The National Institute for Occupational Safety and Health (N IO SH ) recommends that employee exposure to dibromochloropropane in the workplace be controlled so that no worker will be exposed to dibromochloropropane in excess of 10 ppb (0.1 mg/cu m) in air. The N IO SH recommendations is to restrict exposure to very low levels that can still be reliably measured in the workplace. The recom mended exposure limit of 10 ppb is above the lowest level at which a reliable estimate of occupational ex posure to dibromochloropropane can be determined at this time. The recommended standard contains recommendations for medical surveillance, informing employees of hazards, sanitation, work practices, la beling and posting, personal protective clothing and equipment, monitoring and recordkeeping.
The recommended standard is designed to pro tect the health and provide for the safety of em ployees for up to a 10-hour shift, 40-hour workweek, over a working lifetime. Compliance with all sec tions of the standard should, at the minimum, sub stantially reduce adverse effects of exposure to dibro mochloropropane in the workplace. The employer should regard the recommended workplace environ mental limit as the upper bondary for exposure and make every effort to keep the exposure as low as possible.
The possible effects on the health of employees chronically exposed to DBCP may include sterility, diminished renal function, and degeneration and cir rhosis of the liver. In addition, ingestion of daily doses of DBCP by mice and rats has been found to result in the appearance of gastric cancers in both sexes of both species and in mammary cancers in female rats. Although an increased risk for cancer has not been seen with inhalation exposures, these results are not definitive, therefore the risk of cancer due to occupational exposure to DBCP remains a continuing concern. There are indications from in vitro experiments that mutagenic effects may occur also, but there has been no study yet of this possi bility with mammalian subjects. Employees should be told of these possible effects and informed that some 20-25 years of experience in the manufacture and formulation of DBCP has not yet called such effects in employees of the pesticide industry to the notice of physicians and epidemiologists. A more detailed review of the known health effects are given in Enclosure 1.
The recommended standard is part of a continu ing series of recommendations developed by NIOSH in accordance with the Occupational Safety and Health Act of 1970. The recommended standard is being transmitted to the Department of Labor, September 2, 1977, for review and consideration in the prepara tion of an emergency temporary standard. If research by NIOSH results in the development of improved methods for sampling and analysis of dibromochloro propane in air from the occupational environment, information regarding the new methods will be for warded to the Department of Labor.

# I. RECOMM ENDATIONS FOR A TEMPORARY EMERGENCY STANDARD FOR OCCUPATIONAL EXPOSURE TO DIBROMOCHLOROPROPANE
The National Institute for Occupational Safety and Health (N IO SH ) recommends that employee exposure to dibromochloropropane (DBCP) in the workplace be controlled by adherence to the follow ing sections. The standard is designed to protect the health and provide for the safety of employees for up to a 10-hour work shift, 40-hour workweek, over a working lifetime. Compliance with all sections of the standard should, at the minimum, substantially reduce the effects of DBCP on the health of em ployees and provide for their safety. The employer should regard the recommended workplace environ mental limit as the upper boundary for exposure and make every effort to keep the exposure as low as possible. The criteria and standard will be subject to review and revision as necessary.
The possible effects on the health of employees chronically exposed to DBCP may include sterility, diminished renal function, and degeneration and cirrhosis of the liver. In addition, ingestion of daily doses of DBCP by mice and rats has been found to result in the appearance of gastric cancers in both sexes of both species and in mammary cancers in female rats. Although an increased risk for cancer has not been seen with inhalation exposures, thescresults are not definitive, therefore the risk of cancer due to occupational exposure to DBCP remains a continuing concern. There are indications from in vitro experiments that mutagenic effects may occur also, but there has been no study yet of this possibility with mammalian subjects. Employees should be told of these possible effects and informed that some 20-25 years of experience in the manufacture and formula tion of DBCP has not yet called such effects in employees of the pesticide industry to the notice of physicians and epidemiologists. A more detailed re view of the known health effects are given in En closure 1.
Sampling methods utilizing both charcoal and Florisil tubes have been reported to NIOSH as acceptable for measurements at the recommended en vironmental limit. However, an evaluation of the suggested methods has not yet been completed by NIOSH. Such a laboratory evaluation should be completed in the first part of FY 78.
"Occupational exposure to dibromochloropro pane" refers to any workplace situation in which DBCP is manufactured, formulated, or stored. All sections of the standard shall apply where there is occupational exposure to DBCP. Section 1 -Environmental (W orkplace Air) (a) Concentration
Dibromochloropropane shall be controlled in the workplace so that no employee is exposed to airborne dibromochloropropane, at a concentration greater than 10 parts per billion (approximately 0.1 m g/cu m) determined as a time weighted average (T W A ) con centration for up to a 10-hour work shift, 40-hour workweek.
(b) Sampling and Analytical Methods The environmental limit represents a concentra tion of dibromochloropropane measurable by reported sampling and analytical methods. Section 2 -Medical Medical surveillance shall be made available to employees as outlined below:
(a) Comprehensive preplacement or initial med ical and work histories with emphasis on reproductive experience and menstrual history.
(b) Comprehensive physical examination with emphasis on the genito-urinary tract including testicle size and consistency in males.
(1 ) Semen analysis to include sperm count, motility and morphology.
(2 ) Other tests, such as serum testosterone, serum follicle stimulating hormone (FSH ), and serum lutenizing hormone (L H ) may be carried out if, in the opinion of the responsible physician, they are indicated. In addition, screening tests of the renal and hepatic systems may be considered.
(3) A judgment of the worker's ability to use positive pressure respirators.
(c) Employees shall be counseled by the physi cian to ensure that each employee is aware that DBCP has been implicated in the production of effects on the reproductive system including sterility in male workers. In addition, they should be made aware that cancer has been produced in some animals. W hile the relevancy of these findings are not yet clearly de fined, they do indicate that both employees and employers should do everything possible to minimize exposure to DBCP.
(d ) Periodic examinations containing the ele ments of the preplacement or initial examination shall be made available on at least an annual basis.
(e) Examinations of current employees shall be made available as soon as practic?ble after the promulgation of a standard for DBCP.
(f) Medical surveillance shall be made available to any worker suspected of having been exposed to DBCP.
(g) Pertinent medical records shall be maintained for all employees subject to exposure to DBCP in the workplace. Such records shall be maintained for at least 30 years after termination of employment. These records shall be made available to the desig nated medical representatives of the Secretary of Health, Education, and W elfare, of the Secretary of Labor, of the employer, the employee, or former employee.

# Section 3 -Labeling and Posting
A label shall be placed on each shipping and storage container of dibromochloropropane and all areas where there is occupational exposure to dibromochloropropane shall be posted.
All warning signs shall be printed both in English and in the predominant language of non-Englishreading workers. Illiterate workers and workers read ing languages other than those used on labels and posted signs shall be informed of the hazardous areas and shall be informed of the instructions printed on labels and signs.
( (1 ) Engineering controls shall be used wher ever needed to keep airborne dibromochloropropane concentrations below the recommended occupational exposure limit. Compliance with this limit may be achieved by the use of respirators under the following conditions only:
(A ) During the time necessary to install or test the required engineering controls.
(B ) For nonroutine operations, such as emergency maintenance or repair activities.
(C ) During emergencies when air con centrations of dibromochloropropane may exceed the recommended occupational exposure limit.
(2) W hen a respirator is permitted by para graph (a )( 1 ) of this section, it shall be selected and used pursuant to the following requirements:
(A ) The employer shall ensure that no employee is exposed to dibromochloropropane be cause of improper respirator selection, fit, use, or maintenance.
(B ) The employer shall establish and en force a respirator program meeting the requirements of 29 CFR 1910.134 as amended.
(C ) The employer shall provide respira tors in accordance with Table 1-1 and shall ensure that the employee uses the respirator provided when necessary.
(D ) Respiratory protective devices de scribed in Table 1-1 shall be those approved under the provisions of 30 CFR 11.
(E ) Respirators specified for use in higher concentrations of dibromochloropropane may be used in atmospheres of lower concentrations.
(F ) The employer shall ensure that res pirators are adequately cleaned and maintained, and that employees are instructed and drilled, at least annually, in the proper use and testing for leakage of respirators assigned to them.
(G ) Respirators shall be easily accessible and employees shall be informed of their location.
(b ) Eye protection Eye protection shall be provided by the employer and used by the employees where eye contact with liquid dibromochloropropane is likely. Selection, use, and maintenance of eye protective equipment shall be in accordance with the provisions of the American National Standard Practice for Occupational and Ed ucational Eye and Face Protection, ANSI Z87. . Unless eye protection is afforded by a respirator hood or facepiece, protective goggles  or a face shield (8-inch minimum) shall be worn at operations where there is danger of contact of the eyes with liquid dibromochloropropane be cause of spills or splashes. If there is danger of liquid dibromochloropropane striking the eyes from under neath or around the sides of the face shield, safety goggles shall be worn as added protection.
(c) Protective Clothing Protective clothing shall be resistant to the pene tration and to the chemical action of dibromochloro propane. Additional protection, including gloves, bib-type aprons, boots, and overshoes, shall be pro vided for, and worn by, each employee during any operation that may cause direct contact with liquid dibromochloropropane. Supplied-air hoods or suits resistant to penetration by dibromochloropropane shall be worn when entering confined spaces, such as pits or storage tanks. In situations where heat stress is likely to occur, supplied-air suits, preferably cooled, are recommended. The employer shall ensure that all personal protective clothing is inspected regularly for defects and is maintained in a clean and satis factory condition by the employee. Section 5 -Informing Employees of Hazards from Dibromochloropropane (a) All new and present employees working where occupational exposure to dibromochloropro pane may occur shall be informed orally and in writ ing of the hazards, relevant signs and symptoms of exposure, appropriate emergency procedures, and proper conditions and precautions concerning safe use and handling of dibromochloropropane. This infor mation should be readily available to all employees involved in the manufacture, formulation, or storage of dibromochloropropane and shall be posted in prominent positions within the workplace.
(b) All employees involved with the manufac ture, formulation, or storage of dibromochloropro pane shall be informed that it has been implicated in human reproductive abnormalities and has induced gastric cancers in animals following oral intubation.
(c) Employers shall institute a continuing edu cation program to ensure that all employees have cur rent knowledge of job hazards, maintenance pro cedures, cleanup methods, emergency procedures, and evacuation procedures. This program shall include at least :
Emergency procedures and drills. Instruction in handling spills and leaks.
Decont? mination procedures. Location and use of firefighting equipment. First-aid procedures, equipment location, and use. Rescue procedures. Confined space entry procedures. Records of such training shall be kept for inspection by authorized personnel as required. This program shall be held for all employees with occupational exposure to dibromochloropropane at intervals not greater than quarterly, or whenever there is a process change.
(d ) Information as required shall be recorded on the "Material Safety Data Sheet," or on a simi lar form approved by the Occupational Safety and Health Administration, U.S. Department of Labor. Section 6 -W ork Practices (a) Emergency Procedures For all work areas where emergencies may occur, the employer shall take all necessary steps to ensure that employees are instructed in and follow the pro cedures specified below and any others appropriate to the specific operation or process.
(1 ) Procedures shall include at least pre arranged plans for re-entry into areas where dibromo chloropropane leaks or spills have occurred for clean up, decontamination, or maintenance purposes.
(2) Evacuation alarm systems shall be pro vided by the employer.
(3 ) Personal protective equipment and cloth ing as specified in Section 4 shall be used by trained personnel essential to emergency operations.
(4) Nonessential employees shall be evacu ated from hazardous areas during emergencies. Per imeters of these areas shall be delineated, posted, and secured. The employees in adjacent areas shall be trained in evacuation procedures if these work areas become involved.
(5) O n!/ personnel trained in the emer gency procedures and protected against the attendant hazards shall shut off sources of dibromochloropro pane, clean up spills, control and repair leaks, and fight fires in dibromochloropropane areas.
(6) F.refighting procedures shall be estab lished for areas where flammable materials are used with dibromochloropropane. Chemical foam, carbon dioxide, or dry chemicals shall be used for fighting fires in areas where dibromochloropropane is present. Proper protective respirators and clothing shall be worn by all personnel in the hazard area until con centrations of airborne dibromocholorpropane have been demonstrated by monitoring to be below the recommended occupational exposure limit.
(7 ) Showers, eyewash fountains, and wash room facilities shall be provided and so located as to be readily accessible to workers in all areas where skin or eye contact with liquid dibromochloropropane is likely. If liquid dibromochloropropane is splashed on the clothing or skin, contaminated clothing shall be promptly removed and the skin washed thoroughly with soap and water. If liquid dibromochloropropane gets into the eyes, they shall be irrigated immediately with copious quantities of running water.
(8) Medical attention shall be provided promptly for any affected worker. Such exposures shall be reported to the immediate supervisor by the affected worker or by a fellow employee.
(b) Control of Airborne Dibromochloropropane (1) Suitable engineering controls designed to limit exposure to dibromochloropropane to that prescribed in Section 1(a) shall be used. The use of completely enclosed processes is the recommended method of control for dibromochloropropane. Local exhaust ventilation may also be effective, used alone or in combination with process enclosure. W hen a local exhaust ventilation system is used, it shall be designed to prevent the accumulation or recirculation of ventilation control or process air in the work room, to maintain dibromochloropropane concentra tions below the limit of the recommended standard, and to remove dibromochloropropane from the breath ing zones of employees. Exhaust systems discharging into outside air must conform with applicable local, state, and federal air pollution regulations. Ventila tion systems shall be subjected to regular preventive maintenance and cleaning to ensure effectiveness, which shall be verified by periodic airflow measure ments at least every 3 months. Measurements of sys tem efficiency shall also be made immediately by personnel properly attired in specific protective equip ment when any change in production, process, or con trol might result in increased concentrations of air borne dibromochloropropane. Tempered makeup air shall be provided to work areas in which exhaus ventilation is operating.
(c) Handling of Dibromochloropropane and General W ork Practices (1 ) W ritten operating instructions and emer gency medical procedures shall be formulated and posted where dibromochloropropane is handled or used.
(2) Prompt medical attention shall be pro vided if there is known or suspected exposure to dibromochloropropane, whether or not symptoms are present.
(3) The employer shall ensure that safety showers, eyewash fountains, and other emergency equipment is in proper working order through reg ularly scheduled inspections performed by qualified maintenance personnel.
(4 ) Dibromochloropropane operating systems shall be inspected daily for signs of leaks by person nel attired in specified protective equipment. All equipment including valves, fittings, and connections shall be checked for tightness and good working order. All newly made connections shall be checked for Jeaks immediately after dibromochloropropane is introduced by trained personnel attired in prescribed personal protective equipment.
(5 ) If there is a leak, the leak shall be cor rected immediately. W ork shall resume normally only after necessary repair or replacement has been completed, the area has been ventilated, and the concentration of dibromochloropropane has been de termined by monitoring to be below the recommended occupational exposure limit.
(6 ) Transportation and use of dibromo chloropropane shall comply with all applicable local, state, apd federal regulations. Strict adherence to the pesticide container label requirements for appli cation and personal protection shall be followed. Additional standards for pesticide use by agricultural workers can be found in 40 CFR 170.
(7 ) W hen dibromochloropropane containers are being moved, or when they are not in use and are disconnected, valve protection covers shall be in place. Containers shall be moved only with the proper equipment and shall be secured to prevent dropping or loss of control while moving.
(8 ) Process valves and pumps shall be read ily accessible and should not be located in pits and congested areas.
(9 ) Containers and systems shall be handled and opened with care. Approved protective equip ment as specified in Section 4 shall be worn whileopening, connecting, and disconnecting dibromo chloropropane containers and systems. Adequate ventilation shall be available to prevent exposure to dibromochloropropane when opening containers and systems.
(10) Personnel shall work in teams when di bromochloropropane is first admitted to a system, while repairing leaks, or when entering a confined or enclosed space.
(d ) W ork Areas (1) Dibromochloropropane Hazard Areas A hazard area shall be considered as any space workers may enter that has physical characteristics and sources of dibromochloropropane that could re sult in air concentrations exceeding the recommended limit. Exits shall be plainly marked and shall open outward. Emergency exit doors shall be conveniently located and shall open into areas which will remain free of contamination in an emergency. At least two separate means of exit shall be provided from each room or building in which dibromochloropropane is stored, handled, or used in quantities that could create a haza'rd.
(2 ) Confined or Enclosed Spaces Entry into confined spaces, such as tanks, pits, process vessels, tank cars, sewers, or tunnels, where there may be limited egress shall be controlled by a permit system. Permits shall be signed by an author ized employer representative certifying that preven tive and protective measures have been followed.
Confined spaces which have contained dibromo chloropropane shall be thoroughly ventilated to en sure an adequate supply of oxygen, tested for dibro mochloropropane and other contaminants, and inspected for compliance with these requirements prior to each entry. Adequate ventilation shall be maintained while workers are in the space. Leakage of dibromochloropropane into the confined space while work is in progress shall be prevented by dis connecting and blanking the dibromochloropropane supply lines. An individual entering confined spaces shall be furnished with appropriate personal protec tive equipment and protected by a lifeline harness tended by another worker outside the space, who shall also be equipped for entry with approved per sonal protective equipment and who has contact with a third party. Communication (visual, voice, signal line, telephone, radio, or other suitable means) shall be maintained by the standby person with the employee inside the confined or enclosed space. A third employee, equipped to proceed to the aid of the other two if necessary, shall have general surveillance of their activities.
(e) Storage (1 ) Storage facilities shall be designed to contain spills completely within a surrounding dike and to prevent contamination of workroom air.
(2 ) Storage of dibromochloropropane in the same area as reactive metals, such as aluminum or magnesium, or as liquid ammonia shall be pro hibited.
(3 ) Storage containers shall be periodically inspected for leakage.
(4 ) Ventilation switches and emergency res piratory equipment shall be located outside storage areas in readily accessible locations which will be free of dibromochloropropane in an emergency.
(f) Spills, Leaks, and W aste Disposal (1 ) If dibromochloropropane leaks or is spilled, the following steps shall be taken:
(A ) Evacuate all nonessential person nel from the area.
(B ) Adequately ventilate the area of the spill or leak to prevent accumulation of the vapor.
(C ) If in liquid form, collect spilled ma terial for reclamation or absorb in vermiculite, dry sand, earth, or similar nonreactive material.
(D ) If in solid form, collect spilled ma terial in the most convenient and safe manner for reclamation or for disposal.
(2 ) Personnel entering the spill or leak area shall be furnished with appropriate personal protec tive equipment. All other personnel shall be ex cluded from the area.
(3 ) AH wastes and residues containing dibromochloropropane shall be collected in dibromochloropropane resistant containers and incinerated or buried in such a manner that no dibromochloropropane or toxic decomposition products are released to the environment. (b ) Appropriate locker rooms shall be available for changing into required protective clothing in ac cordance with 29 CFR 1910.141(e). Clothing con taminated with liquid dibromochloropropane shall be immediately removed and placed in a closed container in a well-ventilated area for later disposal or decon tamination. Employers shall require personnel who work with dibromochloropropane to shower before leaving the workplace at the end of a workday.
(c) Employers shall ensure that employees who handle dibromochloropropane wash their hands thoroughly with soap and water before eating, smok ing, or using toilet facilities.
(d ) The storage, dispensing, preparation, and consumption of food, beverages, or tobacco shall be prohibited in dibromochloropropane work areas.
(e) The employer shall ensure that personnel who launder and clean clothing or equipment con taminated with dibromochloropropane are provided adequate personal protective equipment to prevent exposure and shall ensure that these employees are aware of the potential hazards of exposure to di bromochloropropane. Section 8 -M onitoring and Recordkeeping Requirements (a) Industrial hygiene surveys shall be made in any workplace where dibromochloropropane is han dled, processed, or stored. Records of these surveys, including the basis for concluding that environmental concentrations are below the recommended limit shall be maintained. Surveys shall be repeated every month or whenever a process change is made.
(b ) W here exposure concentrations have not been determined, they shall be determined as soon as practicable after the promulgation of a standard based on these recommendations. (c) Requirements set forth below apply to work areas where there is occupational exposure to dibro mochloropropane.
(1) An adequate number of samples shall be collected monthly for the evaluation of the work environment with respect to the occupational expo sure of the employees.
(2) Environmental samples shall be taken when a new process is installed or process changes are made which may cause an increase in environ mental concentrations. Significantly increased pro duction, relocation of existing operations, interrup tion of normal maintenance schedules, or other func tion which may increase dibromochloropropane con centrations shall require resampling and analysis.
(3 ) The minimum number of representative exposure determinations for an operation or process shall be based on variations in exposures and pro duction schedules and in accordance with the provi sions prescribed in Section 1 (b ).
(4) If initial, periodic, or special evaluations indicate that the recommended limit is exceeded, cor rective engineering or other control measures shall be immediately instituted to ensure the safety of em ployees until a concentration below the occupational exposure limit is achieved. In such cases, sampling of each operation and work location shall be conducted until two consecutive employee exposure measure ments, taken at least 1 week apart, reveal that the employee is not exposed to dibromochloropropane above the recommended occupational exposure limit. Employers shall notify in writing, within 5 days, every employee who is found to be exposed to di bromochloropropane above the recommended environ mental limit.
(d ) Employers or their successors shall maintain records which shall include sampling and analytical methods, types of respiratory protection used, con centrations found, and information concerning ex posure of employees to dibromochloropropane. Each employee shall have access to data on his or her own environmental exposures. Pertinent records of occu pational accidents and environmental exposures within the workplace shall be kept for at least 30 years after the worker's employment has ended. Rec ords of occupational exposures applicable to an em ployee should be included in that employee's medical records. The medical representatives of the Secre tary of Health, Education, and W elfare, of the Sec retary of Labor, of the employee or former employee, and of the employer shall have access to all such records.

# I

# APPENDIX I M ETH O D FOR SA M PLIN G D IBRO M O -CH LO RO PRO PA N E IN AIR
The following method is based on detailed reports from two representatives of the Shell Development Company. These reports have been communicated only by telephone. The method has not been pub lished and has not been evaluated in NIOSH labora tories. The method has been tested by Shell with a number of field samples. Procedure 1. An air sample is collected on a tube of Florisil. 2. If the samples cannot be analyzed immediately after collection, the samples should be stored at -200C. The refrigerated samples may be stored for two weeks or less. 3. The l,2-dibromo-3-chloropropane is desorbed from the Florisil with hexane. 4. Analysis is accomplished with a gas chromato graph equipped with an electron-capture detector.

# Useful Range
The method is applicable to air concentrations ranging from 1 to 100 parts per billion (0.01 to 1 m g/cu m ).

# ATTACHMENT I LITERATURE REVIEW FOR DIBROMOCHLOROPROPANE
Background: 1,2-dibrom o-3 -c h lo ro p ro p a n e (DBCP) has the formula CH.,Br-CHBr-CH2C l. It has a gram molecular weight of 236.36. An amber to brown liquid with a pungent odor, DBCP has a specific gravity of 2.09 at 14C referred to water. It has an index of refraction of 1.553 at 14C for the D-line of the emission spectrum of sodium. DBCP has a vapor pressure of less than 1 mm of Hg at 21C and boils at 199C under a pressure of 760 mm of Hg. It is miscible with aliphatic and aromatic hydrocarbons, isopropyl alcohol, 1,2-dichloropropane, tetrachloroethylene, 1,1,2-trichloroethane, and oils. The undiluted material has no flash nor fire point. Because DBCP has been diluted commonly with kero sene or other flammable solvents, the preparations available in the market place may have flash points in the vicinity of 35-36C (Tagliabue closed cup).
DBCP has been used in agriculture as a nematocide since 1955, being supplied for such use in the forms of liquid concentrate, emulsifiable concentrate, powder, granules, and solid material. Formulations of DBCP were registered for use as fumigant nematocides in 1964 on evidence that residues of the material as such would not remain on harvested raw agricultural commodities and that the only residue would consist of inorganic bromides. Newsome et al. (1977) reported, however, that substantial amounts of DBCP were found in radishes (up to 0.20 ppm) and carrots (up to 1.55 ppm in roots and 0.64 ppm in the tops) grown in soil treated with this fumigant. The estimated use of DBCP in the United States in recent years has ranged from 3.6 million pounds in 1971 to 12.3 million pounds in 1972 (USDA esti mates) .
In 1971,' more than 59% of the DBCP used was applied in the Pacific Coast states (Andrilenas, 1974). The material is sold under such names as Nemagon, Fumazone, Nemafume, Nemaset, and Nematox.
On August 5, 1977, the National Institute for Occupational Safety and Health (N IO SH ) was re quested by the Oil, Chemical and Atomic Workers (O CA W ) union to conduct a health hazard evalua tion at the Oxidental Chemical Company plant in Lathrop, California. This request was made when representatives of OCAW learned that a number of workers at this plant had abnormally low sperm counts.
On August 9 and 10, NIOSH conducted a walk through inspection of the Lathrop plant and met with representatives from the company, the local union, and California OSHA. NIOSH staff also met with Dr. W horton, Univ. of Calif., Berkeley, who had consulted with the company and the union previ ously and who had conducted medical examinations of the affected employees. Medical examinations of a number of additional employees have subsequently been conducted by NIOSH staff in conjunction with Dr. Whorton.
On August 12, the Occupational Safety and Health Administration in a telegram alerted approxi mately 80 manufacturers and formulators to the po tential hazard of worker exposure to DBCP. On August 23, a guideline document detailing suggested work practices was forwarded to these same affected companies.
On August 19, the Director, NIOSH, wrote to the major manufacturers of DBCP requesting infor mation to fully evaluate the extent of the hazard posed by exposure to DBCP.
Animal Toxicity. Torkelson et al. (1961) re ported that results of studies of the toxicity of DBCP for various species of animals by two different labora tories (A and B). Rakhmatulayev (1971)  Rakhmatulayev listed the effects of lethal doses as being brief central excitation followed by depression, analgesia, uncoordinated activity of skeletal muscles, and paralysis of limbs. Torkelson et al. (1961) reported also that DBCP as a 1 r /c solution in propylene glycol or as undiluted liquid dropped into conjunctival sacs of rabbits' eyes produced slight irritation and pain of the conjunctivae and iris. These effects disappeared after 1-2 days. W ashing the eyes with water 30 seconds after contact with DBCP did not alter the conjunctival and iridial responses.
Rakhmatulayev 350 316 Applications of 0.5 ml of DBCP to the shaven backs of 4 rabbits produced slight erythema in abraded areas of skin and no signs of irritation in intact skin (Torkelson et al., 1961). Repetition of such applications resulted in only a slight crustiness of the skin after 20 applications. The dermis and subcutaneous tissue at the site of application in one rabbit had extensive necrosis and infiltration with polymorphonuclear leucocytes upon microscopic ex amination. An unspecified number of other rabbits subjected to repeated, covered applications of a lO'/r solution of DBCP in the methylether of dipropylene glycol to their shaven bellies, the applications being renewed every 24 hours up to a total of 10 applica tions, had no lesions other than slight hyperemia and scaliness of the skin at the site of application. Per cutaneous LD50's for the rabbit were 1400 m g/kg when undiluted DBCP was applied for 24 hours and 500 m g/kg when DBCP was applied as a 10% solu tion in propylene glycol.
Rats reported by Torkelson et al. (1961) to have been exposed to vaporized DBCP were observed to become apathetic, sluggish and ataxic but not to be completely narcotized. Clouding of the cornea or lens was seen with exposures to the higher concentra tions (up to about 400 ppm ). Laboratory A found that the LC50 fell from about 400 ppm with a 1-hour exposure to one of about 110 ppm for a 7-hour expo sure. Laboratory B did not estimate LC50's but ob tained mortalities in groups of rats that suggest a relationship between duration of exposure and LC50 fairly similar to that found by laboratory A within the range of durations of exposure used by the latter group. Laboratory B found that a concentration of about 290 ppm killed 2/12 rats at an exposure dura tion of 12 minutes, 3/12 rats at one of 30 minutes, and 3/12 rats at one of 60 minutes. These values suggest, but do not demonstrate, that the same straight line relationship between log concentration and duration of exposure found by Laboratory A for durations of 1 to 7 hours may not obtain with dura tions of exposure less than 1 hour.
Fifty inhalation exposures lasting for 7 hours, 5 days/week, of male rats to a concentration of DBCP of 5 ppm killed 0/15 animals, one to 10 ppm killed 2/15, and one to 20 ppm killed 10/15. Even the lowest of these concentrations produced a decrease of 18.6% in the mean weight of the testes. This was not a statistically significant decrease. Ex posure to the next higher concentration (10 ppm) produced a statistically significant decrease (49.0% ) in the mean weight of the testes. Exposure to that concentration also resulted in a significant increase in the weight of the kidney (31.7% )-These studies were performed by Laboratory A (Torkelson et al., 1961).
Laboratory B (Torkelson et al., 1961) exposed male and female rats to 50 7-hour exposures to 12 ppm of DBCP. These exposures resulted in the deaths of 8/20 male and of 10/20 female rats, de generative changes in the seminiferous tubules, reduc tion in the number of sperm cells, increase in the proportion of abnormal sperm cells, increase in the number of Sertoli cells in the males, significant in creases in the weights of the kidneys in both sexes with cloudy swelling of the epithelium of the proxi mal convoluted tubules and increased amounts of interstitial tissue in the kidneys of the males, and dilatation of the sinusoids and centrilobular conges tion in the livers of both sexes.
Laboratory B (Torkelson et al., 1961) also gave to guinea pigs and rabbits 66 7-hour exposures to va porized DBCP in a concentration of 12 ppm. These exposures killed no animals but did result in statis tically significant decreases in the mean weights of the testes in both species. Two female monkeys exposed for 50 and 60 times, respectively, to 12 ppm of DBCP developed severe leukopenias and anemias. The concentrations of bromide in the sera of the ex posed rats, guinea pigs, and rabbits ranged between 6.7 and 12.8 m g/100 ml whereas those of the control animals of these 3 species ranged from 0 to 7.8 m g /100 ml. Torkelson et al. (1961) reported also the results from a 90-day feeding study with rats of both sexes. The concentrations of DBCP in the diet were 0, 5, 20, 50, 150, 450, and 1350 ppm. The kidneys of female rats fed diets with concentrations of 20 or more ppm of DBCP and the livers of those fed diets containing 450 or more ppm were significantly heavier than those of the controls. Only those males fed the diet includ ing 1350 ppm of DBCP had kidneys and livers sig nificantly heavier than those of the controls.
These studies revealed that DBCP had two out standing toxic effects in subacute exposures: an antispermiogenic effect in the male and a nephrotoxic effect that occurred in both sexes of the rat, but espe cially in the female. Laboratory B was able to show that neither the adrenocorticotropic hormone (A C T H ), cortisone, nor testosterone altered bene ficially the effect of DBCP on the testes. Indeed, testosterone enhanced the atrophic effect of DBCP.
The final bit of information in the paper by Torkelson et al. (1961) was that men given brief exposure to a concentration of 1.7 ppm of DBCP described a definite, not unpleasant, odor. The auth ors recommended that occupational exposure to DBCP be controlled to hold the airborne concentration of the nematocide below 1 ppm. Rakhmatulayev (1971) also reported results from a subacute (2l/2 months' duration) and a chronic (8 months' duration) experiment using rats and administering DBCP by mouth in doses of 17.5-70 m g7kg (subacute) and .0005-5 m g/kg (chronic). The most sensitive indicators of toxic activity by DBCP in these experiments were reductions in the weight of the testes and in duration of motility of spermatozoa, decreased avidity of leucocytes for en gulfing bacteria and decreased rate of positive con ditioning. These effects were present with the dose of 0.05 mg/kg, but not with that of 0.005 m g/kg, in the chronic exposure study. Faydysh (1973) performed another study of the effect of prolonged administration (5 months) of DBCP in oral doses of 0.05, 0.5, and 5.0 m g/kg. The two highest doses were observed to decrease both the activity of neutrophils in engulfing and digesting bacteria and the concentration of these cells in the blood. These results confirm the report of Rakhmatulayev (1971) mentioned just above. Because phagocytically-mediated immunity is one of the defensive mechanisms of the body against conditions related to proliferation of abnormal cells, these effects of DBCP may contribute to the carcinogenic activity of this compound in experimental animals. Faydysh et al. (1970) and Faydysh and Avkhimenko (1974) studied further the effects of DBCP on testicular function. In the first study, 10 male rats were given daily oral doses of 70 m g/kg of DBCP in sunflower seed oil. Ten other male rats were given corresponding volumes of the sunflower seed oil alone. Five of the rats given DBCP died between days 20 and 25 of the experiment; the other 5 lived through the 45 days of the experiment. At necropsy, all internal organs were pallid and the gastric mucosa was noted to have been thinned. Although the blood was not examined specifically, the authors' description of the general appearance of the internal organs and of the vascular system raises a suspicion that there was marked anemia. The major parenchymatous organs, particularly the liver and kidneys, and the testes had undergone pro nounced necrotic effects. The livers contained areas of cirrhosis replacing necrotised tissue and the spleens had areas of necrosis in both the white and the red pulps. The parenchyma destroyed in the testes also was replaced by scar tissue. Some regenerative ac tivity was visible in the parenchymatous organs. The second paper demonstrated that similar changes could be accomplished by a daily dose of 0.5 m g/kg given during a longer period of time. This suggests that DBCP exerts some relatively, or possibly completely, irreversible action that eventually accumulates to pro duce a deleterious effect on target organs. Reznik and Sprinchan (1975) studied the gona dotropic actions of DBCP in both male and female rats. Single oral doses of 100 m g/kg or daily doses of 10 mg/kg, administered for 4 to 5 months, were used. The single dose produced within one week a decrease in the sperm count in the semen from 4.90.2 m illion/m g to 2.60.3 million /mg. At the same time, there was a decrease in the duration of mortility of the spermatozoa from about 31 minutes to about 15 minutes. In the females, the estrus cycle was prolonged, both estrus and diestrus becoming longer.
The repeated doses of DBCP eventually pro duced effects similar to those that followed the single large dose. By the fourth month of administration, the concentration of spermatozoa in the semen was 2.50.5 m illion/m g vs 4.90.3 m illion/m g in the controls and the duration of motility of the sperma tozoa Was 29 minutes whereas that of spermatozoa from,control rats was 51 minutes. During the first month of daily doses, 24% of the females developed atypical estrus cycles; by the fifth month, this figure rose to 70% . At the same time, the duration of the cycles increased; 57% of the females became acyclic by the fifth month. It is apparent, therefore, that an effect on sperm count in the male may not be the only effect on human fertility from occupational ex posure to DBCP and that the possibility of induction of sterility in female employees needs to be con sidered also.
No experimental study of teratogenic or muta genic activities by DBCP in mammals has been found. Rosenkranz (1975) examined the effects of this sub stance on two strains of E. coli and on two of the tester strains of Salmonella typhimurium: TA 1530 and TA 1538. DBCP was mutagenic for the first of these tester strains but not for the second, indicating that it induces mutations of the base-substitution but not of the frame-shift type. The finding that DBCP inhibited growth of a strain of E. coli deficient in D NA polymerase to nearly 2.4x the extent of its in hibition of that of a strain with a normal complement of the polymerase indicates that its principal effect is on the DNA. These results are reminiscent of those of Vogel and Chandler (1974) in which they found that 1,2-dibromopropane was definitely mutagenic in Drosophila. As pointed out by these latter auth ors, the important property of vicinal 1,2-dibromides is that in solution they readily rearrange to form the very reactive bromonium ions. This ability would not be modified importantly by substitution of a chlorine atom on the third carbon of propane.
The National Cancer Institute undertook in 1972 studies of the possible carcinogenicity of DBCP, as one of a group of halogenated compounds. As early as 14 weeks after the initiation of administration by stomach tube of daily doses of 24 m g/kg of DBCP dissolved in corn oil, 5 times per week, several female rats were found to have palpable mammary tumors (Olson et al., 1973). Female rats given daily doses of 12 m g/kg of DBCP had not developed mammary tumors. After the fourteenth week, the closes were increased to 30 and 15 m g/kg/day. These doses were continued up to a total duration of the experiment of 54 weeks. During this period, 7 males and 11 females of the 50 rats of each sex given each dose of DBCP used in the experiment died without tumors. Seventeen of the male rats and 33 of the females given the high dose developed squamous carcinomas of the forestomach and 12 of the females had adenocarcinomas of the breast. Five female rats given the low dose of DBCP developed mammary carcinomas and 4 males and 14 females developed gastric carcinomas. One male among the 20 rats of each sex used as vehicle controls developed a tumor that was not described more specifically. Groups of 50 male mice given 160 or 80 m g/kg/day of DBCP for 14 weeks, 200 or 100 m g/kg/day for the next 13 weeks, and 260 or 130 m g/kg/day for 25 weeks and numerically similar groups of female mice given 120 or 60 m g/kg/day for the first 14 weeks and thereafter given the same doses as the males developed 14 gastric carcinomas in males and 9 in females on the high dose, and 3 in each sex on the low dose of DBCP. N o mammary carcinomas developed in the female mice and no tumors of any sort developed in the vehicle controls (20 of each sex for each species).
A report in abstract form (Powers et al., 1975) at a later stage of the same study (after 78 weeks) changed the results in a quantitative way only, the incidence of mammary adenocarcinoma in female rats increasing to 54% and that of squamous cell carcinoma of the stomach exceeding 60% in the rats and 90% in the mice.
A draft of the final report of the contractor (Hazleton Laboratories America, 1977) to the N a tional Cancer Institute reveals that male B6C3F1 mice received 160 or 80 m g/kg/day of DBCP by gavage for 11 weeks, 200 or 100 m g/kg/day for 14 weeks and 260 or 130 m g/kg/day for 22 or 33 weeks, respectively. The time weighted average daily doses were 219 m g/kg for the high-dose group and 113 m g/kg for the low-dose group. The female mice of the same strain received 120 or 60 m g/kg/day during the first 11 weeks and thereafter received the same doses as the males. The time-weighted average doses for the females were 209 m g/kg and 109 m g/kg. Osborne-Mendel rats of the two sexes were given identical doses: 24 or 12 m g/kg for the first 9 weeks, 15 m g/kg for 60 weeks (males) or 64 weeks (fem ales), followed by a 5-week observation period for the males, for the low-dose group, and 30 m g/kg for 55 weeks for the high dose group. For both male and female rats, the time-weighted average daily doses, 5 days/week, were 15 m g/kg for the low dose group and 29 m g/kg for the high dose one.
The preliminary estimates are that the growth of male mice decreased slightly after the first 8 weeks on the high dose and after 22 weeks on the low dose. The growth of the females may have decreased after 32 weeks on the high dose. Mortality among the male mice increased after 36 weeks on the high dose and after 38 weeks on the low dose; that among the females increased after 36 weeks on the high dose and after 43 weeks on the low dose. The incidences of gastric cancer in male mice were 93.5% on the low dose and 97.9% on the high dose. No other tumors were reported in the mice but toxic nephro pathy was found in 23.8% and 93.8% of male mice on the low and high doses, respectively.
The similar preliminary estimates for rats are that the growth of the females decreased slightly after 9 weeks on either the low or the high dose. Mortality among the male rats increased after 47 weeks on the high dose and after 60 weeks on the low dose; that among female rats increased after 28 weeks on the high dose and after 31 weeks on the low dose. The incidences of gastric cancer were 76% on the low dose and 59% on the high dose. In the females, adenocarcinoma of the breast appeared in 48% of the rats on the low dose and 62% of those on the high dose. In both sexes of this species, there were appreciable occurrences of other malignant and be nign tumors (50% and 18% in males on the low and high doses, respectively, and 14% and 20% in the females on the low and high doses). The most common of these tumors were hemangiomas and hemangiosarcomas.
Among the control rats, mammary carcinoma occurred in 10% of the female colony controls and in none of the vehicle controls. Hemangiomas or hemangiosarcomas occurred in about 5.3% of male colony control rats and 15% of the females; they appeared in 5.0% of female vehicle control rats and in none of the male ones. Cancer of the forestomach was found in no control rats or mice.
Toxic nephropathy was found in 23-9% of male mice and 28% of female mice on the low dose and in 93.7% of male and female mice on the high dose of DBCP. Among fats, this type of lesion was found in 100% of both male and female rats on the low dose of DBCP and in 98% and 100% of the male and female rats, respectively, on the high dose of this compound.
W ard and Habermann (1974), perhaps using some of the animals from the study just summarized, reported that the squamous cell carcinomas of the forestomach induced in mice and rats by gavage of DBCP directly into the stomach invaded the wall of the stomach and metastasized in peritoneal surfaces, especially in rats. The metastatic tumors frequently were associated with peritonitis and abscesses.
On the basis of these studies with experimental animals, DBCP appears to have only slight irritative r effect on intact skin or serous surfaces of the body, but to be somewhat more irritative of respiratory mucous membranes. In two rodent species, it appears to be carcinogenic, affecting mammary tissue in the female rat and producing invasive gastric carcinomas after direct introduction into the stomachs of either sex of mice and rats. Malignant neoplasms have not been reported in rats exposed to vaporized DBCP in concentrations that killed 40 to 50% of the ex posed animals and that lasted for long enough to allow the appearance of mammary carcinomas in the exposed females if a time course similar to that fol lowing gavage obtained. The likelihood of induc tion of malignancies by occupational exposures to DBCP is difficult to predict from these studies, there fore. It seems possible that, if ingestion of DBCP can be avoided, there will be small, if any, prob ability that exposure to DBCP will induce cancer. On the other hand, no one can be certain at present that this is true. In addition, the undoubted activity of this nematocide in disturbing reproductivity physi ology, which has been demonstrated in the male employee but apparently has not been recognized ir. the female, an d . in producing renotoxic and hepatotoxic effects in rodents indicate that dedicated efforts to minimize exposure to this compound are necessary. There is no good quantitative basis for an occupa tional exposure limit, but the finding by Rakhmatulayev (1971) that repeated daily doses of 0.05 m g/kg of DBCP to male rats eventually produced decreases in the weight of the testes and in the phagocytic activity of the polymorphonuclear leucocytes indicate that the occupational exposure level should be set at a ceiling of 0.1 m g/cu m (O.Olppm). This figure is based on a daily ventilatory exchange of 18 cu m by a 70 kg man during a 10-hour work day. If all the DBCP inhaled were retained in the employee's body, this would yield a daily dose of 0.0257 m g/kg to the standard man.
The draft report of a 90-day study of the inhala tion toxicity of DBCP (Hazelton Laboratories Amer ica, 1976) indicates that both rats and mice exposed for 6 hours a day, on 5 days in each of 13 weeks, to concentrations of this compound just above 1 ppm underwent slight, but definite, changes in the rate of growth and in pellation. These findings indicate that the ceiling recommended gives a probable margin of safety for man of close to 100.
Comparison of the qualitative and quantitative actions of ethylene dibromide (See N IO SH 's Criteria Document for a review) and DBCP demonstrates that, although the two compounds are similar in their abilities to induce gastric cancers by gavage but ap parently not by other routes of administration, DBCP has actions that have not been reported for ethylene dibromide. Furthermore, it appears to be 10 to 20 times as potent as ethylene dibromide.

# D E P A R T M E N T O F H E A L T H , E D U C A T I O N , A N D W E L F A R E PUBLIC HEALTH SERVICE C E N T E R F O R D I S E A S E C O N T R O L N A T I O N A L I N S T I T U T E F O R O C C U P A T I O N A L S A F E T Y A N D H E A L T H R O B E R T A . T A F T L A B O R