Bacillus globigii (BG) has been called B. subtilis var niger, B. licheniformis and, most recently, B. atrophaeus. It is a Gram-positive, spore-forming, facultative anaerobe commonly found in dust, soil, and water. It is widely used as a biological tracer and has been shown to produce substances that exhibit antimicrobial activity. In Project SHAD, B.globigii was used to simulate biological warfare agents, because it was then considered a contaminant with little health consequence to humans.

BG is now considered a pathogen for humans. Most infections are associated with the experience of invasive trauma (e.g., catheters, surgery) and/or a debilitated health state; thus it is often encountered as a nosocomial pathogen. BG is also a well-known cause of food poisoning, resulting in diarrhea and vomiting. Infections are rarely known to be fatal, although fatal food poisoning has been reported. Ocular infections, bacteremia, sepsis/septicemia, ventriculitis, and peritonitis are the reported types of infection, and they are usually treated with antibiotics. Cases of long-term persistence or recurrence, or of extended latency, have not been found.

Psychogenic effects specifically of BG exposure are not reported. General psychogenic effects of perceived exposure to biological and chemical weapons are found in the supplement under this contract entitled “Psychogenic Effects of Perceived Exposure to Biochemical Warfare Agents.” Prevention of exposure is conscientious hospital and food hygiene. Treatment involves various regimens of antibiotics; the literature provides inconsistent reports on resistance and efficacy of various antimicrobial agents.

Betapropiolactone (beta-propiolactone; BPL) bears the chemical formula C₃-H₄-O₂ and is identified by the Chemical Abstracts Service Registry Number 57-57-8. It normally appears as a colorless liquid with a pungent irritating odor. Beta-propiolactone is soluble in water and miscible with acetone, chloroform, and ethanol.

Beta-propiolactone has been used as a disinfectant. Capable of sporicidal action, it has been employed in the making of vaccines and in the sterilization of surgical instruments and tissue grafts. Other medical sterilization uses have included the sterilization of blood plasma, water, nutrient broth, and milk. Beta-propiolactone has also served as a versatile intermediate in organic synthesis (acrylic acid and esters). In Project SHAD, it was used as a decontaminant.

Beta-propiolactone is quickly hydrolyzed, metabolized, and excreted by mammals. The hydrolysis products excrete rapidly as well. The main metabolite of beta-propiolactone is lactic acid; its main hydrolysis product is hydracrylic acid. The alkylating action of beta-propiolactone reacts with polynucleotides and DNA to form carboxylethyl derivatives, and this process is regarded as responsible for the genotoxicity characteristic of the compound.

Beta-propiolactone is a significant irritant to several systems and has shown permanent effects on the eye, liver, and kidney. Since the 1960s awareness has grown of the compound’s high tumorigenic, genotoxic, and carcinogenic toxicity in animals, which have been observed to occur even from single-dose administration. Human epidemiological, case-study, and in vivo experimental reports have not been found, however, except for reports of a series of Henry Ford Hospital volunteer experiments in the 1950s using beta-propiolactone as an anti-hepatitis blood plasma disinfectant and the testing in 1968 of beta-propiolactone as a disinfectant in reaginic sera administered for allergy studies. The Henry Ford studies reported that human acute and chronic risks from intravenous administration are negligible; the reaginic sera study found minor irritations, displayed vesicles, discoloration, and papules in the areas of human skin inoculation. Related animal studies at Henry Ford did find chronic cumulative toxicity in animals, manifested as weight loss and necrosis of kidney tubules and the liver.

In acute administration in animals, beta-propiolactone has proven an irritant to skin, eyes, and the respiratory and digestive systems. Dermal contact can elicit blisters and burns. Scarring, erythema, and hair loss have been found on mouse skin after 1–6 administrations of 0.8–100 mg of beta-propiolactone.

Ocular administration in rabbits has resulted in pain, miosis, and corneal opacity, which can become permanent. Respiratory exposure is associated with inflammation of the respiratory tract. Oral ingestion can cause stomach and mouth burns. Acute intravenous administration has resulted in liver necrosis and kidney tubular damage. Systemic

Front Matter (R1-R18)

Summary (1-2)

1 Study Rationale and Overview (3-6)

2 Investigating the Potential Health Effects from Participation in Project SHAD (7-9)

3 An Overview of Project SHAD (Shipboard Hazard and Defense) (10-12)

4 Records-Based Data Sources (13-15)

5 Participant Cohort (16-18)

6 Referent Cohort (19-23)

7 Health Survey (24-32)

8 Analysis Structure (33-38)

9 Mortality Results (39-44)

10 Morbidity Results (45-67)

11 Discussion (68-72)

Appendix A Executive Summaries of Reports on Toxicological or Biological Agents (73-100)

Appendix B Questionnaire (101-118)

Appendix C Material Concerning Outreach Survey (119-124)