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Committee on Acute Exposure Guideline Levels; Committee on Toxicology; Board on Environmental Studies and Toxicology; Division on Earth and Life Studies; National Reserch Council. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 15. Washington (DC): National Academies Press (US); 2013 Sep 26.

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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 15.

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4. tert-Octyl Mercaptan1 Acute Exposure Guideline Levels

PREFACE

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 high-priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:

AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [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, nonsensory 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 concentrations that could 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 concentrations for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.

SUMMARY

tert-Octyl mercaptan is a colorless liquid with a disagreeable odor. It is used in polymer modification and as a lubricant additive. It is generally prepared via acid-catalyzed synthesis. It is moderately irritating to the eyes, and may cause headache, nausea, vomiting, and central nervous system (CNS) effects, resulting in dizziness, convulsions, unconsciousness, and respiratory depression (HSDB 2006).

Data were insufficient to derive AEGL-1 values for tert-octyl mercaptan. Therefore, AEGL-1 values are not recommended.

Data on tert-octyl mercaptan were also insufficient to derive AEGL-2 values. In the absence of appropriate chemical-specific data, AEGL-3 values were divided by 3 to derive AEGL-2 values for tert-octyl mercaptan. This approach is justified by the chemical's steep concentration-response curve for lethality in rats.

AEGL-3 values were based on a 4-h BMCL05 (benchmark concentration, 95% confidence limit with 5% response) value for tert-octyl mercaptan of 11.5 ppm, calculated from combined data on female rats (Temple University 1982). This concentration is considered a threshold for lethality and is based on the most sensitive test animals (females). An intraspecies uncertainty factor of 3 was applied and is considered sufficient because the point of departure is based on data from the more sensitive female animals and the steep concentration-response curve for lethality suggests limited intraindividual variability. An interspecies uncertainty factor of 3 was also applied because the limited data suggest no difference in species sensitivity between rats and mice. Therefore, the total uncertainty factor was 10. Values were scaled across time using the equation Cn × t = k, where default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations were used to derive values protective of human health (NRC 2001). The 30-min AEGL-3 value was adopted as the 10-min value because of the uncertainty in extrapolating a 4-h point of departure to a 10-min value.

AEGL values for tert-octyl mercaptan are presented in Table 4-1.

TABLE 4-1. AEGL Values for tert-Octyl Mercaptan.

TABLE 4-1

AEGL Values for tert-Octyl Mercaptan.

1. INTRODUCTION

tert-Octyl mercaptan is a colorless liquid with a disagreeable odor. It is used in polymer modification and as a lubricant additive. It is generally prepared via acid-catalyzed synthesis. It is moderately irritating to the eyes, and may cause headache, nausea, vomiting, and CNS effects, resulting in dizziness, convulsions, unconsciousness, and respiratory depression (HSDB 2006).

The chemical and physical properties of tert-octyl mercaptan are presented in Table 4-2.

TABLE 4-2. Chemical and Physical Data on tert-Octyl Mercaptan.

TABLE 4-2

Chemical and Physical Data on tert-Octyl Mercaptan.

2. HUMAN TOXICITY DATA

2.1. Acute Lethality

Human lethality data on tert-octyl mercaptan were not found.

2.2. Nonlethal Toxicity

Human nonlethal toxicity data on tert-octyl mercaptan were not found. No odor threshold data were available either.

2.3. Case Reports

No case reports on tert-octyl mercaptan were found.

2.4. Developmental and Reproductive Effects

Data on the developmental and reproductive toxicity of tert-octyl mercaptan in humans were not available.

2.5. Genotoxicity

No information regarding the genotoxicity of tert-octyl mercaptan in humans was available.

2.6. Carcinogenicity

No information was available regarding the carcinogenicity of tert-octyl mercaptan in humans.

2.7. Summary

No human data on tert-octyl mercaptan were found.

3. ANIMAL TOXICITY DATA

3.1. Acute Lethality

3.1.1. Rats

Fairchild and Stokinger (1958) exposed groups of five Wistar-derived male rats (body weight 180-220g) to tert-octyl mercaptan at 38, 40, 44, 55, 64, 78, or 110 ppm (analytic concentrations) for up to 4 h, followed by a 15-day observation period. Vapor was generated by either bubbling a stream of nitrogen gas through a midget fritted-glass bubbler, which contained liquid tert-octyl mercaptan, or by passage of nitrogen into a borosilicate glass nebulizer containing the tert-octyl mercaptan. Target concentrations were maintained in an 18-L glass chamber by varying the ratio of air flow volume and tert-octyl mercaptan containing compressed nitrogen. Tert-octyl mercaptan concentrations during exposure periods were measured by absorption of vapors in either isopropyl alcohol or acetone containing an excess of silver nitrate and titrating the uncombined silver amperometrically. Chamber concentrations during tests were uniform after the first 30 min; mean variation was approximately 4%. Clinical signs included respiratory stimulation, followed by CNS stimulation initially characterized by a “threshold effect” consisting of localized minimal convulsive movements in the form of repeated facial and ear twitches. Seizures were observed at all concentrations; the severity, frequency, and latency period for the onset of seizures were concentration related. Propulsive and retropulsive thrusts of the trunk were also observed, followed by circumscribed clonic convulsions of the forebody and forelimbs, resulting in a sitting position while pawing in the air. These effects were followed by generalized clonic seizures of the forelimbs and hindlimbs that caused a loss of upright position. Exophthalmus with conjunctival congestion and salivation accompanied the seizures. Muscle relaxation, irregular labored breathing, and coma preceded death. An LC50 (lethal concentration, 50% lethality) value of 51 ppm was calculated by the investigators. A BMC01 of 34.4 ppm and BMCL05 of 31.8 ppm were also calculated. Mortality data from this study are presented in Table 4-3.

TABLE 4-3. Mortality in Wistar Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

TABLE 4-3

Mortality in Wistar Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

Groups of five male and five female Sprague-Dawley rats were exposed to tert-octyl mercaptan at 0, 7, 15, 19, 29, 59, 71, or 110 ppm for 4 h, followed by a 14-day observation period (Temple University 1982). Exposures were conducted in an 11.4-ft3 stainless-steel chamber. Vapor was generated by heating liquid tert-octyl mercaptan and passing air through at a constant rate. Chamber delivery system parameters were set at values calculated to produce target chamber concentrations. Analyses of tert-octyl mercaptan concentrations in the test atmospheres were performed by colorimetric titration four to 20 times during each 4-h exposure. Clinical signs were noted in females at concentrations of 19 ppm and higher. The animals seized the wire mesh bottom of the exposure chamber with their teeth and claws, their backs were arched and tails extended, and they remained rigidly in this position until death or until the survivors were pried loose by the investigator. Salivation and a final convulsive leap were sometimes observed. Clinical signs included tremors and prostration in two of five males exposed at 71 ppm and all males exposed at 110 ppm. Animals that survived the first 24 h after exposure also survived until the end of the 14-day observation period. All surviving rats gained weight by the end of the observation period, and gross necropsy revealed no abnormalities. LC50 values of 33 ppm (males and females combined), 59 ppm (males), and 17 ppm (females) were calculated by the investigators. BMC01 values of 59.7 ppm (males) and 13.8 ppm (females) ppm and BMCL05 values of 52 ppm (males) and 11.3 ppm (females) were also calculated. Mortality data from this study are presented in Table 4-4.

TABLE 4-4. Mortality in Sprague-Dawley Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

TABLE 4-4

Mortality in Sprague-Dawley Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

Because of the results of the study above indicated that females are much more sensitive than male rats to acute lethality from tert-octyl mercaptan, another study was conducted in female rats. Groups of 10 female Sprague-Dawley rats were exposed to tert-octyl mercaptan at 12, 14, 17, 18, or 19 ppm for 4 h, followed by a 14-day observation period (Temple University 1982). The experimental methods were similar to those described for the previous study. Tremors and clonic convulsions were observed in all test groups. All animals that survived the first 24 h after exposure also survived until the end of the observation period. No signs of hemorrhage or other signs of visible pathology were found in rats that died. At the end of the 14-day observation period, 19 of 21 surviving rats gained weight, and gross necropsy revealed no abnormalities. An LC50 value of 17 ppm (15-19 ppm) was calculated by the investigators. A BMC01 value of 10.7 ppm and BMCL05 value of 10.1 ppm was also calculated. Mortality data from this study are presented in Table 4-5.

TABLE 4-5. Mortality in Female Sprague-Dawley Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

TABLE 4-5

Mortality in Female Sprague-Dawley Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

When the data on female rats presented in Tables 4-4 and 4-5 are combined to calculate benchmark levels, a 4-h BMCL05 of 11.5 ppm and BMC01 of 14.7 ppm result (see Appendix C). Combining the data is acceptable because the data sets are from the same laboratory and used similar experimental methods.

Groups of five male and five female Charles River CD rats were exposed to tert-octyl mercaptan at 23, 24, 25, 73, 77, or 79 ppm (nominal concentrations) for 4 h, followed by a 14-day observation period (Amoco 1979). Exposures were conducted in a 160-L cubical, stainless steel and glass chamber. Test vapors were generated by passing air at a rate of 10 L/min through a round-bottom flask containing tert-octyl mercaptan in a heating jacket. Chamber concentrations were calculated from the ratio of the rate of vapor dissemination to the rate of total chamber airflow. Clinical signs included convulsions, with females affected more frequently and with greater severity than males; clinical signs were observed at 73 ppm or higher in males and at 24 ppm or higher in females. All surviving rats lost weight on day 1 post-exposure compared with pre-exposure values. Male survivors gained weight by the end of the observation period; however, female survivors only maintained their body weight. Rats dying during exposure had red- or pink-colored lungs or lungs with red patches or scattered red pin points at necropsy. No gross pathologic effects were noted in animals killed at the end of the observation period. LC50 values of 50 ppm (males and females combined), 79 ppm (males), and 24 ppm (females) were calculated by the investigators. BMC01 values of 65.9 ppm (males) and 21.5 ppm (females) ppm and BMCL05 values of 63.9 ppm (males) and 21.0 ppm (females) were also calculated. Data from this study are presented in Table 4-6.

TABLE 4-6. Mortality in Charles-River Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

TABLE 4-6

Mortality in Charles-River Rats Exposed to tert-Octyl Mercaptan for 4 Hours.

A group of 10 male Wistar rats was exposed to tert-octyl mercaptan at 330 ppm (nominal concentration) and observed until death (Pharmacology Research Inc. 1970). All of the rats died; deaths occurred within 19, 22, 26, 27, 30, 32, 40, and 49 min of exposure. Clinical signs included muscular spasms, violent clonic convulsions, prostration, and terminal dyspnea.

Fairchild and Stokinger (1958) administered tert-octyl mercaptan by oral gavage in ethanol, intraperitoneal injection, or dermal application to Wistar-derived male rats, followed by 15-day observation periods. An oral LD50 (lethal dose, 50% lethality) of 85.3 mg/kg, an intraperitoneal LD50 of 12.9 mg/kg, and a dermal LD50 of 1,954 mg/kg were reported.

Nine of 10 rats administered tert-octyl mercaptan at 50 mg/kg in sesame oil by stomach tube died within 30-143 min after intubation (Pharmacology Research Inc. 1970). The surviving rat was observed for 5 days. Clinical signs included muscular spasms, violent clonic convulsions, prostration, and terminal dyspnea.

3.1.2. Mice

Fairchild and Stokinger (1958) exposed groups of 10 Swiss-derived male mice (body weight 25-28 g) to tert-octyl mercaptan at 38, 40, 44, 55, 64, or 78 ppm (analytic concentrations) for up to 4 h, followed by a 15-day observation period. Vapor was generated and the test chamber analyzed in the same manner as the study in rats. Clinical signs in the mice were similar to those described for the rat in Section 3.1.1. An LC50 value of 47 ppm was calculated by the investigators. A BMC01 of 34.4 ppm and BMCL05 of 33.6 ppm were also calculated. Mortality data from this study are presented in Table 4-7.

TABLE 4-7. Mortality in Male Swiss Mice Exposed to tert-Octyl Mercaptan for 4 Hours.

TABLE 4-7

Mortality in Male Swiss Mice Exposed to tert-Octyl Mercaptan for 4 Hours.

Groups of five male MF1 mice were exposed to tert-octyl mercaptan at 42, 58, 84, 117, or 167 ppm (nominal concentrations) for 1 h, followed by a 6-day observation period (Pharmacology Research Inc. 1969). Clinical signs were noted at all test concentrations and included hypertonicity, hypersensitivity, and multiple clonic-tonic convulsions. Mortality was 0/5, 2/5, 4/5, 5/5, and 5/5 at concentrations of 42, 58, 84, 117, and 167 ppm, respectively. All deaths occurred during exposure. An LC50 value of 69 ppm was calculated by the investigators. A BMC01 of 37.6 ppm and BMCL05 of 28.4 ppm were also calculated. No further details were available.

Fairchild and Stokinger (1958) administered single dermal applications of tert-octyl mercaptan at 213, 427, or 854 mg/kg to groups of two New Zealand white rabbits, followed by a 72-h observation period. Both rabbits in the 854- mg/kg group died within 8 h, and none of the rabbits in the 213- or 427-mg/kg groups died.

Ten albino rabbits were administered a single dermal application of tert-octyl mercaptan at 200 mg/kg for 4 h, followed by a 5-day observation period (Pharmacology Research Inc. 1970). No mortality or signs of toxicity were observed, and animals had normal body weight gain.

3.1.4. Summary of Animal Lethality Data

Inhalation lethality studies of tert-octyl mercaptan in rats and mice are available. Lethality data suggest a steep concentration-response curve for tert-octyl mercaptan. In studies of male rats exposed to tert-octyl mercaptan for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958), 0% at 59 ppm and 80% at 71 ppm (Temple University 1982), and 0% at 73 ppm and 100% at 79 ppm (Amoco 1979). In a study of female rats exposed to tert-octyl mercaptan for 4 h, mortality was10% at 12 ppm and 100% at 18 ppm. In mice exposed for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958). Rat data suggest that females are much more sensitive to tert-octyl mercaptan than males; calculated 4-h LC50 values were 59 ppm for male rats and 17 ppm for female rats in one study (Temple University 1982) and 79 ppm for males and 24 ppm for females in another (Amoco 1979). Clinical signs were indicative of CNS stimulation followed by central depression and finally death from respiratory failure.

3.2. Nonlethal Toxicity

No animal data on the nonlethal toxicity of tert-octyl mercaptan were found.

3.3. Developmental and Reproductive Effects

No animal developmental and reproductive data on tert-octyl mercaptan were found.

3.4. Genotoxicity

No genotoxicity data on were found.

3.5. Carcinogenicity

No carcinogenicity data on tert-octyl mercaptan were found.

4. SPECIAL CONSIDERATIONS

4.1. Metabolism and Disposition

Metabolism and disposition data for tert-octyl mercaptan were not available.

4.2. Mechanism of Toxicity

Most mercaptans act similarly to hydrogen sulfide and cyanide by interrupting electron transport through inhibition of cytochrome oxidase, and general signs of acute mercaptan poisoning are indicative of central depression and respiratory paralysis, followed by death from respiratory failure (NIOSH 1978). However, data suggest that tert-octyl mercaptan acts differently because an initial effect of CNS stimulation is observed. Fairchild and Stokinger (1958) reported that the stimulatory effects of tert-octyl mercaptan were typical of other CNS stimulants such as picrotoxin and metrazol, and that the compound appeared to act at various levels of the cerebrospinal axis. Convulsive seizures were spontaneous in origin (not triggered by external stimuli), and tert-octyl mercaptan had an analeptic action on the higher CNS centers, as evidenced by the fact that subconvulsant doses stimulated the respiratory and vasomotor centers (Fairchild and Stokinger 1958). The analeptic action was demonstrated by the ability of tert-octyl mercaptan to counteract depression produced by barbiturates. Even though the CNS stimulation is unique to tert-octyl mercaptan, the final result of acute toxicity is similar to other mercaptans: the CNS stimulation was followed by central depression and then death from respiratory failure.

4.3. Structure-Activity Relationships

Acute intraperitoneal, oral, and inhalation data in rats and inhalation data in mice suggest that tert-octyl mercaptan is more toxic than other mercaptans tested (with the exception of phenyl mercaptan) and more toxic than hydrogen sulfide (see Table 4-8).

TABLE 4-8. Comparative Toxicity of Mercaptans.

TABLE 4-8

Comparative Toxicity of Mercaptans.

4.4. Species Variability

Although data are limited, acute lethality studies suggest that rats and mice have similar sensitivity to the lethal effects of tert-octyl mercaptan. The 4-h LC50 is 51 ppm in male rats and 47 ppm in male mice (Fairchild and Stokinger 1958).

4.5. Gender Variability

Experimental data in rats (see Tables 4-4 and 4-5) suggest that females are more sensitive than males to the toxic effects of tert-octyl mercaptan (Amoco 1979; Temple University 1982).

4.6. Temporal Extrapolation

The concentration-time relationship for many irritant and systemically acting vapors and gases may be described by the equation Cn × t = k, where the exponent n ranges from 0.8 to 3.5 (ten Berge et al. 1986). In the absence of data to calculate an empirical value of n, temporal scaling was performed using default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations.

5. DATA ANALYSIS FOR AEGL-1

5.1. Human Data Relevant to AEGL-1

No human data on tert-octyl mercaptan relevant deriving AEGL-1 values were available.

5.2. Animal Data Relevant to AEGL-1

No animal data on tert-octyl mercaptan relevant to deriving of AEGL-1 values were available.

5.3. Derivation of AEGL-1 Values

AEGL-1 values for tert-octyl mercaptan are not recommended because of insufficient data.

6. DATA ANALYSIS FOR AEGL-2

6.1. Human Data Relevant to AEGL-2

No human data on tert-octyl mercaptan relevant to deriving of AEGL-2 values were found.

6.2. Animal Data Relevant to AEGL-2

No animal data on tert-octyl mercaptan relevant to deriving AEGL-2 values were found.

6.3. Derivation of AEGL-2 Values

In the absence of appropriate chemical-specific data, AEGL-3 values were divided by 3 to derive AEGL-2 values for tert-octyl mercaptan. This approach is justified because of the steep concentration-response curve for lethality. (See Section 7.3 for description of lethality data that demonstrates the steepness.) AEGL-2 values were presented in Table 4-9, and calculations are presented in Appendix A.

TABLE 4-9. AEGL-2 Values for tert-Octyl Mercaptan.

TABLE 4-9

AEGL-2 Values for tert-Octyl Mercaptan.

The AEGL-2 values are considered protective for the following reasons. No effects (clinical signs or mortality) were noted in male or female rats exposed to tert-octyl mercaptan at 7 ppm for 4 h (Temple University 1982), and a slightly higher concentration of 12 ppm caused clinical signs (tremors and clonic convulsions) in 90% and mortality in 10% of the female rats (Temple University 1982). If 7 ppm was used as a point of departure and the same time-scaling procedure and uncertainty factors were applied as described earlier, the resulting values (1.4 for the 10- and 30-min, 1.1 ppm for the 1-h, 0.70 ppm for the 4-h, and 0.35 for the 8-h values) would be slightly higher than the AEGL-2 values.

7. DATA ANALYSIS FOR AEGL-3

7.1. Human Data Relevant to AEGL-3

No human data on tert-octyl mercaptan relevant to deriving AEGL-3 values were available.

7.2. Animal Data Relevant to AEGL-3

A 4-h LC50 value of 51 ppm was calculated by Fairchild and Stokinger (1958) for Sprague-Dawley rats; a BMC01 of 34.4 ppm and BMCL05 of 31.8 ppm were also calculated from this study.

In another study of Sprague-Dawley rat (Temple University 1982), 4-h LC50 values of 33 ppm (males and females combined), 59 ppm (males), and 17 ppm (females) were calculated by the investigators; BMC01 values of 59.7 ppm (males) and 13.8 ppm (females) and BMCL05 values of 52 ppm (males) and 11.3 ppm (females) were also calculated. In a follow-up study with female Sprague-Dawley rats (Temple University 1982), a 4-h LC50 value of 17 ppm (15-19 ppm) was calculated by the investigators; a BMC01 value of 10.7 ppm and BMCL05 value of 10.1 ppm were also calculated. Combining the female rat data from the original and follow-up studies yields a 4-h BMCL05 of 11.5 ppm and BMC01 of 14.7 ppm.

In a study with Charles River rats (Amoco 1979), 4-h LC50 values of 50 ppm (males and females combined), 79 ppm (males), and 24 ppm (females) were calculated by the investigators; BMC01 values of 65.9 ppm (males) and 21.5 ppm (females) ppm and BMCL05 values of 63.9 ppm (males) and 21.0 ppm (females) were also calculated.

In a mouse study (Fairchild and Stokinger 1958), a 4-h LC50 value of 47 ppm was calculated by the investigators; a BMC01 of 34.4 ppm and BMCL05 of 33.6 ppm were also calculated. In another mouse study (Pharmacology Research Inc. 1970), a 1-h LC50 value of 69 ppm was calculated by the investigators; a BMC01 of 37.6 ppm and BMCL05 of 28.4 ppm were also calculated.

7.3. Derivation of AEGL-3 Values

The 4-h BMCL05 value of 11.5 ppm calculated from the combined female rat data (Atochem 1982) was used as the point of departure for AEGL-3 values. That concentration is considered a threshold for lethality based on the most sensitive test animals (females). This point of departure was chosen over the most conservative benchmark value calculated from a single study (10.1 ppm) because the statistical goodness-of-fit was much greater for the combined data set (p = 0.86) than for a single data set (p = 0.15). An intraspecies uncertainty factor of 3 was applied and was considered sufficient because the point of departure is based on data from the more sensitive female rats. Calculated 4-h LC50 values were 59 ppm for male rats and 17 ppm for female rats in one study (Temple University 1982) and 79 ppm for males and 24 ppm for females in another (Amoco 1979). Also, the steep concentration-response curve implies limited intraindividual variability. In studies of male rats exposed to tert-octyl mercaptan for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958), 0% at 59 ppm and 80% at 71 ppm (Temple University 1982), and 0% at 73 ppm and 100% at 79 ppm (Amoco 1979). In a study of female rats exposed to tert-octyl mercaptan for 4 h, mortality was10% at 12 ppm and 100% at 18 ppm. In mice exposed for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958). An interspecies uncertainty factor of 3 was applied because the limited data suggest no difference in species sensitivity between rats and mice (the 4-h LC50 is 51 ppm for male rats and 47 ppm for male mice [Fairchild and Stokinger 1958]). Therefore, the total uncertainty factor was 10. Values were scaled across time using the equation Cn × t = k, where default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations were used to derive values protective of human health (NRC 2001). The 30-min AEGL-3 value was adopted as the 10-min value because of the uncertainty in extrapolating a 4-h point of departure to a 10-min value.

AEGL-3 values for tert-octyl mercaptan are presented in Table 4-10, and calculations are provide in Appendix A.

TABLE 4-10. AEGL-3 Values for tert-Octyl Mercaptan.

TABLE 4-10

AEGL-3 Values for tert-Octyl Mercaptan.

8. SUMMARY OF AEGLs

8.1. AEGL Values and Toxicity End Points

AEGL-1 values are not recommended for tert-octyl mercaptan because of insufficient data. AEGL-2 values were derived by dividing the AEGL-3 values by 3, and the AEGL-3 values were based on a threshold for lethality in female rats (BMCL05). AEGL values for tert-octyl mercaptan are presented in Table 4-11.

TABLE 4-11. AEGL Values for tert-Octyl Mercaptan.

TABLE 4-11

AEGL Values for tert-Octyl Mercaptan.

8.2. Comparisons with Other Standards and Guidelines

There are no other exposure standards or guidelines for tert-octyl mercaptan.

8.3. Data Adequacy and Research Needs

Human data on tert-octyl mercaptan are limited. Additional data on toxicity in females in species other than rats would be helpful.

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  • Temple University. Initial Submission: Final Report on a Study to Establish an LC50 Concentration of t-Octyl Mercaptan in Adult Sprague-Dawley Rats of Both Sexes (Final), September 17, 1982. 1982. (Submitted to EPA by Atochem North America, Inc., King of Prussia, PA with Cover Letter Dated 12/23/91). EPA Document No 88920000497. Microfiche No. OTS0534950.
  • tenBerge WF, Zwart A, Appelman LM. J. Hazard. Mater. 3. Vol. 13. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases; pp. 301–309.

APPENDIX A DERIVATION OF AEGL VALUES FOR TERT-OCTYL MERCAPTAN

Derivation of AEGL-1 Values

AEGL-1 values are not recommended for tert-octyl mercaptan because of insufficient data.

Derivation of AEGL-2 Values

In the absence of relevant data to derive AEGL-2 values and because tert-octyl mercaptan has a steep concentration-response curve, AEGL-3 values were divided by 3 to estimate a threshold for inability to escape.

10-min AEGL-2:2.3 ppm ÷ 3 = 0.77 ppm
30-min AEGL-2:2.3 ppm ÷ 3 = 0.77 ppm
1-h AEGL-2:1.8 ppm ÷ 3 = 0.60 ppm
4-h AEGL-2:1.2 ppm ÷ 3 = 0.40 ppm
8-h AEGL-2:0.58 ppm ÷ 3 = 0.19 ppm

Derivation of AEGL-3 Values

Key study:Temple University. 1982. Initial Submission: Final Report on a Study to Establish an LC50 Concentration of t-Octyl Mercaptan in Adult Sprague-Dawley Rats of Both Sexes (Final), September 17, 1982. Submitted to EPA by Atochem North America, Inc., King of Prussia, PA with Cover Letter Dated 12/23/91. EPA Document No, 88920000497. Microfiche No. OTS0534950.
Toxicity end point:4-h threshold for lethality in female rats, BMCL05 of 11.5 ppm
Time scaling:
  • Cn × t = k (default values of n = 3 for extrapolating to shorter durations and n = 1 for extrapolating to longer durations); time scaling not performed for the 10-min AEGL-3 because of the uncertainty in extrapolating a 4-h point of departure to a 10-min value.
  • (11.5 ppm)1 × 4 h = 46 ppm-h
  • (11.5 ppm)3 × 4 h = 6,084 ppm-h
Uncertainty factors:
  • 3 for interspecies differences
  • 3 for intraspecies variability
Modifying factor:Not applicable

Calculations:

10-min AEGL-3:2.3 ppm (30-min AEGL-3 value adopted)
30-min AEGL-3:
  • C3 × 0.5 h = 6,084 ppm-h
  • C = 23 ppm
  • C = 23 ppm ÷ 10 = 2.3 ppm
1-h AEGL-3:
  • C3 × 1 h = 6,084 ppm-h
  • C = 18 ppm
  • C = 18 ppm ÷ 10 = 1.8 ppm
4-h AEGL-3:11.5 ppm ÷ 10 = 1.2 ppm
8-h AEGL-3:
  • C1 × 8 h = 46 ppm-h
  • C = 5.8 ppm
  • C = 5.8 ppm ÷ 10 = 0.58 ppm

APPENDIX B ACUTE EXPOSURE GUIDELINE LEVELS FOR tert-OCTYL MERCAPTAN

AEGL-1 VALUES

Data are insufficient to derive AEGL-1 values for tert-octyl mercaptan; therefore, AEGL-1 values are not recommended. Absence of AEGL-1 values does not imply that concentrations below the AEGL-2 are without effect.

AEGL-2 VALUES

10 min30 min1 h4 h8 h
0.77 ppm (4.6 mg/m3)0.77 ppm (4.6 mg/m3)0.60 ppm (3.6 mg/m3)0.40 ppm (2.4 mg/m3)0.19 ppm (1.1 mg/m3)

Data adequacy: Data inadequate to derive AEGL-2 values. AEGL-3 values were divided by 3 to estimate thresholds for the inability to escape.

AEGL-3 VALUES

10 min30 min1 h4 h8 h
2.3 ppm (14 mg/m3)2.3 ppm (14 mg/m3)1.8 ppm (11 mg/m3)1.2 ppm (7.2 mg/m3)0.58 ppm (3.5 mg/m3)

Reference: Temple University. 1982. Initial Submission: Final Report on a Study to Establish an LC50 Concentration of t-Octyl Mercaptan in Adult Sprague-Dawley Rats of Both Sexes (Final), September 17, 1982. Submitted to EPA by Atochem North America, Inc., King of Prussia, PA with Cover Letter Dated 12/23/91. EPA Document No. 88920000497. Microfiche No. OTS0534950.

Test species/Strain/Sex/Number: Rat, Sprague-Dawley, females, 10/group

Exposure route/Concentrations/Durations: Inhalation; 7, 15, 19, 29, 59, 71, 110 ppm and 12, 14, 17, 18, 19 ppm for 4 h

Effects:

Concentration (ppm)Mortality
70/5
151/5
195/5
295/5
595/5
715/5
1105/5
121/10
143/10
175/10
1810/10
1910/10

BMCL05 = 11.5 ppm

BMC01 = 14.7 ppm

End point/Concentration/Rationale: Threshold for lethality, BMCL05 of 11.5 ppm

Uncertainty factors/Rationale:

Interspecies: 3, data suggest no difference in species sensitivity between rats and mice (4-h LC50 is 51 ppm for male rats and 47 ppm male mice [Fairchild and Stokinger 1958]). Intraspecies: 3, considered sufficient because the point of departure is from the more sensitive female rats. Calculated 4-h LC50 values were 59 ppm for male rats and 17 ppm for female rats in one study (Temple University 1982) and 79 ppm for males and 24 ppm for females in another (Amoco 1979). Also, the steep concentration-response curve implies limited intraindividual variability. In studies of male rats exposed to tert-octyl mercaptan for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958), 0% at 59 ppm and 80% at 71 ppm (Temple University 1982), and 0% at 73 ppm and 100% at 79 ppm (Amoco 1979). In a study of female rats exposed to tert-octyl mercaptan for 4 h, mortality was10% at 12 ppm and 100% at 18 ppm. In mice exposed for 4 h, mortality was 0% at 38 ppm and 100% at 64 ppm (Fairchild and Stokinger 1958).

Modifying factor: Not applicable

Animal-to-human dosimetric adjustment: Not applicable

Time scaling: Cn × t = k; default values of n = 3 when extrapolating to shorter durations and n = 1 when extrapolating to longer durations to derive values protective of human health (NRC 2001). The 30-min AEGL-3 value was adopted as the 10-min value because of the uncertainty in extrapolating a 4-h point of departure to 10-min value.

Data adequacy: Well-conducted studies in rats and mice. Additional studies of females in species other than rats species would be useful.

APPENDIX C BENCHMARK CALCULATION FOR TERT-OCTYL MERCAPTAN

Temple University (1982): Combined female data for two studies

Probit Model (Version: 2.9; Date: 09/23/2007)

Input Data File: C:\BMDS\UNSAVED1.(d)

Gnuplot Plotting File: C:\BMDS\UNSAVED1.plt

Fri Jun 13 10:37:19 2008

BMDS MODEL RUN

The form of the probability function is:

P[response] = Background

+ (1-Background) * CumNorm(Intercept+Slope*Log(Dose)),

where CumNorm(.) is the cumulative normal distribution function

Dependent variable = COLUMN2

Independent variable = COLUMN1

Slope parameter is restricted as slope >= 1

Total number of observations = 13

Total number of records with missing values = 0

Maximum number of iterations = 250

Relative Function Convergence has been set to: 1e-008

Parameter Convergence has been set to: 1e-008

User has chosen the log transformed model

Default Initial (and Specified) Parameter Values

Background = 0

Intercept = -2.865

Slope = 1.09606

Asymptotic Correlation Matrix of Parameter Estimates

 BackgroundIntercept
Background1-0.19
Intercept-0.191

(***The model parameter(s) -slope have been estimated at a boundary point, or have been specified by the user, and do not appear in the correlation matrix).

Parameter Estimates

VariableEstimateStandard Error95.0% Wald Confidence Interval
Lower Confidence LimitUpper Confidence Limit
Background0.134430.05791670.02091530.247945
Intercept-50.75510.346663-51.4345-50.0756
Slope18NA  

NA: indicates that this parameter has hit a bound implied by some inequality constraint and thus has no standard error.

Analysis of Deviance Table

ModelLog (likelihood)No. ParametersDeviance TestDFP-value
Full model-18.79313   
Fitted model-22.80228.01802110.7117
Reduced model-60.1424182.698812<0.0001

AIC: 49.6039

Goodness of Fit

   Scaled  
DoseEstimated ProbabilityExpectedObservedSizeResidual
0.00000.13440.67205-0.881
7.00000.13440.67205-0.881
15.00000.15370.768150.287
19.00000.98934.946550.233
29.00001.00005.000550.000
59.00001.00005.000550.000
71.00001.00005.000550.000
110.00001.00005.000550.000
12.00000.13441.344110-0.319
14.00000.13491.3493101.528
17.00000.65026.502510-0.996
18.00000.91199.11910100.983
19.00000.98939.89310100.329

Chi-square = 6.19; DF = 11; P-value = 0.8602

Benchmark Dose Computation

Specified effect = 0.05

Risk type = Extra risk

Confidence level = 0.95

BMD = 15.3075

BMDL = 11.5133

Probit Model (Version: 2.9; Date: 09/23/2007)

Input Data File: C:\BMDS\UNSAVED1.(d)

Gnuplot Plotting File: C:\BMDS\UNSAVED1.plt

Fri Jun 13 10:40:03 2008

BMDS MODEL RUN

The form of the probability function is:

P[response] = Background

+ (1-Background) * CumNorm(Intercept+Slope*Log(Dose)),

where CumNorm(.) is the cumulative normal distribution function

Dependent variable = COLUMN2

Independent variable = COLUMN1

Slope parameter is restricted as slope >= 1

Total number of observations = 13

Total number of records with missing values = 0

Maximum number of iterations = 250

Relative Function Convergence has been set to: 1e-008

Parameter Convergence has been set to: 1e-008

User has chosen the log transformed model

Default Initial (and Specified) Parameter Values

Background = 0

Intercept = -2.865

Slope = 1.09606

Asymptotic Correlation Matrix of Parameter Estimates

 BackgroundIntercept
Background1-0.19
Intercept-0.191

(***The model parameter(s) -slope have been estimated at a boundary point, or have been specified by the user, and do not appear in the correlation matrix).

Parameter Estimates

VariableEstimateStandard error95.0% Wald Confidence Interval
Lower confidence limitUpper confidence limit
Background0.134430.05791670.02091530.247945
Intercept-50.75510.346663-51.4345-50.0756
Slope18NA  

NA: indicates that this parameter has hit a bound implied by some inequality constraint and thus has no standard error.

FIGURE C-1. Probit model with 0.95 confidence level.

FIGURE C-1Probit model with 0.95 confidence level

Analysis of Deviance Table

ModelLog (likelihood)No. ParametersDeviance TestDFP-value
Full model-18.79313   
Fitted model-22.80228.01802110.7117
Reduced model-60.1424182.698812<0.0001

Goodness of Fit

   Scaled  
DoseEstimated probabilityExpectedObservedSizeResidual
0.00000.13440.67205-0.881
7.00000.13440.67205-0.881
15.00000.15370.768150.287
19.00000.98934.946550.233
29.00001.00005.000550.000
59.00001.00005.000550.000
71.00001.00005.000550.000
110.00001.00005.000550.000
12.00000.13441.344110-0.319
14.00000.13491.3493101.528
17.00000.65026.502510-0.996
18.00000.91199.11910100.983
19.00000.98939.89310100.329

Chi-square = 6.19; DF = 11; P-value = 0.8602

Benchmark Dose Computation

Specified effect = 0.01

Risk type = Extra risk

Confidence level = 0.95

BMD = 14.7388

BMDL = 10.2853

APPENDIX D CATEGORY PLOT FOR tert-OCTYL MERCAPTAN

FIGURE D-1. Category plot of toxicity data and AEGL values for ethyl mercaptan. The decimal point is lost on this log-scale plot.

FIGURE D-1Category plot of toxicity data and AEGL values for ethyl mercaptan. The decimal point is lost on this log-scale plot

TABLE D-1Data Used in Category Plot for tert-Octyl Mercaptan

SourceSpeciesSexNo. ExposuresppmMinutesCategoryEffect
AEGL-1   NR10AEGL 
AEGL-1   NR30AEGL 
AEGL-1   NR60AEGL 
AEGL-1   NR240AEGL 
AEGL-1   NR480AEGL 
AEGL-2   0.7710AEGL 
AEGL-2   0.7730AEGL 
AEGL-2   0.6060AEGL 
AEGL-2   0.40240AEGL 
AEGL-2   0.19480AEGL 
AEGL-3   2.310AEGL 
AEGL-3   2.330AEGL 
AEGL-3   1.860AEGL 
AEGL-3   1.2240AEGL 
AEGL-3   0.58480AEGL 
 RatMale1382402Seizures
 RatMale140240PLMortality 1/6; seizures
 RatMale144240PLMortality 1/5; seizures
 RatMale155240PLMortality 3/5; seizures
 RatMale1642403Mortality 5/5; seizures
 RatMale1782403Mortality 6/6; seizures
 RatMale11102403Mortality 6/6; seizures
 RatMale/Female172400No effects
 RatMale/Female115240PLMortality: male 0/5; female 1/5
 RatMale/Female119240PLMortality: male 0/5; female 5/5
 RatMale/Female129240PLMortality: male 0/5; female 5/5
 RatMale/Female159240PLMortality: male 0/5; female 5/5
 RatMale/Female171240PLMortality: male 4/5; female 5/5
 RatFemale112240PLMortality 1/10
 RatFemale114240PLMortality 3/10
 RatFemale117240PLMortality 5/10
 RatFemale1182403Mortality 10/10
 RatFemale1192403Mortality 10/10
 RatMale/Female1232402Convulsions
 RatMale/Female124240PLMortality: male 0/5; female 1/5
 RatMale/Female125240PLMortality: male 0/5; female 5/5
 RatMale/Female173240PLMortality: male 0/5; female 5/5
 RatMale/Female177240PLMortality: male 4/5; female 5/5
 RatMale/Female1792403Mortality: male 5/5; female 5/5
 MouseMale1382402Seizures
 MouseMale140240PLMortality 2/10
 MouseMale144240PLMortality 4/10
MouseMale155240PLMortality 9/10
MouseMale1642403Mortality 10/10
MouseMale1782403Mortality 10/10
MouseMale142602Convulsions
MouseMale15860PLMortality 2/5
MouseMale18460PLMortality 4/5
MouseMale1117603Mortality 5/5
MouseMale1167603Mortality 5/5

For category: 0 = no effect, 1 = discomfort, 2 = disabling, 3 = lethal; PL = partially lethality.

Footnotes

1

This document was prepared by the AEGL Development Team composed of Cheryl Bast (Oak Ridge National Laboratory), Gary Diamond (SRC, Inc.), Chemical Manager Glenn Leach (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances), and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001).

Copyright 2013 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK201341

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