Toxicity of white phosphorus

Animal data support the acute oral toxicity of white phosphorus. Mortality rates of > 20%... 

White Phosphorus. There is limited information on the dermal toxicity of white phosphorus. Dermal effects were not reported in humans or animals following inhalation exposure. Very few human studies reported dermal effects following acute ingestion of white phosphorus. 

Information on the developmental toxicity of white phosphorus, other than effects on growing bones, is limited to two oral exposure studies (Bio/dynamics 1991 IRDC 1985), which administered a relatively low dose of white phosphorus. A nonsignificant (p>0.05) decrease in the incidence of viable pups and increase in the incidence of stillbirths was observed in the offspring of rats exposed to 0.075 mg/kg/day. These effects were not observed in a similarly designed study in which rats were exposed to 0.075 mg/kg/day (Bio/dynamics 1991). Anomalies or malformations were not observed in either of these studies. Because these studies used relatively low doses, their usefulness in predicting whether exposure to white phosphorus would result in developmental toxicity is limited. 

White Phosphorus Smoke. The lack of information on the metabolism and mechanism of action of white phosphorus smoke and the limited information on the toxicity of white phosphorus smoke precludes identifying biomarkers of exposure. 

White Phosphorus Smoke. There is no information on populations that would be usually susceptible to the toxicity of white phosphorus smoke. Based on human and animal inhalation studies, it is possible that individuals with pre-existing respiratory problems may be more sensitive. 

Most of the information on the toxicity of white phosphorus in humans comes from case reports of individuals who intentionally or accidentally ingested a single dose of phosphorus that was a component of poison or fireworks. These case reports provide information on acute systemic effects, possible immunological effects, neurological effects, reproductive effects, and death in humans. In addition to these case reports of single exposures, there are several case reports of children ingesting white phosphorus for an intermediate duration these studies provide information on intermediate systemic effects and developmental effects. Information on chronic oral and dermal exposure in humans is limited to occupational exposure studies in which workers were exposed to white phosphorus via inhalation, oral, or dermal routes. Some limited information on chronic systemic effects is available from these studies. There is limited information on the toxicity of inhaled white phosphorus in humans. Several occupational exposure studies are available however, only a limited number of parameters were assessed in these studies. 

White Phosphorus. No information on developmental toxicity in humans was located. In two one-generation reproduction studies, the incidence of developmental effects in rats orally exposed to white phosphorus was not significantly different from the incidence in vehicle-only controls (Bio/dynamics 1991 IRDC 1985). These studies administered relatively low doses of white phosphorus, and additional oral studies utilizing higher exposure levels could help determine the potential developmental toxicity of white phosphorus. Inhalation and dermal studies would provide information on developmental toxicity by these routes. 

White Phosphorus Smoke. There is limited information on the human toxicity of white phosphorus smoke. Respiratory effects have been observed following acute-duration exposure to white phosphorus smoke (Walker et al. 1947 White and Armstrong 1935). 

Sparling DW et al., Toxicity of white phosphorus to waterfowl Acute exposure in mallards, J. Wildlife Dis., 33, 187, 1997. 

With the use of the rapid fire detection and water deluge, there was no mass fire and the mix was ckrped into water for continued fire suppression. Any fire with RP results in the formation of white phosphorus (WP). WP must be covered with water since it ignites spontaneously when exposed to air. Processing studies were conducted to determine the best methods for pollution abatement since UP/water mixtures are toxic at 29 pob for blue gill bream and since high levels of phosphorus [reported as total phosphorus may not be durped into the environment. 

Sparling, D.W., Day, D., and Klein, P. Acute toxicity and sublethal effects of white phosphorus in mute swans, Cygnus olor, Arch. Environ. Contam. Toxicol, 36(3) 316-322, 1999. 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of white phosphorus and white phosphorus smoke. 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. 

Humans occupationally exposed to phosphorus probably ingested some airborne white phosphorus. In a study of 71 humans occupationally exposed to fumes/vapors and paste containing white phosphorus, oral exposure to phosphorus passed from hand to mouth was likely, because the workers constantly handled a paste containing 4-6% white phosphorus, and washroom facilities at the plants were inadequate (Ward 1928). White phosphorus-related deaths occurred in 0 of 44 and 2 of 27 of the workers exposed for intermediate and chronic durations, respectively. In the two cases of death, the workers died from complications related to phossy jaw, a degenerative condition affecting the soft tissue, bones, and teeth of the oral cavity. In this condition, the toxic effects of white phosphorus probably result from the local irritant action of white phosphorus on tissues in the mouth. Thus, white phosphorus paste passed from hand to mouth and the local action of airborne white phosphorus on the oral cavity may have contributed to the development of phossy jaw, and subsequent death, of these two workers. It is not known whether white phosphorus ingested and absorbed into the systemic circulation contributed to the development of phossy jaw in the two workers that died (Ward 1928). Details of this study are provided in Section 2.2.2.2. 

White Phosphorus Smoke. There is limited information on the toxicity of white phosphoms smoke. Based on this information, the respiratory tract appears to be the most sensitive target. Because white phosphoms smoke contains a number of phosphoms compounds and a small amount of white phosphoms, the toxicity of white phosphoms smoke cannot be extrapolated from human and animal studies involving exposure to white phosphoms. 

The lowest LOAEL value (0.083 mg/kg/day) in healthy humans ingesting white phosphorus for an intermediate duration was identified in the Sontag (1938) study. Lower LOAEL values have been identified in children with rickets (Phemister 1918). Because these children had a pre-existing condition, these data were not considered reliable. Other systemic effects and neurological effects were observed at this dose. This study was not selected as the basis of an intermediate-duration oral MRL because it is a case report of a single child and no assessment of hepatic or renal toxicity (liver and kidneys are two primary targets of white phosphorus toxicity) was made. 

Information on exposure levels was not reported in the human chronic-duration studies. A LOAEL value of 0.2 mg/kg/day was identified in a chronic dog study for skeletal effects (Fleming et al. 1942). However, this study was not selected as the basis for a chronic-duration oral MRL because the study authors did not specify which organs were examined, and thus it is not known whether the liver and kidneys (two primary targets of white phosphorus toxicity) were examined. In addition, this LOAEL value is higher than the intermediate LOAEL value for increased mortality in pregnant dams (Bio/dynamics 1991 IRDC 1985). 

No intermediate-duration inhalation MRL was derived. Only one intermediate-duration inhalation study was identified. In this study, rats were exposed to several concentrations of white phosphorus smoke for 15 minutes/day (Brown et al. 1981). The study suggests that the respiratory tract is the most sensitive end point of toxicity. 

White Phosphorus. White phosphorus is highly toxic via the oral route. Many case reports of deaths resulting from intentional or accidental ingestion of white phosphorus in rat and cockroach poison and firecrackers were located (Diaz-Rivera et al. 1950, 1961 Dwyer and Helwig 1925 Hann and Veale 1910 Humphreys and Halpert 1931 McCarron et al. 1981 Rao and Brown 1974 Rubitsky and Myerson 1949 Simon and Pickering 1976 Tally et al. 1972 ... 

The high mortality rates in pregnant rats may indicate a parturition-related sensitivity to the toxic effects of white phosphorus. Upon histopathological evaluation of selected tissues (heart, liver, kidneys, uterus, ovaries, and testes/epididymides), the only finding considered treatment related was an increased incidence of centrilobular liver necrosis in 8/30 treated females (Bio/dynamics 1991). 

These data suggest that the kidneys are one of the primary targets of white phosphorus toxicity. It is likely that white phosphorus, which is absorbed through the lungs and skin, would also affect the kidneys... 

White Phosphorus. Studies have shown that pregnant rats are more susceptible than nonpregnant female and male rats to the lethal effects of white phosphorus during late gestation or parturition. It is not known if pregnant women would also represent an unusually susceptible population. Human exposure to white phosphorus has shown that the liver, kidney, and cardiovascular systems are some of the primary targets of toxicity. Individuals with pre-existing liver, kidney, heart, or circulatory disorders may be unusually susceptible to white phosphorus toxicity. 

White Phosphorus Smoke. There is a limited amount of available information on human toxicity of white phosphoms smoke. These acute-duration human exposure studies monitored for systemic effects following inhalation exposure. Death, systemic effects, and developmental effects have been observed in animals exposed to airborne white phosphoms smoke for acute and intermediate durations. Reproductive and neurological end points have also been monitored following intermediate-duration inhalation exposure. No dermal exposure studies were located. 

The targets of toxicity following dermal exposure cannot be identified because of the limited number of end points examined in the Ward (1928) study. No intermediate-duration dermal bum studies were identified. Inhalation, oral, and dermal (nonbum and bum) exposure studies would be useful to determine the primary targets of white phosphorus toxicity and dose-response relationships. There are populations surrounding hazardous waste sites that might be exposed to white phosphoms for similar durations. 

White Phosphorus Smoke. No chronic-duration inhalation or dermal exposure studies for humans and animals were located. The available intermediate-duration inhalation exposure study (Brown et al. 1981) did not examine carcinogenic end points. Chronic-duration inhalation and dermal exposure studies that examine a number of end points as well as carcinogenicity would be useful in determining the targets of white phosphorus smoke toxicity as well as its carcinogenic potential. 

White Phosphorus Smoke. Decreased body weight and survival were observed in pups exposed to white phosphorus smoke in utero and during the lactation period (Brown et al. 1981 Starke et al. 1982). The authors suggested that these effects on the pups may be the result of impaired suckling. A study that tested this hypothesis would be useful in determining the potential of white phosphorus smoke to induce developmental effects. No dermal developmental toxicity studies were located studies examining this route would be useful in assessing human health risk. 

The human data suggest that the immune system is a target of white phosphorus toxicity however, no information on the potential of white phosphorus to impair immune function is available. Animal studies assessing the results of a battery of immune function tests could be useful in determining the immunotoxic potential of white phosphorus. Information on different routes of exposure could be useful in assessing if effects are route specific. 

White Phosphorus Smoke. Based on the limited available information on the toxicity of airborne white phosphorus smoke, it appears that humans and animals have similar targets of concern. Toxicokinetic studies in a variety of animal species would be useful in determining which animal species is an appropriate model for human toxicity to white phosphorus smoke. 

---