The Occupational Safety and Health Act of 1970 emphasizes the need for standards to protect the health and provide for the safety of workers occupationally exposed to an ever-increasing number of potential hazards. The National Institute for Occupational Safety and Health (NIOSH) evaluates all available research data and criteria and recommends standards for occupational exposure. The Secretary of Labor will weigh these recommendations along with other considerations, such as feasibility and means of implementation, in promulgating regulatory standards. NIOSH will periodically review the recommended standards to ensure continuing protection of workers and will make successive reports as new research and epidemiologic studies are completed and as sampling and analytical methods are developed. The contributions to this document on thiols by NIOSH staff, other Federal agencies or departments, the review consultants, the reviewers selected by the Society of Toxicology and the American Industrial Hygiene Association, and Robert B. O'Connor, M.D., NIOSH consultant in occu pational medicine, are gratefully acknowledged. The views and conclusions expressed in this document, together with the recommendations for a standard, are those of NIOSH. They are not necessarily those of the consultants, the reviewers selected by professional societies, or other Federal agencies. However, all comments, whether or not incorporated, were considered carefully and were sent with the criteria document to the Occupational Safety and Health Administration for consideration in setting the standard. The review consultants and the Federal agencies which received the document for review appear on pages v and v i .# III. BIOLOGIC EFFECTS OF EXPOSURE I. RECOMMENDATIONS FOR A THIOL STANDARD
NIOSH recommends that employee exposure to thiols in the workplace be controlled by adherence to the following sections.
The recommended standard is designed to protect the health and provide for the safety of employees for up to a 10-hour workshift, in a 40-hour workweek, during a working lifetime.
Compliance with all sections of the recommended standard should prevent adverse effects of exposure to thiols on the health of employees and provide for their safety.
Techniques recommended in the standard are valid, reproducible, and available to industry and government agencies.
Sufficient technology exists to permit compliance with the recommended standard.
Although NIOSH considers the recommended workplace environmental limits to be safe levels based on current information, employers should regard them as the upper boundaries of exposure and make every effort to maintain exposures as low as is technically feasible.
The criteria and recommended standard will be reviewed and revised as necessary.
These criteria and the recommended standard apply to exposure of employees to selected monofunctional organic sulfhydryl compounds, specifically, the 14 n-alkane thiols having the general molecular formula C^I^+ISH (where n = 1 , 2...12, 16, and 18), the aliphatic cyclic thiol, cyclohexanethiol, and the aromatic thiol, benzenethiol; hereinafter they may be referred to as "thiols." Synonyms for thiols include mercaptans, thioalcohols, and sulfhydrates.
Because of systemic effects, absorption through the skin on contact, and possible dermal irritation, "occupational exposure to thiols" is defined as work in any area where thiols are produced, processed, stored, or otherwise used.
If thiols are handled or stored in intact, sealed containers, eg, during shipment, NIOSH recommends that only Sections 3, 5(a), and 6(g) of this proposed standard apply. If exposure to other chemicals also occurs, provisions of any standard applicable to the other chemicals shall be followed.

# Section 1 -Environmental (Workplace Air) (a) Concentration
(1) Occupational exposure shall be controlled so that no employee is exposed to benzenethiol at concentrations in excess of 0.5 milligrams per cubic meter (mg/cu m) of air (0.1 ppm in air by volume) determined as a ceiling concentration for any 15-minute period.
(2) Occupational exposure to aliphatic thiols shall be controlled so that employees are not exposed at concentrations greater than the limits, in milligrams per cubic meter of air, shown in Table 1-1 as a ceiling concentration for any 15-minute period.
(3) Occupational exposure to mixtures of thiols shall be controlled so that no employee is exposed at an equivalent concentration for the mixture greater than that calculated by the formula given in 29 CFR 1910.1000 (d)(2)(i).

# (b) Sampling and Analysis
Procedures for the collection and analysis of workroom air samples shall comply with those given in Appendix I or with any method shown to be at least equivalent in precision, sensitivity, and accuracy.

# Section 2 -Medical
Medical surveillance shall be made available as outlined below to all workers occupationally exposed to thiols.
(a) Preplacement examinations shall include at least:
(1) Comprehensive medical and work histories with special emphasis directed to symptoms and signs of disorders of the central and autonomic nervous systems, the cardiovascular system, and the skin.
(2) Physical examination giving particular attention to the nervous and cardiovascular systems.
For workers subject to occupational exposure to benzenethiol, eye examinations shall be included in addition to the above-mentioned systems.
(3) An evaluation of the worker's ability to use positive pressure respirators.
Criteria should include the presence of significant obstructive or restrictive pulmonary disease or cardiopulmonary impairment.
(4) White blood cell counts (WBC's) (total and differential), hematocrit, hemoglobin concentration in whole blood, total bilirubin, and urinalysis.
The value of estimations of fecal urobilinogen in distinguishing jaundice due to hemolytic anemia from that due to other common causes should be kept in mind.

# (b)
Periodic examinations shall be made available at least annually to any workers who have been occupationally exposed to thiols and shall include:
(1) Interim medical and work histories.  (2) Physical examination as described in (a)(2) above.
(3) Laboratory examinations as described in (a)(4) above.
( location, a label that bears the trade name or other common name of the product and information on the effects of exposure to the compound on human health.
The information shall be arranged as in the example below for all the thiols except benzenethiol.

# SPECIFIC THIOL (Trade or Common Name) DANGER COMBUSTIBLE MAY BE HARMFUL IF ABSORBED THROUGH SKIN, INHALED, OR INGESTED MAY CAUSE IRRITATION OF SKIN KEEP CONTAINERS CLOSED WHEN NOT IN USE
For methanethiol, ethanethiol, propanethiol, butanethiol, pentanethiol, and cyclohexanethiol, the word FLAMMABLE shall be used instead of COMBUSTIBLE in the above example and the following caution shall be added to the label: Exposure to vapor from large spills may produce unconsciousness.
For benzenethiol, the information shall be arranged as in the example below:

# BENZENETHIOL (Trade or Common Name) DANGER COMBUSTIBLE MAY BE FATAL IF ABSORBED THROUGH SKIN, INHALED, OR INGESTED MAY CAUSE IRRITATION OF EYES AND SKIN KEEP CONTAINERS CLOSED WHEN NOT IN USE
On all labels, the following information shall be included as in the example below: Do not get on skin, in eyes or mouth, or on clothing. Avoid breathing vapor. Use only with adequate ventilation. Keep containers closed when not in use. Wash hands and face thoroughly before eating, drinking, smoking, or using toilet.

# First Aid:
Remove victims to fresh air immediately. Give artificial respiration if needed. Give oxygen if breathing is impaired.

# Call a physician.
In case of skin contact, immediately flush with copious quantities of water, then wash with soap and water. In case of eye contact with benzenethiol or with mixtures that contain benzenethiol, the affected eye shall be treated with not more than two drops of 0.5% silver nitrate (AgNOs), applied from a bougie or other previously sealed container, and then flushed with copious quantities of water. Eyes contacted by thiols other than benzenethiol shall be flushed with copious amounts of water. A physician should be consulted promptly about any eye contact with solid or liquid thiols. For methanethiol, ethanethiol, propanethiol, butanethiol, pentanethiol, and cyclohexanethiol, the word FLAMMABLE shall be used in place of COMBUSTIBLE in the above example.
For benzenethiol, the information shall be arranged as in the example below:

# DANGER! COMBUSTIBLE BENZENETHIOL PRESENT IN AREA MAY BE FATAL IF ABSORBED THROUGH SKIN, INHALED, OR INGESTED MAY BE IRRITATING TO EYES AND SKIN
Do not get on skin, in eyes or mouth, or on clothing. Do not breathe vapor. Keep containers closed when not in use.

# In an emergency involving thiols,
all affected personnel shall be provided with immediate first aid, followed by prompt medical evaluation and care.
In the event of skin or eye contact with liquid thiols, skin and eyes shall be flushed with copious amounts of water.
In case of eye contact with benzenethiol or with a mixture including benzenethiol, the affected eye shall be treated with no more than two drops of a 0.5% solution of silver nitrate (AgN03 ), applied from a bougie or other previously sealed container, and then flushed with copious quantities of water.
For further discussion, see Appendix II.   shall be provided and worn in any operation in which there is a reasonable possibility that thiols may be splashed into the eyes.

# (b) Skin Protection
Depending on the operations involved and the probable or likely extent of dermal exposure, protective clothing and equipment, including gloves, aprons, suits, boots, and face shields (8-inch minimum) with goggles, shall be worn to prevent skin contact with particulate or splashed liquid thiols. (2) When use of respirators is permitted, the respirator shall be selected and used pursuant to the following requirements: This information shall be kept on file at each establishment or department and shall be readily accessible to all employees occupationally exposed to thiols.

# (e)
In an emergency involving thiols, all affected personnel shall be provided with immediate first aid, followed by prompt medical evaluation and care.
In the event of skin or eye contact with liquid thiols, skin and eyes shall be flushed with copious amounts of water.
In case of eye contact with benzenethiol or with a mixture including benzenethiol, the affected eye shall be treated with no more than two drops of a 0.5% solution of silver nitrate (AgN03), applied from a bougie or other previously sealed container, and then flushed with copious quantities of water.
For further discussion, see Appendix II. In retrospect, they recommended that the then current maximum allowable concentration (MAC) of 10 ppm be respected and that respiratory protection be provided in cases of extended exposure above the MAC.
In 1941, Cristescu  described a case of mixed thiol poisoning at an oil refinery in Ploesti, Rumania.
A workman descended into a pit to empty a trap containing condensate from a line through which methane-, ethane-, and other volatile thiols from a cracking process passed in transit to a burning stack.
Refinery rules for this operation required the use of a gas mask, as well as the presence of a second person to observe from outside the pit, but neither of these regulations was followed.
Two hours later, the man was found unconscious at the bottom of the pit sitting on a chair, his head bent over his chest.
He was quickly hospitalized. for all these thiols was nausea on exposure at a sufficiently high concentration.
Benzenethiol also caused headache in some observers.

# Perceiving the need to consider the obnoxious odor of thiols in the formulation of standards for air purity in industrial premises, Blinova

# Precise information on the olfactory threshold for ethanethiol was acquired by exposing volunteers to ethanethiol at various concentrations below what the author  called the resorptive effect, by which he may have meant
the dose inducing some symptom or sign of systemic toxicity. The volunteers inhaled the vapor continuously for 3 hours/day for 5-10 days from a special device, which was not described.
The pulse and respiration rates and blood pressures of the subjects were measured, as were the fatigue response (by an unexplained method), the sensitivity of the olfactory analyzer, and the response of the taste analyzer to sweet and bitter substances.
The chronaxie of the visual apparatus of the eye was also measured by use of what was described as an electronic pulsed stimulator that applied weak electric discharges to the eyeball. These measurements were made before and after each exposure to an experimental mixture.
The state of fatigue was also estimated during 5 minutes in each of the 1st, 2nd, and 3rd hours of inhaling a mixture.
The volunteers were subjected also to a control experiment in which they inhaled pure air.
The tests produced no significant changes other than decreases in blood pressure and pulse rate that were considered physiologic responses to forced rest.

# In the first experiment with ethanethiol, three volunteers were exposed to the compound at 10 mg/cu m (3.94 ppm) .
One of the volunteers, a woman, had a uniform response throughout the 10-day test with no tendency toward either intensification or habituation.
Observations on the two men were made, therefore, for only 5 days. The woman's olfactory threshold rose from 6.2 0.26 to 12 0.18 ml.
The corresponding shifts for the two men were from 9.4 2.7 to 11.0 1.8 ml and from 6.0 0.9 to 16.0 0 ml. Thus, weakened olfactory responses to ethanethiol were observed after 3-hour inhalation exposures.
No changes in taste were reported. The rheobase of the visual apparatus lowered to some extent.
For the woman the rheobase before exposure was 4.1 0.11 volts (V) and after exposure it was 3.6 0.33 V.
Corresponding values for the two men were 4.8 0.45 V and 30 0.73 V before and 3.0 0.48 and 2.1 0.25 V after exposure. Error analysis indicated some fatigue.
All volunteers recorded, from the beginning of the experiment, a fairly strong smell resembling that of onions, garlic, or gasoline; the intensity of the odor lessened after about 1.5-2 hours . Each person complained of such sensations as periodic nausea, irritation of the mucous membranes of the mouth and lips and, less frequently, the nose, a feeling of head heaviness, and fatigue.
In the second experiment conducted about a month later, the same individuals were exposed to ethanethiol at 1 mg/cu m (0.394 ppm) . Increases in the olfactory threshold, but to a lesser extent than in the first experiment, were observed.
The woman had an increase from 5.8 0.15 to 7.3 0.52 ml, and the corresponding changes for the two men were 6.7 0.8 to 7.5 0.94 ml and 7.3 0.25 to 11.0 0.45 ml. Neither a change in taste nor a lowering of the original rheobase of the eye was observed.
The three subjects reported a moderate odor, resembling that of onions, that disappeared entirely halfway through the experiment, but no other unpleasant symptoms.
In view of the above findings and in consideration of tests of its chronic toxicity in animals, 0.001 mg/liter was tentatively recommended by Blinova as the maximum permissible concentration of ethanethiol for factories.
This study  showed that the inhalation of ethanethiol led to an increase in the olfactory threshold more sensitively than it did to any other index studied.
No other cumulative effects were noticed during the 5-10 days.

# In 1969, Wilby  reported on the variability in recognition of odor thresholds by panel members in a study initiated by the Pacific Lighting System of Southern California.
The 18 sulfur compounds chosen for the study on the basis of their predominant occurrence in natural gas included methanethiol, ethanethiol, 1-propanethiol, and 1-butanethiol.

# The panelists chosen were not previously trained in odor threshold work .
All were company employees working in the same building. Comprising the panel were five men (two smokers) and four women (one smoker) aged 18-35; six men (four smokers) and seven women (four smokers) aged 36-55; and seven men (four smokers) and six women (two smokers) aged 56-66.
All testing was done outdoors during clement weather when "no ambient odors" were present.
A two-step dilution procedure was adopted to obtain threshold concentrations in the ppb range.
First, a gas mixture of highly purified methane containing a few ppm of a thiol was confined at 200 psig in a specially constructed and cleaned 1.7-cu ft stainless steel pressure vessel and allowed to equilibrate for 24 hours. The gas mixture was then analyzed for the thiol by hydrogenation followed by estimation of H 2S by the methylene blue method and by gas chromatography.
The latter procedure permitted detection of oxidation of the thiol to a disulfide.

# Second, dilution
to the olfactory thresholds was accomplished with special odorometers.
For each test, a series of concentrations, in increments of 100,2 , was presented to the panel in random order. The author estimated that the overall accuracy of estimation of the concentration was 30%. The panelists walked in single file past three odorometers, pausing at each to take one or two breaths and to note on their test cards whether they detected an odor.
The threshold concentration was defined as the lowest concentration the respondent could smell consistently, not necessarily the lowest concentration reported.
The ratio of highest to lowest odor threshold concentration was determined for each panelist as a measure of the range of response of the panelists.
The odor thresholds were presented in histograms for the different compounds.
The histograms yielded estimates for the median and mean threshold concentrations, which are given in Table III   Overall, the lack of data to support the statements made in the text and the paucity of details about experimental procedures diminish the utility of this report.
In 1978, a report  was published on the inhalation toxicity of methanethiol in white rats. Ninety rats were divided into 9 groups, each containing 5 males and 5 females.
Each group was placed in a custom-built 75-liter glass chamber prior to a 4-hour exposure period.
Eight groups of rats were exposed to methanethiol at eight concentrations ranging from 400 to 800 ppm (788 to 1,576 mg/cu m ) . The remaining group of rats was sham exposed to check for mortality arising from conditions other than actual gas exposure.
After exposure, the rats were separated by sex and observed for the subsequent 14 days.
Gross pathologic observations were made on the 2-week survivors as well as on those that died. For static exposures, the desired thiol concentrations were achieved by injecting the required amount of thiol through a rubber septum in the lid of the chamber into which the rat had been placed.
Occasional analysis of chamber air showed that actual concentrations varied by 5% at a 1%-by-volume (10,000 ppm) concentration and by less than 25% at the 0.1%-by-volume (1,000 ppm) concentration.
For the determination of dose-response relationships, the animals were observed until they had completely lost the righting reflex or until they had been exposed to the thiol for 15 minutes. The concentration of thiol in the blood was determined after a 4-minute exposure. The accuracy of the sampling technique and analytical procedure was such that the recovery was found to be within 2 % of the calculated amount taken. For ip and oral administration, the aliphatic thiols were given undiluted.
Benzenethiol was administered orally as an 8% V/V solution in ethanol and ip as a 5% V/V solution in ethanol.
For estimation of absorption from the skin's surface, areas of skin approximately 3 cm square, or 6 x 10 cm, of the upper midbacks of rats and rabbits, respectively, were clipped as close to the skin as possible without causing abrasions.
Measured amounts of undiluted benzenethiol were dropped on the clipped areas of the skin.   Male and female albino rats weighing 100-150 g were exposed to pentanethiol in a 9-liter desiccator.
The authors assumed that the calculated pentanethiol concentration was probably slightly higher than an analytically estimated one would have been.
Six rats were exposed to pentanethiol at 2,000 ppm (8,520 mg/cu m) for 4 hours. Two, three, or four (exact number not stated) of six rats died during the 14-day observation period.
On the basis of these results, the authors concluded that the degree of hazard associated with exposure to pentanethiol is moderate.
As

# Dodecanethiol and the
thiol mixture applied to the skin at concentrations of 3.4 0.1 mg/liter and 2.9 0.12 mg/liter, respectively, caused marked local effects, as well as general poisoning, in both rats and mice; no further information was provided.
This study indicates that the higher molecular weight thiols have a low toxicity in comparison with the lower molecular weight thiols.
( Persistent hepatitis was found in the mice, and there were a "few cases" of bronchopneumonia and pyogenic abscesses of the liver and lungs.
The 43% mortality of the mice was most probably caused by hepatitis, pneumonia, and lung and liver abscesses. Methanetniol may have contributed to the morbidity and mortality.

# The subchronic toxicity of ethanethiol for rats and rabbits was studied by Wada .
Ethanethiol was prepared as either a 10 or 30% solution in peanut oil and injected into groups of rats and rabbits.
One group of rats and rabbits was injected sc with 0.01 ml/kg of ethanethiol daily. In another group, some of the rats were injected with 0.09 ml/kg of ethanethiol daily, and others were injected with 0.09 ml/kg of ethanethiol every other day.
In one more group, rabbits were injected initially with 0.03 ml/kg of ethanethiol every other day.
After an unspecified period of time, the injected volume was changed to 0.01 ml/kg of ethanethiol. The injections were continued for 1 year or until the animal died.

# All animals developed localized necrosis at the site of injection, with rabbits generally developing more serious effects .
The intensity of the necrosis increased in proportion with the concentration injected.
When injection ceased, the necrotic tissue was gradually replaced with scar tissue.
Rabbits injected with 0.01 ml/kg of ethanethiol either daily or eyery other day had reductions in red blood cell counts (RBC's) and hemoglobin.
Leukocyte and reticulocyte counts both increased. The degree of change generally was related to the dose.
The most marked microscopic changes in both rats and rabbits were found in the spleen. given oral dosages of butanethiol at 20 mg/10 0 g thrice daily on the 1st and 2nd day and at 40 mg/100 g on the 3rd and 4th day developed adrenal necrosis, apparently in the cortex. The degree of necrosis was not described.
None of the rats developed duodenal ulcers. None of the rats given a similar dosage schedule of ethanethiol for only 3 days developed either adrenal necrosis or duodenal ulcers.
No other studies have indicated these types of changes.

# Fairchild and Stokinger
, in 1958, reported a study on the subchronic toxicity of benzenethiol in rats. Six male rats, weighing 180-220 g, were injected ip with nine doses of 3.5 mg/kg benzenethiol, ie, one-third the ip L D S0, as a 2% V/V solution in ethanol for 3 weeks.

# One rat died on the 7th day,
The remaining rats had no significant weight loss, and no signs of cumulative toxicity were noted. When the rats were necropsied, only minor lesions were found.
The repeated irritation of ip injections apparently caused a fibrous thickening of the splenic capsule. Enlargement of the spleen was found in most of the rats, and hyperemia of the adrenal medulla was found in all rats. Some rats had a mild degree of what was called at that time cloudy swelling in the tubules of the kidneys, with hyaline casts in the lumina.
These pathologic changes are similar to those noted following acute exposure to benzenethiol, as described previously.
(2) Heptanethiol through Octadecanethiol; Cyclohexanethiol Gage  reported in 1970 on the subchronic inhalation toxicity of many industrial chemicals, including dodecanethiol, in rats. Two male and two female rats, with an average weight of 200 g, were exposed to a "nearly saturated atmosphere" of dodecanethiol for up to 6 hours/day, 5 days/week, for 4 weeks (a total of 20 exposures).
During the 20 exposures, no signs of toxicity were noted.
After the last exposure, urine was collected overnight.
The following day, samples of lungs, liver, kidneys, spleen, and adrenals were collected for microscopic examination. The heart, jejunum, ileum, and thymus were also assayed for some of the chemicals studied; whether these organs were taken from the rats exposed to dodecanethiol was not stated.
Microscopic examination of these tissues revealed all to be normal.

# The subchronic inhalation toxicity of dodecanethiol and of a mixture of C ? through C X1 thiols to rats was reported by Gizhlaryan
 in 1966. Thirty-two male and female rats inhaled air saturated with thiols from a 750-liter chamber, 4 times/week for 5.5 months (length of daily exposure unspecified).
The saturation level of dodecanethiol was 3,400 mg/cu m (411 ppm)
and that for the thiol mixture was 2,900 mg/cu m. The flanks of five albino guinea pigs (300-500 g) of either sex were depilated manually 24 hours before commencement of the daily application of 0.2 ml of a 20% solution of each thiol in acetone for 10 days, or until signs of contact dermatitis were evident.

# No changes in body weight, oxygen consumption, ability of the CNS
Erythema, induration, and eczematous crusts were considered positive indications of contact dermatitis. One month after the final application of the thiol solution, the opposite flank of the animal was shaved and painted with the solution if the animal had exhibited contact dermatitis during the 10 -day period of application.

# None of the thiols tested had a primary irritating effect as judged by the absence of local changes within 48 hours after the first application .
If signs of dermatitis developed within 3 days or more after the first application, the author considered the thiol to have exhibited contact-sensitizing ability.
Ordinarily, at least 5 days are considered necessary for development of a sensitization response.
The severity of the response was graded according to the intensity of the reaction and the time that had elapsed between the first application and appearance of dermatologic signs.
With respect to contact sensitization, dodecanethiol was rated "intense," octanethiol as "moderate," and butanethiol as "absent or negative." When animals were painted with octanethiol and dodecanethiol only once, about half the animals developed dermatitis; when animals were painted again on the opposite flank 1 month later, signs of sensitivity appeared within 24 hours, as compared with control animals (3-5 days). The duration of the dermatitis was not stated, however.

# Brooks et al , in 1957,
reported some effects of a number of compounds, including octanethiol, dodecanethiol, and octadecanethiol, on mouse skin.
Male albino mice 7-10 weeks old were used in the tests. Either pure liquids or solutions in ether were applied in 0.2-ml quantities to a shaved area on the backs of mice either on the 1st, 3rd, and 5th days of the experiment or on 6 days over a 2-week period.
The skin was removed on the 6th or the 14th day and cut into 1.5-x 2-cm sample patches.
The epidermis was isolated from the dermis, the epidermal patches were dried and weighed, and cholesterol and delta-7-cholestenol (D7-cholestenol) in the epidermal patches were determined.
The results are shown in Table III

# Bagramian and associates  and Bagramian and Babaian
 reported on the mutagenic potential of dodecanethiol, chloroprene, and ammonia in rats.
Six to eight white rats, weighing 180-250 g, inhaled a combination of chloroprene, dodecanethiol, and ammonia for up to 4 months.

# Chromosomal aberrations in bone marrow cells in both the anaphase and telophase stages of cell division were determined using acetocarmine.
A relative increase in the number of chromosomal aberrations in the exposed animals over that in the control animals was observed in both experiments.
In one experiment , after approximately 24 hours of inhalation of chloroprene (1.96 1.04 mg/cu m), dodecanethiol (5.02 1.96 mg/cu m), and ammonia (19.8 mg/cu m ) , the production of abnormal chromosomal aberrations increased from 5.5% in the controls to 8 .8% in the test animals.
After weekly exposure to chloroprene, dodecanethiol, and ammonia at the above concentrations for 4 months, the number of chromosomal aberrations was 1 1 .1 % above that of the control animals (P < 0.05).

# In another experiment 
, at the end of 120 days of exposure (daily exposure period not specified) to chloroprene (0.89  0.9 mg/cu m ) , dodecanethiol (0.12 0.03 mg/cu m ) , and ammonia (2.07 0.27 mg/cu m ) , the test group had 1 0 .1 % chromosomal aberrations, whereas the control group had 5.3%
(P = 0.01).

# The increase in aberrations consisted mainly of an increase in the number of chromosomal fragments.

# The mutagenic studies on Drosophila by Garrett and Fuerst

# SUMMARY OF EFFECTS ON ANIMALS OF SINGLE EXPOSURES TO THIOLS

# 4-6 Extrapolation of the curve constructed with these values indicates that the excretion of isotopic carbon through the lungs as carbon dioxide would become essentially zero between 6 and 7 hours after the injection .
This means that about 60% of the methyl moiety of methanethiol must be used in some other way within the body than by oxidation to carbon dioxide. The animal was killed 2 hours after the last dose; the liver proteins were isolated, and the amino acid contents were identified and determined by column radiography.
Most of the activity was present in the serine peak. A small fraction of the methanethiol appeared as the sulfoxide, approximately in the same location as alanine.
Two other small peaks, which could not be identified, also appeared.
The authors thought that one of these peaks may have been due to aspartic acid.
Very little radioactivity was found in the cystine peak; this may have been due to loss during isolation of the amino acids.
Differing amounts of radioactivity were found in tissue choline, creatine, and serine.
For the third experiment, one 200-mg male rat was given a total of 2 mg of 3^-labeled methanethiol in four ip doses, given at 2 -hour intervals; 92% of the administered dose was excreted in the urine within 8 hours [ One hour after administration, excreted urine was extracted with benzene and the aqueous layer was acidified with sulfuric acid and extracted with ether.
The benzene-and water-soluble products were analyzed by thin-layer chromatography and gas-liquid chromatography. Urine from rats not fed the above compounds was treated with labeled thiols to detect any in vitro decomposition products. The only benzene-soluble product isolated from the urine was MPS02.
The water-soluble products appeared to consist of p-and o-hydroxy MPS02 in all cases.
In the control urine, 30% of the added benzenethiol was converted to diphenyl disulfide (DPDS), and no MPS02 was recovered.
Based on these findings, it appeared that 3 sS-labeled benzenethiol readily underwent S-methylation in vivo followed by oxidation to MPS and then to MPS02. Similarly, guinea pigs and mice dosed with ethanethiol excreted ethylmethyl sulfone In addition, methylation of the thiol followed by oxidation leads to excretion of some of the sulfur as the sulfone of the methylated thiol.
This metabolic pathway seems to become more important in the thiols of larger molecular weight.

# (b)
The sulfur atom of the thiol group is not incorporated into the cysteine or methionine sulfur in mammals   The sebaceous glands were described as normal.

# The only available toxicity data on cyclohexanethiol suggested that the iv L D
When a total dose of 500 mg was applied to the skin of mice, the epidermal delta-7-cholestenol concentration was not affected, and the sebaceous glands were not damaged.
Cyclohexanethiol (WW Wannamaker III, written communication, December 1977) when applied to the skin of mice at a dose of 100 mg/kg killed all the animals in 24 hours. No other data on skin sensitization in animals were found.
In summary, all thiols behave as weak acids, their chemical reactivity being due essentially to the -SH group.
The predominant biologic effect of exposure to thiol vapors is on the CNS. Toxicity via the inhalation route of administration is of importance in the case of the Cj-Cg group of alkane thiols and the dermal route in the case of C 7-C 12 , Ci6> and Cis alkane thiols and cyclohexanethiol, the former group being more volatile than the latter.
Such a distinction, however, does not apply when ocular exposure is considered.
Benzenethiol is the most toxic of all the thiols included in this document.
It is pertinent to recognize that all the thiols have strong odor that constitute a nuisance at concentrations far lower than those at which they cause signs and symptoms of toxicity.
In general, the low molecular weight thiols have a more obnoxious odor than the high molecular weight thiols at comparable concentrations.
On the basis of similarity in the toxicity, the n-alkane thiols Cj-C^, C 16, and C 18 and cyclohexanethiol can be considered together as a group whereas benzenethiol needs to be considered separately because of its relatively higher toxicity.

# Carcinogenicity, Mutagenicity, Teratogenicity and Effects on Reproduction
No data on teratogenicity or effects on reproduction have been found. There are, however, a few reports 'dealing with the mutagenic and carcinogenic potential of thiols.

# Bagramian and associates  and B?gramian and Babaian
 reported on the mutagenic potential of dodecanethiol admixed with chloroprene and ammonia.
Rats were exposed to the combined vapors of the three substances. These three substances are components of "LNT-1 Latex."
The incidence of aberrations was found to be increased in experimental rats compared with that in the controls.
Eleven workers employed in a "LNT-1 Latex" factory were also studied . The peripheral blood lymphocytes obtained from each individual were cultured and examined.
More chromatid breaks were found in the lymphocytes of these individuals than in those of a group of five employees from a shoe factory who served as controls. A linear response was obtained with 1-9 vtmol of thiols.

# Based on the information presented in these studies
Analytical methods aimed at measuring methanethiol in the atmosphere of kraft paper mills take into account the presence of other sulfur compounds such as dimethyl sulfide, dimethyl disulfide, hydrogen sulfide, and sulfur dioxide; these compounds usually occur at concentrations higher than that of methanethiol.   In emergencies or other operations where airborne concentrations are unknown, respiratory protection must be provided to employees.
The type of respirator required is described in Tables 1 In case of eye contact with benzenethiol or with a mixture including benzenethiol, the affected eye shall be treated with not more than two drops of a 0.5% solution of silver nitrate (AgN03), applied from a bougie or other previously sealed container, and then flushed with copious quantities of water. When eye contact with any thiol has taken place, the affected person should be referred to a physician after eyewashing has been completed.

# Material Handling
Employers must establish material-handling procedures to ensure that employees are not exposed at hazardous concentrations or amounts of thiols. A sealed container is one that has been closed and kept closed so that there is no release of thiols.
An intact container is one that has not deteriorated or been damaged to the extent that the contained thiol is released. Because sealed, intact containers would pose no threat of exposure to employers, it should not be necessary to comply with required monitoring and medical surveillance requirements in operations involving only such containers.
If, however, containers are opened or broken so that the contained thiols are released, then all provisions of the recommended standard should apply.      Any difference between the "found" and "true" concentrations may not represent a bias in the sampling and analytical method but rather a random variation from the experimentally determined "true" concentration.
Therefore, the method has no bias.
(c) The coefficient of variation is a good measure of the accuracy of the method since the recoveries and storage stability were good.
Storage stability studies on samples collected from a test atmosphere at a concentration of 35.9 mg/cu m indicate that collected samples were stable for at least 7 days.

# Advantages and Disadvantages (a)
The sampling device is small and portable and involves no liquids. Interferences are minimal, and most of those that do occur can be eliminated by altering chromatographic conditions.
The tubes are analyzed by means of a quick, instrumental method.
(b) One disadvantage of the method is that the amount of sample that can be taken is limited by the number of milligrams that the sorbent will hold before overloading.
When the amount of 1-butanethiol found on the backup section of the sorbent tube exceeds 25% of that found on the front section, the probability of sample loss exists. If the affected person is recumbent, or if the head is tilted back when the person sits or stands, the lids of the eye may be simply spread apart with the first and second fingers of a hand while two drops of the silver nitrate solution are allowed to fall directly on the cornea of the eye.
The eye should be irrigated with normal saline solution or water after the silver nitrate has been given a few seconds to react with benzenethiol. using common names and general class names such as "aromatic amine," "safety solvent," or "aliphatic hydrocarbon" when the specific name is known.
The "%" may be the approximate percentage by weight or volume (indicate basis) that each hazardous ingredient of the mixture bears to the whole mixture.
This may be indicated as a range or maximum amount, ie, "10-40% vol" or "10% max wt" to avoid disclosure of trade secrets.

# D E P A R T M E N T O F H E A L T H , E D U C A T IO N , A N D W E L F A R E P U B L IC H E A L T H S E R V IC E C E N T E R FO R D IS E A S E C O N T R O L N A T I O N A L IN S T IT U T E FO R O C C U P A T I O N A L S A F E T Y A N D H E A L T H R O B E R T A. T A F T L A B O R

# Electroencephalographic Studies
Electroencephalographic (EEG) studies in volunteers should be conducted to determine whether significant stress may result from exposure to thiols. Concentrations of thiols required to significantly change the EEG pattern should be determined and compared with the odor threshold concentrations .

# Skin Effects
The skin-sensitizing effects of butane-, octane-, dodecane-, hexadecane-, and octadecanethiols have been studied in guinea pigs and mice .
The data suggest correlation between the skin effect and the chain length of the higher molecular weight thiols (Cg-C^).
Although no skin effect was observed following exposure to butanethiol, dodecanethiol and octadecanethiol caused intense and moderate dermatitis, respectively, and caused definite delayed effects.
These studies emphasize the need for a more thorough evaluation of the skin effects for all the thiols. Experiments using two or more mammalian species with a skin structure similar to that of humans would be valuable, and experimental conditions such as duration of exposure and dose should simulate occupational exposures.

# Metabolic Studies
Studies on the influence of alkyl, cycloalkyl, and aryl groups on the rate and character of metabolic degradation of thiols may lead to the identification of unique products that might serve as marker metabolites for occupational and environmental monitoring of thiols.  The collection and analysis of odorous gases from kraft pulp mills-IV. A field kit for the collection of the pollutants, and methods for their analysis.  The precision of the method is limited by the reproducibility of the pressure drop across the tubes.
Because the pump is usually calibrated for one tube only, this drop will affect the flowrate and cause the volume to be imprecise.

# Apparatus (a)
Personal sampling pump: Calibrated personal sampling pump, the flowrate of which can be determined within 5% at the recommended flowrate. Analyses should be completed within 1 day after the thiol is desorbed.

# (c) Gas chromatograph conditions:
The following are typical operating conditions for the gas chromatograph:
(1) 50 ml/minute (60 psig) nitrogen carrier gas flow.
(2) 150 ml/minute (30 psig) hydrogen gas flow to detector.
(3) 20 ml/minute (20 psig) oxygen gas flow to detector. No more than a 3% difference in area is expected.
Venting of the acetone solvent for 60 seconds after injection is required at the prescribed gas chromatographic conditions.
If the solvent is not vented, the flame may be extinguished and the detector may temporarily malfunction.
It is not advisable to use an automatic sample injector because of possible plugging of the syringe needle with Chromosorb 104.

# (C)
The area of the sample peak is measured with an electronic integrator or some other suitable device for area measurement, and results are read from a standard curve prepared as discussed in the following section.

# Determination of Desorption Efficiency (a)
The desorption efficiency of a particular compound can vary from one laboratory to another and also from one batch of Chromosorb 104 to another.
Thus, it is necessary to determine the fraction of the specific compound that is removed in the desorption process for a particular batch of Chromosorb 104. N o t e : Since no internal standard is used in this method, standard solutions must be analyzed at the same time that the sample analysis is done.
This will minimize the effect of known day-to-day variations and variations during the same day of the flame-photometric detector response.
(1) Prepare a stock standard solution containing 13.73 mg/ml 1-butanethiol in acetone.
From the above stock solution, appropriate aliquots are withdrawn and dilutions are made in acetone.
Prepare at least five working standards to cover the range of 0.0055-0.165 mg/1.0 ml. This range is based on a 1.5-liter sample.
Prepare a standard calibration curve by plotting concentration of 1-butanethiol in mg/1.0 ml vs square root of peak area.

# Calculations (a)
Read the weight, in mg, corresponding to each peak area from the standard curve.
No volume corrections are needed because the standard curve is based on mg/1.0 ml acetone, and the volume of sample injected is identical to the volume of the standards injected.
Corrections for the blank must be made for each sample: mg = mg sample -mg blank where: mg sample = mg found in front section of sample tube mg blank = mg found in front section of blank tube A similar procedure is followed for the backup sections.