Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 7 (2009) / Chapter Skim
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4 Phenol
4 Phenol
Pages 178-234
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From page 178... ...
P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee)
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. A geometric mean odor detection threshold of 0.060 ppm (range of all critiqued odor thresholds 0.0045-1 ppm)
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. Continuous exposure to phenol vapor at 5 ppm for 90 days caused no hematologic or histologic effects in rhesus monkeys, rats, and mice.
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For the 10-min AEGL-1, the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period, and no supporting studies using short exposure periods were available for characterizing the concentration-time-response relationship. A level of distinct odor awareness (LOA)
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From page 182... ...
The other exposure duration-specific values were derived by time scaling according to the dose-response regression equation Cn × t = k, using the default of n = 3 for shorter exposure periods, because of the lack of suitable experimental data for deriving the concentration exponent. For the 10-min AEGL-2, the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period and no supporting studies using short exposure periods were available for characterizing the concentration-time-response relationship.
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HUMAN TOXICITY DATA 2.1. Acute Lethality No relevant studies documenting lethal effects in humans after inhalation exposure to phenol were identified.
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is liquid at room temperature Color Colorless ACGIH 1996 Assumes a pink to red discoloration on exposure to air and light Synonyms Carbolic acid; hydroxybenzene; ACGIH 1996 phenyl hydroxide; phenol Vapor pressure 0.48 hPa at 20°C IUCLID 1996 0.357 mm Hg at 20°C WHO 1994 1 mm Hg at 40.1°C Weast 1984 3.5 hPa at 25°C IUCLID 1996 2.48 mm Hg at 50°C WHO 1994 10 mm Hg at 73.8°C Weast 1984 18.39 hPa at 80.1°C IUCLID 1996 40 mm Hg at 100.1°C Weast 1984 100 mm Hg at 121.4°C Weast 1984 Density 1.0719 g/cm³ ACGIH 1996 Melting point 43°C Weast 1984 Boiling point 181.75°C Weast 1984 Solubility Very soluble in chloroform, alcohol, ACGIH 1996 ether, and aqueous alkali hydroxides; WHO 1994 67 g/L in water at 16°C Odor Sweet, tarlike odor ACGIH 1996 Sweet and acrid IARC 1999 Explosive limits in air 1.7% (lower) , 8.6% (upper)
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From page 185... ...
Based on tissue concentration autopsy tissue phenol concentrations between 106 and 874 mg/kg, 60 mg/kg in blood 1-d-old newborn Dermal 2% phenol solution in 125-202 mg/kg Cyanosis, death after 11 h, at Hinkel and Kintzel 1968 umbilical bandage Based on tissue concentration, autopsy tissue phenol assuming uniform distribution concentrations between 125 and no elimination and 202 mg/kg 185
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with disinfection fluid in the water reservoir. It should be noted that concentrations in the incubator were measured using simple solid sorbent test tubes.
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The following phenol concentrations were found: 60 mg/L in the blood, 208 mg/L in urine, 106 mg/L in the brain, 116 mg/L in the lung, and 874 mg/L in the kidney. Upon skin contact with liquefied phenol or phenol solutions, symptoms can develop rapidly leading to shock, collapse, coma, convulsions, cyanosis and death (NIOSH 1976; Lewin 1992)
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2.2. Nonlethal Toxicity Although some studies describe odor thresholds for phenol, no studies are available reporting adverse health effects after single inhalation exposures.
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. The American Industrial Hygiene Association reported a geometric mean odor detection threshold of 0.060 ppm (the range of all critiqued odor threshold studies was 0.0045-1 ppm)
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The phenol concentrations in drinking water for the persons in group 1 who had symptoms were more than 1 mg/L (the authors estimated an intake of phenol of 10-240 mg/d)
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Phenol exposure resulted in a statistically significant odds ratio (OR)
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Unfortunately, the phenol exposure was confounded by coexposure to other compounds, such as formaldehyde, asbestos, urea, melamine, hexamethylenediamine, wood dust, plasticizers, carbon black, ammonia, and antioxidants. On the basis of phenol concentrations obtained from historical monitoring and industrial hygiene surveys, the investigators assigned each job/department/year combination to groups with no, low, medium, or high phenol exposure and then calculated cumulative exposure.
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One study evaluated repeated inhalation exposure in guinea pigs. For oral exposure, several studies are summarized in Table 4-4.
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Deichmann and Witherup (1944) administered 2%, 5%, 10%, or 20% aqueous phenol by oral gavage to Wistar rats.
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(1944) exposed 12 guinea pigs to phenol vapor at 100200 mg/m³ (26-52 ppm)
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1990 no effects after 111 ppm Rat 26 24 h/d, 15 d After one day increased activity; during third Dalin and Kristofferson 1974 and fourth day impaired balance, disordered gait and muscle twitchings; sluggish Rat 0.5, 5, or 25 6 h/d, 5 d/w, 2 w No clinical, hematologic or histopathologic Huntingdon Life Sciences effects 1998; Hoffman et al. 2001 Rat 0.0026, 0.026, or 1.3 24 h/d, 61 d Significant motor chronaxy starting at 30 d in Mukhitov 1964 the two highest exposure groups Rat 5 24 h/d, 90 d No hematologic or histopathologic effects Sandage 1961 Rat 26-52 7 h/d, 5 d/w, 74 d No signs of gross or histopathologic change Deichmann et al.
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(1944) exposed sixrabbits to phenol vapor concentrations of 100-200 mg/m³ (26-52 ppm)
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No differences between control and phenol-exposed animals for clinical observations, body weights, food consumption, and clinical pathology were found. The authors stated that "scattered observations of chromodacryorrhea and nasal discharge" were noted during the 2 weeks of exposure.
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(1944) exposed 15 rats whole body to phenol vapor concentrations of 100-200 mg/m³ (26-52 ppm)
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(1981) determined the phenol vapor concentration associated with a 50% reduction in the respiratory rate (RD50)
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Although the number of resorptions was increased in all treated groups compared with the control group, this increase was not dosedependent and was not observed in a previous range-finding study. In the group given 120 mg/kg, fetal body weights were significantly reduced.
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There was no other evidence of altered prenatal viability or structural development. Thus, the high dose of 280 mg/kg/d was a maternal frank effect level and also a developmental LOAEL based on decreased fetal body weight (accompanied by a possible increase in the incidence of cleft palate)
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Rats exposed for 74 days showed neither clinical signs nor histologic alterations (Deichmann et al.
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. Reduced fetal body weights were found in studies using repeated oral gavage and doses of up to 120 mg/kg in CD rats (on gestational days 6-15)
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. The subjects were exposed to phenol vapor concentrations of 5, 10, or 25 mg/m³ (1.3, 2.6, or 6.5 ppm)
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Phenol, in both free and conjugated forms, is excreted rapidly in urine. Human volunteers, exposed to phenol concentrations between 5 and 25 mg/m³ (1.3-6.5 ppm)
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With regard to systemic it has been reported that phenol exposure results in hypotension and arrhythmias in humans and experimental animals (Deichmann and Witherup 1944; Bennett et al. 1950; Stajduhar-Caric 1968; Schaper 1981 Kamijo et al.
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(1944) found species differences after repeated inhalation exposure: 5 of 12 guinea pigs died after 20 exposures to phenol at 26-52 ppm for 7 h/d, 5 d/wk; under the same conditions, rabbits exposed for 88 days showed no signs of overt poisoning but some histologic degeneration in target tissues, and rats exposed for 74 days to the same concentrations developed neither clinical signs nor histologic alterations.
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1969) , and 0.060 ppm (mean odor detection thresholds from the literature)
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requirements for a key study and, therefore, was used for derivation of AEGL-1 values, although it was a repeated exposure study. After exposure of rats for 6 h/d, 5 d/wk for 2 weeks, no histopathologic alterations of the epithelium of the nasal turbinates or other respiratory tract tissues were found.
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to shorter exposure periods and a default value for n of 1 was used for extrapolation to longer exposure times. For the 10-min AEGL-1 the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period, and no supporting studies using short exposure periods were available for characterizing the concentration-timeresponse relationship.
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Rats appeared normal the following day. Because the aerosol concentration was below the vapor pressure at room temperature, it is likely that the animals were actually exposed to phenol vapor (or a vapor-aerosol mixture)
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For the 10-min AEGL-2, the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period, and no supporting studies using short exposure periods were available for characterizing the concentration-time-response relationship. The calculations of exposure concentrations scaled to AEGL-2 time periods are shown in Appendix A
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(1944) found that 5 of 12 guinea pigs died after 20 exposures to phenol at 26-52 ppm for 7 h/d, 5 d/wk; under the same conditions, rabbits exposed for 88 days showed no signs of poisoning but developed degeneration and necrosis in heart, liver, and kidney, and rats exposed for 74 days showed neither clinical signs nor histologic alterations.
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They were derived using the following key studies and methods. The AEGL-1 was based on a repeated inhalation exposure study in rats (Huntingdon Life Sciences 1998; Hoffman et al.
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Aerosol exposure to phenol at 900 mg/m³ (equivalent to phenol vapor at 234 ppm) for 8 h resulted in ocular and nasal irritation, slight loss of coordination, and spasms of the muscle groups at 4 h into the exposure; after 8 h, additional symptoms (tremor, incoordination, and prostration)
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FIGURE 4-1 Categorical representation of all phenol inhalation data.
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The ERPG-3 for phenol is based on the observation that exposure of rats at 235 ppm for 4 h resulted in ocular and nasal irritation, slight loss of coordination and muscular spasms, and no deaths (Flickinger 1976)
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laboratory animals, however, utilized accurate and reliable methods for characterizing exposure concentrations; however, exposure concentrations were often laboratory animals, however, utilized accurate and reliable methods for characterizing exposure concentrations; however, exposure concentrations were often used that did not lead to any adverse effects. Therefore, AEGL-1 values were based on a repeated exposure study in rats, in which no effects were found at the highest exposure concentration tested.
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1978. Phenol poisoning due to contaminated drinking water.
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Part VII. Chronic phenol poisoning with special reference to the effects upon experimental animals of the inhalation of phenol vapor.
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inhalation toxicity and two-week recovery study of phenol vapor in the rat. Huntingdon Life Sciences Study No.
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1964. The effect of low phenol concentrations on the organism of man or animals and their hygienic evaluation.
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2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals.
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1981. Toxic effects of benzene and benzene me tabolites on granulopoietic stem cells and bone marrow cellularity in mice.
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Uncertainty factors: Combined uncertainty factor of 3 1 for interspecies variability 3 for intraspecies variability Calculations: 10-min AEGL-1 10-min AEGL-1 = 19 ppm (73 mg/m³)
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for 8 h resulted in ocular and nasal irritation, slight loss of coordination and spasms of the muscle groups at 4 h into the exposure, after 8 h additional symptoms (tremor, incoordination and prostration) were observed in one of the six animals.
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It takes into account that in every day life factors, such as sex, age, sleep, smoking, upper airway infections, and allergy as well as distraction, increase the odor detection threshold by a factor of 4. In addition, it takes into account that odor perception is very fast (about 5 seconds)
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Phenol 229 to adjust for peak exposure. Adjustment for distraction and peak exposure lead to a correction factor of 4/3 = 1.33.
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inhalation toxicity and two-week recovery study of phenol vapor in the rat. Huntingdon Life Sciences Study No.
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For the 10-min AEGL-1, the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period, and no supporting studies using short exposure periods were available for characterizing the concentration-time-response relationship. (Continued)
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Aerosol exposure at 900 mg/m³ (equivalent to phenol vapor at 234 ppm) for 8 h resulted in ocular and nasal irritation, slight loss of coordination, and spasms of the muscle groups at 4 h into the exposure; after 8 h, additional symptoms (tremor, incoordination, and prostration)
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From page 233... ...
For the 10-min AEGL-2, the 30-min value was applied because the derivation of AEGL values was based on a long experimental exposure period and no supporting studies using short exposure periods were available for characterizing the concentration-time-response relationship. Data Adequacy: Both studies used for the AEGL-2 derivation had shortcomings, that is, aerosol exposures, nominal concentrations, and no description of toxic signs in one study.
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No acceptable vapor or aerosol LC50 studies in experimental animals or suitable reports on lethality after inhalation exposure in humans were available for the derivation of AEGL-3. Therefore, due to insufficient data and the uncertainties of a route-to-route extrapolation, AEGL-3 values were not recommended.
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