The purpose of the memorandum is to exchange information and expertise in the area of occupational safety and health. One product of this agreement is the development of documents to provide the scientific basis for establishing recommended occupational exposure limits. These limits will be developed separately by the two countries according to their different national policies. This document on the health effects of occupational exposure to acrylamide is the fourth product of that agreement. The document was written by Vlasta Molak, Ph.D., D.A.B.T. (DSDTT/NIOSH), and was reviewed by the Criteria Group and by DSDTT/NIOSH.# BACKGROUND

# CHEMICAL AND PHYSICAL PROPERTIES
Acrylamide is an odorless, white, crystalline solid used as a monomer or as a raw material in the production of polyacrylamides and other compounds. Chemical and physical properties of acrylamide are given in Table 1. Because most of the aciylamide monomer is produced and used as an aqueous solution, the physical properties of a 50% aqueous solution of acrylamide are also given (Table 2).

# PRODUCTION AND USE OF ACRYLAMIDE
In 1985,140 million lb (63,600 metric tons) of acrylamide were produced in the United States, and predictions in 1988 indicated that 164 million lb (74,500 metric tons) of this chemical would be produced in 1989 . Total acrylamide production capacity in western Europe was 93.5 million lb (42,500 metric tons) in 1984, and the estimated production in Japan was 90 million lb (41,000 metric tons) in 1982 . Acrylamide is also used and produced in the Soviet Union and China, but production estimates have not been reported .
The reactive acrylamide monomer is used in the production of other compounds (mostly polymers of acrylamide) and as a grouting agent in the construction or rehabilitation of dams, buildings, sewers, tunnels, and other structures.
Acrylamide grouts are used predominantly as barriers against groundwater seepage into sewers. About 95% of the acrylamide produced in the United States is consumed in the production of other compounds and polyacrylamide products that are widely used as (1) flocculents in potable water and wastewater treatment, mineral ore processing, and sugar refining, (2) water flow control agents in oil well operations, and (3) adhesives in papermaking and construction . The remaining 5% is used as a monomer .

# POTENTIAL FOR OCCUPATIONAL EXPOSURE
Data on worldwide occupational exposures to acrylamide are unavailable. However, since exposure occurs during aciylamide production and use, the potential for occupational exposure exists in all countries that produce or import acrylamide. The National Institute for Occupational Safety and Health (NIOSH) estimates that more than 10,000 U.S. workers were potentially exposed to acrylamide monomer during the period 1981-83, either in acrylamide manufacturing and processing or in grouting operations (particularly in sewer grouting) . Other workers that are potentially exposed to variable and intermittent airborne concentrations and possible dermal contact with acrylamide are the researchers and technicians involved in the preparation of polyacrylamide   estimates that 100,000 to 200,000 of these U.S. workers have the potential for exposure.
Because acrylamide is produced by catalytic or sulfuric acid hydration of acrylonitrile (identified by the International Agency for Research on Cancer  as a probable human carcinogen ), acrylamide production workers may also be exposed to acrylonitrile.
Evaluation of exposure data from industrial settings  indicates that in all four U.S. acrylamide production plants, airborne concentrations were generally below 0.3 mg/m3-the occupational exposure limit set by many countries (see the Appendix).
Of the ninety 8-hr time-weighted average (TWA) personal samples collected in the four U.S. acrylamide production plants, only two samples from one of the plants were above 0.3 mg/m3 (0.38 and 0.39 mg/m3). However, many samples exceeded the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) of 0.03 mg/m3 adopted in 1989 .

# Hills and Greife

# EXISTING STANDARDS AND RECOMMENDATIONS
Many international standards for workplace exposures to acrylamide are 0.3 mg/m3 with a skin notation. The current American Conference of Governmental Hygienists (ACGIH) threshold limit value (TLV)  and the current OSHA PEL  are both 0.03 mg/m3. The current Swedish occupational exposure limit is 0.3 mg/m3 with a skin notation and a short-term exposure limit (STEL) of 0.9 mg/m3. See the Appendix for a list of the occupational exposure limits for airborne acrylamide in various countries and a discussion of the bases for recommendations that depart from the frequently cited limit of 0.3 mg/m3.

# TOXICOLOGY

# METABOLISM
Acrylamide  is a small organic molecule that is very soluble in water and can react at both its amide group and its double-bond vinyl group. This reactivity and ease of transport may account for the toxic effects of acrylamide. Studies show that the toxicokinetics and tissue distribution of acrylamide are not significantly dependent on the dose and route of exposure. The parent compound is rapidly eliminated from the tissues. The uptake, distribution, biotrans formation, and elimination, which are summarized below, have been discussed in detail by Dearfield et al. .

# Uptake
No studies were found on the absorption of acrylamide by inhalation. All animal studies involved either oral or dermal exposure, and intraperitoneal (i.p.) or intravenous (i.v.) dosing. The uptake of acrylamide through the gastrointestinal tract of rats was rapid and complete, as indicated by similar excretion profiles of the chemical whether it was administered by i.v. injection or by gavage . Dermal absorption in the rat is less than complete. By comparing blood concentrations after i.v. or dermal administration of acrylamide, Ramsey et al.  calculated that 25% of the applied doses (2 or 50 mg/kg) of acrylamide were absorbed through the skin of rats during the first 24 hr. Frantz et al.  reported that 26% of a 0.5% aqueous solution of acrylamide was absorbed through the skin of rats in 24 hr and that, after the skin was washed, an additional 35% remained in the skin. The data from in vitro experiments were similar . These researchers used excised skin preparations to show that 67% of the applied acrylamide was either absorbed or available for absorption (that is, 54% was absorbed and 13% remained in the skin after washing).

# Distribution and Toxicokinetics
After rats received various doses of acrylamide (0.5 to 100 mg/kg) by i.  1970]. Miller et al.  reported that high percentages of the wC-labeled chemical were found in muscle (48%), skin (15%), blood (12%), and liver (7%), whereas the neural tissues (brain, spinal cord, and sciatic nerve) contained less than 1%. However, when the data were expressed as micromoles (tmoles) of acrylamide/g of tissue, the concentrations of acrylamide in the tissues were similar. In the neural tissues of rats there appears to be no preferential bioconcentration of acrylamide and/or its metabolites that can account for its neurotoxic effects .
Acrylamide has also been reported to distribute readily in the tissues of other animal species. For example, acrylamide was found in the blood, brain, heart, liver, kidneys, and lungs of miniature swine and beagle dogs, with the highest concentrations found in the liver and kidneys . Because the authors did not analyze skin, muscle, and other tissues, it is difficult to compare the results with those reported by Miller et al. . In addition, autoradiographic studies have demonstrated a similar distribution of acrylamide in male and pregnant female mice . Acrylamide was found to cross the placentas of rats, rabbits, dogs, pigs, and mice and to be uniformly distributed in those fetuses .
Ramsey et al.  have examined the effects of multiple oral doses on tissue distribution. When rats were given acrylamide at 0.05 or 30 mg/kg for 13 consecutive days, the ratio of the 14C-labeled chemical in the tissues at the two doses was proportional to the ratio of the doses administered (that is, 600) except in the red blood cells (304), blood plasma (1,089), and testes (934). These data demonstrate that multiple doses of acrylamide do not greatly alter its distribution except at those three sites.  Miller et al.  used rats in a detailed study of the pharmacokinetics and distribution of acrylamide, both as the parent compound and as the total "-labeled chemical after an i.v. dose of 10 mg/kg. The elimination of the parent acrylamide was represented by a single compartment model. In the blood, the parent compound had a half-life of 1.7 hr, and the clearance of the unmetabolized acrylamide from all other tissues but the testes was similar. The testes showed a delay in the time necessary to reach peak concentration-an event attributed to their fat content. After the peak was attained, the parent acrylamide was cleared from the testes in a manner similar to that for other tissues .

# Biotransformation and Elimination
The distribution and the elimination of the total 14C-labeled chemical (representing acrylamide and its metabolites) was slower than that of the parent compound and was best represented by a biphasic curve . In addition, four tissues (liver, kidney, fat, and testes) demonstrated absorptive phases for the total 14C-labeled chemical. Since no absorption phases were noted for the parent acrylamide in the liver and kidney, the increases in the 14C-labeled chemical in these two tissues were attributed to metabolite accumulation. The higher lipid content of the fat and testes and the polar nature of acrylamide were reported by Miller et al.  to have delayed the absorption in these two tissues. The initial portion (half-life of 5 hr) of the biphasic curve was attributed to the metabolism of acrylamide and the binding of its metabolites to biological macromolecules, since only 2% of the total dose of administered acrylamide was excreted as the parent compound. The terminal portion (half-life of 8 days) of the biphasic curve was thought to be the result of the release of acrylamide metabolites from tissue depots and the degradation of acrylamide-protein adducts . Support for these suppositions was provided by Ramsey et al. , who analyzed urine, plasma, and tissue samples in male Fisher 344 rats following either i.v., gavage, or dermal administration of 14C-labeled acrylamide. Their data indicated that the initial phase was due to the loss of the parent compound and that the latter phase resulted from the clearance of acrylamide metabolites.
Because acrylamide affects reproduction, the very slow release of acrylamide or its metabolites from the testes is of particular interest. Although the fat content of the testes may have decreased the uptake of the parent acrylamide, it would not appear to account for its slow excretion. It is possible that acrylamide is metabolized and binds to constituents of the testes. Marlowe et al.  reported that radioactivity appeared in the testes 1 hr after administration and migrated to the seminiferous tubules and head of the epididymis after 9 hr. After 9 days, radioactivity remained only in the tail of the epididymis and in the epithelium of the penis. Marlow et al.  correlated this movement with that of the spermatids.

# Factors That Can Affect Metabolism
Studies of the effects of altering microsomal mixed-function oxidase activity on the expression of acrylamide-induced neuropathy have given disparate results.
Pretreatment of rats with phenobarbital (PB) or DDT  Srivastava et al.  found that pretreatment of rats with PB or DDT decreased the time necessary for onset of acrylamide-induced hind-limb paralysis. This disparity does not appear to be due to variations in experimental protocol, but it may be explained by differences in the animal strains.
The results of using drug metabolism inhibitors are difficult to interpret. For example, SKF 525A (which inhibits microsomal oxidation) has been reported to prevent acrylamide-induced enhance ment of striatal dopamine receptor activity  and to increase the acute toxicity of acrylamide in rats , whereas cobalt chloride has been shown to cause a significant delay in the development of hindlimb paralysis in rats . Presently, no correlation exists between the effects of modifying microsomal metabolism of acrylamide and expression of its toxic effects. Accordingly, identification of metabolic factors important in the toxic manifestations of acrylamide is not possible. Khanna et al.  studied the role of protein deficiency on the neurobehavioral effects of acrylamide in rat pups exposed during pregnancy and early infancy. They demonstrated that acrylamide was more toxic in protein-deficient animals because it decreased the dopamine and benzodiazepam receptor binding and delayed the development of reflexes and other physical milestones in pups.

# TOXICOLOGIC MECHANISMS
Because the most noticeable and earliest detectable effects of acrylamide exposures are neurological effects, numerous studies have attempted to find the mechanism of its action in neural tissues.   found that acrylamide inhibits succinic dehydrogenase (SDH) activity in mitochondrial preparations from rat brain and causes changes in levels of biogenic amines and activities of monoamine oxidase and acetylcholine esterase. Biochemical changes may be responsible for the functional changes observed in neural tissues-for example, changes in membrane capacitance and sodium permeability  remains to be established. However, the fact that acrylamide has been shown to interact with genetic material may have implications for its genotoxic and carcinogenic effects.

# TOXICITY IN HUMANS AND ANIMALS

# Neurotoxic Effects
The

# Developmental and Reproductive Effects
Data on developmental and reproductive effects in animals are summarized in Tables 3 and 4

# GENOTOXIC EFFECTS
The major concern about the genotoxicity of acrylamide is its clastogenic activity (that is, chromosomal breakage and other chromosomal abnormalities). The clastogenic effect of acrylamide appears more pronounced in the germ cells compared with somatic cells. The interaction with germinal tissues suggests the possible heritabUity of acrylamide-induced DNA alterations.

# Gene Mutation Assays

# Chromosomal Assays
Studies that have examined the chromosomal effects of acrylamide have confirmed its clastogenic potential. This effect appears to be more pronounced in the germ cells than in somatic cells. The suggestive reciprocal translocation results raise the possibility that acrylamide-induced alterations to DNA may be transmissible to future generations. A study of heritable translocation in mice  demonstrated that acrylamide is an effective inducer of translocations in postmeiotic germ cells. This result demonstrates that acrylamide may be capable of affecting heritable germ cells in a mammalian system.

# CARCINOGENIC EFFECTS

# Epidemiologic Findings
Collins et al.  studied the mortality of workers in acrylamide production plants. This study was performed by scientists at major production plants. Mortality was tracked for a cohort of 8,854 males from 1925 to 1983. This cohort (2,293 of whom were exposed to acrylamide) consisted of four plant populations in the United States and the Netherlands. Followup was completed for 95% of the cohort. At the end of the study 2,148 individuals were deceased, and death certificates were obtained for 95%. The underlying cause of death was coded by a nosologist. Exposure estimates were developed for all jobs at each of the four plants using exposure data collected at each plant and information obtained from plant personnel who had knowledge of past jobs and processes. Exposure to acrylamide was defined as a cumulative exposure greater than 0.001 mg/m3-years, which is approximately equivalent to a 1-day exposure to an average concentration of 0.3 mg/m3. Data on smoking history were available for only a third of the cohort. Standardized mortality ratios (SMRs) and internally standardized rate ratios were employed to estimate the risk.
According to the authors, a particular strength of their study was the ability to detect a 25% increase in total cancer, a 50% increase in respiratory cancer, and a threefold increase in brain and other central nervous system cancers based on a two-tailed, 5% significance level with a power of 80%.
The SMRs for all causes for both exposed and unexposed groups were significantly less than expected, which may be the result of both initial selection and the ongoing benefits of employment (i.e., the healthy worker effect). An excess of total cancer deaths was not observed among the exposed workers. A slight increase in cancer of the respiratory system (30 observed versus 26.3 expected) was not statistically significant. Analyses of trends by cumulative exposure showed no increased risk of mortality with increasing exposure. Because smoking history was obtained for only a third of the cohort, it was impossible to determine whether smoking habits had confounded the results.

# Sobel et al.
 examined mortality in a group of 371 workers assigned to acrylamide monomer or polyacrylamide operations. Exposure to acrylamide was categorized on the basis of a review of job classifications. Before 1957, personal TWA exposures to acrylamide in the monomer production areas were 0.1 to 1.0 mg/m3. The data from 1957 to 1970 indicated that exposures to acrylamide were 0.1 to 0.6 mg/m3. After 1970, personal exposures to acrylamide were <0.1 mg/m3 for all job classifications. Associated with the production of acrylamide monomer is the potential for exposure to acrylonitrile. The possible confounding effect of this exposure was not formally addressed in this study; but in a previous epidemiologic study , no effects could be directly related to acrylonitrile under the conditions of exposure. The total number of deaths from malignancies was slightly elevated (11 observed versus 7.9 expected ), but this result was apparently due to the excess in a subgroup that was also exposed to organic dyes . Overall, the results did not indicate an excess of cancers from exposures to acrylamide. However, these results may be due to the small cohort size, limited followup, and short duration of exposure (274 workers were exposed for less than 5 years). Given the size of the total cohort and the period of observation, the study had only an 80% likelihood (power) of detecting a twofold or greater increase in total cancer incidence.

# Evidence of Carcinogenicity in Animals
Studies in rats and mice indicate that acrylamide is an animal carcinogen . Acrylamide was tested for skin-tumor-initiating activity in Senear mice and for the ability to induce lung adenomas in A /J mice . In a mouse skin initiation-promotion assay, 6-to 8-week old female Senear mice were divided into groups of 40 and treated topically, by gavage, or by i.p. injection with acrylamide dissolved in water. Acrylamide was tested at doses of 12.5, 25, and 50 mg/kg for six applications by the three routes over a 2-week period, resulting in total doses of 75, 150, and 300 mg/kg. Ethyl carbamate, a known initiator, was used for a comparison in doses of 30,100, and 300 mg/kg in one application administered topically, by gavage, or i.p. A tumor promotion regimen was started 2 weeks after the last of the tumor-initiating doses of acrylamide. One microgram of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a known tumor promoter, was applied topically 3 times/week for 20 weeks. Tumor incidences were charted from weekly observation. Surviving animals were sacrificed at 52 weeks and histopathological evaluations were done on all gross lesions. A highly significant (p<0.01) dose-response relationship existed for time to first tumor and for the total number of tumors in treated animals. The effect was more pronounced with i.p. and gavage treatment than with topical application. However, without application of TPA promotion, no increase occurred in tumor yield, either with acrylamide or ethyl carbamate treatment. In this assay system, acrylamide was therefore confirmed as being a tumor initiator.
In a bioassay for lung adenoma in mice, groups of 40 male and 40 female, 8-week-old A /J mice received doses of 6.25, 12.5, or 25 mg/kg of acrylamide by gavage in an aqueous solution three times/week for 8 weeks . Animals were sacrificed at 7 months of age. Acrylamide increased the yield of lung adenomas in both sexes in a dose-related manner; the average number of tumors per animal increased from 0.2 to 1.4. The dose-response relationship was statistically significant (p<0.01) when both the number of animals with tumors and the multiplicity of tumors in each dose group were tested using logit regression model analysis. In the same investigation, groups of 16 male and 16 female, 8-week-old A /J mice received i.p. injections of 1, 3, 10, 30, or 60 mg/kg acrylamide three times/week for 8 weeks. The average number of tumors per animal increased from 0.4 to 2.2. The number of lung adenomas increased with the dose up to 30 mg/kg. The dose-response relationship was statistically significant (p<0.01) by the logit regression model. Because acrylamide increased the lung tumor yield by two routes of administration in the absence of a promoter, the authors concluded that acrylamide acted as a complete carcinogen in this test system.
In a subsequent study , groups of 40 female Swiss-ICR mice were administered an oral dose of 0, 12.5, 25, or 50 mg/kg acrylamide six times in a 2-week period. Ethyl carbamate served as a positive control and was administered in the same way at concentrations of 50 mg/kg. Two weeks after the last dose, a tumor promotion regimen was started. The regimen consisted of 3 weekly applications of 2.5 fig TPA dissolved in acetone to the shaved back of each animal. Another group of mice treated with 50 mg/kg acrylamide did not receive promotion treatment. The appearance of skin tumors was observed weekly, and after 52 weeks of study, the surviving animals were sacrificed and evaluated histologically for skin and lung tumors. When TPA treatment followed, acrylamide produced a dose-related increase in the number of animals that bore skin tumors (33% in the high-dose group versus none in the control group). Without TPA treatment there was no significant increase. The number of lung tumors (adenoma and carcinoma) was increased by acrylamide treatment in a dose-related manner (4 tumors in the control group and 11 tumors in the 50-mg/kg group). This increase was also observed in the absence of TPA (14 tumors in the 50 mg/kg group). This study confirms the initiating effects of acrylamide on the skin of Senear mice and the carcinogenic effects of acrylamide on the lungs of A /J mice.
Acrylamide administered in drinking water to female and male F344 rats for 2 years caused a statistically significant increase in the incidence of benign and malignant tumors at several sites in both sexes . Groups of 90 male and 90 female rats were maintained on drinking water providing acrylamide intakes of 0, 0.01, 0.1, 0.5, or 2.0 mg/kg per day. Ten rats per sex per treatment group were randomly selected for examination after 6, 12, or 18 months of study. Cumulative mortality showed no apparent dose relationship until the 21st month of study. From that time to the conclusion of the study at 24 months, mortality increased in the group receiving 2.0 mg/kg per day. No overt signs of neurotoxicity or other effects were attributable to acrylamide treatment. Rats in the group receiving the highest dose had an increased number of palpable masses, subsequently identified as subcutaneous or skin tumors. The number of tumors by site is listed in Table 5. In females, tumor incidence increased in the mammary glands, CNS, thyroid gland follicular epithelium, oral tissues, uterus, and clitoral gland. In males, tumor incidence increased in the CNS, the thyroid gland follicular epithelium, and the scrotal mesothelium. These increases occurred in the group receiving the highest dose (2.0 mg/kg per day). The only statistically significant increases (p<0.05) at the 0.5-mg/kg per day dose were the incidence of scrotal mesotheliomas in male rats and the incidence of combined mammary and clitoral gland tumors in female rats . 1 Includes only adrenal benign tumors.
Tumors only (no "proliferations").

# METHODS FOR MONITORING EXPOSURES

# EXPOSURE MONITORING
A worker's exposure to airborne acrylamide should be determined by using a personal sampling train consisting of a glass-fiber filter in a Swinnex cassette (13-mm) followed by a silica gel tube. Plastic cassettes (37-mm) yielded poor recoveries of acrylamide and are therefore unsuitable. Samples should be collected at a maximum flowrate of 1 liter/min for a minimum of 2 hr; the maximum air volume should be 120 liters. The silica gel tube should then be treated with methanol to extract the acrylamide. An important step in this method is the transfer of the glass-fiber filters to glass vials containing 1 ml of methanol immediately after sampling to avoid losses of acrylamide from the filter by evaporation. Analysis should be conducted by gas chromatography using a nitrogen/phosphorus detector. The limit of detection for this procedure is 1.3 parts per billion (ppb) (0.004 mg/m3). This method is described in Method 21 of the OSHA Analytical Methods Manual .

# BIOLOGICAL MONITORING
The International Programme on Chemical Safety (IPCS) has recommended that a biological monitoring method for acrylamide be developed based on the determination of the adduct formed with hemoglobin . However, no biological monitoring test acceptable for routine use has yet been developed for acrylamide.

# RELATIONSHIP BETWEEN EXPOSURE AND ADVERSE HEALTH EFFECTS
No data are available from studies in humans to establish an occupational exposure limit for acrylamide on the basis of neurotoxic, developmental, reproductive, or carcinogenic effects. However, many studies demonstrate a relationship between exposure and adverse health effects in animals. These studies are the bases for occupational exposure limits recommended by many organizations and government agencies. A few of these studies are described here.   5 NOEL = no-observable-effect level; LOEL = lowest-observable-effect level.
The linearized multistage procedure was followed by EPA , with GLOBAL 86 as the computer program. Among the models that showed adequate fit with one to six stages, the model that gave the least q^ (slope factor) was selected as the model with which to calculate carcinogenic risks using the lifetime average daily exposures provided by the exposure assessment for acrylamide. For the female rats with tumors of the thyroid, oral cavity, uterus, CNS, or mammary glands, this model had two stages. The cancer potency factor obtained for acrylamide by the linearized multistage procedure was 4.5 (mg/kg per day)'1. The cancer potency factor describes the increased risk of developing cancer over a 70-year lifetime per unit of exposure where the unit of exposure is expressed as mg chemical/kg body weight per day. When based on an experimental animal study, the cancer potency factor is the 95% upper confidence limit slope of the dose-response relationship for a carcinogen as the dose approaches zero. Calculated upper-bound excess risks for individuals exposed to acrylamide are presented in Table 7. The highest risks were estimated for sewer repair workers, whose excess risks ranged from 10'1 to 10'2. EPA calculated that exposure to airborne concentrations of 0.

# RESEARCH NEEDS
Very few studies address dermal absorption o f acrylamide, although the dermal route may be the most significant one for acrylamide exposure in the workplace . Therefore, quantitative studies should be performed to assess the absorption o f aciylam ide through the skin.
Because dermal exposure appears to be a significant route o f acrylamide uptake and it is difficult to monitor dermal exposures routinely, it is important to develop biom onitoring that can accurately reflect total exposure to acrylamide. A valid biomonitoring technique for acrylamide is presently unavailable. However, the literature on the toxicokinetics o f acrylamide indicates that biom oni toring may be feasible either in urine or blood. M ore than 50% o f the given dose is reported to be excreted in urine as the m etabolite N-acetyl-S-(3-amino-3-oxy-propyl)cysteine . By collecting the urine o f workers whose exposure is monitored, it may be feasible to correlate the total exposure (that is, both inhalation and skin) to acrylamide with measured concentrations or total amounts o f m etabolites in 24-hr urine samples.
Another possibility for biomonitoring is measurement o f acrylamide binding to red blood cells. Hashimoto and Aldridge  observed that after rats received a single i.v. dose o f UC acrylamide, the radioactivity in blood after 24 hr was entirely associated with red blood cells. Miller et al.  found that the concentration o f 14C in whole blood reached a plateau at 12% o f the total dose after 1 hr and remained constant throughout the time period examined (7 days). The binding to erythrocytes accounted for essentially all o f the remaining radioactivity in the w hole blood. In vitro studies showed that acrylamide was covalently bound to cysteine residues in protein and, on acidic hydrolysis, the adduct yielded a compound with chromatographic properties identified as S-( 2

# SUMMARY
Acrylamide is an odorless, white, crystalline solid used as a monomer or as a raw material in the production o f polyacrylamides. Workers potentially exposed to acrylamide monomer are employed in acrylamide manufacturing and processing, grouting operations, and research and analytical laboratories.
Only the acrylamide monomer is toxic; polyacrylamide products are generally nontoxic. Acrylamide monomer may be neurotoxic, carcinogenic, genotoxic, and hazardous to reproduction. Recent studies confirm that acrylamide exposures cause cancer and reproductive effects in animals, but epidem iologic studies have not demonstrated these effects in humans. Key Words: Acrylamide, carcinogenicity, dermal exposures, grouting, neurotoxic effects, occupational exposure, polyacrylamide, reproductive effects.

# APPENDIX. INTERNATIONAL STANDARDS FOR WORKPLACE EXPOSURES TO ACRYLAMIDE
This appendix lists occupational exposure lim its for airborne acrylamide in various countries (Table A -