M E M O R A N D U M

To:		William Balke, Perrin Quarles Associates, Inc.

cc:		Margaret Sheppard, U.S. EPA

		Erin Birgfield, U.S. EPA

		

From:		Naida Gavrelis, ERG

		Whitney Long, CIH, ERG

Date:		June 8, 2004

Subject:	EPA Contract No. 68W02029, Work Assignment No.108: Analysis of
Health and Environmental Impacts of ODS Substitutes—Evaluating the
need to set a short-term exposure or ceiling limit for n-propyl bromide

Introduction/Summary

The purpose of this memorandum is to assist EPA in determining whether a
short-term exposure limit should be set for n-propyl bromide (nPB). To
accomplish this task, ERG reviewed the reason for and the manner in
which such limits are generally selected, and applied this knowledge to
what is known about exposure and shorter-term health effects associated
with nPB.

The available data suggest that current information is inadequate to
develop a short-term exposure limit (STEL) or ceiling limit for nPB.
Additionally, it is not clear that such a limit would result in a
substantial improvement in worker safety and health. This conclusion is
based on the following points, which provide the framework for
subsequent discussions:

Our understanding of the definition and derivation of STELs.

The lack of concrete exposure levels associated with reports of
subjective health effects in humans, as well as the lack of evidence of
more defined acute toxicity endpoints. 

The extent to which the proposed 8-hour time-weighted-average (8-hr TWA)
will also limit workers’ short-term exposure levels.

Reported short-term exposure levels of nPB from workplace and simulation
studies.

Available animal data (lethality and acute toxicity) for short-term nPB
exposures offer little additional insights.

Discussion

Definition and derivation of STELs or ceiling values

Short-term and ceiling values are intended to minimize toxic effects
related to peak exposure of a contaminant. Such values are necessary
when immediate acute response to an air contaminant is possible, and is
independent of the total daily dose or when chronic effects are
dose-rate response related. As defined by the American Conference of
Governmental Industrial Hygienists (ACGIH), a STEL is:

The concentration to which it is believed that workers can be exposed
continuously for a short period of time without suffering from 1)
irritation, 2) chronic or irreversible tissue damage, or 3) narcosis of
sufficient degree to increase the likelihood of accidental injury,
impair self-rescue, or materially reduce work efficiency (ACGIH 2003).

STEL values are not an independent exposure guideline, but instead are
intended to supplement time-weighted average (TWA) exposure limits when
the characteristics of a substance indicate that the 8-hr TWA exposure
level is insufficient to protect workers from harmful effects of
short-term exposure (ACGIH 2004). ACGIH recommends STELs only in cases
where toxic effects have been reported from high short-term exposure in
either humans or animals (ACGIH 2003). Ceiling values are the absolute
maximum concentration allowed during any part of a working day. Because
instantaneous monitoring is not feasible, the ceiling can be assessed by
sampling over a period of not more than 15 minutes (ACGIH 2003).

In general, the Occupational Safety and Health Administration (OSHA)
establishes STELs or ceiling limits when the toxicological evidence for
a particular substance indicates that the 8-hour TWA PEL alone would be
insufficient to protect employees from experiencing adverse effects
related to short-term exposure to elevated concentrations of that
substance. [See Attachment 1 for a discussion of trends in ACGIH and
OSHA STEL/ceiling limits set for other substances.]

Available human health effects data for nPB

Workers exposed to nPB have reported effects such as eye and throat
irritation, headache, and blurred vision, but symptoms have not been
consistent between workplaces and neither exposure-effect levels, nor
exposure-response relationships have been defined. Several workplace
evaluations reviewed below provide examples of the symptoms reported
with full-shift exposures to nPB. Note that nPB was contaminated with a
notable percentage of 2-bromopropane at one of the workplaces.

The National Institute for Occupational Safety and Health (NIOSH)
evaluated nPB exposures and health effects/symptoms in several
facilities. In one such facility employees sprayed an aerosol nPB
adhesive product. Initially, full-shift nPB exposure levels were between
41 and 143 parts per million (ppm) (mean 65.9 ppm), with 15- and
5-minute exposure levels in a similar range. These results suggest that
airborne nPB concentrations were relatively constant throughout the day
(i.e., peak measured exposures did not greatly exceed average daily
exposures), thus the full-shift TWA results were not the result of a few
short periods of elevated exposure (NIOSH 2002). 

By the time the medical survey was conducted at this site, recent
changes in the ventilation system had reduced nPB exposures at this
facility to daily mean levels of 16.6 to 23.3 ppm, with occasional
results still exceeding 25 ppm. Some employees reported symptoms
consistent with solvent overexposure (headache, blurred vision);
however, headache was the only effect that varied significantly between
the exposed and a control group. Symptom reviews, blood tests,
neurological testing, and reproductive histories obtained by NIOSH
(2002) were inadequate to determine whether chronic nPB exposure
resulted in health effects. 

At another facility evaluated by NIOSH (2000), workers reported
headaches, nausea, “feeling faint,” and mucous membrane irritation
when the company started using nPB as a degreasing solvent. These
complaints were not reported after the process was enclosed and local
exhaust ventilation installed. Air sampling conducted by NIOSH after
controls were installed indicated full-shift exposure levels were
generally less than 1 ppm, with occasional short-term results up to 8.4
ppm. No sampling was conducted before the process was controlled. 

Ichihara et al. (2004) indicated that in a Chinese nPB manufacturing
plant, 10 to 30 percent of workers exposed to nPB at TWA levels between
76 ppm and 170 ppm (the maximum result) for 12 hours reported nose,
throat, and eye irritation, or malaise and/or headache. These symptoms
were less common (10 percent) in workers exposed to daily average levels
between 56.9 ppm and 76 ppm. No “severe chronic symptoms suggestive of
neurological damage” were found in either group. The symptomology at
this workplace may be somewhat compromised by the impure nPB, which
contained 0.83 percent 2-bromopropane (isopropyl bromide); that amount
is 4-16 times the amount of 2-bromopropane allowed by EPA in its
proposed rule. The authors note that “…the present neurological or
mucous-irritating symptoms may not be specific to 1-bromopropane [nPB]
exposure but could be also caused by 2-bromopropane. This argument is
based on the fact that the frequencies of almost all symptoms did not
differ from those in [a similar previous] investigation, when
2-bromopropane was the main product, although the frequency of headache
rather decreased significantly.” In the earlier study, employee
exposures to 2-bromopropane ranged from 0 to16 ppm. 

Although findings such as these suggest some workers may experience
effects from short-term nPB exposure, these studies do not offer
adequate information about acute exposures to suggest an appropriate
level for a STEL. The draft TLV documentation for nPB that EPA requested
that ERG review also indicates that there are not data to support the
derivation of a STEL. It is possible that more concrete data collected
in the future might provide adequate information to develop a STEL
(possibly somewhere within the range of 25 and 100 ppm). It is also
possible that the 8-hr TWA exposure levels may prove adequate to
minimize symptoms of short term as well as chronic exposure.

Extent to which the proposed 8-hour AEL for nPB will protect workers

The 8-hr TWA exposure levels for nPB currently under consideration by
the EPA (18 ppm and 25 ppm) will also limit workers’ short-term
(15-minute) exposures. To achieve the indicated 8-hr TWAs, a single
short-term nPB exposure levels could not exceed 576 ppm and 800 ppm,
respectively. That is, if the exposure of an employee to nPB exceeded a
level of 576 ppm for 15 minutes, the resulting 8-hr TWA exposure of that
employee would inevitably exceed the 18 ppm limit, even if the employee
had no additional exposure to nPB that day. This conclusion may be
proven by the equation shown below for time-weighted averages:

[(C1)(T1)+(C2)(T2)+(Cx)(Tx)…]/480 minutes = 8-hr TWA

Where 	C = concentration of contaminant in air.

			T = duration (in minutes) of exposure at a specific concentration.

When C1 is 576 ppm and T1 is 15 minutes, and if there is no additional
exposure during the work shift (i.e., C2 through Cx are 0 ppm), the
resulting 8-hr TWA is 18 ppm. It is important to note that if C1 is
greater than 576 ppm, or if any other exposure occurs during the day,
the 8-hr TWA will exceed 18 ppm.

More importantly, multiple short-term exposure levels would be limited
dramatically by the 8-hr TWA exposure level under consideration. As an
example of this point, an 8-hr TWA exposure of 18 ppm could not be
achieved if an employee experienced three short-term nPB exposures (15
minutes each) at 40 ppm and a level of 17 ppm for the remainder of the
workshift.

Known or suspected short-term exposure levels for nPB

Although a simulation study showed that short-term exposure levels of
nPB can reach 1,100 ppm in a worker’s breathing zone during a 15
minute period of aerosol solvent spraying (a task expected to generate
high airborne concentrations), time-weighted calculations indicate that
a worker exposed to this level could not achieve an 8-hr TWA result less
than 34 ppm, even if the worker experienced no other nPB exposure during
the remainder of the shift (OAR-2002-0064-0044, Attachment F). Thus the
8-hr TLV levels under consideration would prevent this level of peak
exposure. Workplace air sample results indicate that short-term exposure
levels are typically lower than 1,100 ppm during nPB solvent spraying.
In another study, eight available short-term (15-minute) sampling
results obtained during solvent spraying ranged from 45 to 254 ppm
(OAR-2002-0064-0015). These short-term levels could occur only
occasionally in a workplace that achieves the 8-hr TWAs under
consideration.

Relevance of available acute toxicity of nPB in animals

As indicated in Attachment 1, short-term exposure limits are rarely
based on animal lethality data. Nonetheless, we reviewed the available
acute lethality concentrations (LC50s) for nPB for some added
perspective, and note that the reported LC50 for nPB ranges from
approximately 7,000 ppm (4 hour exposure in rats) to 14,000 ppm (Kim et
al. 1999; Elf Atochem, 1997). Reported clinical signs included
respiratory distress and general weakness. Little other animal acute
toxicity data were identified. As noted in the proposed rule, no
cutaneous reactions were observed following dermal application of 2,000
ppm nPB in Sprague-Dawley rats and skin sensitization studies in guinea
pigs were negative. 

References

ACGIH. 2004. TLV Chemical Substance Introduction; Introduction to the
Chemical Substances TLVs. American Conference of Governmental Industrial
Hygienists (ACGIH), Cincinnati, Ohio. Internet web site last accessed
April 9:   HYPERLINK "http://www.acgih.org/Products/tlvintro.htm" 
http://www.acgih.org/Products/tlvintro.htm 

ACGIH. 2003. TLVs® and BEIs® Based on the Documentation of the
Threshold Limit Values for Chemical Substances and Physical Agents &
Biological Exposure Indices. American Conference of Governmental
Industrial Hygienists (ACGIH), Cincinnati, Ohio.

Elf Atochem. 1997. Study of acute toxicity on n-propyl bromide
administered to rats by vapour inhalation. Determination of the 50%
lethal concentration. Study No. 95122. Study Director F. Schorsch.
Verneuil-en-Halatte, France: Laboratorie d’Etudes de Toxicologie
Experimentale, as cited in NTP 2002.

Ichihara G, Weihua L, Ding X, et al. 2004. A survey on exposure level,
health status, and biomarkers in workers exposed to 1-bromopropane.
American Journal of Industrial Medicine 45:63-75.

Kim HY, Chung YH, Jeong JH Lee YM, et al. 1999. Acute and repeated
inhalation toxicity of 1-bromopropane in SD rats. J Occup Health
41:121-28.

NIOSH. 2000. Health Hazard Evaluation Report, Trilithic, Inc.,
Indianapolis, Indiana (HETA-2000-0233-2845) [abstract]. National
Institute for Occupational Safety and Health, Cincinnati, Ohio.

NIOSH. 2002. Health Hazard Evaluation Report STN Cushion Company,
Thomasville, North Carolina (HETA #2000-0410-2891). National Institute
for Occupational Safety and Health, Cincinnati, Ohio. August.

NTP. 2002. NTP-CERHR expert panel report on the reproductive and
developmental toxicity of 1-bromopropane. National Toxicology Program.
U.S. Department of Health and Human Services. Center for the Evaluation
of Risk to Human Reproduction. NTP-CERHR-1-BP-02. March 2002. 

OAR-2002-0064-0015. Docket Submission: Summary of Data on Workplace
Exposure to n-Propyl Bromide Summary of Data on Workplace Exposure to
n-Propyl Bromide, dated May 21, 2003.

OAR-2002-0064-0044. Attachment F. Docket Submission: Electronic
Industries Alliance; Tech Spray, L.P. Memo RE nPB and aerosol exposure
dated July 22, 2003.

Attachment 1

Review of Some Short-Term Exposure Level (STEL)/Ceiling Levels

Set by ACGIH and OSHA.

To evaluate whether a STEL/ceiling limit should be developed for nPB,
ERG reviewed the levels and basis for STEL/ceiling limits set by other
agencies or organizations such as the American Industrial Hygiene
Association (ACGIH), and Occupational Safety and Health Administration
(OSHA) for a selected list of chemicals. 

Table 1 presents examples of several STEL/ceiling levels and their
basis. We attempted to present a cross-section of substances, including
other halogenated solvents, with a range of acute health effects and
available toxicity data. The overall trends observed through this
exercise are summarized below.

Like occupational exposure limits established to protect against chronic
health effects, STEL/ceiling levels are typically determined on a
case-by-case basis and depend on a host of exposure and toxicity factors
(see associated ERG memorandum of June 8, 2004, addressed to Perrin
Quarles Associates, Inc., titled Evaluating Approaches for Setting
Occupational Limits).

STEL/ceiling levels are intended to protect against acute health
effects, the most common being irritation (of eyes, mucous membranes, or
skin). Irritation is the primary basis for approximately 75 percent
(132) of the 177 STEL/ceiling values listed by ACGIH (2003).

Animal lethality values (LC50s) are not typically cited as the basis for
ACGIH TLVs/STEL/ceiling values and, although noted, generally have
little direct influence on the levels selected. Whenever available,
information on the human experience is emphasized. For example, ACGIH
set a STEL of 200 parts per million (ppm) for n-butyl acetate (TWA-TLV
150 ppm) based on mucous membrane irritation experienced by volunteer
human subjects exposed for 3 to 20 minutes to levels of 200 to 295 ppm.
A 4-hour LC50 for n-butyl acetate of 391 ppm was reported but not a
notable factor in the TLV recommendation (ACGIH, 2001). 

The ACGIH STEL/ceiling levels examined were typically set at levels
close to the lowest observed effect level (LOEL) or No Observed Effect
Level (NOEL). When reported levels were considered imprecise, an
intermediate value was selected as the STEL/ceiling level. This was the
case with ethanolamine, for which slight systemic effects were reported
in animal models at 5 ppm. Because chemical clearance promotes recovery,
and the animals tested clear ethanolamine more rapidly than humans,
ACGIH set a TLV of 3 ppm and STEL at 5 ppm.

STEL/ceiling levels tend to be set lower (i.e., below the NOEL) when
health effects are observed in humans after very brief periods of
exposure. For example, subjects reported dizziness after a 6-minute
exposure to heptane at 1,000 ppm. ACGIH set the STEL at 500 ppm (with a
TWA-TLV of 400 ppm).

As shown in Table 1, the ACGIH STEL/ceiling levels are rarely more than
2 or 3 times the TLV. The STEL for carbon dioxide (30,000 ppm) is a rare
exception at 6 times the TLV (5,000 ppm). This STEL is set to limit the
increased ventilation rate human subjects experienced when exposed to
carbon monoxide for 2 to 8 hours at 39,500 ppm. This effect was not seen
at 27,600 ppm.

Some STEL/ceiling levels are based on analogous exposure, such as the
TLV for fluoride (2 ppm) that was used as the basis for the carbonyl
fluoride TLV (2 ppm) and STEL (5 ppm). Toxicity to carbonyl fluoride
resembles fluoride toxicity.

STEL/ceiling levels are occasionally set in the absence of an TLV
exposure level. ACGIH set only a ceiling level of 1 ppm (with no 8-hr
TWA) for chloroacetone, to minimize lacrimation and irritation. Exposure
to 26 ppm of this substance (reportedly an effective war gas) is
intolerable after 1 minute of exposure and a level of 605 ppm is lethal.

A STEL/ceiling level can be set based on a combination of factors. In
the case of phenlyphosphine, a ceiling level of 0.05 ppm (again with no
TLV) was based on “obnoxious” odor detected readily by volunteers at
0.57 ppm, respiratory tract irritation, dermatitis, and hematological
effects. Testicular degeneration was observed in two species at 2.2 ppm.

STEL levels set by OSHA follow similar trends. The 1997 standard on
methylene chloride included a STEL that, according to the preamble and
subsequent summaries, was set at 125 ppm based on CNS depression
observed at occupational levels as low as 175 ppm. In experimental
studies, human subjects experienced CNS depression at 200 ppm after 4
hours, or 300 ppm after 1.5 hours. The permissible exposure level (PEL)
was set at 25 ppm, to reduce the risk that exposed workers would develop
cancer (Federal Register, 1997, 1998).

References 

ACGIH. 2003. TLVs® and BEIs® Based on the Documentation of the
Threshold Limit Values for Chemical Substances and Physical Agents &
Biological Exposure Indices. American Conference of Governmental
Industrial Hygienists (ACGIH), Cincinnati, Ohio.

ACGIH. 2001. Documentation of Threshold Limit Values and Biological
Exposure Indices. American Conference of Governmental Industrial
Hygienists (ACGIH), Cincinnati, Ohio.

Federal Register. 1998. Amendment to OSHA Final Rule: Occupational
Exposure to Methylene Chloride. 63 FR 50711-50723.

Federal Register. 1997. OSHA Final Rule: Occupational Exposure to
Methylene Chloride. 62 FR 1494-1



Table 1.  Basis for Some ACGIH and OSHA Short-Term Exposure Levels

Chemical

CAS	8-hour

TWA

(ppm)	STEL/

CEILING

(ppm)	Basis for STEL

American Conference of Governmental Industrial Hygienists (ACGIH)

Acetic Acid

64-19-7	10 	15	A TLV-TWA of 10 ppm and a STEL of 15 ppm are recommended
to prevent undue irritation.  It has been reported that exposure at
800-1200 ppm cannot be tolerated for longer than 3 minutes.  Workers
exposed for 7-12 years at concentrations of 60 ppm, plus one hour daily
at 100-260 ppm, had no injury except slight irritation of the
respiratory tract, stomach, and skin. Industrial experience has shown
that 10 ppm is relatively non-irritating.

Allyl chloride

107-05-1

	1 	2 	The TLV Committee continues to recommend a TLV of 1 ppm as an
8-hour TWA with a  STEL of 2 ppm. Single 6-hour exposure concentrations
were 200, 300, 5100, 800, 1000, 1200, or 2000 ppm for rats and 500, 800,
1000, 1200, or 2000 ppm for mice. In human tests, volunteers were
evaluated in the presence or absence of the characteristic odor of allyl
chloride at a concentration of 3 ppm for 1-3 minutes independently. 10
in 13 volunteers reported a definite odor, but no irritation.

Benzene	0.5	2.5	A TLV-TWA of 0.5 ppm and a TLV-STEL of 2.5 ppm are
recommended to minimize the potential for leukemogenesis. The STEL is
recommended to protect against excess risk of leukemia due to the dose
rate-dependent hematopoietic toxicity of benzene, and the concept that
dose rate is more important than cumulative dose. Dose rate-based
analyses of a rubber worker cohort predicted measurable leukemogenic
risk (total leukemias and acute myleogenous leukemias) at peak benzene
concentrations of 20 to 25 ppm. 

n-Butyl acetate

123-86-4	150 	200 	A STEL of 200 ppm is recommended to control the
excursions that produced mucous membrane irritation in the volunteers at
exposures of 200 to 300 ppm for 3 to 20 minutes. A 4-hour LC50 of 156
ppm was reported for Wistar rats and 4-hour LC50 of 391 was reported for
Sprague-Dawley rats.

Carbon dioxide

124-38-9	5,000 	30,000 	TLV-TWA of 5,000 ppm for carbon dioxide is
recommended.  This value provides a good margin of safety from
asphyxiation and from undue metabolic stress, provided normal amounts of
oxygen are present in the inhaled air. In light of the short-term
exposure studies of Sinclair and associates, it appears that a STEL of
30,000 ppm is appropriate. Volunteers exposed to 27,600 ppm and 39,500
ppm for 2 to 8 hours daily reported very little difficulty performing
psychological tests and only noted increased ventilation rate at the
higher level.

Carbon tetrabromide

558-13-4	0.1 	0.3 	Based on described animal work, a TLV-TWA of 0.1 and
a STEL of 0.3 are recommended (no observed effect level). This chemical
caused severe eye irritation, permanent corneal damage, and slight skin
irritation in studies with rabbits [dose not mentioned]. Acute exposure
at high concentrations in humans caused upper respiratory irritation and
injury to the lungs, liver and kidneys. Chronic exposure effects at very
low levels will be almost entirely limited to liver injury.

Carbonyl fluoride

353-50-4	2 	5 	The toxic effects of inhaled COF2 resemble the toxic
effects of hydrogen fluoride. The long-term toxic effects are caused by
fluoride generated by hydrolysis, therefore a TLV-TWA of 2 ppm and a
TLV-STEL of 5 ppm for COF2 are recommended. The LC50 determinations were
for a 1-hour exposure followed by a 14-day, post-exposure, observation
period. The LC50 values for the 8-and 24-week-old rats were 360 and 460
ppm, respectively.

Chloroacetone

1 ppm (C)	A TLV-Ceiling of 1 ppm is recommended for chloroacetone to
minimize adverse lacrimation and irritation of the respiratory tract,
skin, and eyes. Chloroacetone is reportedly effective as a war gas,
because a concentration of 605 ppm was found to be lethal after 10
minutes, and 26 ppm was intolerable after 1 minute of exposure. Acute
inhalation studies provided a 1-hour LC50 of 262 ppm (nominal
concentration) in Sprague-Dawley rats.

o-Chlorostyrene

2039-87-4	50 	75 	Limited evidence indicates that the odor-warning
property of o-chlorostyrene does not offer adequate warning and that
vapor concentrations must approach 400-600 ppm to discourage exposures
to unacclimated workers. One study concluded that 100 ppm induced a
marginal effect and suggested that a TWA exposure of workers not exceed
50 ppm. By structural analogy of o-chlorostyrene to styrene, for which
short-term exposure of human at 100 ppm has demonstrated neuropathic and
narcotic effects, a short-term limit is considered necessary. Therefore,
a TLV-TWA of 50 ppm and a STEL of 75 ppm are considered adequate to
reduce the significant risk of liver and kidney damage, neuropathy, and
narcosis to exposed workers.

Dichloroacetylene

0.1 (C)	A TLV-Ceiling of 0.1 ppm is recommended to minimize the
potential for nausea and more serious systemic effects, including
neurotoxicity and cancer reported only in animals. In humans,
dichloroacetylene causes headache, loss of appetite, extreme nausea and
vomiting; concentrations of 0.5 to 1.0 ppm produced disabling nausea.

Ethanolamine

141-43-5

	3 	6 	The continuous exposures performed by Weeks, in which an odor
threshold of 3-4 ppm has been reported, at 5 ppm resulted in only slight
systemic effects. The condition of continuous exposure tends to confer a
greater toxicity on laboratory animals than intermittent exposure. The
increase is related to the rate of elimination; the longer retained, the
greater the toxicity. The 5 ppm approximate response threshold would
appear to have a reasonable safety factor for intermittent exposure, but
in view of the more rapid elimination of ethanolamine by the rat, the
TLV Committee recommends a TLV-TWA of 3 ppm and a STEL of 6 ppm to
provide for a possible greater human susceptibility.

Glutaraldehyde

0.05 (C)	A TLV-Ceiling of 0.05 ppm was recommended in 1976, and revised
in 1979 to 0.2 ppm, then changed back to 0.05 ppm in 1997. Studies
reported nose, throat, skin and eye irritation; headaches; and other
symptoms associated with airborne exposure to glutaraldehyde at or below
0.1 ppm, all based on short-term (15-minute) personal sample results. No
clear dose-response relationships in humans have been established for
airborne glutaraldehyde exposure, suggesting that exposures be kept as
low as possible. Rat LC50/LD50 values as low as 24-40 ppm have been
reported, after 4-hour inhalation studies.

Heptane

142-82-5	400	500 	Inhalation of 1,000 ppm heptane for 6 minutes was
associated with a slight dizziness; inhalation of higher concentrations
for shorter periods resulted in marked vertigo, incoordination, and
hilarity. Exposures of 4 minutes to high levels (5,000 ppm) produced
complaints of nausea, loss of appetite, and a "gasoline-like" taste that
persisted for several hours after cessation of exposure. Accordingly a
TLV-TWA of 400 ppm and a STEL of 500 ppm are recommended for heptane.

Hydrogen sulfide

7783-06-4	10 	15 	According to the National Institute of Occupational
Safety and Health (NIOSH), hydrogen sulfide is the leading cause of
sudden death in the workplace. It is not considered a cumulative toxin
since it is rapidly oxidized to sulfates and excreted through the
kidney.  Lethal hydrogen sulfide toxicity following inhalation of 1,000
to 2,000 ppm paralyzes the respiratory center and breathing stops. At
concentrations between 500 and 1,000 ppm, the carotid bodies are
stimulated causing hyperapnea which is followed by apnea. A TLV-TWA of
10 ppm and a STEL of 15 ppm is recommended as these limits should
provide protection against the significant health risks of sudden death,
eye irritation, neuroasthenic symptoms, or permanent central nervous
system effects. 

Iron pentacarbonyl

13463-40-6	0.1 	0.2 	In a comparison of the 30-minute LC50 values for
nickel carbonyl and iron pentacarbonyl in rats, iron pentacarboyl had
about one-third the acute lethal potency as nickel carbonyl. The
30-minute LC50 values for iron pentacarbonyl for mice and rats are 275
ppm and 115 ppm, respectively. While there is no information on the
health effects of exposure of humans to iron pentacarbonyl, the clinical
picture of acute exposure to high concentrations is expected to resemble
that of nickel carbonyl. The immediate symptoms of headache and
dizziness are followed in 12 to 36 hours by fever, cyanosis, cough, and
dyspnea. Degenerative changes in the CNS have been reported for the
related nickel carbonyl. Brief suggested 0.1 ppm as an "action point"
for occupational exposure and recommended respiratory protection for
workers exposed to a greater level. Based on such information a TLV-TWA
of 0.1 ppm and a STEL of 0.2 ppm is recommended for iron pentacarbonyl.

Isoamyl alcohol

123-51-3	100 	125 	Human volunteers complained of slight throat
irritation at 100 ppm isoamyl alcohol and of ocular and upper
respiratory tract irritation after exposure at 150 ppm for 3 to 5
minutes. Base on these data and by analogy with the irritation data for
n-butyl alcohol, a TLV-TWA of 100 ppm and a TLV-STEL of 125 ppm are
currently recommended for isoamyl alcohol.

Methyl acetate

79-20-9	200 	250 	Methyl acetate is irritating to the eyes and mucous
membranes of animals and exposed workers. It has caused narcosis in
animals exposed at high concentrations. Methyl acetate is metabolized to
methanol in a manner proportional to the exposure level. Accordingly, by
analogy with the toxicological properties of methanol, a TLV-TWA of 200
ppm and a STEL of 250 ppm are recommended for methyl acetate.

Methyl chloride

74-87-3	50 	100 	A no-observed-adverse-effect level for reproductive
effects in rodents has been reported in the range of 150 ppm to 475 ppm;
following repeated exposure of concentrations greater or equal to 500
ppm in animals, methyl chloride showed reprotoxicity and teratogenicity.
Though available data show no adverse, irreversible effects after
repeated exposure to 100 to 200 ppm, the TLV is based on performance
decrements observed in workers exposed to less than 100 ppm. The STEL is
intended to limit peak exposures to this level. During physical exams,
no health problems were reported in humans with chronic exposure in the
range of 5 to 78 ppm.

Methyl formate

107-31-3	100 	150 	Occupational exposure to vapors of methyl formate and
other solvents that involved visual disturbances narcosis, irritation of
mucous membranes, and dyspnea. No adverse effects were noted after
exposure of human volunteers at 1,500 ppm methyl formate for 1 minute.
After exposure at 1600 ppm it was associated with pulmonary edema in
animals, and at 5,000 ppm, it caused narcosis. A TLV-TWA of 100 ppm for
methyl formate is recommended, with at STEL of 150 ppm.

Pentaborane

19624-22-7	0.005 	0.015 	The LC50 values for pentaborane reported from
single inhalation exposures of rats and mice are, respectively: for 5
minutes, 67 ppm and 40 ppm; for 15 minutes, 31 ppm and 19 ppm; for 30
minutes, 15 ppm and 11 ppm; and for 60 minutes, 10 ppm and 6 ppm. for
single 4-hour exposures, LC50 values are 6 ppm for rats and 3 ppm for
mice. Accidental exposures of workers show that inhaled pentaborane can
result in signs and symptoms consistent with CNS intoxication. In a
study performed by Levinskas, animals exposed repeatedly to pentaborane
vapor at calculated concentrations of 1 ppm for 4 weeks and at 0.2 ppm
for 6 months. Following inhalation exposures at 1 ppm, all species lost
weight. Rats ere appreciably less active, and the rabbits developed
ataxia. At 0.2 ppm, monkeys were apathetic, suffered anorexia, and
appeared anesthetized. Based on that study the subchronic
lowest-observed-effect concentration indicates that the TLV should be
less than 0.2 ppm because it is presumed that humans are not less
sensitive to pentaborane intoxication than are experimental animals.
Therefore, a TLV-TWA of 0.005 ppm and a STEL of 0.015 ppm are
recommended for pentaborane. 

Phenylphosphine

0.05 (C)	A TLV Ceiling of 0.05 ppm is recommended to minimize the
potential for objectionable odor, respiratory tract irritation,
dermatitis, and hematological effects. Reproductive effects (testicular
degeneration) have been observed in dogs and rats exposed to 2.2 ppm
phenylphosphine by inhalation. A three-person odor panel readily
detected “obnoxious” odors at concentrations of 0.57 ppm
phenylphosphine 

n-Propanol (n-Propyl alcohol)

71-23-8	200 	250 	n-Propyl alcohol is an irritant to the eyes and mucous
membranes. It has caused narcosis in animal at high concentrations. Deep
narcosis occurred in 60 minutes at 24,500 ppm and in 240 minutes at
4,100 ppm. In human studies, fatality has been attributed to acute
ingestion of n-propanol. A TLV-TWA of 200 ppm, intermediate between the
limits for isopropyl alcohol and the various butyl alcohols, is
recommended, along with a STEL of 250 ppm.

Tetrachloroethylene	25	100	A TLV-TWA of 25 ppm and a TLV-STEL of 100 ppm
are recommended to minimize the potential for eye irritation and central
nervous system symptoms (headache, dizziness, sleepiness and
incoordination) that may occur from prolonged exposure at 100 to 200 ppm
(5.5 to 7-hour exposures); the STEL is also intended to protect against
the risk of anesthetic effects. LC50  (4-hour) values were observed at
4,000 ppm in rats and 5,000 ppm in mice.

Toluene-2,4-diisocyanate (TDI)

584-84-9	0.005 	0.02 	Investigations of TDI exposures have concluded
that normal workers were unaffected by occasional TDI exposures at or
near 0.02 ppm (although chronic exposure to 0.02 ppm have been
associated with sensitization). The TLVs are intended to minimize the
potential for irritation of the eyes, mucous membranes, and respiratory
tract. 

1, 1, 2-Trichloro-1, 2, 2-trifluoroethane

76-13-1	1,000 	1,250 	Animal studies indicate low acute toxicity of
inhaled CFC-113. The 4-hour LC50 value for rats ranges form 52,000 to
68,000 ppm, while a 2-hour lethal concentrations for rats, guinea pigs,
mice, and rabbits range from 50,000 to 120,000 ppm. Morgan found that >
50% of an inspired 7 mg of CFC-113 inhaled as a single dose was exhaled
immediately; 19.8% was retained after 30 minutes. NIOSH reviewed 4
reports of 12 fatalities resulting from occupational exposure to
CFC-113. In most of these cases, exposure concentration was not
reported, but in one of the deaths (due to cardiac arrhythmia) the
exposure was for 1 minute and the CFC-113 concentration measured 24
hours after exposure was 7,600 ppm. A TLV-TWA of 1000 ppm and a STEL of
1250 ppm are recommended to minimize the potential to systemic toxicity
and cardiac sensitization form exposure to CFC-113.

Vinyl toluene

25013-15-4	50 	100 	When animals received 92 to 100 7- to 8-hour
inhalation exposures of the mixture of a meta- and para-isomer at 1,250
ppm, there was an increase in renal and hepatic weights and fatty
degeneration of the liver. Human subjects noted ocular and upper
respiratory tract irritation at 400 ppm vinyl toluene concentration;
strong objectionable odor at 300 ppm; and strong, tolerable odor at 200
ppm. At 50 ppm, the odor was detectable, but there was no irritation of
mucous membranes. The toxicological properties of vinyl toluene appear
to be similar to those of styrene. A TLV-TWA of 50 ppm and a STEL of 100
ppm by analogy with styrene and as being consistent with the data on and
properties of vinyl toluene. 

Occupational Safety and Health Administration (OSHA)

Methylene Chloride

75-02-2	25 	125 	STEL set at 125 ppm based on CNS depression observed at
occupational levels as low as 175 ppm. In experimental studies, human
subjects experienced CNS depression at 200 ppm after 4 hours, or 300 ppm
after 1.5 hours.  

Sources: 

ACGIH. 2001. Documentation of Threshold Limit Values and Biological
Exposure Indices. American Conference of Governmental Industrial
Hygienists, Cincinnati, Ohio.

Federal Register 1997; 1998

 The use conditions set forth in the proposed rule for each end use
provide that nPB not contain more than 0.05% 2-bromopropane.

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