Phosphorus trichloride PROPOSED 1 : 05/ 2002 United States Environmental Protection Agency Office of Pollution Prevention and Toxics PHOSPHORUS TRICHLORIDE (CAS Reg. No. 007719 12 2)

PROPOSED ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs)

"PUBLIC DRAFT"

Federal Register  May 2002 PROPOSED 1: 05/ 2082 PHOSPHORUS TRICHLORIDE (CAS Reg. No. 007719 12 2)

PROPOSED ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs)

Oak Ridge National Laboratory, managed by UT Battelle, LLC, for the U. S. Dept. of Energy under contract DE AC05 000R22725.

2 PHOSPHORUS TRICHLORIDE PREFACE PROPOSED 1: 092002 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92 463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/ AEGL Committee) has been established to identify, review and interpret relevant toxicologic and other scientific data and develop AEGLs for %ligh priority, acutely toxic chemicals.

AEGEs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes to 8 hours. AEGL 2 and AEGL 3 levels, and AEGL 1 levels as appropriate, will be developed for each of five exposure periods (10 and 30 minutes, 1 hour, 4 hours, and 8 hours) and will be distinguished by varying degrees of severity of toxic effects. It is believed that the recommended exposure levels are applicable to the general population including infants and children, and other individuals who may be sensitive and susceptible. The three AEGLs have been defined as follows:

AEGL 1 is the airborne concentration (expressed as ppm or mg/ m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, non sensory effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.

AEGL 2 is the airborne concentration (expressed as ppm or mg/ m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long lasting adverse health effects, or an impaired ability to escape.

AEGL 3 is the airborne concentration (expressed as ppm or mg/ m3) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life threatening health effects or death.

Airborne concentrations below the AEGL 1 represent exposure levels that can produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold levels for the general public, including sensitive subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that certain individuals, subject to unique or idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.

... 111 3 PHOSPHORUS TRICHLORIDE PROPOSED 1: 092002 TABLE OF CONTENTS ... PWlEFAGE ...................................................................... 111 LISTOFAPPENDICES ............................................................ v LISTOFTABLES ................................................................ v EXECUTIVESUMMARY ......................................................... vi 1 . INTRODUCTION ......................................................... 1 2 . HUMANTOXICITYDATA ................................................. 2 2.1 AcuteLethality ...................................................... 2 2.2 NonlethalToxicity ................................................... 2 2.3 Epidemiologic Studies ................................................. 4 2.4 DevelopmentaVReproductive Toxicity ..................................... 4 2.4 Genotoxicity ........................................................ 4 2.6 Carcinogenicity. ..................................................... 4 2.7 Summary .......................................................... 4 3 . ANIMALTOXICITYDATA ................................................. 4 3.1 AcuteLethality ...................................................... 4 3.1.1 Rats ........................................................ 4 3.1.3 Cats ......................................................... 5 3.2.1 Rats ........................................................ 5 6 3.2.3 Cats ........................................................ 6 3.4 Genotoxicity ........................................................ 6 3.6 Summary .......................................................... 7 3.1.2 Guinea pigs ................................................... 5 3.2 Nonlethal Toxicity ................................................... 5 3.2.2 Guineagigs ..................................................

3.3 DevelogmenWRegroductive Toxicity ..................................... 6 3.5 Carcinogenicity ...................................................... 6 ............................................... SPECIAL CONSIDERATIONS 7 7 4.1 Metabolism and Disposition ............................................ 4.2 Mechanism of Toxicity ................................................ 7 4.3 Structure Activity Relationships .......................................... 8 4.4 Other Relevant Information ............................................. 8 4.4.1 Species Variability .............................................. 8 4.4.2 Concurrent Exposure Issues ...................................... 8 iv PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 5 . DATA ANALYSIS AND PROPOSED AEGL 1 .................................... 8 5.1 Summary of Human Data Relevant to AEGL 1 ............................... 8 5.2 SurnmaryofAnimalDataRelevanttoAEGL 1 .............................. 8 5.3 Derivation of AEGL 1 ................................................ 8 6 . DATA ANALYSIS AND PROPOSED AEGL 2 ................................... 9 6.1 Summary of Human Data Relevant to AEGL 2 .............................. 9 Summary of Animal Data Relevant to AEGL 2 ............................... 9 6.2 6.3 Derivation of AEGL 2 ............................................... 10 7 . DATA ANALYSIS AND PROPOSED AEGL 3 .................................. 11 7.1 Summary of Human Data Relevant to AEGL 3 .............................. 11 7.2 Summary of Animal Data Relevant to AEGL 3 ............................. 11 7.3 Derivation of AEGL 3 ............................................... 1B 8 . SUMMARY OF PROPOSED AEGLS ......................................... 12 8.1 AEGL Values and Toxicity Endpoints .................................... 12 8.2 Comparison with Other Standards and Criteria ............................. 13 8.3 Data Adequacy and Research Needs ..................................... 15 9 . REFERENCESCITED ..................................................... 16 APPENDIX A (Derivation of AEGL Values) ........................................... APPENDIX B (Derivation Summaries for Phosphorus Trichloride AEGL Values) ............... 18 24 LIST OF TABLES TABLE 1 . Physical and Chemical Data for Phosphorus Trichloride ....................... 1 TABLE 2 . Acute Lethality of Phosphorus Trichloride in Laboratory Species ................ 7 TABLE 3 . AEGL 1 for Phosphorus Trichloride ...................................... 9 TABLE 4 . AEGL 2 for Phosphorus Trichloride ..................................... 10 TABLE 6 . Extant Standards and Guidelines for Phosphorus Trichloride .................. 13 TABLE 5 . AEGL 3 for Phosphorus Trichloride .............. : ...................... 12 V PHOSPHORUS TRICHLORIDE PROPOSED I: 05! 2002 EXECUTIVE S W R Y Phosphorus trichloride (CAS no. 007719 12 2) is a colorless, clear fuming liquid with a pungent, irritating odor. In the presence of water, the chemical decomposes rapidly in a highly exothermic reaction to phosphonic acid, hydrogen chloride? and pyrophosphonic acids.

No acute lethality data are available in humans. Qualitative data regarding human exposures indicate signs and symptoms of exposure consistent with a highly irritating chemical; ocular and dermal irritation, respiratory tract irritation, shortness of breath, and nausea.

Lethality data in animals are available for rats, cats, and guinea pigs. Cursory studies conducted nearly one hundred years ago in Germany provided preliminary data on lethal and nonlethal effects in cats and guinea pigs following various treatment regimens with inhaled phosphorus trichloride. Although results of the studies indicated the respiratory tract to a be a critical target, the methods and results of these studies were not verifiable. Weeks et al. (1964) reported 4 hr LC,, values of 104.5 ppm and 50.1 ppm for rats and guinea pigs, respectively. An unpublished study by Hazleton Laboratories (1 983) identified a NOAEL of 3.4 ppm and a LOAEL (histopathologic changes in the respiratory tract) of 1 1 pprn following repeated exposure (6 hrs/ day, 5 daydweek for four weeks) of rats. There are no data regarding reproductive/ developmental toxicity, genotoxicity , or carcinogenicity of phosphorus trichloride. Definitive data regarding the mechanism of action of phosphorus trichloride are unavailable. Decomposition products (hydrogen chloride, phosphonic acid, and pyrophosphonic acids) are responsible, at least in part, for the contact irritation reported by humans, and the irritation and tissue damage observed in animal species.

The concentration time relationship for may irritant and systemically acting vapors and gases may be described by Cn x t = k , where the exponent n ranges from 0.8 to 3.5. Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the c" x t = k equation. For 10 minute AEGL 3 values were set at equivalence to the 30 minute values due to uncertainties in extrapolating from the experimental exposure durations of 4 hours and greater.

Quantitative data consistent with AEGL 1 effects were unavailable. Occupational exposures of humans to 1.8 3.6 ppm for 2 6 hours and exposure of rats to 3.4 ppm for 6 hours/ day, 5 days/ week for 4 weeks were without notable effect. These data can be considered a NOAEL for AEGL 1 effects. Because they were derived from controlled experiments, the AEGL 1 values were based upon the Hazleton Laboratories (1983) report. These data as well as the AEGL 1 values are supported by the human experience data reported by Sassi (1952). The interspecies uncertainty factor was limited to 3 because of the concordance of the animal data with the human experience and because the most sensitive species tested (guinea pig) was only about 2 fold more sensitive. The intraspecies uncertainty factor was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. Additional reduction of the AEGL 1 values would be inconsistent with available human and animal data .

Information consistent with AEGL 2 effects were limited to an occupational exposure report and a multiple exposure study with rats. For occupational exposures, there was notable irritation following 2 6 vi 6 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 hours of exposure to approximately 14 27 ppm phosphorus trichloride and more severe but reversible irritation following exposures of 1 8 weeks. Reports providing qualitative information but no exposure terms affirmed the potential for respiratory tract irritation following acute exposures to phosphorus trichloride. Data for rats showed upper respiratory tract involvement following multiple exposures over 4 weeks to 1 1 ppm but not to 3.4 ppm (Hazleton Laboratories, 1983). For development of AEGL 2 values, the 1 1 ppm exposure in rats was considered a NOAEL for AEGL 2 effects. Uncertainty factor application was the same as for the AEGL 1 tier.

AEGE 3 values were developed based upon a 3 foPd reduction of the 4 hr LCs0 (Weeks et al., 1964) as an estimate of the lethality threshold (50.1 ppd3 = 16.7 ppm). A total uncertainty factor adjustment of 10 was used to develop the AEGL 3 values. Animal data indicated some variability in the toxic response to phosphorus trichloride with guinea pigs being the more sensitive among the species tested. Therefore, uncertainty adjustment regarding interspecies variability was limited to 3. To account for intraspecies variability, a factor of 3 was applied. The uncertainty of intraspecies variability was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. The total uncertainty factor of 10 may be justified by human exposure data showing that repeated 2 to 6 hour exposures of up to 27 ppm were without life threatening consequences. Furthermore, the results ofthe Hazleton Laboratories (1 983) study showed no fatalities in rats following multiple 6 hour exposures to 1 1 ppm. The AEGL values for phosphorus trichloride are presented in the table below.

effects; based upon respiratory a Based upon animal data, lethality may be delayed.

References Hazleton Laboratories. 1 983. Subacute inhalation toxicity study in rats  phosphorus trichloride. Final Report. Project No. 241 141. Hazleton Laboratories America, Inc. Unpublished.

Weeks, M. H., Mussleman, N. P., Yevich, P. P., Jacobson, K. H., Oberst, F. W. 1964. Acute vapor toxicity of phosphorus oxychloride, phosphorus trichloride and methyl phosphonic dichloride. Amer. Ind. Hyg. J. 25: 470 475.

vii 7 PMBSPHQRUS TIRICHLQRIDE PROPOSED 1: 05/ 2802 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 25 27 28 29 30 31 32 33 34 35 36 37 38 1. INTRODUCTION Phosphorus trichloride (CAS No. 007719 12 2) is a colorless, clear, finning liquid with a pungent, irritating odor (Fee et al., 1996). Odor threshold information is unavailable for this chemical. The primary use of phosphorus trichloride is for the production of phosphonic acid which, in turn, is used in the production of the herbicide, glyophosphate. Phosphorus trichloride decomposes rapidly in water in highly exothermic reactions. It may also decompose in moist air to hydrochloric acid and hydrated phosphoric acid. The reaction products include phosphonic acid, hydrogen chloride, pyrophosphonic acids, depending on the mole ratio of water and phosphorus trichloride (Fee et al., 1996). If the mole ratio of water and phosphorus trichloride is greater than three, the following reaction will occur.

PCl, + 3H20 + H3PO3 +3HC1 If the mole ratio is 2.5 to 3, reaction products will be a mixture of phosphonic acid and p yrophosphonic acids.

0 0 0 II II II I I I 3PC13 + 8H20 + 9HCl +HPOPH +HPOH HO OH OH TABLE 1. PHYSICAL AND CHEMICAL DATA FOR PHOSPHORUS TRICMLORIDE Conversion factors in Beliles and Beliles, 1993 1 PHOSPHORUS TRICHLORIDE PROPOSED I: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 2. HUMAN TOXICITY DATA 2.1 Acute Lethality No acute lethality exposure response data or case reports are currently available.

2.2 Nonlethal Toxicity Sassi (1952) summarized twenty cases of acute (2 6 hours) or "subacute" (1 8 weeks of work) exposures of workers to phosphorus trichloride. The concentration of phosphorus trichloride in the workrooms ranged from 10 20 mdm3 ( 1.8 3.6 ppm) under normal conditions to 80 150 mg/ m3 ( 14 27 ppm) during periods when the plant was "out of order". The method by which the concentrations were determined was not stated in the translated abstract. For the acute exposures, workers experienced a burning sensation in the eyes and throat, photophobia, chest tightness, dry cough, and slight bronchitis which occurred within 2 6 hours of exposure. For the "subacute" exposures, pharyngeal irritation, coughing, catarrh, dyspnea, and asthmatic bronchitis occur at 1 8 weeks of exposure. Slight increases in body temperature and moderate leucocytosis with neutrophilia were also reported for both exposures. Signs and symptoms reportedly resolved in three to six days for the acute exposures and 10 15 days for the subacute exposures. An abstract by Wason et al. (1982) provided information on an assessment of 27 individuals exposed to phosphorus trichloride released in a railroad accident in 1980. The report indicated that the phosphorus trichloride reacted with water used to disperse the spillage and with air moisture that resulted in the release of phosphoric and hydrochloric acids and phosphorus oxides. No information was provided regarding weather conditions (e. g., wind, temperature, humidity) at the time of the accident. Signs and symptoms were characteristic of exposure to irritants and included burning eyes (86%), shortness of breath (59%), throat irritation (59%), lacrimation (59%), headache (48%), nausea (48%), burning sensation on the skin (44%), and sputum production (41%). Additional effects occurring in 33% or less of the patients included chest pains, wheezing, skin rash, blurred vision, vomiting, and abdominal pain. Lactate dehydrogenase was mildly elevated and serum bilirubin andor serum transaminases were elevated in three individuals. Results of pulmonary hction tests showed greater severity of effect with decreasing distance from the release site. At two months, 86% of the individuals who were within 1/ 16 mile were hypoxemic while only 50% of those 1/ 16 to 1/ 8 mile distance were hypoxemic. There were no exposure durations provided (probably > 1.5 hours as described below) and no exposure concentrations were measured or estimated. Wason et al. (1984) reported in more detail on the railroad accident involving spillage of phosphorus trichloride. The report focused on seventeen individuals (16 men and one woman, ages 2 1 59 years), seven of whom were requested to return for follow up study after the initial medical examination. Signs and symptoms of exposure included eye, skin and throat irritation, nausea, vomiting, blurred vision, headache, and various effects associated with respiration and ventilation (e. g., wheezing, cough, chest pain, dyspnea, sputum production). Chest X rays of all subjects were normal and there was no evidence of hepatic toxicity. Spirometry tests revealed that the subjects (10 of 17) who were closest (within 1 10 yards) to the accident site had a significant decrease in vital capacity, maximal breathing capacity, FEV,, and maximal ventilatory flow rate at 25% of vital capacity. An improvement in the ventilatory changes was seen one month later. Subjects closer to the release site appeared to exhibit signs and symptoms of greater severity. It was also found that patients that were exposed for less than one and a half hours had 2 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 significantly (p= 0.02) greater maximal expiratory flow rates at 25% of vital capacity than did those individuals exposed for longer periods. Water was used to disperse the spilled phosphorus trichloride and, as noted in the report, the actual exposure most likely involved phosphonic acid and hydrochloric acid more so than phosphorus trichloride. Eight subjects were exposed for less than one and a half hours and nine were exposed longer (duration no1 specified). Pulmonary function tests in the seven follow up patients one month after the accident revealed significant improvements in vital capacity, FEV,, peak expiratory flow rate, and maximal expiratory flow rate at 50% vital capacity. Although this report provides information regarding the nonlethal effects in humans following exposure to phosphorus trichloride, there were no data on the exposure concentrations and it is uncertain as to the precise chemicals (i. e., phosphorus trichloride and/ or its degradation products) to which the people were exposed. A NIOSH health hazard evaluation of workers at the FMC plant in Nitro, West Virginia revealed that those with known repeated exposures to phosphorus oxychloride and/ or phosphorus trichloride experienced a significantly higher (p< O. OO 1) prevalence (65%) of occasional respiratory symptoms (chest tightness, wheezing, difficulty breathing) compared to unexposed workers (5%) (Tharr and Singal, 1980). However, no correlation was found between results of pulmonary function tests on the workers and exposure to these chemicals. The study utilized 37 exposed workers and 22 unexposed workers. Most air samples were below detection limits although one employee (with respiratory protection of a chlorine gas mask) was exposed to 6 mg phosphorus trichloride/ m3 (1 ppm) for one hour during a truck loading operation (no effects were reported for this individual).

workers from the aforementioned FMC Corp. group revealed that half of the exposed workers reported significantly (p< O ,002) more episodes of respiratory effects (wheezing, breathlessness, and chest tightness) compared to the unexposed workers who reported no such effects (Moody, 1981). Results of pulmonary function tests did not reveal significant findings regarding effects of phosphorus trichloride (or phosphorus oxychloride) exposure. No significant difference in pulmonary function (FEV,) was found in the exposed workers vs the unexposed workers over a two year period. The small sample size, however, reduces the power of the study to detect such changes and, therefore, compromises the apparent negative finding. Although lacking exposure terms, there is information regarding accidental releases of phosphorus trichloride in Illinois (pers. comm.). Two significant releases of phosphorus trichloride occurred in 1988 fi om a chemical plant in Sauget, Illinois. The first, on April 17, resulted from overfilling a railroad tanker, with an estimated 6,000 12,000 pounds released in the railroad yard. The plume caused the evacuation of approximately 22 square blocks, and 417 citizens of neighboring Rush City and East St. Louis, Illinois reported to area hospitals for treatment. Two of these citizens were admitted overnight and subsequently released. Eye and respiratory irritation were the main symptoms reported. The second incident resulted from failure of a rupture disk during start up procedures at the plant on July 3 1. It was calculated that no more than 50 pounds of phosphorus trichloride were released from the plant, and the plant's security and industrial hygiene personnel were able to visually track and bound the plume that moved into Rush City. Their reports indicated that the plume traveled approximately two miles before dissipating. This plume caused 244 citizens to report to area hospitals for treatment. Eight of these citizens were admitted; seven were kept overnight and released, while the eighth was kept for three days before release. This patient's history of asthma contributed to the severity of effects, and the asthma was also aggravated by the exposure to the phosphorus trichloride. The main complaints of the citizens were eye, nose, and throat irritation. No measurements of airborne concentrations were made during either incident. A follow up study conducted by NIOSH on 26 of the exposed workers and 1 1 of the unexposed 2.3 Epidemiologic Studies 3 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 a 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 No epidemiologic studies of phosphorus trichloride toxicity are currently available.

2.4 DevelopmentaYReproductive Toxicity Data regarding the reproductive/ developrnental toxicity of phosphorus trichloride in humans are not available.

2.5 Genotoxicity No human genotoxicity data for phosphorus trichloride are currently available.

2.6 Carcinogenicity Information regarding the potential carcinogenicity of phosphorus trichloride in humans is not available.

2.7 Summary There are no data regarding lethal exposures of humans to phosphorus trichloride but some information on nonlethal exposures is available. Workers exposed to phosphorus trichloride following a railroad car spill exhibited signs and symptoms consistent with exposure to a highly irritating chemical. Although the reports of this accident describe qualitatively the effects of exposure, there are no quantitative exposure response terms. Pulmonary function deficits (e. g., vital capacity, FEVI, peak expiratory flow rate, maximal expiratory flow rate at 50% vital capacity) that correlated with distance from the release showed improvement at one month following the exposure. The effects reported could be attributed to phosphorus trichloride decomposition products (phosphonic acid and hydrogen chloride) as well as the parent compound. In an occupational exposure setting, workers experienced a burning sensation in the eyes and throat, photophobia, chest tightness, dry cough, and slight bronchitis following 2 6 hours of exposure to approximately 14 27 ppm phosphorus trichloride. Exposure of workers to these levels for 1 8 weeks resulted in pharyngeal irritation, coughing, catarrh, dyspnea, and asthmatic bronchitis. Increases in body temperature and moderate leucocytosis with neutrophilia were also reported for both exposure durations, but all signs and symptoms resolved upon removal from the exposure.

3. ANIMAL TOXICITY DATA 3.1 Acute Lethality 3.1.1 Rats Weeks et al. (1 964) reported on the acute lethality of phosphorus trichloride in female rats exposed for four hours to an atmosphere of phosphorus trichloride generated by passing nitrogen gas through the liquid test material. Chemical analysis was used to determine the amount of the test material in the exposure chamber. The rats were observed for 14 days after removal from exposure. The rats were restless and exhibited labored breathing during the exposure. During the exposure, the eyes were closed and there was considerable porphyrin secretion around the eyes. Deaths occurred over a period of ten days indicating, under the conditions of this experiment, a notable latency period in the lethal response. The 4 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 4 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 nostrils and paws of the exposed rats exhibited swelling, edema, discoloration and subsequent sloughing of tissues that was consistent with the activity of a corrosive agent. Microscopic examination revealed necrosis of epithelium and supporting structures in the nostrils but pulmonary damage was considered to be negligible. The investigators noted that the primary site of damage appeared to be the kidneys and was characterized by nephrosis of tubules in the cortico medullary region. A 4 hr LC5,, of 104.3 pprn was calculated and reported by the investigators. The exposure concentrations tested to obtain this value were not reported and, therefore, there was no infoxmation regarding the exposure response relationship.

3.1.2 Guinea pigs Weeks et al. (1964) also examined the lethal response of guinea pigs exposed for four hours to phosphorus trichloride. The experimental protocol was as described for the experiments with rats (Section 3.1.1). Based upon the published report, the response of guinea pigs was similar to that of rats; restlessness, signs of ocular and nasopharyngeal irritation, and renal damage. With the exception of the 4 hr LCso of 50.1 ppm, no additional exposure response data were provided.

pigs exposed to 623 ppm phosphorus trichloride died shortly after 3 hours of exposure. Results of early inhalation exposure experiments reported by Butjagin (1904) showed that guinea 3.1.3 Cats Butjagin (1904) reported that test animals (guinea pigs and cats) died shortly after 3 hour exposure to 623 ppm. In another experiment, one cat exposed to 694 ppm died after 306 minutes.

3.2 Nonlethal Toxicity 3.2.1 Rats Although the Weeks et al. (1964) study reported on lethality in rats exposed to phosphorus trichloride, no information was provided regarding nonlethal effects.

In an unpublished study conducted for the Monsanto Company (Hazleton Laboratories, 1983), groups of 15 Sprague Dawley rats (1 S/ sex/ group) were exposed to phosphorus trichloride vapor/ aerosol for 6 hours/ day, 5 daydweek for four weeks. Over the four week period, nominal exposure concentrations were 0.5, 3.0, or 10.0 ppm and analytical concentrations were 0.49, 3.37, and 10.96 ppm. The test atmosphere was generated by passing air (200 990 cc/ minute .depending upon the test concentration group) over the headspace above a non specified volume of phosphorus trichloride in a flask. The vapor was then carried to the test chambers via Teflon@ tubing. Sample concentrations were determined three times per day by collecting chamber samples in impingers containing 20 mL of sodium hydroxide. The samples were subsequently analyzed in a chloride meter and expressed as ppm phosphorus trichloride. Over the 4 week exposure period, concentration excursions deviated from target values by 2.0,. +12.3, and +9.6% for the low, medium, and high dose groups, respectively. A control group was exposed to filtered air under the same conditions. No rat died during the exposure period and no treatment related adverse effects were observed. All rats were sacrificed and necropsied on day 29. Histological alterations in the maxillo and nasoturbinates and in the lateral wall of the nasal cavity were observed in seven male and four females of the high dose group; the remaining high dose rats exhibited no remarkable findings in the nasal cavities and turbinates. Squamous metaplasia of the respiratory epithelium was also present in six males and four 5 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 females of the high dose group. There were no treatment related effects on hematologic or biochemical parameters, and no ophthalmologic effects or body weighuorgan weight changes were observed. Under the conditions of this study, 3.4 ppm was considered a No Observed Adverse Effect Level (NOAEL) in rats.

32.2 Guinea Pigs In experiments reported by Butjagin (1904), guinea pigs were exposed to phosphorus trichloride at various concentrations for different durations (1  6 hours). Only minor effects (restlessness, salivary and nasal secretions, coughing, irregular respiration) were observed following 6 hour exposure to 0.7 1 ppm or 1 hour exposure to 1.78 to 5.36 ppm. In the report summary, it was also noted that exposures of 50 90 ppm for one hour produced severe signs of toxicity. The phosphorus trichloride concentrations were determined by measurement of chlorine. It appears that only 1 to 3 animals were used for any given exposure and, for some experiments, the same animals were used.

3.2.3 Cats Butjagin (1904) also conducted experiments with adult cats (2.1 4.0 kg) exposed to phosphorus trichloride as previously described for guinea pigs. The results were similar to those reported for the guinea pigs; 6 hour exposure to 0.71 ppm or 1 hour exposure to 1.78 to 5.36 ppm produced signs of restlessness and nasopharyngeal irritation. Six hour exposures to concentrations of 135 to 303 ppm rapidly produced signs of severe irritation (salivary, nasal, and ocular secretions, breathing through the mouth, irregular and severely labored respiration). Histological examination at six to seven days after exposure revealed severely damaged nasal septum and bronchioles, and pulmonary edema. Inasmuch as these animals were terminated for necropsy, it is likely (based upon the findings) that they may not have survived. In summary, the study author reported that one hour exposure to 50 90 ppm resulted in severe signs of toxicity. It appears that for at least some of the experiments, the same cats were used.

3.3 DevelopmentaVReproductive Toxicity No data are available regarding the developmental/ reproductive toxicity of phosphorus trichloride in animals.

3.4 3.5 3.6 Genotoxicity No data are currently available regarding the genotoxicity of phosphorus trichloride.

Carcinogenicity No data are available regarding the carcinogenic potential of phosphorus trichloride in animals.

Summary of Toxicity Data In Animals Definitive quantitative exposure response toxicity data in animals were limited. Median lethal exposure concentrations for rats &d guinea pigs are available and shown in Table 2. A report by Weeks et 6 13 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 Species Rat Cat 1 2 3 4 5 6 7 8 9 10 11 12 Lethality Value Reference 4 hrLCx, : 104.3 ppm lethality at 306 min, 694 ppm Weeks et al., 1964 Butjagin, 1904 13 ~ ~~

Cat Guinea pig Guinea pig 14 lethality at 3 hours, 623 ppm 4 hr LCso : 50.1 ppm lethality at 3 hours, 623 ppm ButjaginJ 904 Weeks et a1., 1964 ButjaginJ904 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 al. (1964) provided an adequate description of experimental protocol and 4 hr EC,, value for rats (4 hr Lcs0= 104.3 gpm) and guinea pigs (4 hr ECs0= 50. 1 ppm). Additional data obtained from limited numbers of cats and guinea pigs exposed to various concentrations of phosphorus trichloride for varying durations described both lethal and nonlethal responses (Butjagin, 1904). An unpublished study by Hazleton Laboratories (1983) showed that multiple 6 hour/ day exposures of male and female rats to phosphorus trichloride at 11 ppm over four weeks produced only histologic changes in the nasal turbinates while exposure to 3.4 ppm failed to produce any notable effects. The available information affirms that exposure to vapors of phosphorus trichloride may produce dermal, ocular, and nasopharyngeal irritation as well as pulmonary and renal damage. Additionally, based upon limited data in rats, cats and guinea pigs, there appears to be latency period in the lethal response to phosphorus trichloride.

~~

rTABLE 2. ACUTE LETHALITY OF PHOSPHORUS TRICHLORIDE IN LABORATORY SPECIES1 4. SPECIAL CONSIDERATIONS 4.1 Metabolism and Disposition Data on the metabolism and disposition of phosphorus trichloride are not currently available.

4.2 Mechanism of Toxicity The mechanism of toxicity of phosphorus trichloride is currently unknown. The lethal toxicity of phosphorus trichloride does not, however, appear to be explained solely by the activity of the irritant degradation products (hydrogen chloride and phosphonic acid). The rapid exothermic reaction in the presence of water may contribute to localized tissue damage and also explain, in part, the greater toxicity of phosphorus trichloride relative to hydrogen chloride and phosphonic acid.

4.3 Structure Activity Relationships 7 PHOSPHORUS TRICHLORIDE PROPOSED 1: 0512002 ]I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 Barbee et al. (1995) conducted an acute toxicity study of oxalyl chloride (COCl), in which groups of 10 rats were exposed for one hour to 0,462,866, 1232, 1694, or 2233 pprn. The 1 hr LC,, was found be 1840 ppm. Phosphorus trichloride produces many of the same signs and symptoms as does phosphorus oxychloride following acute inhalation exposures (Weeks et al., 1964; ACGIH, 1991) and also undergoes rapid hydrolysis to phosphonic acid and hydrogen chloride.

4.4 Other Relevant Information 4.4.1 Species Variability Data are insufficient to reliably describe species variability in the toxic response to inhaled phosphorus trichloride.

4.4.2 Concurrent Exposure Issues No concurrent exposure issues of special concern have been identified that could be directly incorporated in the development of AEGL values for phosphorus trichloride.

5. DATA ANALYSIS AND PROPOSED AEGL 1 5.1 Summary of Human Data Relevant to AEGL 1 Quantitative human data consistent with AEGL 1 effects were not available. Information regarding human exposures to phosphorus trichloride indicate acute exposures result in dermal and ocular irritation, irritation of the respiratory tract, headache, nausea, and shortness of breath.

5.2 Summary of Animal Data Relevant to AEGL 1 The only animal data available that were consistent with AEGL 1 severity effects were those provided in the report by Butjagin (1904). In this study, cats and guinea pigs exposed to phosphorus trichloride concentrations of 0.71 to 1.78 ppm for up to six hours exhibited restlessness, salivary and nasal secretions, coughing, and irregular respiration. Hazleton Laboratories (1983) reported a NOAEL of 3.4 ppm for rats following multiple 6 hr/ day exposures. This was bounded by a NOEL of 0.5 ppm and LOAEL (1 1 ppm).

5.3 Derivation of AEGL 1 Data consistent with AEGL 1 effects come from an older study in cats and guinea pigs (Butjagin, 1904). There are no odor threshold data and no quantitative data in humans. Because of the uncertainties regarding exposure atmosphere measurements from a study conducted almost 100 years ago and the fact that individual test animals may have been exposed to multiple exposure regimens, the data from Butjagin (1904) were not used in the development of AEGL 1 values. Data from the Hazleton Laboratories study suggested that an exposure above 0.5 ppm may be consistent with AEGL 1 effects as multiple 6 hour exposures to this concentration over a four week period were without effect. The Hazleton Laboratories study identified 3.4 ppm as a NOAEL for rats receiving multiple 6 hour exposures over a period of 4 8 PHOSPHORUS TRICHLORIDE PROPOSED 1: 8§/ 2002 TABLE 3. AEGL 1 VALUES FOR PHOSPHORUS TRICHLORIDE AEGL Level 1 0 min 3 O min 1 hr 4 hr 8 hr AEGL 1 0.78 ppm 0.78 ppm 0.62 ppm 0.39 ppm 0.26 ppm ? 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1% 19 20 21 22 23 24 25 26 27 2% 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 weeks. Sassi (1952) reported that occupational exposures of 1.8 to 3.6 ppm for 2 to 6 hours were without notable effect. Hn lieu of additional data. the experimentally determined NOAEL 3.4 ppm was considered a NOAEL for development of AEGE 1 values. Data for humans and animals indicate some variability in the toxic response to phosphorus trichloride. However, upon comparison to human data (albeit limited), rodents appear to be somewhat more sensitive to the respiratory effects of phosphorus trichloride. Therefore, uncertainty adjustment regarding interspecies variability was limited to 3. To account for intraspecies variability, a factor of 3 was applied. The uncertainty of intraspecies variability was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. The attenuated uncertainty factors may be justified by the limited human exposure data (Sassi, 1952) suggesting that humans could experience 2 to 6 hour exposures of up to 3.6 ppm with no apparent effect and the fact that AEGL 1 development is based upon an exposure that was without a discernible effect. The AEGL 1 values for phosphorus trichloride are shown in Table 3 and their derivations shown in Appendix A.

6. DATA ANALYSIS AND' PROPOSED AEGL 2 6.1 Summary of Human Data Relevant to AEGL 2 Quantitative exposure response data in humans are not available for development of AEGL 2 values for phosphorus trichloride. Information regarding the human experience is limited to qualitative notations regarding signs and symptoms (ocular, dermal, and respiratory tract irritation, and ventilatory effects). The information in these reports suggest that acute exposure to phosphorus trichloride could cause irritation severe enough to impair egress from a contaminated area. Sassi (1953) reported that workers experienced a burning sensation in the eyes and throat, photophobia, chest tightness, dry cough, and slight bronchitis following 2 6 hours of exposure to approximately 14 27 ppm phosphorus trichloride. Although these effects could possibly impair escape, thereby by qualifylng as being consistent with AEGL 2 tier effects, the method@) by which the exposure concentrations were determined was not reported. Exposure concentrations were not provided in other reports (with the exception of the anecdotal data by Tharr and Singa1,1980) and information on exposure duration was limited.

6.2 Summary of Animal Data Relevant to AEGL 2 Quantitative data in animals regarding effect severity consistent with AEGL 2 were limited to data on guinea pigs and cats reported by Butjagin (1904). The robustness of these data are, however, limited due to the small numbers of animals in each experiment (Le., 1  3) and the fact that some of the animals were apparently used in more than one experiment. This becomes a significant concern considering the additive nature of irritatiodtissue damage and the possible latency in activity for some adverse effects of phosphorus trichloride (e. g., pulmonary damage and renal toxicity). Consistent with human acute exposure 9 PMQSPHQRBIS TRICHLORIDE PRQPOSED 1: 85/ 26) 02 AEGL Level AEGL 2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 0 min 30 min 1 hr 4 hr 8 hr 2.5 ppm 2.5 ppm 2.0 ppm 1.3 ppm 0.83 pprn reports, the predominant response by animals is characterized by ocular, nasopharyngeal, and pulmonary irritation and subsequent tissue damage. Animal data are not sufficient to provide a meaningful exposure response relationship. The responses of cats and guinea pigs in the Butjagin study were reportedly more severe at higher concentrations and occurred more quickly. In the Butjagin (1904) report, cats and guinea pigs exposed to 5.36 ppm for one hour exhibited restlessness, signs of nasopharyngeal irritation, and irregular respiration. A 6 hour exposure of cats to concentrations of 135 to 303 ppm resulted in s i p s of severe irritation and respiratory distress. Histological examination of the cats exposed to 135 to 303 pprn revealed perforated nasal septa, bronchial damage, and pulmonary edema. Additionally, Weeks et al. ( 1964) noted renal damage in rats exposed to lethal concentrations of phosphorus trichloride. However, exposure response data were not provided regarding this effect. The Hazleton Laboratories study (1983) in rats showed that multiple 6 hour exposures to 11 ppm. over a four week period produced histologic alterations in the nasal turbinates but no effects on ophthalmologic hematologic or biochemical parameters, and no overt signs of toxicity. Because the nasal lesions were the result of multiple exposures (5 daydweek) over four weeks and not of a severity consistent with the AEGL 2 tier, a threshold for AEGL 2 effects in rats is likely at an undetermined concentration above 11 ppm for a single six hour exposure.

6.3 Derivation of AEGL 2 Data upon which to base AEGL 2 development are limited. Sassi (1953) reported on occupational exposures of 2 6 hour durations to concentrations of 14 27 ppm that produced effects that could be considered only marginally consistent with AEGL 2. As previously noted, the animal data reported by Butjagin (1904) are deficient for the purpose of AEGL development. Although the results from the Hazleton Laboratories (1983) study in rats exposed to for 6 hours/ day, 5 daydweek for four weeks did not define a response consistent with AEGL 2 severity, the 11 ppm exposure that resulted in histopathologic alterations in the respiratory tract may be considered a NOAEL for AEGL 2 severity effects. Uncertainty factor application and time scaling were as described for AEGL 1. Data from available reports suggest that humans are not especially sensitive to the effects of phosphorus trichloride when compared to laboratory animals. As such fbrther reduction of AEGL values by the application of greater uncertainty factors dose not appear warranted. The AEGL 2 values for phosphorus trichloride are shown in Table 4 and their derivation outlined in Appendix A.

31 32 33 34 35 10 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05L2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 7. DATA ANALYSIS AND PROPOSED AEGL 3 7.1 Summary of Human Data Relevant to AEGL 3 Quantitative data are not available regarding lethality in humans exposed to phosphorus trichloride,

4 2 Summary of Animal Data Relevant to AEGL 3 Weeks et al. (1964) provided 4 hr LC50 values of 104.3 ppm and 50.1 ppm, respectively, for rats and guinea pigs. In early experiments by Butjagin (1904), guinea pigs and cats exposed to 623 ppm phosphorus trichloride died within three hours, and a cat exposed to 694 ppm died after 306 minutes of exposure. In the absence of any additional quantitative data, the median lethality values derived by Weeks et al. may be considered as a basis for AEGL 3 development and also serve to a limited extent as an index of species variability. Because the exposure response data used to derive the median lethality values were not provided, it is not possible to determine the exposure response relationship.

7.3 Derivation of AEGL 3 Because the median lethality values provided by Weeks et al. (1964) represent the only quantitatively determined estimates regarding the lethal response to acute inhalation of phosphorus trichloride, they may be considered as the basis for AEGL 3 development. The 4 hr LC50 values for rats (104.3 ppm) and guinea pigs (50.1 ppm) suggest a species variability. In the absence of exposure response data, the lethality threshold was estimated as a 3 fold reduction of the rat 4 hr LCso (104.3 p p d 3 = 34.8 PPm). The concentration time relationship for many irritant and systemically acting vapors and gases may be described by C" x t = k , where the exponent n ranges from 0.8 to 3.5. Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the c" x t = k equation. Because of the uncertainty in extrapolating from a 4 hour exposure to a 10 minute exposure, the latter was set equal to the 30 minute AEGL 3. A total uncertainty factor adjustment of 10 was used to develop the AEGL 3 values. Data for humans and animals indicate some variability in the toxic response to phosphorus trichloride with guinea pigs being the more sensitive ( 2 fold) among the laboratory animals. Limited data regarding human exposures showed that 2 to 6 hour exposures to 14 27 ppm were not life threatening (Sassi, 1952). Therefore, uncertainty adjustment regarding interspecies variability was limited to 3. To account for intraspecies variability, a factor of 3 was applied. The uncertainty of intraspecies variability was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. The attenuated uncertainty factors may be further justified by limited human exposure data (Sassi, 1952) suggesting that humans could experience repeated exposures of up to 27 ppm without life threatening consequences. The resulting AEGL 3 values are presented in Table 5 and their derivation is shown in Appendix A. Because the lethal response in guinea pigs and rats was delayed up to 10 days, note of possible delayed response has been made regarding AEGL 3 values.

11 (8 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 a Based upon animal data, lethality may be delayed 8. SUMMARY OF PROPOSED AEGLS 8.1 AEGL Values and Toxicity Endpoints The AEGL 1 values are based upon a NOAEL an laboratory study in which rats received multiple exposures over a period of four weeks. Although a conservative assumption, the use of a NOAEL in the development of the AEGL 1 values may be justified by the relative paucity of definitive exposure response data. and the fact that limited information regarding the human experience indicates that 2 to 6 hour exposures to 1.8 3.6 ppm was without effect. The AEGL 2 values were based on histopathologic alterations detected in the respiratory tract of rats following multiple exposures over four weeks. The effects on the respiratory tract were consistent with mode of action of phosphorus trichloride and, therefore, were considered a NOAEL for the AEGL 2 tier effect level (i. e., the effects were neither disabling nor irreversible). Information regarding the human experience suggests that 2 to 6 hour exposures to 1.8 3.6 ppm were without effect and that exposure to 14 27 ppm resulted in irritation of the eyes and upper respiratory tract, photophobia, chest tightness, and bronchitis. Therefore, further reduction of the AEGL 2 values does not appear to be warranted. The AEGL 3 values were developed based upon lethality data in laboratory species. The AEGL 3 values were developed based upon a 4 hr LCso value for rats provided in a study by Weeks et al., 1964. Data pertaining to the human experience also indicate respiratory involvement as a critical effect.

12 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 8.2 Comparison with Other Standards and Criteria Existing standards and criteria for phosphorus trichloride are presented in Table 6 .

TABLE 6. Extant Standards and Guidelines for Phosphorus Trichloride 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31    Einsaztolerannvert  (Germany) '

MAC    (The Netherlandsy NR: Not recommended. Numeric values for AEGL 1 and AEGL 2 are not recommended due to 8 hour 0.26 ppm 0.83 ppm 1.8 ppm

0.5 ppm 0.2 ppm

0.2 ppm 0.5 ppm 0.5 ppm 0.2 ppm e lack of availab data. Absence of these values does not imply that exposure below the AEGL 3 is without adverse effects.

13 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 P 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 'ERPG (Emergency Response Planning Guidelines, American Industrial Hygiene Association) (AIHA, 1994) The ERPG 1 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to one hour without experiencing other than mild, transient adverse health effects or without perceiving a clearly defined objectionable odor. The EWG 2 is the maximum airborne concentration below which it is believed nearly dl individuals could be exposed for up to one hour without experiencing or developing irreversible or other serious health effects or symptoms that could impair an individual's ability to take protective action. The EWG 3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to one hour without experiencing or developing life threatening health effects. As of 2001, phosphorus trichloride values are categorized as under Ballot, Review, and Consideration.

EEGL (Emergency Exposure Guidance Levels, National Research Council) (NRC, 1985) is the concentration of contaminants that can cause discomfort or other evidence of irritation or intoxication in or around the workplace, but avoids death, other severe acute effects and long term or chronic injury.

OSHA PEL TWA (Occupational Health and Safety Administration, Permissible Exposure Limits  Time Weighted Average) (OSHA, 1993) is defined analogous to the ACGIH TLV TWA, but is for exposures of no more than 10 hourdday, 40 hourdweek.

* OSHA PEL STEL (Permissible E osure Limits  Short Term Exposure Limit) (OSHA, 1993) is defined analogous to the ACGIH 2~ STEL.

e IDLH (Immediately Dangerous to Life and Health, National Institute of Occupational Safety and Health) (NIOSH, 1996) represents the maximum concentration from which one could escape within 30 minutes without any escape impairing symptoms, or any irreversible health effects.

NIOSH REL TWA (National Institute of Occupational Safety and Health, Recommended Exposure Limits  Time Weighted Average) (NIOSH, 1999) is defined analogous to the ACGIH TLV TWA.

g NIOSH REL STEL (Recommended Exposure Limits  Short Term Exposure Limit) (NIOSH, 1999) is defined analogous to the ACGIH TLV STEL.

ACGIH TLV TWA (American Conference of Governmental Industrial Hygienists, Threshold Limit Value  Time Weighted Average) (ACGIH, 1997) is the time weighted average concentration for a normal S hour workday and a 40 hour work week, to which nearly all workers may be repeatedly exposed, day after day, without adverse effect.

ACGIH TLV STEL (Threshold Limit Value  Short Term Exposure Limit (ACGIH, 1997 is defined as a 15 minute TWA exposure which should not be exceeded at any time d wing the work h y even if the S hour TWA is within the TLV TWA. Exposures above the TLV TWA up to the STEL should not be longer than 15 minutes and should not occur more than 4 times per day. There should be at least 60 minutes between successive exposures in this range.

J MAK (Maximale Arbeitsplatzkonzentration [Maximum Workplace Concentration Deutsche Forschungs gemeinschaft [German Research Association], Germany) (DF 24 , 1999) is defined analogous to the ACGIH TLV TWA. 1 2 3 4 5 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 MAK Spitzenbegrenzung (Kategorie II, 2) Peak Limit Catego II, 2] (DFG, 1999 constitutes the maximum average concentrahon to which wor 5iz ers can be exposel? rfor a period up to 3 0 minutes, with no more than 2 exposure periods per work shift, total exposure may not exceed 8 hour MAK.

Einsatztoleranzwert Action Tolerance Levels] (Vereiqigung zur Forderung des deutschen BrandschutzGs e. V. [IFederabon I or the Advancement of German Fire Prevenuon]) conwtutes a concentrahon to which unprotected firemen and the general population can be exposed to for up to 4 hours without any health risks.

J MAC (Maxlmaal Aanvaarde Concentratie [Maximum Accepted Concentration]) SDU Uitgevers under the auspices of the Ministry of Social Affairs and Employment], The Hague, 4 he Netherlands [2 000) is defined analgous to the ACGIH TLV TWA 8.3 creates substantial uncertainty regarding the exposure response relationship for the toxic response to this chemical. Although qualitative data are available regarding the acute inhalation toxicity of phosphorus trichloride in humans, quantitative exposure response data are lacking. Quantitative exposure response data are severely limited for nonlethal responses in animals. These deficiencies result in an incomplete picture of the exposure concentration response curve and exposure duration response for phosphorus trichloride. Additional data are also needed regarding the mechanism of action, possible systemic effects (e. g., renal toxicity), and latency in the toxic responses (e. g., pulmonary damage) following acute inhalation exposure to phosphorus trichloride. Data Adequacy and Research Needs The overall robustness of the data base for phosphorus trichloride toxicity is poor. The lack of data 15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 PHOSPHORUS TRICHLORIDE 9, REFERENCES CITED PROPOSED 1: 05/ 2002 ACGIH (American Conference of Governmental Hygienists). 11991. Documentation ofthe Threshold Limit Values and Biological Exposure Indices. 6th ed. ACGH, Cinc., OH. pp. 1261 1262.

ACGM. (American Conference of Governmental Hygienists). 1997. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH.

AIHA (American Industrial Hygiene Association). 1999. The ATHA 1999 Emergency Response Planning Guideline an d W or k PI e E n vi ro n m en ta 1 E P 2IC X os UT e L ev el G ui de H d b S an 0 0 ' k. A m er In d 16 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 US tri a1 H gig ie ne A ss oc F ai rf ax V A Barbee, S. J., Stone, J. J., Hilaski, R. J. 1995. Acute inhalation toxicology of oxalyl chloride. Am. Ind. Hyg. J. 56: 74 76.

Beliles, R. P., Beliles, E. M. Phosphorus, selenium, tellurium, and sulfur. In: Clayton, G. D., Clayton, F. E., Eds. Patty's Industrial Hygiene and Toxicology. Vol. II. 4th ed., John Wiley & Sons, Inc., New York. pp. 790 791.

Budavari, S., O'Neil, M. J., Smith, A., Heckelman, P. E., Kennedy, J. F., Eds. 1996. Phosphorus trichloride. The Merck Index. Merck and Co., Whitehouse, NJ.

Butjagin, P. W. 1904. Experimentelle Studien uber den Einflufs technisch und hygienisch wichtiger Gase und Diimpfe auf den Organismus. Teil XII. Studien uber phosphortrichlorid. Archiv f. Hyg. 49: 307 335.

Fee, D. C., Gard, D. R., Yang, C H. 1996. Phosphorus compounds. In: Kirk Othmer Encyclopedia of Chemical Technology. Pp. 761 765. Vol. 18. John Wiley & Sons, New York.

German Research Association peutsche Forschungsgemeinschaft). 1 999. List of MAK and BAT Values 1999. Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area. Report No. 35.

Hazleton Laboratories. 1983. Subacute inhalation toxicity study in rats  phosphorus trichloride. Final Report. Project No. 24 1 1 4 1, Hazleton Laboratories America, Inc. Unpublished.

HSDB (Hazardous Substances Data Bank). 1998. On line Moody, P. 1981. Health hazard evaluation Report HETA 81 089 965 FMC Corporation, Nitro, West Virginia. US. Dept. Health and Human Services, Center for Disease Control, National Institute for Occupational Safety and Health, Cincinnati, OH.

NOSH (National Institute for Occupational Safety and Health). 1994. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLHS). National Institute for Occupational Safety and Health, Cincinnati, OH; PB94195047, National Technical Information Service, Springfield, VA.

17 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 NIOSH (National Institute for Occupational Safety and Health). 1999. NOSH Pocket Guide to Chemical Hazards.

18 N 1 0 5 R P bl ic at io n 9 4 1 1 6, U .s D eP t. H ea It h d H m 5 er vi ce s; U .s G er n m en t Pr in ti n U an U an ov PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 26) 02 1 2 3 4 5 6 7 8 9 IO 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 g 0 f3 i ce W as hi f3t n, D .c ,

n 0 OSHA (Occupational Safety and Health Administration). 1999. Limits for Air Contaminants. Table 2 1. Code of Federal Regulations 29, Part 1910. Office of the Federal Register National Archives and Records Administration.

RTECS (Registry of Toxic Effects of Chemical Substances), 1998. On line retrieval.

Sassi, C. 1952. Occupational poisoning due to phosphorus trichloride. AMA Arch. Ind. Hyg. Occ. Med. 7, 178. (English translation of abstract.)

ten Berge, W. F., Zwart, A., Appelman, L. M. 1986. Concentration time mortality response relationship of irritant and systemically acting vapours and gases. J. Hazard. Materials 13: 301 309.

Tharr, D. G., Singal, M. 1980. Health hazard evaluation determination. Report No. HHE 78 90 739, FMC Corp., Specialty Chemicals Div., Nitro, WV. NTIS Publ. No. PB 83 161 190.

Wason, S., Gomolin, I., Gross, P., Lovejoy, F. H., Jr. 1982. Phosphorus trichloride exposure  a follow up study of 27 exposed patients. Vet. Human Toxicol. 24: 275 276.( ubsfracf)

Wason, S., Gomolin, I., Gross, P., Mariam, S., Lovejoy, F. H. 1984. Phosphorus trichloride toxicity preliminary report. Amer. J. Med. 77: 1039 1042.

Weeks, M. H., Mussleman, N. P., Yevich, P. P., Jacobson, K. H., Oberst, F. W. 1964. Acute vapor toxicity of phosphorus oxychloride, phosphorus trichloride and methyl phosphonic dichloride. Amer. Ind. Hyg. J. 25: 470 475.

19 PHOSPHORUS TRI(@ IHLQRI[ DE PROPOSED 1: 6) 5/ 2002 APPENDIX A DERIVATION OF AEGL VALUES 20 27 1 2 3 4 5 4 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 PHOSBHQRUS TRICHLORIDE DERlVATIQN OF AEGL B VALUES Key study: Hazleton Laboratories, 1983 Toxicity endpoint: NOAEL of 3.4 ppm for rats following multiple exposure at 6 hrs/ day, 5 days/ week for 4 weeks.

Scaling:

Uncertainty factors:

1 O min AEGL 1 30 min AEGL 1 l hr AEGL 1 4 hr AEGL 1 8 hr AEGL 1 PROPOSED 1: 05// 2002 The concentration time relationship for may irritant and systemically acting vapors and gases may be described by C x t = k , where the exponent n ranges from 0.8 to 3.5 (ten Berge et al., 1986). Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = P when extrapolating to longer time points using the eP, x t = k equation. (3.4 ppm) ' x 6 hrs = 20.4 ppm * hrs (n = 1) (3.4 ~p m )~ x 6 hrs = 235.8 ppm3 * hrs (n = 3)

Interspecies UF = 3; the attenuation of this uncertainty factor is justified by the fact that the guinea pig appears to be the most sensitive species tested and because limited human exposure data (Sassi, 1952) indicate that humans have experienced routine occupational exposures of up to 3.6 ppm without effect. Intraspecies UF = 3; contact irritation and subsequent tissue damage appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociaton and direct corrosive action of these components on epithelial surfaces. Additional application of uncertainty factor adjustment would provide AEGL 3 values that are inconsistent with limited data on human exposures.

The 10 minute AEiGL 1, was set equivalent to the 30 minute value due to uncertainties in extrapolating from the 6 hour experimental exposure duration.

C3 x 0.5 hr = 235.8 ppm3 hr C =7.78ppm 30 min AEGL 1 = 7.78 ppm/ lO = 0.78 ppm (4.4 mg/ m3)

C3 x 1 hr = 235.8 ppm3 hr C =6.18ppm l hr AEGL 1 =6,18ppm/ lO =0.62ppm( 3.5mg/ m3)

C3 x 4 hrs = 235.8 ppm3 hr C = 3.89 ppm 4 hr AEGL 1 = 3.89 ppm/ lO = 0.39 ppm (2.2 mg/ m3)

C' x 8 hrs = 20.4 ppm hr C =2.55ppm 8 hr AEGL 1 = 2.55 ppm/ lO = 0.26 pprn (1.5 mg/ m3)

21 PHQSPMORUS TRICHLORIDE PROPOSED I: 05f2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 DERIVATION OF AEGE 2 Key study: Hazleton Laboratories, 1983 Toxicity endpoint: LOAEL of 11 ppm for respiratory tract histopathologic changes in rats following multiple exposure at 6 Rrslday, 5 daystweek for 4 weeks.

Scaling: The concentration time relationship for may irritant and systemically acting vapors and gases may be described by c" x t = k , where the exponent n ranges from 0.8 to 3.5 (ten Berge et al., 1986). Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the C" x t = k equation. (1 1 pprn) ' x6hrs = 66 ppm  hrs (n = 1) (1 1 ~p m )~ x 6 hrs = 7986 ppm3 hrs (n = 3)

Uncertainty factors: Interspecies W = 3; the attenuation of this uncertainty factor is justified by the fact that the guinea pig appears to be the most sensitive species tested and because limited human exposure data (SassiJ952) indicate that humans have experienced routine occupational exposures of up to 3.6 ppm without effect. Intraspecies UF = 3; contact irritation and subsequent tissue damage appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical disswiaton and direct corrosive action of these components on epithelial surfaces. Adjustments using a greater level of uncertainty uncertainty would provide AEGL 2 values that are inconsistent with limited data on human exposures.

1 0 min AEGL 2 The 10 minute AEGL 2, was set equivalent to the 30 minute value (2.5 ppm) due to uncertainties in extrapolating from the 6 hour experimental exposure duration to a 1 0 minute duration.

30 min AEGL 2 1 hr AEGL 2 4 hr AEGL 2 C3 x 0.5 hr = 7986 ppm3 hr C =25.2ppm 30 min AEGL 2 = 25.2 ppm/ lO = 2.5 ppm (14 mg/ m3)

C3 x 1 hr = 7986 ppm3* hr C = 20.0 ppm 1 hr AEGL 2 = 20.0 ppm/ lO = 2.0 ppm (1 1 mg/ m3)

C3 x 4 hrs = 7986 ppm3 hr C = 12.6ppm 4 hr AEGL2 = 12.6 ppm/ lO = 1.3 ppm (7.3 mg/ m3)

22 PHOSPHORUS TRICHLORIDE 1 8 hr AEGL 2 2 3 4 C'x8hrs =66ppmhr C =8.25ppm 8 hr AEGL 2 = 8.25 ppm/ lO = 0.83 ppm (4.6 mg/ m3)

23 PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 PHOSPHORUS TRICHLORIDE DERIVATION OF AEGL 3 Key study:

Toxicity endpoint: Lethality threshold estimated as 3 fold reduction in the 4 hr LCso for rats Weeks et al. 1964 (104.3 ppd3 = 34.8 pprn), delayed response possible. PROPOSED 1: 05/ 2002 Scaling:

Uncertainty factors:

1 0 min AEGL 3 30 min AEGL 3 1 hr AEGL 3 4 hr AEGL 3 8 hr AEGL 3 The concentration time relationship for may initant and systemically acting vapors and gases may be described by C" x t = k , where the exponent n ranges fiom 0.8 to 3.5 (ten Berge et al., 1986). Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the c" x t = k equation. (34.8 pprn) ' x 4 hrs = 139.2 ppm 9 hrs (n = 1) (34.8 ~p m )~ x 4 hrs = 168,576.8 ppm3 * hrs (n = 3)

Interspecies UF = 3; the attenuation of this uncertainty factor is justified by the fact that the guinea pig appears to be the most sensitive species tested and because limited human exposure data (Sassi, 1952) indicate that humans have experienced exposures of up to 27 ppm without life threatening consequences Intraspecies UF = 3; contact initation and subsequent tissue damage appear to be due, in part, to hydrogen chloride and phosphoric acid resulting from chemical dissociaton and direct corrosive action of these components on epithelial surfaces. Additional application of uncertainty factor adjustment would provide AEGL 3 values that are not consistent with limited data on human exposures or with the results ofrepeated exposures in rats wherein exposure to 1 1 ppm 6 hrdday, 5 daydweek for 4 weeks showed only histologic changes in the upper respiratory tract and no overt signs of toxicity Due to uncertainties in extrapolating from a 4 hour to lo minute exposure, the 1 0 minute AEGL 3 is set equivalent to the 3O minute value (7.0 ppm).

C3 x 0.5 hr = 168,576.8 ppm3 hr C = 69.6 ppm 30 min AEGL 3 = 69.6 ppm/ lO = 7.0 ppm (39 mg/ m3)

C3 x 1 hr = 168,576.8 ppm3* hr C =55.2ppm I hr AEGL 3 = 55.2 ppm/ lO = 5.6 ppm (31 mg/ m3)

C3 x 4 h r ~ = 168,576.8 ppm3 hr C = 34.8 ppm 4 hr AEGL 3 = 34.8 ppm/ lO = 3.5 ppm (20 mg/ m3) '

24 PHOSPHORUS TRICHLORIDE C' x 8 hrs = 139.2 ppmhr C = 117.4 pgm 8 hrAJ5GL 3 = 17.4 ppm/ lO = 1.8 ppm (10 mg/ m3> 1 2 3 25 PROPOSED 1: 05/ 2002 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 APPENDIX B DERIVATION SUMMARY FOR PHOSPHORUS TRICHLORIDE AEGL VALUES 3 3 PHOSPHORUS TRICHLORIDE PROPOSED 1: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 ACUTE EXPOSURE GUIDELINES FOR PHOSPHORUS TRICHLORIDE (GAS NO. 7719 12 2)

mGL 1 VALUES 10 minutes 30 minutes 1 hour 4 hours 8 hours 0.78 ppm 0.78 ppm 0.62 ppm 0.39 ppm 0.26 ppm Reference: Hazleton Laboratories, 1983 Test SpecieslStrainlNumber: Sprague Dawley rats; 1 S/ sex/ group Exposure RouteJConcentrationsDurations: Inhalation exposure (whole body) to 0,0.5,3.0, or 10.0 ppm (nominal) for 6 hrslday, 5 dayslweek for 4 weeks Toxicity Endpoint: No effects noted at 3.4 ppm (analytical) following multiple exposure of rats over 4 weeks Time Scaling: The concentration time relationship for may irritant and systemically acting vapors and gases may be described by Cn x t = k , where the exponent n ranges from 0.8 to 3.5. Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the Cn x t = k equation. For 10 minute AEGL 1, values were set at equivalence to the 30 minute values due to uncertainties in extrapolating from the experimental exposure durations of 4 hours or greater.

Concentratioflime SelectionRationale: In the absence of exposure response data specific for AEGL 1 effects, the exposure to 3.4 ppm at 6 hrs/ day, 5 daydweek for 4 weeks was selected as a conservative basis for AEGL development.

Uncertainty FactorsRationale: Total uncertainty application of 10. The interspecies uncertainty factor was limited to 3 because of the concordance of the animal data with the human experience and because the most sensitive species tested (guinea pig) was only about 2 fold more sensitive. The intraspecies uncertainty factor was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. Furthermore, the AEGL 1 is based upon a conservative assumption and additional reduction of the AEGL 1 values would be inconsistent with available human and animal data.

Modifying Factor: Not applicable Animal to Human Dosimetric Adjustments: Not applicable Data Quality and Support of the AEGL Values: Neither human nor animal quantitative exposure response data are available regarding effects consistent with AEGL 1 definition.. The 3.4 ppm exposure of rats over 4 weeks was selected as a NOAEL for AEGL 1. Although likely to be a conservative basis for developing AEGL 1 values, it may be justified due to the relative paucity of data on the toxic response to this chemical.

27 PHOSPHORUS TRICHLORIDE PROPOSED 1: 0512002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 ACUTE EXPOSURE GUIDELINES FOR PHOSPHORUS TRICHLORIDE (CAS NQ@ 7'719 12 2)

AEGL 2 VALUES 10 minutes 30 minutes 1 hour 4 hours 8 hours 2.5 ppm 2.5 ppm 2, O ppm 1.3 ppm 0.83 ppm Reference: Hazleton Laboratories, 1983 Test SpeciedStraidNumber: Sprame Dawley rats; 1 5/ sex/ grouu Exposure Route/ Concentrations/ Durations: Inhalation exposure (whole body) to 0,0.5,3.0, or 10.0 ppm (nominal) for 6 hrs/ day, 5 daysfweek for 4 weeks Toxicity Endpoint: Histopathologic alterations in respiratory tract in rats exposed to 1 1 ppm (analyt~ cal), 6 hrs/ day, 5 daydweek for 4 weeks. There were no concurrent hematologic or biochemical alterations indicative of a toxic response, and there were no ophthalmologic effects.

Time Scaling: The concentration time relationship for may irritant and systemically acting vapors and gases may be described by C" x t = k , where the exponent n ranges from 0.8 to 3.5. Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the C" x t = k equation. For 10 minute AEGL 2, values were set at equivalence to the 30 minute values due to uncertainties in extrapolating fiom the experimental exposure durations of 4 hours or greater.

~~ ~ ~~

Concentration/ Time SelectiodRationale: The multiple exposure of rats to 1 1 ppm over 4 weeks was considered a conservative estimate and NOAEL for AEGL 2 effects @e., the effects were neither disabling nor irreversible).

Uncertainty FactorsRationale: Total uncertainty application of 10. The interspecies uncertainty factor was limited to 3 because of the concordance of the animal data with the human experience and because the most sensitive species tested (guinea pig) was only about 2 fold more sensitive. The intraspecies uncertainty factor was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting from chemical dissociation. Furthermore, the AEGL 2 is based upon a histopathologic changes in the respiratory tract which were not necessarily irreversible or disabling. Additional reduction of the AEGL 2 values would be inconsistent with available human and animal data.

Modifjring Factor: Not Applicable Animal to Human Dosimetric Adjustments: Not applicable Data Quality and Support of the AEGL Values: Limited information regarding the human experience indicated that 2 to 6 hour exposures to 1.8 3.6 ppm were without effect and that exposure to 14 27 ppm irritation of the eyes and upper respiratory tract, photophobia, chest tightness, and bronchitis. Because the effects were neither disabling nor irreversible, the endpoint used for AEGL 2 development is considered a NOAEL for AEGL 2 effects.

28 PHOSPHORUS TRICHLORIDE PROPOSED I: 05/ 2002 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 ACUTE EXPOSURE GUIDELINES FOR PHOSPHORUS TRICHLORIDE (CAS NO. 77119 12 2)

AEGL 3 VALUES 10 minutes 30 minutes 1 hour 4 hours 8 hours 7.0 pprn 7.0 ppm 5.6 ppm 3.5 ppm 1 .8 ppm Reference: Weeks, M. H., Mussleman, N. P., Yevich, P. P., Jacobson, K. H., Oberst, F. W. 1964. Acute vapor toxicity of phosphorus oxychloride, phosphorus trichloride and methyl phosphonic dichloride. h e r . Ind. Hyg. J. 25: 470 475.

Test SpecieslStraiidNumber: female rats /strain not specifiW20 per group Exposure Route/ Concentrations/ Durations: inhalatiordmedian lethal concentrations derived but exposure concentrations Toxicity Endpoint: estimated lethality threshold by 3 fold reduction of rat 4 hr LC50 of 104.3 ppm Time Scaling: The concentration time relationship for may irritant and systemically acting vapors and gases may be described by e x t = k , where the exponent n ranges from 0.8 to 3.5. Due to the limited toxicity data for this chemical, an empirical derivation of n was not possible. In the absence of an empirically derived exponent (n), and to obtain conservative and protective AEGL values, temporal scaling was performed using n = 3 when extrapolating to shorter time points and N = 1 when extrapolating to longer time points using the C" x t = k equation. not specified14 hrs (34.8 pprn) ' x 4 hrs = 139.2 ppm + hrs (n = 1) (34.8 ~p m )~ x 4 hrs = 168,576.8 ppm3 hrs (n = 3)

Concentratioflime Selectionmationale: a 3 fold reduction of the rat 4 hr LCso (104.3 ppd3 = 34.8 ppm) was used as Uncertainty FactorsMationale: an estimate of the lethality threshold.

Total Uncertainty: 10 Interspecies UF = 3 Intraspecies UF = 3 Data for humans and animals indicate some variability in the toxic response to phosphorus trichloride but LCso values for rodents exhibited approximately a 2 fold difference. The uncertainty for intraspecies variability was limited to 3 because primary effects of phosphorus trichloride (irritation and subsequent tissue damage) appear to be due, in part, to hydrogen chloride and phosphonic acid resulting fiom chemical dissociation and the direct corrosive action of these on epithelial tissue. The overall uncertainty factor adjustment of 10 may be justified by limited human exposure data suggesting that humans could experience exposures of up to 27 ppm without life threatening consequences. Furthermore, the results of a multiple exposure studies in rats (1 1 ppm 6 brdday, 5 daydweek for 4 weeks) showed only histologic changes in the upper respiratory tract and no overt signs of toxicity.

Modifying Factor: none applied Animal to Human Dosimetric Adjustments: insufficient data 29 PHOSPHORUS TRICHLORIDE PROPOSED I: 05/ 2002 Data Quality and Support for the AEGL Values: Lethality data are limited to two species and quantitative data for humans are limited. However, comparison ofthe AEGL 3 values with available data do not support application of uncertainty adjustment greater than that currently applied. Data suitable for determining exposure time relationsRips are also lacking and impact on temporal extrapolation efforts. A delayed response is possible as demonstrated in the Weeks et al. (1 964) study in which deaths of guinea pigs occurred up to 10 days post exposure.

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