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Appendix 2 Chlorine Trifluoride Acute Exposure Guideline Levels
Pages 53-91

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From page 53...
... Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Subcommittee on Acute Exposure Guideline Levels.
From page 54...
... Exposure to 1.17 ppm for 3 h was extrapolated using a combined interspecies and intraspecies uncertainty factor of 10 (3 for interspecies differences [the dog was more sensitive than the rat] and 3 for intraspecies differences in sensitivity [slight irritation should occur at a similar level among the general population]
From page 55...
... were available for the monkey, rat, and mouse. Based on similar respiratory rates, gross respiratory tract anatomy, amount and distribution of types of respiratory epithelium, and airflow patterns, the monkey was considered the most appropriate model for deposition of ClF3 and its decomposition products in the human respiratory tract.
From page 56...
... It is one of the most reactive of the halogen TABLE 2-1 Summary of AEGL Values for Chlorine Trifluoride End point Classification 10 min 30 min 1h 4h 8h (Reference) AEGL–1 0.12 0.12 0.12 0.12 0.12 Slight irri (Nondisabling)
From page 57...
... . Chlorine trifluoride has been used in nuclear reactor fuel processing (to convert uranium to gaseous uranium hexafluoride)
From page 58...
... ships cylinders containing either 13 or 26 pounds. Chlorine trifluoride is a potent, rapidly-acting mucous membrane irritant.
From page 59...
... Exposure to sufficiently high ClF3 concentrations may cause skin and mucous membrane irritation (Teitelbaum 2001) as well as headache, abdominal pain, and dyspnea (Longley et al.
From page 60...
... TABLE 2-3 Acute Inhalation Toxicity in Laboratory Animals 60 Concentration Exposure (ppm) Time Species Effecta Reference Monkey 230 1h MacEwen and Vernot LC50 1970 127 1h No deaths; signs of sneezing, coughing, and gagging Dog 21 6 hb Extreme eye and mucous membrane irritation, singed Horn and Weir 5.15 6 hb hair; recovery by next morning except inflamed eyes 1955; 1956 1.17 6 hb irritation, salivation, sneezing, lacrimation, coughing nasal discharge within 45 min, lacrimation after 3 h Rat 800 13-14 min Dost et al.
From page 61...
... Mouse 178 1h MacEwen and Ver LC50 125 1h No deaths; signs of lacrimation, salivation, labored not 1970; Vernot et breathing, and rhinorrhea; bloody discharge from al. 1977 eyes and nares a LC50 values were obtained 14 days post-exposure (MacEwen and Vernot 1970)
From page 62...
... demonstrated general paresis, labored breathing, and cyanosis prior to coma and death. Massive alveolar and interstitial hemorrhages involving the entire lungs were present in all animals that died.
From page 63...
... Two dogs were exposed to an average concentration of 1.17 ppm for 6 h/day, 5 days/week for 6 months (Horn and Weir 1956)
From page 64...
... . Chlorine trifluoride was measured by drawing a known quantity of the chamber atmosphere through sodium hydroxide solution and then analyzing for chloride.
From page 65...
... Twenty rats (sex and strain not stated) were exposed to an average concentration of 1.17 ppm for 6 h/day, 5 days/week for 6 months (Horn and Weir 1956)
From page 66...
... Concentrationdependent ocular, mucous membrane, and pulmonary tract irritation was noted in dogs at 1.17, 5.15, and 21 ppm for an exposure duration of 6 h. The dog was more sensitive than the rat to the irritant effects of airborne ClF3 as no signs of irritation were observed in a group of 20 rats during the first day of exposure to 1.17 or 5.15 ppm; rhinorrhea, lacrimation, and singed hair were observed in both species during the first day of exposure to 21 ppm.
From page 67...
... . In the moist respiratory tract, ClF3 is predicted to hydrolyze to ClOF which further degrades to ClO2F and ClF (Dost et al.
From page 68...
... . Two of five rats that inhaled 500 ppm ClO2 for 15 min died, and all 8 rats exposed to 1,000 ppm ClO2 for 30 min died.
From page 69...
... show great similarity in these three factors (Schreider 1986) , and the monkey is a more appropriate model for extrapolation of inhalation toxicity data for irritants to humans than is the rodent.
From page 70...
... DATA ANALYSIS FOR AEGL-1 5.1. Human Data Relevant to AEGL-1 No human data relevant to the calculation of an AEGL-1 were located.
From page 71...
... The AEGL-1 was based on nasal discharge observed in dogs during the first 3 h of exposure to 1.17 ppm. The 1.17 ppm concentration for an exposure duration of 3 h was divided by a combined interspecies and intraspecies uncertainty factor of 10 (3 for interspecies differences [the dog was more sensitive than the rat]
From page 72...
... Two dogs exposed to 5.15 ppm, 6 h/day, 5 days/week, for 6 weeks showed salivation, lacrimation, rhinorrhea, blinking of the eyes, severe coughing, and sneezing. The duration of ClF3 exposure required to induce these signs was not clearly stated, but "signs of mucous membrane irritation" observed in dogs during the first day appeared to be reversible by the end of the first day as the dogs at that time "did not appear markedly affected." A group of twenty rats exposed to the same concentration did not appear to be affected either during the exposure or at the end of the first day (Horn and Weir 1955)
From page 73...
... The data set for the monkey did not allow calculation of a reliable LC01. TABLE 2-7 AEGL-2 Values for Chlorine Trifluoride 10 min 30 min 1h 4h 8h 8.1 ppm 3.5 ppm 2.0 ppm 0.70 ppm 0.41 ppm (31 mg/m3)
From page 74...
... 74 1000 No Effect 100 Discomfort Disabling AEGL-3 10 ppm Some Lethality Lethal 1 AEGL-2 AEGL AEGL-1 0 0 60 120 180 240 300 360 420 480 Minutes FIGURE 2-1 Animal toxicity data and AEGL values for chlorine trifluoride.
From page 75...
... Using the same uncertainty factors and time scaling relationship as for the monkey, the AEGL-3 values based on the mouse data are very similar, 89, 38, 23, 7.7, and 7.7 ppm for the 10- and 30 min and 1-, 4-, and 8 h time periods, respectively. Chlorine trifluoride decomposes within seconds to HF among other products (MacEwen and Vernot 1970)
From page 76...
... No time scaling was applied as tolerance develops to the slight irritation that defines the AEGL-1. The AEGL-2 was based on obvious irritation observed in dogs exposed to an average concentration of 5.15 ppm for 6 h.
From page 77...
... , but used different species. The ERPG-3 was calculated by dividing the 1-h LC50 TABLE 2-9 Summary of AEGL Values Exposure Duration Classification 10 min 30 min 1h 4h 8h AEGL-1 0.12 ppm 0.12 ppm 0.12 ppm 0.12 ppm 0.12 ppm (Nondisabling)
From page 78...
... The ERPG-2 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 irreversible or other serious health effects or symptoms that could impair an individual's ability to take protection action. The ERPG-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.
From page 79...
... . Workplace exposure limits, as 8 h ceiling values, are all 0.1 ppm and are intended to control and prevent the noxious ocular, mucous membrane and pulmonary irritation associated with exposure to ClF3.
From page 80...
... 2004. Documentation of the Threshold Limit Values and Biologi cal Exposure Indices: Chlorine trifluoride.
From page 81...
... 1970. Toxic Hazards Research Unit Annual Technical Report: 1970.
From page 82...
... 2004. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 4.
From page 83...
... 2005. Chlorine Di oxide: Interim Acute Exposure Guideline Levels.
From page 84...
... FIGURE A-1 Chlorine trifluoride: LC50 values for three species -- monkey, rat, and mouse (Horn and Weir 1955; MacEwen and Vernot 1970; Dost et al.
From page 85...
... a Each uncertainty factor of 3 is actually the geometric mean of 10 which is 3.16; 3.16 × 3.16 = 10. Derivation of AEGL-2 for Chlorine Trifluoride Key study: Horn and Weir 1955 Toxicity end point: Strong irritation in dogs exposed to a concentration of 5.15 ppm for 6 h.
From page 86...
... Uncertainty Factors: 2 for interspecies 3 for intraspecies combined uncertainty factor of 6 C1.3 × t = k (this document; based on LC50 concentration Scaling: and exposure duration relationships in Horn and Weir [1955] , MacEwen and Vernot [1970]
From page 87...
... Chlorine Trifluoride 87 k = 3173.2 ppm1.3 · min 10 min 3173.2 ppm1.3 · min/10 min = 84 ppm AEGL-3: 30 min 3173.2 ppm1.3 · min/30 min = 36 ppm AEGL-3: 1h 3173.2 ppm1.3 · min/60 min = 21 ppm AEGL-3: 4h 3173.2 ppm1.3 · min/240 min = 7.3 ppm AEGL-3: 8h 3173.2 ppm1.3 · min/480 min = 4.3 ppmb AEGL-3: b Because the time-scaled 8 h AEGL-3 value of 4.3 ppm is inconsistent with the experimental data, the 8-h value was set equal to the 4-h value of 7.3 ppm.
From page 88...
... Uncertainty Factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 -- The dog is a sensitive species for nasal irritation and provides a good model for humans. Dogs exposed to 1.17 ppm showed obvious lacrimation after 3 h yet rats showed no effects at the same concentration for 6 h.
From page 89...
... Uncertainty Factors/Rationale: Total uncertainty factor: 10 Interspecies: 3 -- The dog is a sensitive species for nasal irritation and provides a good model for the human. Dogs exposed to 5.15 ppm (Continued)
From page 90...
... 1970. Toxic Hazards Research Unit Annual Technical Report: 1970, AMRL-TR-70-77, Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, OH.
From page 91...
... Uncertainty Factors/Rationale: Total uncertainty factor: 6 Interspecies: 2 -- Based on the similarity in respiratory parameters among primates. In addition, effects were similar among species and LC50 values varied by less than a factor of two for the monkey, rat, and mouse (indicating similar species sensitivity)


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