Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 20 (2016) / Chapter Skim
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2 Chloroformates Acute Exposure Guideline Levels
2 Chloroformates Acute Exposure Guideline Levels
Pages 10-132
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From page 10... ...
The alkyl substituent is responsible for the thermal stability of the chloroformate in the following order of decreasing stability: aryl (e.g., benzyl chloroformate, phenyl chloroformate) > primary alkyl (e.g., methyl chloroformate, ethyl chloroformate, n-propyl chloroformate, n-butyl chloroformate)
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(air = 1) Point, °C Point, °C limit limit Methyl 94.5 Slightly 20.5 (25)
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From page 12... ...
. j Stauffer Chemical Company (1983)
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From page 13... ...
Chlorof oformates Acutee Exposure Gu uideline Levels 13 other chloroformates were not foun nd. Data on atmmospheric hydrrolysis, the effefect of relattive humidity on hydrolysis rates, and perrsistence in thhe atmosphere of chlorofformates were not available.
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From page 14... ...
Pulmonary edema frequently occurs, and its symptoms may not manifest for several hours after exposure and may be aggravated by physical exertion. Delayed pulmonary edema resulting in hospitalization and requiring treatment has occurred in people accidentally exposed to unknown concentrations of methyl chloroformate (Schuckmann 1972; Penkovitch and Anikin 1988)
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From page 15... ...
– – 8,000 Isobutyl chloroformate – – – 8,000 sec-Butyl chloroformate – – – – Benzyl chloroformate – – 85 16,800 Phenyl chloroformate – – 30 – 2-Ethylhexyl – – 33.9 – chloroformate Ethyl chlorothioformate – – 45 2,770 (mercaptan) Hydrogen chlorideb 3,124 – a See sections on the individual chloroformates for the sources of the LC50 values.
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From page 16... ...
Environmental Protection Agency and the Canadian Health and Welfare Department (EPA 1983) , 618 of 867 non-acute toxicity studies (including subacute, sub-chronic, carcinogenicity, reproductive toxicity, genotoxicity, and neurotoxicity studies)
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From page 17... ...
No acute inhalation data appropriate for deriving AEGL-2 values for methyl chloroformate were available. Thus, the AEGL-2 values were calculated by taking one-third of the AEGL-3 values.
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From page 18... ...
2.1 ppm (8.2 mg/m3) Ethyl chloroformate AEGL-1 (nondisabling)
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From page 19... ...
0.91 ppm (7.2 mg/m3) Ethyl chlorothioformate AEGL-1 (nondisabling)
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From page 20... ...
Supporting information for this mode of action comes from observations in rats of nasal irritation and respiratory effects (e.g., pulmonary congestion, pulmonary edema, and increased pulmonary weights) in short-term repeated-exposure studies of methyl chloroformate (Gage 1970; Kenny et al.
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From page 21... ...
2.2. Chemical and Physical Properties Methyl chloroformate hydrolyzes in water to form methanol, carbon dioxide, and hydrogen chloride.
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From page 22... ...
22 Acute Exposure Guideline Levels TABLE 2-6 Chemical and Physical Properties of Methyl Chloroformate Parameter Value Reference Common name Methyl chloroformate HSDB 2014a Synonyms Carbonochloridic acid, methylethyl ester; HSDB 2014a chlorocarbonic acid, methylethyl ester; chloroformic acid methyl ester; formic acid, chloro-, methyl ester; methyl chlorocarbonate; K-stoff; methoxycarbonyl chloride; TL 438 CAS registry no. 79-22-1 HSDB 2014a Chemical formula C2H3ClO2 HSDB 2014a Molecular weight 94.5 HSDB 2014a Physical state Colorless liquid HSDB 2014a Melting point -81°C HSDB 2014a Boiling point 71.0°C HSDB 2014a Flash point 12.2°C HSDB 2014a Density HSDB 2014a Vapor 3.26 g/L (air = 1)
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From page 23... ...
2.3.3. Developmental and Reproductive Toxicity No developmental or reproductive studies of acute human exposure to methyl chloroformate were available.
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From page 24... ...
TABLE 2-7 Mortality in Charles River Albino Rats Exposed to Methyl Chloroformate for 1 Hour Concentration, ppm Males Females Males and Females 0 0/5 0/5 0/10 145 4/5 0/5 4/10 173 5/5 2/5 7/10 233 5/5 4/5 9/10 274 5/5 1/5 6/10 BMCL05 – – 74 ppm LC50 – – 163 ppm Abbreviations: BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality. Source: Adapted from IBT 1975.
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From page 25... ...
Methyl chloroformate was administered into the incoming air stream just before it entered the chamber port, and exposure concentrations were calculated by dividing the total amount sprayed into the chamber by the total cubic feet of air circulated through the chamber. All animals died within 18 h of exposure (see Table 2-8)
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From page 26... ...
Methyl chloroformate concentrations were measured every 15 min during exposure using a single beam photometer, and were measured analytically every 120 min using gas chromatography. Clinical signs observed in all treatment groups in a concentration-related manner included palpebral fissure narrowed or closed; increased grooming; squatting posture; accelerated, irregular, and jerky respiration; gasping; drowsiness; staggering movements; wimpering and crackling breathing sounds; sneezing; and piloerection.
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From page 27... ...
Pulmonary emphysema with petechial hemorrhages and dilation on the right side of the heart were observed at necropsy. TABLE 2-9 Mortality in SPF Wistar Rats Exposed to Methyl Chloroformate for 4 Hours Concentration, ppm Males Females Males and Females 35 0/5 0/5 0/10 45 0/5 0/5 0/10 57 5/5 3/5 8/10 73 5/5 5/5 10/10 LC50 51 ppm 53 ppm – BMCL05 – – 42.4 ppm BMC01 – – 47.8 ppm Abbreviations: BMC05, benchmark concentration, 1% response; BMCL01, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality.
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From page 28... ...
Pulmonary edema and emphysema and bilateral dilation of the heart were found at necropsy. Death occurred in 10/10 rats exposed to an "atmosphere enriched or saturated" with methyl chloroformate vapor (20°C)
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From page 29... ...
In a repeated-exposure study, groups of five male and five female Sprague-Dawley rats were exposed to methyl chloroformate at 0, 0.13, 0.38, 1.01, 3.1, or 8.8 ppm for 6 h/day, 5 days/week for 4 weeks (BASF 1993)
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From page 30... ...
2.4.3. Developmental and Reproductive Toxicity Developmental and reproductive studies regarding animal exposure to methyl chloroformate were not available.
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From page 31... ...
Human Data Relevant to AEGL-1 No human data on methyl chloroformate consistent with the definition of AEGL-1 were available.
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From page 32... ...
1986 Mouse 52.4 30 min RD50 Carpenter 1982a Repeated Exposure Rat 0.40 6 h/d, 3 d No effects BASF 1999a Rat 2.15 6 h/d, 3 d Histopathology BASF 1999a Rat 3.98 6 h/d, 3 d Histopathology, decreased body weight BASF 1999a Rat 7.83 6 h/d, 3 d Clinical signs, histopathology, decreased body weight BASF 1999a Rat 1.9 6 h/d, 5 d No effects Kenny et al. 1992 Rat 6.2 6 h/d, 5 d Clinical signs consistent with irritation, focal epithelia Kenny et al.
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From page 33... ...
Rat 19.5 6 h/d, 5 d Clinical signs consistent with irritation, focal epithelia hyperplasia, Kenny et al. 1992 inflammatory and erosive mucous membrane changes, petechial lung bleeding, increased lung weight, pneumonia Rat 0.40 6 h/d, 5 d/wk, 2 wk No effects BASF 1999a Rat 2.15 6 h/d, 5 d/wk, 2 wk Histopathology BASF 1999a Rat 3.98 6 h/d, 5 d/wk, 2 wk Histopathology, cell proliferation BASF 1999a Rat 7.83 6 h/d, 5 d/wk, 2 wk Clinical signs, histopathology, cell proliferation, increased BASF 1999a lung weight Rat 1 6 h, 15 exposures No effects Gage 1970 Rat 5 6 h, 15 exposures Nasal irritation, lethargy Gage 1970 Rat 20 6 h, 15 exposures Nasal irritation, respiratory difficulty, lethargy, lung pathology, Gage 1970 renal congestion Rat 0.13 6 h/d, 5 d/wk, 4 wk No effects BASF 1993 Rat 0.38 6 h/d, 5 d/wk, 4 wk No effects BASF 1993 Rat 0.40 6 h/d, 5 d/wk, 4 wk No effects BASF 1999a Rat 1.01 6 h/d, 5 d/wk, 4 wk Larynx lesions BASF 1993 Rat 2.15 6 h/d, 5 d/wk, 4 wk Histopathology, cell proliferation BASF 1999a Rat 3.1 6 h/d, 5 d/wk, 4 wk Nasal turbinate histopathology, larynx lesions BASF 1993 Rat 3.98 6 h/d, 5 d/wk, 4 wk Histopathology, cell proliferation BASF 1999a Rat 7.83 6 h/d, 5 d/wk, 4 wk Clinical signs, histopathology, cell proliferation, increased lung weight BASF 1999a Rat 8.8 6 h/d, 5 d/wk, 4 wk 3/10 deaths in final week of exposure, clinical signs, decreased body BASF 1993 weight, hematologic effects, pulmonary congestion, increased lung weight, nasal turbinate histopathology, larynx lesions Rat 0.40 6 h/d, 5 d/wk, 13 wk No effects BASF 1999a Rat 2.15 6 h/d, 5 d/wk, 13 wk Histopathology, cell proliferation BASF 1999a (Continued)
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From page 34... ...
34 TABLE 2-12 Continued Species Concentration, ppm Exposure Duration Effect Reference Rat 3.98 6 h/d, 5 d/wk, 13 wk Histopathology, cell proliferation, decreased body weight BASF 1999a Rat 7.83 6 h/d, 5 d/wk, 13 wk 4/10 deaths-males (after 24, 32, 36, or 41 exposures) , clinical signs, BASF 1999a histopathology, cell proliferation, increased lung weight, decreased body weight Abbreviations: BMCL01, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality; RD50, concentration that reduces the respiratory rate by 50%.
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From page 35... ...
2.6.2. Animal Data Relevant to AEGL-2 No acute animal data on methyl chloroformate consistent with the definition of AEGL-2 were available.
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Human Data Relevant to AEGL-3 Human lethality data on methyl chloroformate were anecdotal and lacked reliable concentration and exposure duration information. Thus, those reports were not appropriate for establishing AEGL-3 values.
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From page 37... ...
The AEGL-3 values are further supported by the results of repeatedexposure studies. No deaths occurred in rats exposed to methyl chloroformate at 7.8 ppm for 6 h/day, 5 days/week for 4 weeks (BASF 1999a)
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From page 38... ...
TABLE 2-16 Standards and Guidelines for Methyl Chloroformate Exposure Duration Guideline 10 min 30 min 1h 4h 8h AEGL-1 NRa NRa NRa NRa NRa AEGL-2 4.0 ppm 2.8 ppm 2.2 ppm 1.4 ppm 0.70 ppm (16 mg/m3)
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From page 39... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate.
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From page 40... ...
3.3.3. Developmental and Reproductive Toxicity Developmental and reproductive studies of acute human exposure to ethyl chloroformate were not available.
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From page 41... ...
TABLE 2-18 Chemical and Physical Properties of Ethyl Chloroformate Parameter Value Reference Common name Ethyl chloroformate HSDB 2003a Synonyms Ethyl chlorocarbonate HSDB 2003a CAS registry no. 541-41-3 HSDB 2003a Chemical formula C3H5ClO2 HSDB 2003a Molecular weight 108.5 HSDB 2003a Physical state Water-white liquid HSDB 2003a Melting point -80.6°C HSDB 2003a Boiling point 95°C HSDB 2003a Flash point 27.8°C HSDB 2003a Vapor density 3.7 g/L (air = 1)
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From page 42... ...
The report suggests that ethyl chloroformate is a respiratory-tract irritant and is capable of inducing delayed pulmonary edema, but no exposure concentration or duration information was available. No humans studies of the developmental toxicity, reproductive toxicity, genotoxicity, or carcinogenicity of ethyl chloroformate were available.
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From page 43... ...
Pulmonary congestion and edema were found at necropsy. Death occurred in 11/12 rats exposed to an "atmosphere enriched or saturated" with ethyl chloroformate vapor (20°C)
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From page 44... ...
3.4.2. Developmental and Reproductive Toxicity Studies concerning the developmental and reproductive toxicity of ethyl chloroformate were not found.
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From page 45... ...
Human Data Relevant to AEGL-1 No human data on ethyl chloroformate consistent with the definition of AEGL-1 were available.
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From page 46... ...
Human Data Relevant to AEGL-2 No appropriate human data on ethyl chloroformate consistent with the definition of AEGL-2 were available.
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From page 47... ...
Human Data Relevant to AEGL-3 No human data on ethyl chloroformate consistent with the definition of AEGL-3 were available.
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From page 48... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 49... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. b ERPG-1 (emergency response planning guidelines, American Industrial Hygiene Association)
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From page 50... ...
Supporting information for this mode of action comes from observations in rats of nasal irritation and respiratory effects (e.g., pulmonary inflammation, pulmonary edema, and emphysema) in short-term repeated-exposure studies of isopropyl chloroformate (Gage 1970; Collins and Proctor 1984)
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From page 51... ...
4.3.3. Developmental and Reproductive Toxicity Developmental and reproductive studies on acute human exposure to isopropyl chloroformate were not available.
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From page 52... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. TABLE 2-26 Chemical and Physical Properties of Isopropyl Chloroformate Parameter Value Reference Common name Isopropyl chloroformate HSDB 2014b Synonyms Carbonochloride acid, 1-methylethyl ester; HSDB 2014b carbonochloridic acid, 1-methylethyl ester; chloroformic acid isopropyl ester; formic acid, chloro-, isopropyl ester; isopropyl chlorocarbonate; isopropyl chloromethonate CAS registry no.
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From page 53... ...
Acute Lethality 4.4.1.1. Rats Groups of five male and five female young adult Charles River albino rats were exposed to nominal concentrations of isopropyl chloroformate vapor at 300, 1,640, or 15,600 ppm for up to 1 h (IBT 1970b)
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From page 54... ...
In an acute oral toxicity study (IBT 1971) , groups of two male and two female Charles River albino rats were administered isopropyl chloroformate by gavage at 118.5, 177.8, 266.7, or 400 mg/kg and observed up to 14 days.
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From page 55... ...
In another study (Anderson 1984) , groups of four male Swiss-Webster mice were exposed head only to isopropyl chloroformate vapor at nominal concentrations of 0, 177, 306, 443, or 883 ppm for 15 min.
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From page 56... ...
4.4.3. Developmental and Reproductive Toxicity No developmental or reproductive toxicity studies of isopropyl chloroformate were available.
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From page 57... ...
4.4.6. Summary Animal toxicity data on isopropyl chloroformate are sparse.
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From page 58... ...
Rat 25 (analytical) 6 h/d, 5 d Decreased body weight Collins and gain, increased pulmonary Proctor 1984 weight, enlarged bronchial lymph nodes, peribronchiolar mononuclear cell infiltrate, focal pulmonary emphysema.
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From page 59... ...
4.6.3. Derivation of AEGL-2 Values No appropriate acute inhalation data on isopropyl chloroformate consistent with the definition of AEGL-2 were available.
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From page 60... ...
Supporting information for this mode of action comes from observations in rats of nasal irritation and respiratory effects (e.g., pulmonary inflammation, pulmonary edema, and emphysema) in short-term repeated-exposure studies of isopropyl chloroformate (Gage 1970; Collins and Proctor 1984)
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From page 61... ...
AEGL-2 values were estimated by dividing the AEGL-3 values by 3, and AEGL-3 values were based a nonlethal concentration identified in a repeated-exposure study. A derivation summary and category plot of the AEGL values and toxicity data are presented in Appendixes C and D, respectively.
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From page 62... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. b ERPG-1 (emergency response planning guidelines, American Industrial Hygiene Association)
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From page 63... ...
Acute inhalation lethality studies of isopropyl chloroformate conducted in accordance with current testing standards would help provide confirmation of the available animal toxicity data and provide chemical-specific acute 1-hour inhalation toxicity data to support the AEGL values.
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From page 64... ...
(19 mg/m3) isopropyl chloroformate a Treatment of people exposed to chloroformates should consider that pulmonary edema frequently occurs, but its symptoms may not manifest for several hours after exposure and may be aggravated by physical exertion.
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From page 65... ...
5.3.3. Developmental and Reproductive Toxicity Developmental and reproductive studies on acute human exposure to n-propyl chloroformate were not available.
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From page 66... ...
Acute Lethality 5.4.1.1. Rats Groups of five male and five female young adult Charles River albino rats (320 g, average weight)
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From page 67... ...
. Clinical signs included vigorous escape behavior, severe mucous membrane irritation, and gasping.
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From page 68... ...
Although RD50 values are not used in the development of AEGL values, an RD50 was reported, the data was reported and no dose response relationship was observed, limiting its usefulness in development of an AEGL3. Results of the study are summarized in Table 2-38.
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From page 69... ...
Human Data Relevant to AEGL-1 No human data on n-propyl chloroformate consistent with the definition of AEGL-1 were available.
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From page 70... ...
Human Data Relevant to AEGL-3 No human data on n-propyl chloroformate consistent with the definition of AEGL-3 were available.
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From page 71... ...
Data were also insufficient for deriving AEGL-2 and AEGL-3 values, so the AEGL values for isopropyl chloroformate were adopted for n-propyl chloroformate, as available data indicate that the two chemicals have similar toxicity.
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From page 72... ...
Acute inhalation lethality studies of n-propyl chloroformate conducted in accordance with current testing standards would help provide confirmation of the available animal toxicity lethality data and provide chemical-specific data to support the AEGL values.
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From page 73... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate.
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From page 74... ...
6.3.4. Genotoxicity Genotoxicity studies on acute human exposure to allyl chloroformate were not available.
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From page 75... ...
Clinical signs were observed in all exposure groups and included decreased activity, body tremors, constricted pupils, diarrhea, emaciation, epistaxis, gasping, lacrimation, nasal discharge, piloerection, polyuria, ptosis, respiratory gurgle, and salivation. Nine of the 10 rats exposed at 33.7 ppm gained weight over the 14-day observation period, and the tenth animal retained a constant weight.
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From page 76... ...
6.4.5. Summary Animal toxicity data on allyl chloroformate include one well-conducted rat lethality study, which described clinical signs consistent with severe irritation.
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From page 77... ...
6.6.3. Derivation of AEGL-2 Values No appropriate acute inhalation data on allyl chloroformate consistent with the definition of AEGL-2 were available.
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From page 78... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 79... ...
(1.3 mg/m3) a Treatment of people exposed to chloroformates should consider that pulmonary edema frequently occurs, but its symptoms may not manifest for several hours after exposure and may be aggravated by physical exertion.
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From page 80... ...
Supporting information for this mode of action comes from observations of nasal irritation and respiratory effects (pulmonary inflammation, pulmonary edema, and emphysema) observed in humans and animals for several chloroformates evaluated in this report.
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From page 81... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. TABLE 2-48 Chemical and Physical Properties of n-Butyl Chloroformate Parameter Value Reference Common name n-Butyl chloroformate Kreutzberger 2001 Synonyms Butyl chlorocarbonate; BG Chemie 2005 butoxycarbonyl chloride; chloroformic acid, butyl ester CAS registry no.
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From page 82... ...
2001a Solubility Miscible in chloroform, benzene, ether; O'Neil et al. 2001a gradually decomposes in water Conversion factors in air 1 mg/m3 = 0.18 ppm – 1 ppm = 5.6 mg/m3 TABLE 2-50 Chemical and Physical Properties of sec-Butyl Chloroformate Parameter Values Reference Common name sec-Butyl chloroformate Kreutzberger 2001 Synonyms Carbonochloridic acid, ChemIDplus 2012 1-methylpropyl ester CAS registry no.
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From page 83... ...
. Clinical signs included vigorous escape behavior, severe mucous membrane irritation, and gasping.
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From page 84... ...
Pulmonary weights were increased in high-concentration males and females and in mid-concentration females. In a repeated-exposure study, groups of five male and five female Sprague-Dawley rats were exposed to n-butyl chloroformate at 0, 0.50, 1.8, or 5.1 ppm for 6 h/day, 5 days/week for 4 weeks (HRC 1990)
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From page 85... ...
7.4.3. Developmental and Reproductive Toxicity No information on the developmental or reproductive toxicity of n-butyl chloroformate, isobutyl chloroformate, or sec-butyl chloroformate was found.
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From page 86... ...
n-Butyl chloroformate was negative in both bacterial reverse-mutation and mammalian-cell chromosome-aberration assays; no genotoxicity data were available for isobutyl chloroformate or sec-butyl chloroformate. No developmental toxicity, reproductive toxicity, or carcinogenicity data on n-butyl chloroformate, isobutyl chloroformate, or sec-butyl chloroformate were available.
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From page 87... ...
Human Data Relevant to AEGL-2 No human data on n-butyl chloroformate, isobutyl chloroformate, or secbutyl chloroformate consistent with the definition of AEGL-2 were available.
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From page 88... ...
7.7.2. Animal Data Relevant to AEGL-3 Death occurred in 4/10 rats exposed to n-butyl chloroformate at 200 ppm for 1 h (BASF 1970g)
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From page 89... ...
AEGL Values and Toxicity End Points Data were insufficient to derive AEGL-1 values for n-butyl, isobutyl, or sec-butyl chloroformate, so no values recommended. For n-butyl chloroformate, no appropriate acute inhalation data consistent with the definition of AEGL-2 were available.
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From page 90... ...
Mortality rates in rats exposed to benzyl chloroformate for 4 h were 0/10 at 18.6 ppm and 5/10 at 84.6 ppm (BASF 1990a) ; clinical signs in surviving rats resolved (were reversible)
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From page 91... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate.
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From page 92... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 values is without adverse effects. TABLE 2-56 Chemical and Physical Data on Benzyl Chloroformate Parameter Value Reference Common name Benzyl chloroformate HSDB 2014d Synonyms Carbonochloridic acid phenyl methyl ester; HSDB 2014d carbobenzoxy chlorode; chloroformic acid benzyl ester; benzyl carbonyl chloride CAS registry no.
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From page 93... ...
Acute Lethality Groups of five male and five female SPF Wistar rats were exposed to benzyl chloroformate at 18.6 or 84.6 ppm (analytic concentrations) for 4 h, followed by a 14-day observation period (BASF 1990a)
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From page 94... ...
Human Data Relevant to AEGL-1 No human data on benzyl chloroformate consistent with the definition of AEGL-1 were available.
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From page 95... ...
. Lethality data on benzyl chloroformate provide evidence of a steep curve; mortality rates in rats exposed for 4 h were 0/10 at 18.6 ppm and 5/10 at 84.6 ppm (BASF 1990a)
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From page 96... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 97... ...
A derivation summary and category plot of the AEGL values and toxicity data are presented in Appendixes C and D, respectively.
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From page 98... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate, isopropyl chloroformate, and n-butyl chloroformate.
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From page 99... ...
Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. TABLE 2-62 Chemical and Physical Properties of Phenyl Chloroformate Parameter Value Reference Common name Phenyl chloroformate IPCS 2005c Synonyms Carbonochloridic acid phenyl IPCS 2005c ester; phenyl chlorocarbonate; phenoxycarbonyl chloride; formic acid, chloro-, phenyl ester CAS registry no.
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From page 100... ...
Acute Lethality 9.4.1.1. Rats Groups of five male and five female SPF Wistar rats were exposed to phenyl chloroformate at 15.6, 74.9, or 159.3 ppm (analytic concentrations)
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From page 101... ...
Mortality data from this study are summarized in Table 2-63. TABLE 2-63 Mortality in Rats Exposed to Phenyl Chloroformate for 4 Hours Males Females Males and Females 15.6 ppm 0/5 2/5 2/10 74.9 ppm 4/5 5/5 9/10 159.3 ppm 5/5 5/5 10/10 LC50 46.8 ppm 15.8 ppm 28 ppm BMCL05 7.45 ppm 0.49 ppm 3.2 ppm BMC01 45.8 ppm 8.99 ppm 41.5 ppm Abbreviations: BMC01, benchmark concentration with 1% response; BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality.
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From page 102... ...
TABLE 2-64 Mortality in Rats Exposed to Phenyl Chloroformate for 4 Hours Males Females Males and Females 1.76 ppm 0/5 0/5 0/10 44.5 ppm 4/5 3/5 7/10 97 ppm 5/5 4/5 9/10 156 ppm 5/5 5/5 10/10 311 ppm 5/5 5/5 10/10 LC50 38.9 ppm 43 ppm 39.6 ppm BMCL05 0.68 ppm 1.9 ppm 1.33 ppm BMC01 27 ppm 31 ppm 5.3 ppm must be an error correct value is 29 ppm Abbreviations: BMC01, benchmark concentration with 1% response; BMCL05, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality. Source: Hofmann 1989.
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From page 103... ...
No clinical signs or additional details were provided. Death occurred in 0/12, 4/6, 6/6, and 6/6 rats exposed to an "atmosphere enriched or saturated" with phenyl chloroformate vapor (20°C)
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From page 104... ...
Human Data Relevant to AEGL-1 No human data on phenyl chloroformate consistent with the definition of AEGL-1 were available.
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From page 105... ...
. Lethality data on phenyl chloroformate provide evidence of a steep curve; mortality rates in rats exposed for 4 h were 2/10 at 15.6 ppm, 7/10 at 44.5 ppm, and 9/10 at 74.9 ppm (Hofmann 1989; BASF 1990b)
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From page 106... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 107... ...
A derivation summary and category plot of the AEGL values and toxicity data are presented in Appendixes C and D, respectively.
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From page 108... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 109... ...
rat BMCL05 (BASF 1985) a Treatment of people exposed to chloroformates should consider that pulmonary edema frequently occurs, but its symptoms may not manifest for several hours after exposure and may be aggravated by physical exertion.
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From page 110... ...
10.3.6. Summary No reports on the lethal toxicity, nonlethal toxicity, developmental toxicity, reproductive toxicity, genotoxicity, or carcinogenicity of 2-ethylhexyl chloroformate in humans were available.
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From page 111... ...
Clinical signs during exposure included closed palpebral fissure, red ocular and nasal discharge, irregular respiration, restlessness, squatting posture, and ruffled fur in the 26.6-, 34.3-, and 46.9-ppm groups. Clinical signs during the post-exposure observation period included irregular respiration, respiratory sounds, reddish nasal discharge, and staggering in the 46.9-ppm group.
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From page 112... ...
TABLE 2-72 Mortality in Wistar Rats Exposed to 2-Ethylhexyl Chloroformate for 4 Hours Males and Males Time to Death Females Time to Death Females 22.8 ppm 0/10 – 0/10 – 0/20 26.6 ppm 4/10 2 on day of exposure 1/10 Day 14 post-exposure 5/20 2 on day 1 post-exposure 34.3 ppm 7/10 2 on day of exposure 2/10 Day 1 post-exposure 9/20 5 on day 1 post-exposure 46.9 ppm 10/10 8 on day of exposure 10/10 3 on day of exposure 20/20 2 on day 1 post-exposure 7 on day 1 post-exposure LC50 29.9 ppm 36.3 ppm 33.9 ppm BMCL05 18.1 ppm 26.0 ppm 20.1 ppm BMC01 19.7 ppm 31.9 ppm 21.1 ppm Abbreviations: BMCL01, benchmark concentration, 95% lower confidence limit with 5% response; LC50, lethal concentration, 50% lethality. Source: BASF 1985.
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From page 113... ...
. No animal data on the developmental toxicity, reproductive toxicity, genotoxicity, or carcinogenicity of 2-ethylhexyl chloroformate were available.
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From page 114... ...
. Lethality data on 2-ethylhexyl chloroformate provide evidence of a steep curve; mortality rates in rats exposed for 4 h were 0/20 at 22.8 ppm, 5/20 at 26.6 ppm, 9/20 at 34.3 ppm, and 20/20 at 46.9 ppm (BASF 1985)
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From page 115... ...
10.7.2. Animal Data Relevant to AEGL-3 Two lethality studies of rats exposed to 2-ethylhexyl chloroformate for 4 h were available (BASF 1985; WIL Laboratories, Inc.
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From page 116... ...
. Use of these factors is consistent with the ones applied in calculating AEGL-3 values for the structural analogs, methyl chloroformate (see Section 2.7.3)
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From page 117... ...
. Lethality data on ethyl chlorothioformate provide evidence of a steep curve; the mortality rate in rats exposed for 4 h was 4/20 at 33 ppm, 14/20 at 59 ppm, and 20/20 at 65 ppm.
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From page 118... ...
TABLE 2-77 AEGL Values for Ethyl Chlorothioformatea End Point Classification 10 min 30 min 1h 4h 8h (Reference) AEGL-1 NRb NRb NRb NRb NRb Insufficient (nondisabling)
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From page 119... ...
1970 Conversion factors in air 1 mg/m3 = 0.20 ppm – 1 ppm = 5.1 mg/m3 11.3.3. Developmental and Reproductive Toxicity No developmental or reproductive toxicity studies of acute human exposure to ethyl chlorothioformate were available.
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From page 120... ...
, groups of 10 male and 10 female Sprague-Dawley rats were exposed to ethyl chlorothioformate at 0, 33, 59, 65, 69, or 124 ppm for 4 h, followed by a 14-day observation period. The exposure protocol was similar to that described in the Stauffer Chemical Company (1982)
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From page 121... ...
. Ethyl chlorothioformate was negative in an Ames assay, and no animal data on the nonlethal toxicity, developmental toxicity, reproductive toxicity, or carcinogenicity of ethyl chlorothioformate were available.
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From page 122... ...
. Lethality data on ethyl chlorothioformate provide evidence of a steep curve; mortality rates in rats exposed for 4 h were 4/20 at 33 ppm, 14/20 at 59 ppm, and 20/20 at 65 ppm (Stauffer Chemical Company 1983)
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From page 123... ...
11.7.2. Animal Data Relevant to AEGL-3 The following 4-h LC50 values for ethyl chlorothioformate were estimated from lethality studies of rats (Stauffer Chemical Company 1983)
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From page 124... ...
The only animal toxicity data were from lethality studies in rats. TABLE 2-82 AEGL Values for Ethyl Chlorothioformatea Classification 10 min 30 min 1h 4h 8h AEGL-1 NRb NRb NRb NRb NRb (nondisabling)
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From page 125... ...
2006a. Methyl Chloroformate (CAS Reg.
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From page 126... ...
1980a. Acute Inhalation Toxicity LC50 of Methyl Chloroformate as a Vapor After 4-hour Exposure in Sprague-Dawley Rats [in German]
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From page 127... ...
1993. Initial Submission: Subacute Inhalation Toxicity of Chloroformic Acid Methyl Ester in Rats.
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From page 128... ...
1981a. Acute Vapor Inhalation Range-Finding, LC50, and Toxicity Study of Methyl Chloroformate in Rats.
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From page 129... ...
1975. Acute Vapor Inhalation Toxicity Study with Methyl Chloroformate in Rats.
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From page 130... ...
2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Substances.
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From page 131... ...
1968. A fatal methyl chloroformate intoxication and 13 other incidences of health impairment after exposure to methyl chloroformate [in Ger man]
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From page 132... ...
2002. Acute Vapor Inhalation Toxicity Study of 2-Ethylhexyl Chloroformate in Albino Rats.
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Key Terms
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