4
Red Phosphorus Smoke
BACKGROUND INFORMATION
The military application of phosphorus smokes for environmental screening can contain either white phosphorus or red phosphorus in various matrices (e.g., felt, butyl rubber, or polymer epoxy binders). The compositions of the various phosphorus smokes are similar, being composed primarily of polyphosphoric acids with less than 1% trace levels of organic compounds. This chapter provides an evaluation of the health effects of red phosphorus (RP) in combination with butyl rubber (BR).
Military Applications
Red phosphorus is not manufactured by the U.S. Army and is obtained from sources outside the United States (e.g., People's Republic of China) and shipped to Pine Bluff Arsenal in Arkansas for blending and filling operations for certain munitions and testing (Mitchell and Burrows 1990). In Army field use, red phosphorus smoke is deployed explosively from grenades and mortar shells.
The obscurant portion of the grenades consists of a 95:5 mixture of red phosphorus and styrene-butadiene rubber (butyl rubber) in the presence of methylene chloride, which is later removed by low temperature drying (Lundy and Eaton 1994). Analysis of samples for methylene chloride found none present (Brazell et al. 1984). The purpose of the butyl rubber is to reduce the cloud-pillar effect found with pure red phosphorus. This mixture of red phosphorus and butyl rubber (RP-BR) also contains two other compounds. The red phosphorus is coated with about 1.25% (by weight) of insulating oil, and approximately 1% talc or silica is added to break up and improve uniformity of the pattern.
Red phosphorus is also the major ingredient in mortar rounds used to generate smoke. In that use, it is combined with sodium nitrate and an epoxy binder in a ratio of 80:14:6 parts by weight, respectively.
Physical and Chemical Properties
The red allotropic form of elemental phosphorus is intermediate to the black and white varieties in reactivity. Red phosphorus reacts slowly with oxygen and water vapor and can evolve phosphine gas, which is highly toxic. The reaction is extremely slow at normal temperatures and humidities and is not considered to be a factor in the deployment of phosphorus munitions in military operations. However, this reaction can be catalyzed by metal ions (e.g., iron and copper), which can markedly increase the oxidation rate. The physical and chemical properties of red phosphorus are listed below:
Formula: |
Polymeric (P4)n |
CAS no.: |
7723-14-0 |
Molecular weight: |
123.9n |
Density: |
2.34 g/cm3 |
Melting point: |
Sublimes at 416°C |
Heat of sublimation: |
19.7 kcal/mol |
Ignition temperature: |
280°C in air |
Solubility: |
Insoluble in organic solvents, negligible in water |
Occurrence and Use
Phosphorus is the 11th most abundant element in the earth's crust. It commonly occurs in the lithosphere in igneous, sedimentary, and metamorphic rock. Depending upon the nature of interatomic bonds established during its formation, solid elemental phosphorus can occur in three allotropic forms: black, white, or red.
In the biosphere, phosphorus is an essential nutrient in the formation of structural biomolecules, such as membrane phospholipids; functional macromolecules, such as nucleic acids and adenosine triphosphate; and metabolic intermediates, such as sugar phosphates. Human activities, such as the manufacture and use of detergents, fertilizers, and water softeners, contribute to phosphorus in the environment.
Combustion Products
The combustion products associated with RP-BR have been chemically and physically characterized by the U.S. Army. Table 4-1 summarizes the composition of phosphoric acids in RP-BR smoke. The combustion products of RP-BR and white phosphorus impregnated in felt, also used by the Army to generate an obscuring smoke, are similar under the same burn conditions (Ramsey et al. 1985). The particles are composed primarily of various phosphoric acids present as a complex mixture of polymeric forms with organic compounds and inorganic gases only at trace levels. Phosphorus trioxide is particularly likely to be formed, which is of interest because it reacts with water to form phosphoric
TABLE 4-1 Composition of the Phosphoric Acids in RP-BR Smoke from Static Burn
Component |
Composition % |
Orthophosphate |
22.8 |
Pyrophosphate |
19.6 |
Tripolyphosphate |
13.3 |
Tetrapolyphosphate |
11.5 |
P5-P13 |
32.8 |
Higher polyphosphates |
Low |
Source: Brazell et al. (1984). |
acid and phosphine (Ballou 1981). The relative proportion of the different acids of phosphorus in RP-BR smoke changes with time after it is generated, but the predominate component of the smoke remains phosphoric acid (orthophosphate) (Ballou 1981; Mitchell and Burrows 1990). Only trace amounts of phosphine have been measured in some cases (Ballou 1981).
Measurement of the mass median aerodynamic diameter (MMAD) of RP-BR aerosol particles generated to test the toxicity of the smoke in animals have ranged from 0.4 to 1.6 µm, and geometric standard deviations ranged from 1.5 to 1.9 (Aranyi 1984, Aranyi et al. 1988b; Ballou 1981). All measurements of RP-BR smoke reported or recommended in this chapter are referred to in milligrams of total particulates per cubic meter.
TOXICOKINETICS
No studies were available on the toxicokinetics of RP-BR smoke or its components.
TOXICITY SUMMARY: ELEMENTAL RED PHOSPHORUS
Red phosphorus is a relatively inactive allotrope of phosphorus. Little, if any, significant toxicity appears to be associated with
elemental red phosphorus unless it is contaminated with white phosphorus (Mitchel and Burrows 1990; Lundy and Eaton 1994). No dermal irritation was noted when red phosphorus was applied to the skin of rabbits at doses of 0.5 g per site. Similarly, dermal application of the element to guinea pigs resulted in no skin irritation or sensitization. Interdermal injection resulted in only slight irritation. Doses of 100 mg did not result in rabbit eye irritation. In Fischer 344 rats, the oral LD50 was reported to be greater than 10 g/kg (Mitchell and Burrows 1990).
TOXICITY SUMMARY: RED PHOSPHORUS-BUTYL RUBBER
Effects in Humans
No studies have been conducted on the effects of RP-BR smoke in humans. However, Mitchell and Burrows (1990) estimated that human exposure to RP-BR at concentrations of about 2,000 mg/m3 for longer than 15 min might result in death. They suggested further that acute exposure at concentrations of 1,000 mg/m3 should be considered intolerable and that 700 mg/m3 is the highest tolerable concentration; above that, masks must be worn (Mitchell and Burrows 1990). Others have reported that concentrations exceeding 100 mg/m3 were unendurable for all workers except the ''inured" worker (ACGIH 1991).
Effects in Animals
Dermal Exposures
When air samples of combusted RP-BR were collected using an electrostatic precipitator and the residue (0.1 mL) was instilled in the eyes of rabbits, severe irritation and corneal ulceration were evident. When this same material was administered to the intact
or abraded skin of rabbits clipped free of hair, severe irritation was produced (Weimer et al. 1977).
Inhalation Exposures
One-Time Exposures
Lethality. The concentration lethal to 50% (LC50) of Sprague-Dawley rats that were exposed to RP-BR smoke for 1 hr on 5 consecutive days was estimated to be 2,320 mg/m3 (Aranyi et al. 1988a). In contrast, daily 4-hr exposures for 5 days at lower concentrations (i.e., W 1,000 mg/m3) did not produce significant mortality (Aranyi et al. 1988a). Other reports estimated that a single 1-hr LC50 for rats was approximately 4,000 mg/m3 (Ballou 1981; Shinn et al. 1985). The presence of butyl rubber in the smoke was assumed to be toxicologically insignificant. In both reports, the animals continued to die during the 14-day observation period following exposure, indicating that both acute and delayed effects resulted from these 1-hr exposures. Twenty percent died after a 1-hr exposure at 3,100 mg/m3, and eight of nine died within 2 days of a 1-hr exposure at 8,460 mg/m3 (Ballou 1981). Lethal effects were accompanied by symptoms of respiratory distress, including pulmonary edema, congestion, and atelectasis. Ballou (1981) found that the application of Haber's law (i.e., effects are proportional to the exposure concentration (C) multiplied by the duration (or time, T) of the exposure, or the CT product) predicted lethality of such smokes with a 65% error. Several studies indicate that exposure concentration, instead of the CT product, is the major determinant of lethality over relatively short exposures (Shinn et al. 1985; Aranyi et al. 1988a; Lundy and Eaton 1994).
Weimer et al. (1977) studied the acute effects of a single exposure to RP-BR smoke with a wide range of exposure CT values in three species of animals. For rats, average exposure concentrations ranged from 1,128 to 1,882 mg/m3, and exposure durations
ranged from 60 to 240 min, producing CT values of 67,685 to 451,680 mg·min/m3. For guinea pigs, exposure concentrations ranged from 120 to 2,277 mg/m3, and exposure durations ranged from 5 to 150 min, producing CTs from 45,570 to 451,680 mg•min/m3. For dogs, exposure concentrations ranged from 1,212 to 1,882 mg/m3, and exposure durations ranged from 30 to 240 min, producing CTs from 45,570 to 451,680 mg•min/m3.
Weimer et al. (1977) found the CT products lethal to 50% (LCT50) of rats, guinea pigs, and dogs tested were 222,700, 4,040, and more than 451,700 mg·min/m3, respectively. The exposure time in these studies varied from 5 min to 240 min. No rats died following exposure at 1,128 mg/m3 for 60 min, and 4 of 10 died after exposure at 1,676 mg/m3 for 120 min. For the guinea pig, 4 of 10 died from a 10-min exposure at 352 mg/m3; whereas none died from a 5-min exposure at 120 mg/m3. No deaths occurred among dogs exposed to the highest dose studied (1,882 mg/ for 240 min). These studies indicate that RP-BR smoke is only slightly toxic to the rat and dog, but that the guinea pig is more sensitive. Table 4-2 summarizes the acute lethality data.
Skin and Eye Irritation. Weimer et al. (1977) reported conjunctivitis in rats exposed at 1,813 mg/m3 for 180 min and in dogs exposed at 1,882 mg/m3 for 240 min. No conjunctivitis was apparent 3 days after exposure ended. In the rat, however, that exposure concentration resulted in 9 of 10 deaths over a 6-day period after exposure (Weimer et al. 1977).
Pulmonary Effects. Ballou (1981) found that gross pathology in rats following exposure to high concentrations of airborne RP-BR smoke varied somewhat with concentration, but the pathology consistently involved the laryngeal and proximal tracheal regions. As indicated in Table 4-2, at the highest exposure concentration tested (8,460 mg/m3 for 1 hr), eight of nine animals died within 2 days. Seven of those had significant laryngeal and tracheal lesions that consisted of a fine fibrinlike coat on the laryngeal and proximal tracheal mucosa. Pulmonary edema and hemorrhage were
TABLE 4-2 Acute Lethality of Red Phosphorus-Butyl Rubber Smoke
Species |
Exposure Duration |
Exposure Concentration (mg/m3) |
End Points and Comments |
Reference |
Rat |
1 hr/d, 5 d |
2,320 |
LC50 |
Aranyi et al. 1988a |
Rat |
4 hr/d, 5 d |
W 1,000 |
No significant mortality |
Aranyi et al. 1988a |
Rat |
1 hr |
4,000 |
LC50 |
Ballou 1981; Shinn et al. 1985 |
Rat |
1 hr |
8,460 |
8/9 died with 2 d |
Ballou 1981 |
Rat |
1 hr |
3,100 |
20% lethality |
Ballou 1981 |
Rat |
60 min |
1,128 |
No deaths |
Weimer et al. 1977 |
|
120 min |
1,676 |
4/10 died |
|
|
150 min |
1,625 |
5/10 died |
|
|
180 min |
1,572 |
8/10 died |
|
Guinea pig |
5 min |
120 |
No deaths |
Weimer et al. 1977 |
|
10 min |
352 |
4/10 died |
|
|
15 min |
484 |
7/10 died |
|
|
10 min |
797 |
9/10 died |
|
Dog |
≤ 240 min |
≤ 1,882 |
No deaths |
Weimer et al. 1977 |
prominent. The only rat that survived the exposure had laryngeal edema, small fibrin tags in the central larynx, and essentially no epiglottis. All the other concentrations tested (5,360, 4,330, and 3,150 mg/m3 for 1 hr and 1,530 mg/m3 for 4 hr) also resulted in some lethality in the exposed groups. At all these concentrations, the animals showed marked laryngeal and epiglottal erosion, hemorrhage, ulceration with fibrin deposition, enlarged lymph nodes, edema with pulmonary congestion, and mucus accumulation in the trachea.
In the series of experiments conducted to estimate LCT50 values
for rats, guinea pigs, and dogs, Weimer et al. (1977) stated that the animals were not visible for observation during exposure. Following exposure, however, all animals displayed signs of respiratory distress at all exposure concentrations. The lowest exposure concentrations tested for the rat, guinea pig, and dog were 1,128 mg/m3 for 60 min, 120 mg/m3 for 5 min, and 1,519 mg/m3 for 30 min, respectively. Animals were hypoactive and salivating. As the CT values increased, distress became more marked. Those effects persisted for up to 2 days after exposure.
Following a one-time 3.5-hr exposure of rats at 1,000 mg/m3, Aranyi et al. (1988b) observed a large reduction in pulmonary bacteriocidal activity, from 80% activity in the controls to 35% activity in the exposed group.
Other Effects. Weimer et al. (1977) also reported some extrapulmonary effects following inhalation of RP-BR. Male rats exposed at 1,676 mg/m3 for 120 min had kidney weights that were significantly less than control weights. Also, body weights were significantly lower after exposure at 1,625 mg/m3 for 150 min. Both of those concentrations also produced significant mortality. The authors stated that the gross pathology and histopathological evaluations of the rats, guinea pigs, and dogs failed to show any lesions that could be attributed to the smoke inhalation. No significant changes in blood hematology or chemistry developed in dogs, guinea pigs, or rats that could be agent-related.
Repeated Exposures
Skin and Eye Irritation. Weimer et al. (1980) reported transient ocular irritation in rats exposed to RP-BR smoke concentrations of 0 (control), approximately 22 mg/m3, and approximately 165 mg/m3 for 8 min per day, 5 days per week, for 12 weeks (60 rats per group). During the eighth week, a reddening and swelling of the eyelids was noted in rats at both concentrations. Those effects subsided by the end of the exposure. Several control rats also
displayed similar reddened eyelids. The number of animals with eye irritation exposed to the control, low, and high concentrations of RP-BR smoke was 3, 8, and 14, respectively. Although no statistical analyses were performed, the dose-response relation suggests that this effect was attributable to the RP-BR exposure.
Pulmonary Effects. Weimer et al. (1980) also examined the pulmonary effects of repeated exposures to two concentrations of RP-BR. Two strains of rats (Sprague-Dawley and Fischer 344), two strains of mice (Swiss and A-strain), guinea pigs, and rabbits were used. The test animals were exposed for 5 days per week over 12 weeks. The low exposure concentration resulted in a cumulative CT of 10,705 mg•min/m3 and a mean daily exposure CT of 178 mg•min/m3. The mean daily exposure time was about 8 min. At the high exposure concentration, the cumulative CT was 81,691 mg•min/m3; the mean daily exposure CT was 1,319 mg•min/m3, and the mean daily exposure duration was 8 min. The daily exposure concentrations ranged from 8 to 43 mg/m3 (average 22 mg/m3) for the low exposure concentration. For the high exposure concentration, RP-BR concentrations were between 80 and 288 mg/m3 daily (average 165 mg/m3).
During the first 3 days of exposure, both strains of rats displayed an increase in breathing rates following exposure to either concentration. Although histological changes were observed in the lungs, trachea, upper respiratory tract, and other organs in both rats and mice, Weimer et al. (1980) stated that these changes were not unlike those observed in the controls. Moreover, the changes were sporadic, and the incidence or severity of the changes was not related to the exposure concentration. The authors concluded that the pathological changes identified could not be attributed to exposure to the smoke. Some of the animals were held for 24 months in clean air after the exposure. No evidence of latent toxic effect or exposure-related tumor formation was found that could be agent-related. However, no long-term cancer bioassays have been conducted on RP-BR smoke aerosol.
At both concentrations, the rabbits and guinea pigs exposed
to RP-BR had a number of morphological lesions in the lung, trachea, nasal turbinates, liver, kidney, heart, testes, ovaries, urinary bladder, and other organs, but these changes also were seen in the controls. Weimer et al. (1980) stated that these changes could not be attributed to the test substance. The high incidence of pathology in the control animals might have resulted from one or more of several factors, including disease, age or source of the animals, or animal housing conditions. Pulmonary function tests performed on exposed guinea pigs indicated that after 3 weeks of exposure, pulmonary resistance decreased at the high and low exposure concentrations, but only in male guinea pigs. This effect was not present following 6, 9, or 12 weeks of exposure. Weimer et al. (1980) concluded that animals exposed repeatedly to RP-BR did not experience short-term or cumulative toxic effects. Thus, the high exposure concentration, 165 mg/m3, could be considered a no-observed-adverse-effect level (NOAEL) for all strains and species of animals tested.
In another set of studies, male and female Sprague-Dawley rats were exposed to RP-BR aerosols ranging in concentrations from 400 to 1,200 mg/m3 for 2.25 hr per day, 4 days per week, for 4 weeks (Aranyi 1983, 1984; Lundy and Eaton 1994). During the exposure, wheezing and labored breathing were observed in the male rats exposed at the high dose. Decreased body weights and reduced food consumption were seen in the male rats during the 4-week exposure, but those conditions returned to normal during the 14-day recovery period.
These authors also examined pulmonary free cells collected by lung lavage and found a slight, but not statistically significant, increase in total number of free cells immediately following exposures at 750 mg/m3 (Aranyi 1983, 1984; Aranyi et al. 1988b). After a 14-day recovery period, the count returned to normal. A significant increase in the protein level in the pulmonary lavage fluid of rats of both sexes after exposure to more than 1,000 mg/m3 indicated pulmonary edema, which was resolved during the recovery period (Aranyi 1984).
The primary lesion of the respiratory tract was terminal
bronchiolar fibrosis, which was evident after exposure at 400 mg/m3 for 3.5 hr per day for 4 consecutive days (Aranyi 1983). The lesion increased in incidence and severity with increasing exposure concentrations and duration, and animals did not exhibit any recovery during the 14 days in clean air. The thickening of the terminal bronchioles and associated alveolar walls was due to the formation of new collagen fibers. Peribronchiolar and perivascular infiltration of eosinophils occurred but regressed during the recovery period (Aranyi 1983). In a separate study, rats exposed at 750 or 1,000 mg/m3 for 2.5 hr per day, 4 consecutive days per week, for 4 weeks resulted in minimal-to-mild terminal bronchiolar fibrosis, but no effect was seen in rats exposed at 400 mg/m3 (Aranyi 1984).
On the basis of these data, investigators conducted two additional studies using the male rat only. The length of exposure was 13 weeks, and the concentrations tested included 50, 180, 300, 750, and 1,200 mg/m3. The exposures were for 2.25 hr per day for 4 days per week (Aranyi 1986; Aranyi et al. 1988a; Lundy and Eaton 1994). Statistically significant decreases in body weights were observed from weeks 1 through 13 in the groups exposed at 750 and 1,200 mg/m3. Food consumption decreased significantly. Of the animals exposed at 1,200 mg/m3, 10.8% died spontaneously or were necropsied in a moribund state. Most of the animals died during the first 2 weeks of exposure and had varying degrees of congestion and small amounts of hemorrhage in the lungs. Animals exposed at 750 and 1,200 mg/m3 that died later in the study had terminal bronchiolar fibrosis and erosions of the laryngeal mucosa with deposition of fibrin on the surface. No exposure-related deaths occurred in the groups exposed at less than 300 mg/m3 (Aranyi 1986).
Any significant changes in pulmonary lavage fluid found after either 4 or 13 weeks of exposure were absent after 8 weeks of recovery in clean air (Aranyi 1983, 1984, 1986; Aranyi et al. 1988a; Lundy and Eaton 1994), indicating that the macrophages returned to their normal state within 8 weeks of exposure. A significant decrease in pulmonary bactericidal activity seen at concentrations
of 300 mg/m3 and above were also completely absent after the recovery period (Aranyi et al. 1988b).
Histologically, the primary exposure-related change seen after termination of the studies was the presence of terminal bronchiolar fibrosis, resulting in a thickening of the alveolar walls and of the most distal portions of the terminal bronchioles at the site where they join the alveolar sacs. Microscopic examination of the lungs showed that at 2 weeks of exposure, 50% of the rats exposed at 750 mg/m3 had minimal fibrosis, and all of the rats exposed at 1,200 mg/m3 had minimal to mild fibrosis. All rats had fibrosis after 4 weeks of exposure at 750 and 1,200 mg/m3 . After the completion of the 13-week study, 100% of the rats exposed at 750 mg/m3 and higher and approximately 50% of the rats exposed at 300 mg/m3 had terminal bronchiolar fibrosis. Minimum fibrosis was found in approximately 25% of the rats exposed at 180 mg/m3. At 50 mg/m3, the lowest concentration tested, no changes were found. The NOAEL for terminal bronchiolar fibrosis from exposure to RP-BR was 50 mg/m3, and the lowest-observed-adverse-effect level (LOAEL) was 180 mg/m3 (Aranyi 1986; Aranyi et al. 1988a).
Biochemical Effects. In the studies of Sprague-Dawley rats exposed to RP-BR aerosols at concentrations ranging from 400 to 1,200 mg/m3 , 2.25 hr per day, 4 days per week, for 4 weeks (Aranyi 1983, 1984), decreased cholesterol and blood urea nitrogen (BUN) values were seen in all RP-BR-exposed males (750 mg/m3 was the lowest concentration tested). In addition, concentration-related decreases in BUN, cholesterol, and triglycerides levels were seen in all RP-BR-exposed females immediately after exposure (400 mg/m3 was the lowest concentration tested). After the recovery period, only female rats exposed at concentrations of 1,000 mg/m3 showed significantly decreased cholesterol and triglyceride levels, and female rats exposed at more than 750 mg/m3 showed decreased BUN levels.
Immunological Effects. In the same studies using the 4-week
exposure period (Aranyi 1983, 1984; Lundy and Eaton 1994), at concentrations of 750 mg/m3, the white-blood-cell (WBC) counts decreased in male rats by the end of the exposure. Increased blood lymphocytes were also seen at the same concentration in the female rats during and after the recovery period. No treatment-related histopathological changes were found outside the respiratory tract (Aranyi 1983, 1984; Lundy and Eaton 1994).
Significant increases in adenosine 5'-triphosphate (ATP) levels in macrophages lavaged from the lung, expressed as ATP/105 cells or ATP/total protein, were observed immediately after the last exposure at 750, 1,000, and 1,200 mg/m3 for male rats and at 400 and 750 mg/m3 for female rats in the 4-week exposure experiments (Aranyi 1984). After recovery, ATP/total protein from male rats exposed at the high dose remained increased, whereas ATP/105 cells and ATP/total protein were increased in macrophages from female rats exposed at 1,000 mg/m3 . A consistent finding was decreased activity of the plasma membrane-associated ectoenzyme 5'-nucleotidase in macrophages in rats exposed at a concentration of at least 750 mg/m3 (Aranyi 1984; Aranyi et al. 1988b). In addition, macrophages of male rats tested after the 14-day recovery also had decreased alkaline phosphatase activity. Decreased activity of 5'-nucleotidase and alkaline phosphatase in macrophages has been associated with enhanced in vitro antitumor and antiviral activity (Lundy and Eaton 1994). These data suggest that a change in alveolar macrophage populations might be induced by exposure to RP-BR that activated these cells (Aranyi et al. 1988a). ATP levels and 5'-nucleotidase activity had returned to normal when the recovery period was extended to 8 weeks. In the 13-week exposure paradigm, increased cellular ATP levels occurred at the lowest exposure concentration tested (300 mg/m3), but decreased activity of 5'-nucleotidase occurred only at exposure concentrations of 750 mg/m3 or higher (Aranyi et al. 1988b).
Neurobehavioral Effects. Of the neurobehavioral variables studied, only locomotor activity was significantly affected by the exposure. Male rats showed increased motor activity at all concentrations
and incomplete recovery after 2 weeks at some concentrations. Females showed a trend toward increased activity but no evidence of such effect after the recovery period (Aranyi 1983, 1984).
Reproductive and Developmental Effects. Weimer et al. (1980) exposed Sprague-Dawley rats 5 days per week for 10 weeks to RP-BR at concentrations of 132 or 1,186 mg•min/m3 and observed no dominant lethal or single-generation reproductive effects. The mean daily exposure duration was approximately 8 min (Weimer et al. 1980; Lundy and Eaton 1994). Weimer et al. (1980) also exposed pregnant rats 5 days per week from gestation days 6 through 15 to RP-BR smoke at 132 or 1,186 mg•min/m3. The mean daily exposure duration was 8 min. The fetuses were examined for skeletal and visceral anomalies. No dose-related increases were seen in any malformation or variations. In a single-generation study using the same exposure concentrations, offspring body weights were decreased on postnatal day (PND) 1 in the high-dose group, with a rebound in body weights in these pups at PNDs 14 and 21. Low-dose male and female offspring were heavier than controls at PNDs 4 to 21 (Weimer et al. 1980). No information was provided on body-weight gain or fertility in adults or on viability, survival, or lactation indices for the above studies. In a separate 12-week exposure study, nonpregnant Sprague-Dawley females in the high-dose group exhibited a significantly lower weight gain after 4 weeks of exposure than females in the control or low-dose groups (Weimer et al. 1980). No effects were reported on testicular toxicity in any of these studies. However, it is not clear what fixative was used to judge histopathology, and formalin fixative is inadequate for testicular tissue. Because of the sparse data, a NOAEL cannot be established in terms of possible male and female reproductive toxicity.
Carcinogenic and Mutagenic Effects. No long-term carcinogenicity studies for RP-BR smokes have been conducted. Micronucleus analysis was performed on bone-marrow polychromatic and normachromatic red blood cells (RBC) and on circulating RBC of
female rats exposed 8 times over a 2-week period to RP-BR at 1,000 mg/m3 for 2.25 hr (Aranyi 1984). The conclusion of the author was that RP-BR is a weak clastogen in the micronucleus test. The results showed a significant clastogenic response in both bone marrow and RBC of rats that were exposed for 2 weeks, but that effect was not found after a 4-week exposure or after a 2-week recovery period. Effects after the 4-week exposure and 2-week recovery period would not be expected because micronuclei are removed from the circulation after 24 to 30 days. The fact that micronuclei are not observed after a 4-week exposure or a 2-week recovery period does not diminish the significance of observations at the end of the 2-week exposure period. These results are consistent with the conclusion that RP-BR is a weak clastogen. These results alone, however, do not allow a conclusion that RP-BR is mutagenic.
Summary of Toxicity Data
Table 4-2 (above) and Table 4-3 (below) summarize the lethal and nonlethal effects of exposure to RP-BR aerosols.
Noncancer Toxicity
Phosphorus smoke aerosols act as irritants because of their high phosphoric acid content. Respiratory irritation and inflammation have been noted in humans and in animal studies.
The effect occurring at the lowest short-term exposure concentration is respiratory distress. Symptoms including labored breathing, hypoactivity, salivation, and redness of the eyes have been reported at exposure concentrations of 1,128 mg/m3 for 1 hr for rats, 1,519 mg/m3 for 30 min for dogs, 1,212 mg/m3 for 90 min for dogs, and 120 mg/m3 for 5 min for guinea pigs (Table 4-3). Reports have indicated that human exposure to concentrations ranging from 100 to 1,000 mg/m3 can be intolerable.
TABLE 4-3 Summary of Nonlethal Effects of Exposure to Red Phosphorus-Butyl Rubber Smoke Aerosol
Category and Species |
Exposure Frequency and Duration |
NOAEL (mg/m3) |
LOAEL (mg/m3) |
End Point and Comments |
Reference |
Effects in Humans |
|||||
Human (workers) |
8 hr/d, 5 d/wk, several years |
— |
100 |
Unendurable except for the ''hardened" worker |
ACGIH 1991 |
Effects in Animals |
|||||
One-Time Inhalation Exposures |
|||||
Skin and Eye Irritation |
|||||
Rat |
180 min |
— |
1,813 |
Conjunctivitis |
Weimer et al. 1977 |
Dog |
240 min |
— |
1,882 |
Conjunctivitis |
Weimer et al. 1977 |
Pulmonary Effects |
|||||
Rat |
1 hr |
— |
3,150 |
Laryngeal and tracheal lesions; pulmonary edema (and some lethality) |
Ballou 1981 |
Rat |
4 hr |
— |
1,530 |
Laryngeal and tracheal lesions; pulmonary edema (and some lethality) |
Ballou 1981 |
Rat |
1 hr |
— |
1,128 |
Respiratory distress; hypoactivity; salivation |
Weimer et al. 1977 |
Rat |
3.5 hr, one time |
– |
1,000 |
Decrease from 80% (control) to 35% bactericidal activity; reversible in clean air (only one exposure concentration tested) |
Aranyi et al. 1988b |
Guinea pig |
5 min |
– |
120 |
Respiratory distress; hypoactivity; salivation |
Weimer et al. 1977 |
Dog |
30 min |
– |
1,519 |
Respiratory distress; hypoactivity; salivation |
Weimer et al. 1977 |
|
90 min |
– |
1,212 |
|
|
Other Effects |
|||||
Rat |
120 min |
– |
1,676 |
Reduced kidney weight (and some lethality) |
Weimer et al. 1977 |
Rat |
150 min |
– |
1,625 |
Reduced body weight (and some lethality) |
Weimer et al. 1977 |
Repeated Inhalation and Ocular Exposures |
|||||
Eye Irritation |
|||||
Rat |
8 min/d, 5 d/wk, 12 wk |
– |
22 |
Transient reddening and swelling of eyelids during 8th wk only |
Weimer et al. 1980 |
Pulmonary Effects |
|||||
Rat (Sprague-Dawley and Fischer) |
8 min/d, 5 d/wk, 12 wk |
165 |
– |
No effects |
Weimer et al. 1980 |
Mice (Swiss and (A strain) |
8 min/d, 5 d/wk, 12 wk |
165 |
– |
No effects |
Weimer et al. 1980 |
Guinea pig |
8 min/d, 5 d/wk, 12 wk |
165 |
– |
No effects |
Weimer et al. 1980 |
Category and Species |
Exposure Frequency and Duration |
NOAEL (mg/m3) |
LOAEL (mg/m3) |
End Point and Comments |
Reference |
Rabbit |
8 min/d, 5 d/wk, 12 wk |
165 |
– |
No effects |
Weimer et al. 1980 |
Rat |
3.5 hr, 4 d |
– |
400 |
Terminal bronchiolar fibrosis |
Aranyi 1983 |
Rat |
2.25 hr/d, 4 d/wk, 4 wk |
♀ : 750 ♂ : 1,000 |
♀ : 1,000 ♂ : 1,200 |
Increased protein in lavage fluid |
Aranyi 1984 |
Rat |
2.25 hr/d, 4 d/wk, 4 wk |
400 |
750 |
Terminal bronchiolar fibrosis |
Aranyi 1984 |
Rat |
2.25 hr/d, 4 d/wk, 13 wk |
– |
300 |
Decreased total cells in pulmonary lavage fluid; reversible in clean air |
Aranyi et al. 1988b |
Rat |
2.25 hr/d, 4 d/wk, 13 wk |
180 |
300 |
Reduced bactericidal activity; reversible in clean air |
Aranyi et al. 1988a,b |
Rat |
2.25 hr/d, 4 d/wk, 13 wk |
50 |
180 |
Terminal bronchiolar fibrosis |
Aranyi 1986; Aranyi et al. 1988a |
Biochemical Effects |
|||||
Rat |
2.25 hr/d, 4 d/wk, 4 wk |
– |
♀: 400 ♂: 750 |
Decrease in cholesterol and BUN levels |
Aranyi 1984 |
Immunological Effects |
|||||
Rat |
2.25 hr/d, 4 d/wk, 4 wk |
400 |
750 |
Decreased white-blood-cell count |
Aranyi 1984 |
A major health concern for repeated inhalation exposures to RP-BR smoke aerosol is development of terminal bronchiolar fibrosis. That condition is irreversible. The induction of fibrosis appears to be influenced by both concentration and duration of exposure. After 2 weeks of exposure, 50% of male rats exposed at 750 mg/m3 had minimal fibrosis, and all the test animals exposed at 1,200 mg/m3 had minimal-to-mild fibrosis. After 4 weeks of exposure, all rats exposed at 750 and 1,200 mg/m3 exhibited fibrosis. After 13 weeks of exposure, 100% of the rats exposed at 750 mg/m3 or more and 30% of the rats exposed at 300 mg/m3 had terminal bronchiolar fibrosis, and 100% of the rats exposed at 180 mg/m3 exhibited minimal fibrosis. At 50 mg/m3, the lowest concentration tested, no changes were found. Based on these studies, the NOAEL for terminal bronchiolar fibrosis in rats was 50 mg/ and the LOAEL was 180 mg/m3.
Carcinogenicity
There is no evidence of carcinogenicity or mutagenicity of RP-BR smoke; however, few tests have been conducted to examine these end points.
EXISTING RECOMMENDED EXPOSURE LIMITS
The American Conference of Governmental Industrial Hygienists (ACGIH 1991) Threshold Limit Values (TLVs), both time-weighted-average (TWA) values (for 8 hr per day, 5 days per week, for 40 years) and short-term exposure limits (STELs), for various components of RP-BR smokes are listed in Table 4-4. ACGIH (1991) recommended the TLV-TWA for phosphoric acid by analogy to comparable experience and data for sulfuric acid. ACGIH (1991) observed that the TLV-TWA is below the concentration that causes throat irritation among unacclimated workers
TABLE 4-4 ACGIH Recommended Exposure Limits
RP-BR Smoke Component |
TLV-TWA |
TLV-STEL |
Phosphine |
0.3 ppm (0.42 mg/m3) |
1.0 ppm (1.4 mg/m3) |
Phosphoric acid |
1.0 mg/m3 |
3.0 mg/m3 |
Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; TLV, Threshold Limit Value; TWA, time-weighted average; STEL, short-term exposure limit. |
and is well below the concentration that is well tolerated by acclimated workers.
SUBCOMMITTEE EVALUATION AND RECOMMENDATIONS
Using the toxicity information described above, the subcommittee developed exposure guidance levels for military personnel exposed during an emergency release and during regular training exercises and for consideration at military-training-facility boundaries to protect nearby communities from emergency or repeated releases of RP-BR smoke.
Military Exposures
Emergency Exposure Guidance Level (EEGL)1
The EEGLs are based on the subcommittee's interpretation of available information in the context of an emergency, when some risk of reversible health effects and discomfort are considered acceptable.
The major toxic end points associated with such short-term exposures would be lethality, respiratory distress and irritation, and pulmonary lesions. All the other effects documented for RP-BR smoke were from studies using longer-term exposures, and extrapolation from those to a 15-min, 1-hr, or 6-hr EEGL would be inappropriate.
The most sensitive response to short-term exposures to RP-BR aerosols is respiratory distress. Data from humans indicate that concentrations as low as 100 mg/m3 can be considered intolerable (Table 4-3). Given the lack of documentation by ACGIH (1991) on how the human LOAEL of 100 mg/m3 was determined, the subcommittee used the animal data to estimate EEGLs. Because the guinea pig might be uniquely sensitive to respiratory irritants, results from this species were not used. Data from the rat and dog indicate a LOAEL for respiratory distress at an exposure concentration of approximately 1,200 mg/m3 for 1 to 1.5 hr (Table 4-3). Using an uncertainty factor of 10 to extrapolate from a LOAEL to a NOAEL and an additional uncertainty factor of 10 to extrapolate from animals to humans, the subcommittee developed a 1-hr EEGL of 10 mg/m3 (i.e., 12 rounded to one significant digit). Assuming that Haber's law applies over relatively short exposure durations (i.e., 15 min to 6 hr), the corresponding 15-min and 6-hr EEGLs (rounded to one significant digit) are 40 and 2 mg/m3, respectively. Therefore, the subcommittee recommends 40, 10, and 2 mg/m3 for 15 min, 1 hr, and 6 hr, respectively, for the EEGLs based on the animal data.
To check their recommendations against the available human information, the subcommittee also estimated an EEGL based on the ACGIH (1991) report. Using a divisor of 10 to extrapolate from a LOAEL of 100 mg/m3 in humans to a NOAEL and assuming the concentration is "intolerable" in an exposure of approximately 1 hr, a 1-hr EEGL is 10 mg/m3. Again applying Haber's law, the corresponding 15-min and 6-hr EEGLs are 40 and 2 mg/m3, respectively. Thus, the EEGLs that the subcommittee developed on the basis of the animal studies are consistent with the human information.
The maximum anticipated total dose for field exposures (i.e., the peak concentration of a single volley of L8A1 grenades) has been estimated to be about 500 mg/m3, and such a cloud would be expected to persist for 1 to 3 min (Weimer et al. 1980). Irritation might be expected following exposure to phosphorus smoke condensates because of the high phosphoric acid content.
Permissible Exposure Guidance Levels (PEGL)2
The PEGL should be similar to the ACGIH TLV-TWA, which appears to protect the worker from occupational exposure. The PEGL is designed to protect specific populations (i.e., military personnel and munitions workers). The combustion products associated with exposure to RP-BR smoke exposure have been characterized chemically. Because the product of concern is primarily phosphoric acid, the existing TLV-TWA for phosphoric acid exposure seems appropriate for military personnel as well. Therefore, establishing another set of exposure limits is not necessary. The PEGL for an exposure of 8 hr per day for 5 days per week (i.e., 40 hr per week) is 1.0 mg/m3.
Public Exposures
Short-Term Public Emergency Guidance Level (SPEGL)3
Assuming that the general population comprises a wide variety of possibly sensitive individuals, an additional uncertainty factor of 10 is appropriate to extrapolate from an EEGL to a level
protective of the general public. Thus, the SPEGLs for a single emergency exposure for RP-BR smoke are 4.0, 1.0, and 0.2 mg/m3 for exposure durations of 15 min, 1 hr, and 6 hr, respectively (i.e., the corresponding EEGL values divided by 10).
Permissible Public Exposure Guidance Level (PPEGL)4
The possibility of repeated contamination of the air during military operations creates the need for establishing some guidance level for the communities in close proximity to Army operations. The Army has estimated that nearby community exposures to smokes and obscurant exposures might be as long as 8 hr per day, perhaps for a lifetime.
The TLV-TWA that has been set for phosphoric acid provides an acceptable concentration to which nearly all workers might be repeatedly exposed, day after day, without adverse effects during their working lifetime. To extend this exposure level to the general population requires the incorporation of an additional uncertainty factor of 10, because the general population might include individuals who are more sensitive to such exposures than are healthy workers.
Dividing the existing TLV-TWA for phosphoric acid of 1.0 mg/m3 by a factor of 10 (for sensitive subpopulations), the PPEGL would be 0.1 mg/m3.
Summary of Subcommittee Recommendations
The subcommittee's recommendations for exposure limits for RP-BR smoke for military personnel are summarized in Table 4-5. The recommendations for RP-BR-smoke concentrations at the boundaries of military-training facilities are summarized in Table 4-6.
TABLE 4-5 EEGLs and PEGL for RP-BR Smoke for Military Personnel
Exposure Guideline |
Exposure Duration |
Guidance Level (mg/m3) |
EEGL |
15 min |
40 |
|
1 hr |
10 |
|
6 hr |
2 |
PEGL |
8 hr/d, 5 d/wk |
1 |
TABLE 4-6 SPEGLs and PPEGL for RP-BR Smoke at the Boundaries of Military-Training Facilities
Exposure Guideline |
Exposure Duration |
Guidance Level (mg/m3) |
SPEGL |
15 min |
4 |
|
1 hr |
1 |
|
6 hr |
0.2 |
PPEGL |
8 hr/d, 5 d/wk |
0.1 |
RESEARCH NEEDS
The subcommittee recognizes the need for further research to better understand the potential toxicity of RP-BR. Research in the following areas will provide better insight into possible health effects of inhalation of RP-BR and help to determine with greater confidence a guidance level that is not overly conservative but is scientifically defensible.
-
Short-term (e.g., 10 min to 8 hr) inhalation studies are needed to evaluate the degree to which Haber's law applies to RP-BR smoke.
-
Research should be undertaken to determine possible reproductive and developmental toxicity in mammals.
-
Studies should be conducted to determine and to identify possible sensitive populations.
-
Performance studies for military personnel operating in a smoke environment could determine if significantly impaired performance could occur.
-
Documentation of the effects of exposure on humans should be developed to the extent possible.
-
Pharmacokinetic and metabolism studies should be conducted to understand the mechanism of toxicity of RP-BR smokes.
-
Further studies on possible mutagenic effects of RP-BR would be appropriate and would aid in clarifying whether this substance is a possible clastogen.
Finally, the subcommittee notes that Army personnel who work with this smoke, trainers in particular, are potentially a rich source of information on the health effects of the smoke. The subcommittee recommends that the Army conduct a prospective study with appropriate controls in which pulmonary-function tests and routine chemistry tests (panel 20 plus Mg and thyroid tests as a minimum requirement) are performed on personnel who are exposed repeatedly to the smoke.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 1991. Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Ed. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio.
Aranyi, C. 1983. Research and Development on Inhalation Toxicologic Evaluation of Red Phosphorus/Butyl Rubber Combustion Products, Phase 2 Report . AD-A158323. IIT Research Institute, Chicago.
Aranyi, C. 1984. Research and Development on Inhalation Toxicologic Evaluation of Red Phosphorus/Butyl Rubber Combustion Products, Phase 3 Report. AD-A173549. IIT Research Institute, Chicago.
Aranyi, C. 1986. Research and Development on Inhalation Toxicologic Evaluation of Red Phosphorus/Butyl Rubber Combustion Products,
Final (Phase 4) Report. AD-A189254. IIT Research Institute, Chicago.
Aranyi, C., M.C. Henry, S.C. Vana, R.D. Gibbons, and W.O. Iverson. 1988a. Effects of multiple intermittent inhalation exposure to red phosphorus/butyl rubber obscurant smokes in Sprague-Dawley rats. Inhalation Toxicol. Premier Issue:65-78.
Aranyi, C., S.C. Vana, J.N. Bradof, and R.L. Sherwood. 1988b. Effects of inhalation of red phosphorus/butyl rubber combustion products on alveolar macrophage responses in rats. J. Appl. Toxicol. 8:393-398.
Ballou, J.E. 1981. Chemical Characterization and Toxicologic Evaluation of Airborne Mixtures, Final Report. AD-A102678. Pacific Northwest Laboratories, Richland, Wash.
Brazell, R.S., J.H. Moneyhun, and R.W. Holmberg. 1984. Chemical Characterization and Toxicological Evaluation of Airborne Mixtures. Chemical and Physical Characterization of Phosphorus Smokes for Inhalation Exposure and Toxicology Studies. Final Report. ORNL/TM-9571. AD-A153 824. Oak Ridge National Laboratory, Oak Ridge, Tenn.
Lundy, D., and J. Eaton. 1994. Occupational Health Hazards Posed by Inventory U.S. Army Smoke/Obscurant Munitions (Review Update). WRAIR/RT-94-0001. AD-A276 774. Walter Reed Army Institute of Research, Washington, D.C.
Mitchell, W.R., and E.P. Burrows. 1990. Assessment of Red Phosphorus in the Environment. Tech Rep. 9005. AD-A221704. U.S. Army Biomedical Research and Development Laboratory, Frederick, Md.
Ramsey R.S., J.H. Moneyhun, and R.W. Holmberg. 1985. The Chemical and Physical Characterization of XM819 Red Phosphorus Formulation and the Aerosol Produced by Its Combustion, Final Report. ORNL/TM-9941. Oak Ridge National Laboratory, Oak Ridge, Tenn.
Shinn, J.H., S.A. Martins, P.L. Cederwall, and L.B. Gratt. 1985. Smokes and Obscurants: A Health and Environmental Effects Data Base Assessment, Phase 1 Report. AD-A185377. Lawrence Livermore National Laboratory, Livermore, Calif.
Weimer, J.T., G. Affleck, J. Preston, J. Lucey, J. Manthei, and F. Lee. 1977. The Acute Effects of Single Exposure to United Kingdom Red Phosphorus Screening Smoke in Rats , Guinea Pigs, Rabbits,
and Dogs. Tech. Rep. ARCSL-TR-77052. Chemical Systems Laboratory, U.S. Army Armament, Munitions and Chemical Command, Aberdeen Proving Ground, Edgewood, Md.
Weimer, J.T., G.E. Affleck, R.L. Farrand, F.K. Lee, and R.J. Pellerin. 1980. The Acute and Chronic Effects of Repeated Exposure to United Kingdom Red Phosphorus Screening Smokes in Rats, Mice, Guinea Pigs, and Rabbits. Tech. Rep. ARCSL-TR-79053. Chemical Systems Laboratory, U.S. Army Armament, Munitions and Chemical Command, Aberdeen Proving Ground, Edgewood, Md.