2.2.2 Oral Exposure - GAZA兵器と人間・資料庫 @ wiki

TOXICOLOGICAL PROFILE FOR WHITE PHOSPHORUS -index
▼2 HEALTH EFFECTS
▼▼2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE

2.2.2 Oral Exposure

• 2.2.2 Oral Exposure -2
  • 2.2.2.2 Systemic Effects
• 2.2.2 Oral Exposure -3
  • 2.2.2.3 Immunological and Lymphoreticular Effects
  • 2.2.2.4 Neurological Effects
  • 2.2.2.5 Reproductive Effects
  • 2.2.2.6 Developmental Effects
  • 2.2.2.7 Genotoxic Effects
  • 2.2.2.8 Cancer

(2.2.2.0 preface)

Studies reporting acute oral exposure of humans to white phosphorus were limited to case reports of intentional or accidental ingestion of match heads, rat poison, cockroach poison, firecrackers, or from military operations. Manufacturers of white phosphorus-containing rat poison have claimed that the only active ingredient in the rat poison was white phosphorus (Peacock 1993). It is likely that white phosphorus was the agent producing toxicity following ingestion of cockroach poison, match heads, and fireworks, although the presence of other toxic compounds cannot be ruled out. Many of the case reports involving acute oral exposure of humans to white phosphorus did not report intake levels. High doses of white phosphorus nearly always induced vomiting, expelling much of the ingested white phosphorus from the body. In addition, gastric lavage to remove white phosphorus from the stomach was performed on many poisoned patients. Thus, doses could not be estimated for end points other than vomiting for all but one of the case reports for humans receiving acute oral exposure to white phosphorus.

Several studies reporting intermediate oral exposure of children to white phosphorus were located. In most cases the white phosphorus was administered as a treatment for rickets, but in some cases white phosphorus was administered to healthy children to prevent the development of rickets. In studies reporting the effects of white phosphorus on bones in children, the doses of white phosphorus.. administered (0.026-0.158 mg/kg/day) were several orders of magnitude lower than those reported following intentional or accidental white phosphorus poisoning.

Humans exposed to white phosphorus in the workplace probably ingested some airborne white phosphorus. One retrospective study indicated that oral exposure to white 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.

No studies were located regarding health effects in human or animals after oral exposure to white phosphorus smoke.

2.2.2.1 Death

Numerous case reports of death following acute oral exposure of humans to white phosphorus were located (Diaz-Rivera et al. 1950,196l; Dwyer and Helwig 1925; Hann and Veale 1910; Humphreys and Halpert 1931; McCarron et al. 1981; Rao and Brown 1974; Rubitsky and Myerson 1949; Simmon and Pickering 1976; Talley et al. 1972; Torrielli et al. 1974; Wechsler and Wechsler 1951; Wertham 1932; Winek et al. 1973).

In one case report, circumstances following ingestion of white phosphorus allowed for estimation of dose (Hann and Veale 1910). A woman consumed .3.9 g of rat poison containing 4% white phosphorus, but did not vomit until the second day after the poisoning, and the vomitus at that time was clear. Thus, little or none of the white phosphorus ingested was lost due to vomiting. The estimated single dose was 2 mg/kg/day. Four days after ingesting the rat poison, the woman died. The cause of death was not reported, but autopsy revealed fatty degeneration and cell transformation in the liver (Hann and Veale 1910).

In case reports of 56 individuals intentionally ingesting large quantities of white phosphorus (0.19-6.3 g) in rat poison, 48.2% of the individuals died, with a 90% death rate in patients ingesting .1.57 g of phosphorus (Diaz-Rivera et al. 1950). Because white phosphorus at these oral exposure levels induced rapid vomiting, the doses for these case reports could not be estimated. In patients that died, symptom prior to death included irreversible vascular collapse; cyanosis, ashen skin color, and deep pallor (probably secondary to vascular collapse); coma; abnormal electrocardiogram readings; evidence of extreme liver and kidney damage, and hypoglycemia (possible secondary to liver damage); and delirium, psychosis, and hallucinations (possibly secondary to brain damage). The cause of death was not reported for each patient, but appeared in most cases to be related to irreversible failure of the liver, kidney, brain, and/or cardiovascular system (Diaz-Rivera et al. 1950). In other case reports, autopsy of patients dying from white phosphorus poisoning nearly always revealed severe damage to one or more of those four systems (Diaz-Rivera et al. 1961; Dwyer and Helwig 1925; Hann and Veale 1910; Humphreys and Halpert 1931; McCarron et al. 1981; Rao and Brown 1974; Wechsler and Wechsler 1951; Wertham 1932). In some cases, pulmonary edema and/or congestion were observed at autopsy (Rao and Brown 1974; Wechsler and Wechsler 1951). In studies reporting the specific cause of death, death was attributed to cardiopulmonary arrest (Diaz-Rivera et al. 1950; Rao and Brown 1974; Simon and Pickering 1976; Winek et al. 1973), peripheral vascular collapse (Diaz-Rivera et al. 1950,1961), liver failure (Diaz-Rivera et al. 1961; McCarron et al. 1981), hypoglycemia (Diaz-Rivera et al. 1961), and gastrointestinal hemorrhage and hemorrhagic bronchopneumonia (Winek et al. 1973).

No deaths were reported in children treated with 0.0264.158 mg/kg/day white phosphorus for as much as 26 months (Compere 1930a; Phemister 1918). An infant became seriously ill during treatment with 0.083 mg/kg/day white phosphorus (timed-weighted average dose for 6 months), but recovered entirely following discontinuation of the dose (Sontag 1938). 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.

A mortality rate of 30% was observed in Wistar rats treated by gavage with 6 mg/kg white phosphorus (Torrielli et al. 1974). The oral LD50 value for Charles-River rats was 3.03 mg/kg for females and 3.76 mg/kg for males (Lee et al. 1975). A mortality rate of 20-35% was observed in mice treated by gavage with 5-6 mg/kg (Hurwitz 1972). LD50 values of 4.82 mg/kg and 4.85 mg/kg were reported for female and male mice, respectively (Lee et al. 1975). In two separate one-generation reproduction studies in rats (IRDC 1985; Bio/dynamics 1991), 30-47% and 53%, respectively, of pregnant females treated by gavage with 0.075 mg/kg/day for 145-204 days (intermediate duration) died (or were killed due to morbidity) in late gestation or during parturition; dams exposed to 0.015 mg/kg/day for similar durations did not have an increased mortality rate (IRDC 1985). Compound-related deaths were not observed in male rats exposed to 0.075 mg/kg/day for similar durations (Bio/dynamics 1991; IRDC 1985).

Mortality was observed in 9 of 21 dogs treated once by gavage with an unknown quantity of white phosphorus from firecrackers (Dwyer and Helwig 1925). A cat died 2 hours after ingesting an unknown amount of white phosphorus (Frye and Cucuel 1969).

The LD50 values and doses associated with death in each species and duration category are recorded in Table 2-2 and plotted in Figure 2-2.

---

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE