiments involved a maximum of three exposures.
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From page 164... ...
of I: CS applied to bare or clothed ares. Among the 105 sub jects, signs and s~ptome due to CS exposure were most marked in the eyes ami respiratory tract.
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From page 165... ...
Repeat exposures to CS may cause allergic contact dermatitis in many of the Edgewood; objects. One could speculate that repeat exposures to CS may also induce idiosyncratic hepatitis or allergic pne~o~tis tn some persons, although no e~rldence of this exists with the Edgewood sub]
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From page 166... ...
1977. Riot control agents .
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From page 167... ...
Biochemi Cal interactions and metabolic fate of riot control agents.
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From page 168... ...
C., Jr., and Cucinell, S .A. Some biological reactions of riot control agents.
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From page 169... ...
Skln sensltlzation potential of the riot control agents CA, DM, CN, and CS in guinea pig8.
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From page 170... ...
A clinicopathologic study of the effects of riot control agents on monkeys.
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From page 171... ...
In juries have resulted f rom their careless use . As of June I, 1975, pen guns were classified as firearms and placed under the controls and restrictions of the Gun Control Act of 1968 by the Bureau of Alcohol, Tobacco, and Firearms, Department of the Treasury.
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From page 172... ...
Only one died. In another test, 20 guinea pigs, eight dogs, and eight monkeys were given a cumulative Ct of 88,000 fig min/m3 in 10 daily exposures; few animals died.
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BallantyDe and Swanston4 examined the acute toxicity of CN administered by several routes in mice, rats, guinea pigs, and rabbits. Tables 4-21 and 4-22 present the results for oral, intravenous, intraperitoneal, and inhalation exposures.
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~ol I I I I l ' I I I I I I I I I I 1 1 1 1 _ ,.
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. tones 1 ly, and Intravenous ly Doaege, LD,o ( 5Z conf idence Route Species mg/kg limite)
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From page 176... ...
The results were as follows: Eyes: O . 5 mg -- no ef fee t 1.0 mg -- transitory conjunctivitis 5.0 mg -- cor~eal opacity Skin: 5.0 mg -- erythema and necrosis Rothberg33 studied sensitization to CN in guinea pigs.
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From page 177... ...
male and female rats and in B6C3F1 hybrid male and female mice. Six groups of 20 rats and mice divided equally tee ' weed sexes were exposed to a CN aerosol by inhalation at concentrations of O (control)
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From page 178... ...
2,20 Acute injuries of the eyes, primarily from ef fects of blast and missiles, may occur from tear-gas weapons, such as pen guns. The intestate ef fects of these in juries te..lude swelling and edema of the lids, with penetration of skin, conjunctive, cornea, aclera, or globe by gunpowder and CN ; conjunctival ischemia and chemosis; corneal edema, erosion, inflammation, or ulceration; and focal hemorrhage.13, 20 In; uri es in Conf ined S paces The use of CN in open spaces, as in riot control, causes copious lac rimation, rhinorrhea, and a burning sensation in exposed skin.
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From page 179... ...
CN aerosols were generated from acetone solutions and had a mass median diameter of about 0.6 ~m. Such particles can reach and remain in the deep region of the respiratory tract.
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From page 180... ...
TEAR~S WEAPONS Forensic Aspects The most popular weapon for personal protection against assaults and robberies over ache last 20 yr i8 the tear-gas pen gun, a simple' inexpensive, inconspicuous device resembling a pen that carries a cartridge loaded with Mace. The load is a 1:1 mixture of CN and silicic anhydrlde; the propellant is smokeless powder.
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From page 181... ...
Rothberg's demons~cration of this in guinea pigs has ample confirmation in cii~cai reports of sensitization in man.33 Penneys et al.29 reported treatlog two patients for allergic contact dermatitis, each having had two or more esposures to the agent. In the course of treatment, one patient was given a patch test with Mace (a formulation containing CN)
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From page 182... ...
. Between 1958 and 1972, 99 Herman subjects underwent experimental exposures to CN at Edgewood Arsenal.
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From page 183... ...
Five of the ~ 968 dermal-exposure sub jects had normal results of laboratory analyses including urinalysis, complete blood count , blood urea nitrogen, alkaline phosphatase, and serum glutamic oxalotransferase -- 7 d after exposure. In summary, among the 68 subjects from Edgewood on whom there are data, there were probably no permanent ocular or pulmonary induries.
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From page 184... ...
Riot control agents. Biomedical and health aspects of the use of chemicals in civil disturbances.
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From page 185... ...
Deneal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity tn guinea pigs.
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From page 186... ...
and Cucinell, S.A. Some biological reac~cions of riot control agents.
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Skin sensitization potential of the riot control agents BBC, DM, CN, and CS in guinea plga .
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Upshall21 exposed pregnant rats and rabbits to CR at several doses and by several routes of administration to test for teratogeni c or embryolethal effects. Inhalation exposure times were 5-7 min for rats and rabbits.
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Rats, rabbits, guinea pigs, and mice were exposed to smokes from grenades, both with and without CR. CR contributed very little to the toxic effects of grenade smokes.
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Guinea pig Fema le 629 ~'5 5-712) Percutaneous Rabbit Female 450 (in corn oil)
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- ~ ~ to to to to to ~ ~ ~ ~ ~ ~ ~ go ·,4 - - - - - o 3: oooo~ ~ ~ x :^ o ~ - o .
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i7 by test ing the ef fee ts of a 51 solut ion of CR ire propylene glycol in the rabbit eye. Owens et al.
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From page 194... ...
The lung surfactant and organelles from which it appears to be derived showed no changes up to 15 d after exposure, when examined by light and electron microscopy. Metabolism ami Physiology Balfour, ~ using tritium-labeled CEt to invest igate uptake aM metabolism, found that both intact cornea of the guinea pig and corneal homogena~ces take up CR readily and metabolize it to a lactam derivative.
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From page 195... ...
Additional studies of Lundy and McKayi6 suggested that the CRluduced increases in heart rate and blood pressure in the cat are deflated by the sympathetic nervous System. Lundy and McKay were aware of the report of Bal~antyne et al.5 describing the cardiovascular change.
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From page 196... ...
Swanston,7 applying procedures developed with CS, measured threshold concentrations of CR in saline solution for produclag blepharospasm: in the rabbit, 7.9 s 10~5 M; in the guinea pig, 3.5 ~ 10~5 M; and in man, 8.6 ~ 10~7 M Threshold concentrations for sensation were 4.9 s '0~7 M in the human eye and 2.l s lo-6 }1 in the human tongue.
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From page 197... ...
Control tests were run with weeer alone and water plus dipropylene glycol monomethyl ether. The control drenches, like other cold showers, caused a mild shock aM a transient increase in blood pressure.
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Several CR subjects exposed in the aerosol chamber commented that CR was milder than "tear gas." The effects of exposure to CR aerosol were transient and predominantly respiratory and ocular. All subjects with aerosol exposures had upper respiratory tract irritation with choking.
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From page 200... ...
The ef fects of skin sprays in the wind tunnel included skin irritation at the exposure site, sometimes accompanied by erythe~a; lacri~tion an conjunctivitis; upper respiratory tract irrltatlon; and, rarely, n.~buess at the exposure site . the ef fects generally began after the exposure and worsened initlal~y.
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From page 201... ...
Riot control agents. Biomedical and health aspects of the use of chemicals in ci^l disturbances.
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The effect of the riot control agent dibenz~b,f) -l,4-osezepine ~ CR)
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From page 203... ...
Furtheneore, because all the early work had been done with DM dispersed in laboratory tents, it was decided to test the results of dispersion from munitions. The immediate responses of various species of an male to DM are as follows: · Hlce , rats, and guinea pigs: The animals become hyperac tine at once.
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From page 204... ...
Punte_ al.7 summarized their observations on mice, ranch, an guinea pigs and stated that animals killed (or dying) after exposure deco OM aerosol at Ct's greater than 500 mg~min/m3 showed hype remia of the trachea, pulmonary congestion, edema, and pneumonia.
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TABLE 4-31 Acute Ichalation ToxiCity of DM Di.~.inated frole · 10: Acetone So lution~ Blise-Calculated Dureeion LCt50. Concentration, of Exposure, btortality Time to Species mg.min/~3 '1~/~3 min Frection Liea~h, ~b !
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From page 206... ...
At the middle expo sure, all superf icial signs of exposure disappeared in 24 h. Two monkeys examined at 12 h showed bronchorrhea, focal pulmonary edema, and pulmonary congestion.
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From page 207... ...
~ examined ache effects of DM on the gastrointestinal tract as a possible factor in poisoning. Using both 1ntravenous and oral lethal doses in dogs, they monitored central venous pressure, right ventricular pressure, cortical electric activity, alveolar C02, respiratory rate, heart rate, electrocardiogram, and gastric activity.
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From page 208... ...
Rothberg9 tested DM for skin sensitization in guinea pigs; the findings were negative. TOXICITY IN HUMANS Ballantynei deacribed the effects of human inhalation exposures to DM as begloning with acute pain in the nose and sinuses.
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From page 209... ...
EF FECT S ON HUMAN SUBJECT S AT EDGEWOOD Sixty-seven human subjects underwent experimental exposure to DM: 29 in 1958 and 38 in 1966-196B, of whom exposure data are available on 23 and 31, respectively. Sub jects were exposed in an aerosol chamber; they wore masks when they entered-, and the masks were often removed after some intervals in the chambe r .
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From page 210... ...
Riot control agents. Biomedical and health aspects of the use of chemicals in civil disturbances.
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From page 211... ...
Skin sensitization potential of the riot control agent~ CA, DM, CN, and CS in guinea pigs.
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From page 213... ...
Table 4-33 shows the concentrations, exposure times, mortality f Factions, and times to death, and Table 4-34 s~ rises the LCtsos .
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From page 214... ...
TABLE 4-33 Mortality of kliseals Exposet to CA Vapor ·t High Concentrations ( 10-day Obeervatioc) e Ourat ion of Ct CoQCeQtr~tioQ, ~sure, Mortality Ti" to Specice oU minje3 ~81m3 mic Praction Death, hb Mouse 6,120 136 4S 1/10 168 8,400 140 60 5/10 144( 5)
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From page 215... ...
740 i8~859 Guinea pig 4, 785 10, 214 -215
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From page 216... ...
Tests of guinea pigs for skin sensitization potential witch CA yield negative results; CN and CS were positive. TOXICITY IN HUMANS Although the human LCtso was arbitrarily set by combining values for eight animal species (Table 4-34)
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From page 217... ...
CA is not a skin irritant or skin senaltizer in animals.
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From page 218... ...
TABLE 4-34 CA Vapor LC&csos for Eight Arrival Speciesa LCtSo, b Species my oin/m3 957: Conf idence Limits Mouse 7,968 7,100 - 8,942 Rat IS, 859 15,151 -23,474 Guinea pig 10,214 8,580 -12,160 Rabbit 8,021 6,714 - 9,582 Monkey 16,287 13,132 -20,201 D°8 12,037 9,161 -15,815 Pig 4,852 3,580 - 6,576 Goat 8,401 7,043 -10,020 All species 11,095 9,661 -12,741 Monkeys -- Monkeys usually were blinking and nabbing their eyes within 1 min. They kept their eyes partially closed most of the time.
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From page 220... ...
Skin sensitization potential of the riot-control; agents CA, DM, CN, and CS in guinea pigs.
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From page 221... ...
Inhalation: rabbit LCLo, 800 mg/m3 for 20 min. Inhalation: guinea pig LCLo, 800 mg/m3 for 20 min.
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From page 222... ...
It has a pungent odor and its effects are evident several hours after exposure. The acute ef facts of PS include burning eye discomfort, lacrimation, headache, photophobia, burning sensat lon in the nose and throat, coughing, nausea ad vomiting with colicky abdominal pain, diarrhea, and occasionally pulmonary edema.
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From page 223... ...
In contrast, flies treated with mustard gas had a frequency of 5.2%. The ses-linked rece8si~re-lethal test in Drosophila continues to be highly regarded in modern genetic toxicology.
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From page 224... ...
Data are not available on 17 subjects exposed to PS irk 1955, 23 in 1956, ntne in 1960, Il in 1965, nine in 1967, three in 1969, and sis in 1971. Apparently, there was minimal gas-mask leakage during the experiments involving the 58 subjects on whom there are records, and the PS had no acute effects on these subjects.
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From page 226... ...
National Cancer Institute .
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From page 227... ...
Absence of lethal effects may well be explained by its powerful odor, which alerts workers to its presence in contaminated areas . Ar~io~al-toxicity data suf fer from variations in the methods used.
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From page 228... ...
U.S. War Department, Chemical Warfare Service, Edgewood Arsenal, Md.
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From page 229... ...
Occupational Safety and Health Administration. Occupational Health Guideline for Chloropicrln, September 1978.
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From page 231... ...
Two reports were obtained, one on animal, the other on human exposures. Punt e _ al.1 compared the eo~lcities of CN, DM, and nonanoyl morpholide in rabbits, rats, mice, and guinea pigs.
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From page 232... ...
TABLE 4-38 Computet Inhalation LD,os for CN, OM, ant Nonanoyl Morphol idea LD,o mg/kgb 5~ R~ts Mice Guinea Pige CN 14.1 58.8 1.1 DN 14.1 17.9 2.4 Nonanoyl morpholide 23.2 104 5. 7 a Dac~ frc~ Punte et al.
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From page 233... ...
Symptoms were relieved in 10-15 min by exposure to fresh air.4 EFFECT S ON HUMAN SUBJECTS AT EDGEWOOD , Ire 1958 ~ 32 sub jects underwent experimental exposure deco nonanoyl morpholide in an aerosol chamber at Edgewood. At least some subjects wore mask.; during exposure.
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From page 234... ...
of 26 subJects esposed ~co nonanoyl morpholide for IS0 s. Reprinted with permlsaion f rom Punte et al .
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From page 235... ...
S Army Chemical Research Laboratory, Edgewood Arsenal, Md.
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From page 236... ...
Attempts to sensitize guinea pigs yielded negative results. Undiluted CHT applied to rabbit eyes caused severe conjunctivitis that cleared in 24 h; there was swelling Of lids, but no corDeal involvement.
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From page 237... ...
No significant changes tn blood pressure, heart rate, or respiration rate were observed . A comparison with CS indicated that CS can produce lung lesions at a Ct of 47,000 mg min/m3 in dogs and 20,000 me min/m3 in moneys.
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From page 238... ...
The compound was therefore judged to be a potent irritant, but relatively harmiese.9 Because of these observations, human volunteers and animals were tested simultaneously at Edgewood. Fourteen men were exposed to various concentrations of CHT to establish an ICtso.
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From page 239... ...
It was reported that CHT was nonmutagenic in a test for dominant lethal mutations in rata . i} Treatment was by inhalation at concentrations of 100 and 4,000 pl/m3; treatment involved single Vermin exposures or five 20-min exposures on consecutive days.
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From page 240... ...
The increase in al kaline phosphatase and the decrease in hemoglobin after CHT exposure are difficult to relate to the exposure. Gi~ren- the available information on CHT and on the Edgewood subjects exposed to the chemical, long-term health effects of the exposure on the sub]
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From page 241... ...
min/md LCt50 ~ ma. min/m3: Guinea pig 36, 439 169, 000 176, 000 Dog 29, 748 57, ~ 71 63, 322 Percutaneous LD,o No data available No data available for dogs, mg/kg a Data f ram Simmons et a' .
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From page 242... ...
TABLE 4-41 Effects of CHT Administered Cutaneously in Nourestrained, Clipped Beagles Decontaminated at 24 hours with Bleach and Watera Sample Compo si t ion, b Dosage mol% Condition ml/kg Results "Control" -- Occluded 0.125 2/2 normal at 24 h f raction 5 0.25 2/2 normal at 24 h Age.
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From page 243... ...
TABLE 4-42 Toxicity of CHT Administered to Skin without Occlusion in Nonrestrained Beagles Held in Saturated Environmenta Mortality Survivor Recovery Time in Environment Dose mI/kg fraction Time,b d . _ 1.5 h: 6 h: Nonatabilized 0.5 0/2 6, 6 I.0 0/2 N.E., 28 Stablllzed 0.5 0/2 N.E., 6 I.0 0/2 6, 20 Nonstabllized 0.5 I/4 6, 7, 23 1.0 3/4 5 Stabilized 0.5 0/4 N.E., 2, 7, 13 I.0 2/4 4, 19 a Data from Simmons _ al.9 b N.E.~neuromuscular effect such as tremors, weakness or atasia noted.
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From page 244... ...
T"~E 4-43 Effect of Deconteeination with Bleach ·nd Water or with Soap Solution ·s~d Water ·t Verious Inter~JlJ after Skin ApplicJtion of CHT ce 1.0 m1/lc to Nonrestrained Bcagles. Deconteminat ion Semple Deconteminant Tiae, min Resul es "Conerot"-fraction 4 (87.5 molX)
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From page 245... ...
T4BLE 4-44 P ~ r c n t e r ~ 1 Tox i c i t y 0 f CHT in Rat, Mouse, and Rabb it Spec ies Roueeb LD,o, mg/kg .
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From page 246... ...
~ Jr. Parenteral toxicity of riot control agents in mice ~ rats ~ and rabbits.
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From page 247... ...
Edgewood Arsenal, Md. November 8, 1977.
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From page 248... ...
Some of the details in connection with exposure of hen volunteere to experimental irritant chemicals are described. Human volunteers were exposed to compounds after review of animal screening data and approval by committees based on a conclusion that the experimental chemic~s were safe for human use.
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From page 249... ...
LACRIMATORY AGENTS The predomloant ef facts of 42 of the 123 irritant chemicals were ocular, including eye irritation, eye closing, lacrimation, and conjunctivitis . Of the 42 lacrimatory agents, 34 caused very mild effected generally eye irritation, sometimes associated with dermal and upper respiratory passage irritation.
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From page 250... ...
In 1963, two subjects underwent short, single exposures to EA 2366, which caused lacrimation and conjunctivitis, respiratory tract irritation and dyspnea, and nausea. Given the available information on subjects exposed to 118539, 123175, 126312, CS36579, and EA 2366 and their short, low~dose exposures, one carrot predict long-term health effects of these agent'.
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From page 251... ...
. Mustard gas is highly reactive and has vesicant and systemic toxic effects.
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From page 252... ...
Reported instances of long-term injury such as carcinogenesis in workers in a Japanese mustard production plant, were associated with exposure at high, long-term dosages. Information is insufficient to project risks associated with smaller exposures to mustard gas; however, serious long-term adverse effects in the small number of soldiers who received one or a few low-dose exposures at Edgewood seem unlikely (except for some cases of permanent scarring)
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From page 253... ...
Like those exposed to mustard gas, the subjects exposed to PS were wearlog gasmasks, and small numbers of soldiers were e Spored to small doses. PS is urn ikely to have produced detectable long-term health ef fects in volunteers exposed at Edgewood.
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From page 254... ...
In t955, it was decided that the most practical source of volunteers would be enlisted men stationed at Army installations in the vicinity of Edgewood Arsenal. It was emphasized that voluntary consent of each human subject was absolutely essential.
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From page 255... ...
Of these, no more than 100 were selected and eventually assigned for a 1-to 2-month period of temporary duty at Edgewood Arsenal. The "incentives" for volunteering consisted of a small monetary allowance (approximately $lO50 a day for temporary duty)
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Key Terms
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information on Chapter Skim is available.