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Data were last evaluated in IARC (1989).
1.1 Chemical and physical data 1.1.1 Nomenclature Chem. Abstr. Serv. Reg. No.: 68-12-2 Chem. Abstr. Name: N,N-Dimethylformamide IUPAC Systematic Name: N,N-Dimethylformamide Synonym: DMF 1.1.2 Structural and molecular formulae and relative molecular mass
O H C N CH3 CH3
Relative molecular mass: 73.09
1.1.3 Chemical and physical properties of the pure substance (a) Description: Colourless to very slightly yellow liquid with a faint amine odour (Budavari, 1996) (b) Boiling-point: 153°C (Lide, 1997) (c) Melting-point: –60.4°C (Lide, 1997) (d) Solubility: Miscible with water and most common organic solvents (Budavari, 1996) (e) Vapour pressure: 3 kPa at 20°C; relative vapour density (air = 1), 2.51 (Verschueren, 1996) (f) Flash-point: 67°C, open cup (Budavari, 1996) (g) Explosive limits: Upper, 15.2%; lower, 2.2%, by volume in air (American Conference of Governmental Industrial Hygienists, 1993) (h) Conversion factor: mg/m3 = 3.0 × ppm Production and use World production of dimethylformamide is estimated to be 125 thousand tonnes (Marsella, 1995). Information available in 1995 indicated that it was produced in 19 countries (Chemical Information Services, 1995). –545– 1.2
IARC MONOGRAPHS VOLUME 71
Dimethylformamide has been termed the universal solvent and is used commercially as a solvent, for example, for vinyl resins, adhesives and epoxy formulations (the latter for use in laminated printed circuit boards); for purification and/or separation of acetylene, 1,3butadiene, acid gases and aliphatic hydrocarbons; in the production of polyacrylic or cellulose triacetate fibres and pharmaceuticals. It is also used as a catalyst in carboxylation reactions; in organic synthesis; as a quench and cleaner combination for hot-dipped tin parts (e.g., for high-voltage capacitors); as an industrial paint stripper; as a carrier for gases, and in inks and dyes in printing and fibre-dyeing applications (American Conference of Governmental Industrial Hygienists, 1991; Lewis, 1993; Marsella, 1994). 1.3 Occurrence 1.3.1 Occupational exposure According to the 1981–83 United States National Occupational Exposure Survey (NOES, 1997), as many as 125 000 workers in the United States were potentially exposed to dimethylformamide (see General Remarks). Occupational exposures to dimethylformamide may occur in the production of the chemical, other organic chemicals, resins, fibres, coatings, inks and adhesives. Exposure also may occur during use of these coatings, inks, adhesives, in the synthetic leather industry, in the tanning industry and in the repair of aircraft (Ducatman et al., 1986; IARC, 1989). 1.3.2 Environmental occurrence Dimethylformamide has been measured in ambient air near a fibre plant and near waste facilities. It has rarely been found in water samples in the United States, other than at sewage treatment plants or in effluents of plants likely to have been using dimethylformamide. Levels measured were very low (WHO, 1991). It has been detected at low levels in drinking-water, surface water, wastewater and ambient air samples (United States National Library of Medicine, 1997). Exposure through the use of dimethylformamide in food processing, food packaging and pesticides may occur, but no data are available (WHO, 1991). Regulations and guidelines The American Conference of Governmental Industrial Hygienists (ACGIH) (1997) has recommended 30 mg/m3 as the 8-h time-weighted average threshold limit value, with a skin notation, for occupational exposures to dimethylformamide in workplace air. Values of 10–60 mg/m3 have been used as standards or guidelines in other countries (International Labour Office, 1991). No international guideline for dimethylformamide in drinking-water has been established (WHO, 1993). 1.4
Studies of Human Cancer
Case reports Ducatman et al. (1986) reported three cases of testicular germ-cell tumour that occurred during 1981–83 among 153 white men who repaired the exterior surfaces and electrical components of F4 Phantom jet aircraft in the United States. This finding led to surveys of two other repair shops at different locations. One repaired F4 Phantom jets while the other repaired different types of aircraft. Four among 680 white male workers in the F4 Phantom shop had testicular germ-cell cancers (approximately one expected) diagnosed during 1970–83. No case of testicular germ-cell cancer was found among 446 white men employed at the facility where different types of aircraft were repaired. Of the seven cases, five were seminomas and two were embryonal-cell carcinomas. All seven men had long work histories in aircraft repair. There were many common exposures to solvents in the three facilities, but the only exposure identified as unique to the F4 Phantom jet aircraft repair facilities was to a solvent mixture containing 80% dimethylformamide [20% unspecified]. Three of the cases had been exposed to this mixture with certainty and three cases had probably been exposed. Levin et al. (1987), in a letter to the editor, described three cases of embryonal-cell carcinoma of the testis in workers at one leather tannery in the United States. According to the authors, all the tanneries they had surveyed used dimethylformamide, as well as a wide range of dyes and solvents. A screening effort to identify additional testicular cancers at the leather tannery with the three cases was undertaken in 1989 (Calvert et al., 1990). Fifty-one of 83 workers employed at the plant between 1975 and 1989 participated. No additional case of testicular cancer was identified. Industry-based studies These case reports led to a cohort study of cancer among employees of the Du Pont company. Chen et al. (1988a) studied cancer incidence among 2530 actively employed workers with potential exposure to dimethylformamide during 1950–70 in Virginia and 1329 employees with exposure to dimethylformamide and acrylonitrile (see this volume) at an acrylic fibre manufacturing plant in South Carolina, United States. Cancer incidence rates for the company (1956–84) and national rates (1973–77) for the United States were used to calculate expected numbers of cases. [The tumour registry of the Du Pont company covers only active workers, but the Working Group noted this would be less of a limitation for testicular cancer than other tumours.] For all workers exposed to dimethylformamide (alone or with acrylonitrile), the standardized incidence ratio (SIR) based on company rates for all cancers combined was [1.1] [95% confidence interval (CI), 0.9–1.4] (88 cases). One case of testicular cancer was found among the 3859 workers exposed to dimethylformamide (alone or with acrylonitrile), with 1.7 expected based on company rates. The SIR for cancer of the buccal cavity and pharynx was [3.4] [95% CI, 1.7–6.2] (11 cases) among workers exposed to dimethylformamide, based on company rates. No such excess for any cancer was found among the 1329 workers exposed to both 2.2
9 (90% CI.. prostate (n = 43). (1989) conducted case–control studies of cancers of the buccal cavity and pharynx (n = 39).) for lung cancer. two acrylic fibre plants that used dimethylformamide as a spinning solvent and a plant using the chemical as a solvent for inks./40. 0.b) but two others had not.548 IARC MONOGRAPHS VOLUME 71 dimethylformamide and acrylonitrile./13. Studies of Cancer in Experimental Animals Dimethylformamide was tested for carcinogenicity by oral administration and subcutaneous injection in one strain of rats.0 (six cases.4) for testicular cancer. 0.9 (n = 15) (90% CI.5–5. year of diagnosis and age at diagnosis). the standardized mortality ratios (SMR) were [0./0. moderate exposure.4–2.0 expected).1 (90% CI. Walrath et al.0 (n = 3) (90% CI.) for buccal cavity and pharynx and [1. Two liver cancer cases and one control were exposed to dimethylformamide giving a logistic regression odds ratio of 6. Relative risks were estimated by Mantel–Haenszel matched analyses and logistic regression (adjusted for plant. 0.1 (90% CI.3) for low and 3. Mantel– Haenszel odds ratios for ever exposed were 0.0 ppm [3. 0.5 exp. testis (n = 11) and malignant melanoma of the skin (n = 39) among workers from four DuPont plants.5] (2 obs.9) for moderate exposure.7 (n = 16) (90% CI.1 exp. 2. 0. 0.6 (2 exposed cases and 2 exposed controls) (90% CI. The plants studied included a dimethylformamide production plant.8– 11. using all controls.9 (90% CI. pay class. 4.5–7. Dimethylformamide measurements were available from all plants.4–72. while ‘moderate’ exposure was defined as workplace levels sometimes above 10 ppm.2 expected). 3. 0. Chen et al.2 (five cases.9] (38 obs.8 exp. Two plants had been previously studied for exposure to acrylonitrile and dimethylformamide (Chen et al. 1988a. liver (n = 6). ‘Low’ exposure was defined as workplace levels consistently below 10 ppm (30 mg/m3). For all workers exposed to dimethylformamide only.5–286) for moderate exposure.3) for buccal cavity and pharynx cancers. Cancers occurring during 1956 to 1985 were identified through the Du Pont Cancer Registry from a combined cohort composed of approximately 8700 workers per year. 0. For each case. wage/salary class and plant. Potential exposure to dimethylformamide was classified as low or moderate (no worker fell in the high category) from job title/work area combinations by a team of two industrial hygienists and an epidemiologist. 1. 3. Odds ratios for testicular cancer by level of exposure were 0.0). [2.5 (n = 17) (90% CI. There was no relationship between cancer of the buccal cavity and pharynx and intensity or duration of exposure: low exposure. SIR. Geometric means for air measurements of dimethylformamide ranged from less than 1.) for all cancers combined. the first two eligible controls from the employment roster were selected matched on year of birth.2–4. 0. No other cancer excesses were reported. sex. Expected numbers (adjusted for age and time period) were based on company rates.6) for low and 11. Odds ratios for malignant melanoma by level of exposure were 1.1–8.3) for prostate cancer and 1. 1. 1.4] (19 obs. (1988b) evaluated mortality in 1950–82 in the same cohort among both active and pensioned employees. In a study in which dimethylformamide was .7–3. SIR.5) for malignant melanoma.0 mg/m3] to about 10 ppm [30 mg/m3].
The first was evaluated by dipping one hand into undiluted dimethylformamide for up to 20 min and by . 25.. No increased tumour incidence was observed (Malley et al.1. 3. Exposure to the highest concentration reduced body weight gain in both sexes but did not affect survival.2 Rat Groups of 87 male and 87 female Crl:CD BR rats. 300 or 1200 mg/m3] in air by whole-body vapour exposure for 6 h per day on five days a week for two years. 55 days old. The highest concentration also increased liver weights in both sexes. the range of historical control incidence for the laboratory was 2.1 Mouse Groups of 78 male and 78 female Crl: CD-1 (ICR) BR mice. metabolism and excretion 4. 300 or 1200 mg/m3] in air by whole-body vapour exposure for 6 h per day on five days a week for 18 months.1 Inhalation exposure 3. 47 days old were administered dimethylformamide (purity. from liquid dimethylformamide and from dimethylformamide vapour. incidences of minimal to mild centrilobular hepatocellular hypertrophy and centrilobular accumulation of lipofuscin/haemosiderin were increased.9%) at 0. 75. At termination. 1989). 1994). distribution.1. < 1% in 4 h). No compound-related effect on survival was evident. Ten males and ten females per group were killed at 12 months.0% (Malley et al.. In both sexes. but a 14. 75. Five males and five females per group were killed at 2 weeks.1. All of these studies were inadequate for evaluation (IARC. who showed that dimethylformamide was much better absorbed (51% in 4 h) than its aqueous solutions (15–60% v/v.and 400-ppm males and 400-ppm females had higher liver weights. 3. In both sexes of the two highest concentration groups.8% incidence of uterine endometrial stromal polyps in high-dose females was observed compared to 1. Percutaneous absorption in vivo was examined by Mráz and Nohová (1992a) in two ways. 3 months and 12 months.DIMETHYLFORMAMIDE 549 administered by intraperitoneal injection in another strain of rats. No increase in tumours occurred. at the two highest exposures. 99. the 100. a small number of uncommon tumours was observed in treated rats. 1994).1 Absorption.1 Humans The penetration of dimethylformamide through excised human skin in vitro was evaluated by Bortsevich (1984).9%) at 0. were administered dimethylformamide (purity. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms 4.0–15. 100 or 400 ppm [0. 25.7% in controls [numerical data not given]. 4. However. 99. centrilobular hepatocellular hypertrophy and hepatic singlecell necrosis were increased. 100 or 400 ppm [0.
as a result of its slower excretion relative to other major metabolites. 3. In addition. Mráz and Nohová (1992b) placed 10 volunteers (5 men. 23 h (13%). Multiple 500 ppm dimethylformamide exposures resulted in . while at the 250 ppm dose. Dimethylformamide was not detected in the plasma after the 10 ppm dose. Sakai et al. N-hydroxymethyl-N-methylformamide. while Casal Lareo and Perbellini (1995) evaluated 22 workers exposed to individual mean dimethylformamide concentrations of 10–20 mg/m3 over three working days. N-hydroxymethylformamide.and 6-h periods or for 6 h per day on 10 days over two weeks. this was not the case at 500 ppm. while wearing light clothing and breathing fresh air through masks. A number of studies of workplace exposure to dimethylformamide have been performed to search for the most appropriate biomarkers of dimethylformamide exposure. 7 h (13%). In both studies. 5 women) in atmospheres of 10. The half-lives of excretion and the urinary recoveries of the metabolites were: dimethylformamide.2 Experimental systems Hundley et al. two men and two women were exposed to 30 mg/m3. (1993a) exposed rats and mice to atmospheres of 10.3% of dose). The percutaneous uptake of dimethylformamide increased with increasing ambient temperature and humidity and contributed some 13–36% of the urinary N-hydroxymethyl-N-methylformamide excreted during combined inhalation and percutaneous exposure to the same concentration of dimethylformamide vapour (Mráz & Nohová.550 IARC MONOGRAPHS VOLUME 71 the application of 2 mmol dimethylformamide over an area of 100 cm2 on the forearm (approximately 1.5 mg/cm2). the absorption rate was 9 mg/cm2/h.1. for 8 h per day on five consecutive days. 2 h (0. 750 and 1500 mg/m3] dimethylformamide for single 1-. Percutaneous uptake of dimethylformamide vapour was evaluated in volunteers exposed to an atmosphere of 50 mg/m3 dimethylformamide for 4 h. 250 and 500 ppm [30. respectively) compared with the increase in dimethylformamide exposure concentration (from 250 ppm to 500 ppm). The uptake from the respiratory tract was 90% and the various urinary metabolites examined accounted for 49% of the retained dose. (1995) examined 10 workers exposed in different ways to up to 8 ppm [24 mg/m3] dimethylformamide. where plasma levels increased two-fold in rats and three-fold in mice between 3 and 6 h of exposure. and the mercapturic acid conjugate. These all showed a good and linear correlation between the amounts of dimethylformamide and N-hydroxymethyl-N-methylformamide in the urine at the end of an 8-h shift and the atmospheric concentration of dimethylformamide. The latter two studies also found that excretion of the mercapturic acid conjugate provides a good indication of the total exposure to dimethylformamide over a prolonged period. (1992) studied over 200 workers exposed to up to 9 ppm [27 mg/m3] dimethylformamide alone or with toluene. Kawai et al. 4 h (22%). 4. 30 and 60 mg/m3 dimethylformamide for 8 h and measured the metabolites in urine collected for up to five days. 1992a). The area under the plasma concentration curve (AUC) values for dimethylformamide after a single 6-h exposure increased disproportionately (8-fold and 29-fold increases in rats and mice. N-acetyl-S-(N-methylcarbamoyl)cysteine. steady-state plasma levels were approached after 6 h of exposure.
In all cases. Both N-hydroxymethyl-N-methylformamide and N-methylformamide formed from dimethylformamide undergo further oxidative metabolism. while the amounts of substances analysed as ‘N-methylformamide’ . As was found in rats and mice.. which is a major metabolite of dimethylformamide in animals and humans. 1993) (Figure 1). N-(Hydroxymethyl)-N-methylformamide formed 56–95% of the urinary metabolites. These authors also presented data on plasma levels of ‘N-methylformamide’. representing the total of N-hydroxymethyl-N-methylformamide and N-methylformamide. 1993). BALB/c mice and Syrian hamsters 0. Serial blood and urine samples were collected from two cynomolgus monkeys of each sex in groups subjected to whole-body exposure to atmospheres of 30. 1993b).. the plasma ‘N-methylformamide’ concentration being higher than that of dimethylformamide at 0. giving N-hydroxymethyl-N-methylformamide. 1993). 1990) probably methyl isocyanate. depending upon the exposure level and duration of the study.. There have been numerous studies of the metabolism of dimethylformamide in the past 25 years and these have been summarized by Gescher (1993). Kawai et al.1. There occur marked differences between rodent species and humans in the proportions of a dose excreted as these various major metabolites. N-Hydroxymethyl-N-methylformamide was underestimated. Plasma half-lives ranged from 1–2 h for dimethylformamide and 4–15 h for ‘N-methylformamide’. 50 and 500 mg/kg bw) by intraperitoneal injection and collected urine for 60 h (rat). Mráz et al.7 and 7 mmol/kg bw dimethylformamide (approximately 7. for example. (1989) gave male Sprague-Dawley rats. 300 or 1500 mg/m3] dimethylformamide for 6 h per day on five days per week for 13 weeks (Hundley et al.5 h. dimethylformamide and AMCC were very minor urinary metabolites.to 37-fold in male monkeys and 35. 24 h (mice) and 36 h (hamster). determined by gas chromatography. 100 or 500 ppm [90.. or not detected at all. there were disproportionate increases in plasma AUC values of 19. and the dose size introduces further variables. 1992. The formyl group oxidation which is the key step in the formation of AMCC is mediated by CYP2E1 (Mráz et al. There was rapid metabolism. The reaction mediated by human liver microsomes was inhibited by a monospecific antibody against rat liver CYP2E1 (Mráz et al.to 54-fold in females as the atmospheric concentrations increased five-fold from 100 to 500 ppm. The major pathway of dimethylformamide metabolism is hydroxylation of one of the methyl groups. Rosseel et al.. The formation of Nhydroxymethyl-N-methylformamide is a cytochrome P450-dependent reaction mediated by CYP2E1 in rat liver microsomes. 0. which is unstable in many analytical manipulations and readily decomposes to N-methylformamide..DIMETHYLFORMAMIDE 551 lower dimethylformamide AUC values for both rats (to 34%) and mice (to 23%) compared with the AUC values following a single 500 ppm exposure. ‘N-Methylformamide’ levels increased with time of exposure to single 250 ppm doses but did not increase further at 500 ppm. The resulting S-(N-methylcarbamoyl)glutathione undergoes the usual further transformations to give the mercapturic acid N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC). N-demethylation giving formamide and oxidation of the formyl group giving a reactive intermediate (Cross et al. which acylates glutathione. in a number of early studies for this reason (see.
552 IARC MONOGRAPHS VOLUME 71 Figure 1. (1990) and Gescher (1993) . Metabolism of dimethylformamide O CH3 N CH3 C H CYP2E1 HOCH2 N CH3 O C H HCHO H N CH3 O C H H Dimethylformamide N-(Hydroxymethyl)N-methylformamide N-Methylformamide H N CH3 C O CYP2E1 H CYP2E1 O H N O CH3 C H H2O CH3 N C O GSH O HO N CH3 C H H N CH3 O C SG S-(N-Methylcarbamoyl)glutathione O H N CH3 C S CH2 CH COOH NH COCH3 N-Acetyl-S-(N-methylcarbamoyl)L-cysteine From Cross et al.
no signs of liver fibrosis were found.. headaches and dizziness by 18 workers. complex lysosomes and pleomorphic mitochondria with crystalline inclusions (Redlich et al. 36 of 58 workers had elevations of either aspartate aminotransferase or alanine aminotransferase serum activity. no significant alterations in haematological and biochemical blood parameters were found compared with a non-exposed group (143 controls) (Cai et al. the prevalence of alcohol intolerance was also elevated depending on the calculated dose. However. (1991) found a significant corrrelation between high exposure concentrations of dimethylformamide (25–60 ppm) and elevated serum alanine aminotransferase and creatine phosphokinase levels.08 mM and 1. with 8–47% of dose as the former and 8– 37% as the latter.1 mM (Chieli et al. In 183 out of 204 employees in a synthetic leather factory. Purified CYP2E1 from mouse and rat liver microsomes in a reconstituted system is a very active catalyst of dimethylformamide oxidation. Overall. A cluster of toxic liver disease among workers exposed to dimethylformamide was reported by Fleming et al. In a group of 318 workers exposed to dimethylformamide levels of up to 7 ppm (geometric mean [21 mg/m3]).1 Humans An outbreak of liver disease in a fabric-coating factory was investigated by Redlich et al. including nausea and abdominal pain in particular during work. A prolonged susceptibility to alcohol-induced flushing after dimethylformamide exposure was reported in a case report by Cox and Mustchin (1991). anorexia. predominantly to dimethylformamide. (1990). Furthermore. high dimethylformamide exposure concentrations were correlated with symptoms such as dizziness. human subjects exposed to dimethylformamide by inhalation excreted 16–49% of the dose as ‘N-methylformamide’. Among workers with longer exposure. Wang et al. Dimethylformamide was used as a solvent for fabric coating in poorly ventilated areas without appropriate skin protection.DIMETHYLFORMAMIDE 553 and a formamide precursor varied with dose. the turnover being about 10 nmol/ min per nmol P450 for both species.2 Toxic effects 4. were about 0. In comparison. The Km values for mouse and rat CYP2E1. Among 46 workers.. 1990). These data suggest a quantitative difference in the formation of AMCC between species. respectively. most likely in the formation of the reactive carbamoylating intermediate which acylates glutathione. (1988). 1995). Liver biopsies of workers exposed to several organic solvents. the following symptoms were reported: anorexia.. 1992). 8–24% as ‘formamide’ and 10–23% as AMCC. abdominal pain or nausea by 31 workers. compared with one of 12 unexposed. a dose-dependent increase in complaints of subjective symptoms was found. 4.2. nausea and epigastric pain. showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum. . however. alcohol intolerance (facial flushing and palpitations) by 11 workers. the affinities are very different. Thirty-five out of 45 exposed production workers had abnormalities of their liver transaminases. Furthermore. nonproduction workers.
relatively high concentrations of dimethylformamide (in the range of 0.. initiated differentiation and led to simultaneous growth inhibition.3. 1995). no signs of hepatotoxicity were found in non-pretreated mice given the same dose or in pretreated or nonpretreated male Sprague-Dawley rats given up to 2000 mg/kg bw as a single intraperitoneal dose.2). cynomolgus monkeys received whole-body exposures of 0. No exposure-related effect on body weight or a number of haematological parameters and serum chemistry including transaminases occurred. In contrast. cholinesterase and total cholesterol. 4. glutamic pyruvic transaminase. They also found that dimethylformamide is more hepatotoxic than either of two of its metabolites. The hepatotoxicity of dimethylformamide was also investigated by Imazu et al.5 mL/kg bw dimethylformamide for one week.3 Reproductive and developmental effects 4. These effects upon the differentiation state were shown to be associated in certain confluent. Cynomolgus monkeys showed no measurable adverse effect following inhalation of 500 ppm [1500 mg/m3] dimethylformamide for 6 h per day on five days per week for two weeks (Hurtt et al. given as a single intraperitoneal dose of 1000 mg/kg bw. 4.5–1% in the medium). 1989. 1992). In a number of human and rodent cell lines (Hoosein et al. N-hydroxymethyl-N-methylformamide and N-methylformamide.. 90. In a 13-week inhalation study. while glutathione S-transferase activity using 1-chloro-2. Hepatic microsomal cytochrome P450 and hepatic glutathione reductase activity were decreased. 1992. These differences are probably related to the highly different substrate affinities of CYP2E1 in rats and mice (see Section 4.1 Humans No data were available to the Working Group.4-dinitrobenzene as a substrate was induced by about 66%. Van der Bulcke et al. Guilbaud et al. Levine et al. 1990. 1989).2 Experimental systems In acetone-pretreated male CD-1 mice. 1988a. weight gain and preg- . (1994) found increased serum sorbitol dehydrogenase activity after intraperitoneal administration of 4. 1991). 100 or 500 ppm [0.3. Levine & Chakrabarty.1 but not of 1.2. 1990). Grunt et al...4 mmol/kg bw dimethylformamide. transformed cell cultures with a reduction of c-myc levels (Mulder et al.b. (1992) who treated male Wistar rats by daily subcutaneous injections of 0. In male Wistar rats. 1992).554 IARC MONOGRAPHS VOLUME 71 4. which are similar and express their hepatotoxicity earlier. Body weight. 300 or 1500 mg/m3] dimethylformamide for 6 h per day on five days per week (Hurtt et al. Treated rats showed a significant increase in serum glutamic oxaloacetic transaminase. dimethylformamide..2 Experimental systems SPF (Mol:Wist) rats were administered up to 2 mL/kg bw dimethylformamide per day applied in a porous dressing placed on shaved skin either on gestation days 6–15 or on gestation days 1–20 (Hansen & Meyer. 30..1.. resulted in liver necrosis and a strong increase in serum alanine aminotransferase activity (Chieli.
. percentage of motile sperm. The frequency of chromosomal gaps and breaks was 1. which were within the maximal admissible range in the country. It was reported in an abstract that there was no evidence for an increased frequency of chromosomal aberrations in peripheral lymphocytes of a group of workers exposed to dimethylformamide [details not given] (Šrám et al. Eighteen unexposed employees from the same factory were used as controls. age. male cynomolgus monkeys received whole-body exposures of 0.63 mg/m3 (range. (1992) studied the effects of occupational exposure to dimethylformamide on sister chromatid exchange rates in peripheral lymphocytes from 22 dimethylformamideexposed women (aged 22–52 years) in comparison with 22 sex-.59%. di. 300 or 1500 mg/m3] dimethylformamide for 6 h per day on five days per week (Hurtt et al.49%. the mean workplace concentrations during one year before blood sampling were: 12.82% and 2.3 mg/m3 (range.] Chromosomal aberrations in peripheral lymphocytes were also reported in a study of about 40 workers who had been occupationally exposed to trace quantities of 2-butanone (methyl ethyl ketone). 100 or 500 ppm [0. 30. sperm count or abnormal sperm morphology was found. 40 and 35 mg/m3. 1981).4) dimethylformamide.10% (Koudela & Spazier. 5. 4..4 Genetic and related effects 4. 1. Similar but more pronounced effects were observed in rats treated on days 1–20 with the same daily dose..74% at these two sampling times. Subsequent sampling at three six-month intervals. 1992). No significant effect on semen volume. The 22 pairs were divided into three subgroups according to the intensity of their exposure to dimethylformamide: high exposure (8 pairs with mean exposure of . Blood samples were taken at two four-month intervals.58% and 1. gave lower aberration frequencies of 1.1 Humans In a study of chromosomal aberrations in peripheral blood lymphocytes. Seiji et al. as well as an increase in postimplantation loss. 1. The frequencies of chromosomal aberrations were 3.61% and 1. [The Working Group noted that the possible effect of smoking was not taken into account. when exposure was to an average of 180 and 150 mg/m3 dimethylformamide. In a 13-week inhalation study. toluene. 5.1) monomethylformamide and 0. butyl acetate.4% in the controls (Berger et al.01–3. 1985).3 mg/m3 (range.DIMETHYLFORMAMIDE 555 nancy rate were reduced in those rats receiving 2 mL/kg bw per day on days 6–15. respectively. 1985). The lowest effect level in this study was 1 mL/kg bw per day.6–26. A reduction in the number of live fetuses and in fetal weight.3) dimethylamine.2–10.and residencematched controls. cyclohexanone and xylene in addition to dimethylformamide.and trimethylamines as well as dimethylformamide in the then German Democratic Republic. 90. when average dimethylformamide exposures were to 50. The authors commented that the value in the control group was low. 0.4% in the exposed group compared with 0. in comparison with other studies.4. 20 workers exposed to mono-. All subjects were non-smokers and non-drinkers of alcohol as confirmed by medical interview. were also observed at this dose level. Aberration frequencies in two control groups were 1.
] 4.9 mg/m3]). at a dose level of 0.and mediumexposure groups than in their matched pairs (8. dimethylformamide was tested in both the presence and absence of an exogenous metabolic system.9 ppm) and low exposure (9 pairs at 0. 1981). Dimethylformamide did not induce sex-linked recessive lethal mutations in Drosophila melanogaster in experiments where it was used as a solvent for other substances to be tested and the responses were.56 and 7.7 ppm [2. but not in another study at a dose level of 80 000 μg/mL. micronuclei were reported to be induced at a dose of 1 mg/kg bw.007 μg/mL.1 mg/m3] in combination with toluene at 0.66. typhimurium TA98 in the presence of an exogenous metabolic system (Arimoto et al.53 vs 4. but the response occurred at a single.76 vs 5. the database has been expanded. 1992).35 vs 6. 1982).63 ± 1. Sister chromatid exchange frequencies per cell were significantly higher in the high. In no study were sister chromatid exchanges induced in either Chinese hamster or human cells and no chromosomal aberrations were induced in rodent cells. Since then. In most of the in-vitro studies. Dimethylformamide induced a slight increase in unscheduled DNA synthesis in primary rat hepatocyte cultures in one study but not in two others or in studies with mouse and Syrian hamster hepatocytes. In mouse experiments in vivo.26 ± 1.8 ppm [17. typhimurium or in Escherichia coli WP2uvrA and did not induce differential toxicity indicative of DNA damage in bacteria. It was reported to induce mutation in Salmonella typhimurium TA1538 and TA98 in one test with metabolic activation.12) (Seiji et al. but most results for gene mutation or mitotic recombination were negative. compared with those of untreated controls. In one study. in which 30 assay systems were included and more than 50 laboratories contributed data (de Serres & Ashby.57 ± 1. dimethylformamide did not induce gene mutation in any strain of S. but not in the low-exposure group (5. in one study. Chromosomal aberrations were reported to be induced in one study with cultured human lymphocytes.4 mg/m3]). intermediate dose and.556 IARC MONOGRAPHS VOLUME 71 5. . Dimethylformamide was not mutagenic in L5178Y tk+/– mouse lymphoma cells in three studies.. dimethylformamide enhanced the mutagenicity of tryptophan-pyrolysate in S. Gene mutations were not induced in a single study with human fibroblasts.3 ppm [0.2 Experimental systems (see Table 1 for references) Dimethylformamide was one of 42 chemicals selected for study in the International Collaborative Program for the Evaluation of Short-term Tests for Carcinogens.4. medium exposure (5 pairs at 0. in many other studies. while an increased mutation frequency of about two-fold was observed at the highest dose level in one experiment. [The Working Group noted the incomplete reporting of the data. therefore.67 ± 1. respectively). in which intraperitoneal doses up to 2000 mg/kg bw were used.24 ± 1. It induced aneuploidy in Saccharomyces cerevisiae D6 in both the presence and absence of an exogenous metabolic system in a single study and gave positive results in another study for mitotic recombination in yeast. dimethylformamide did not induce sister chromatid exchanges in mouse bone-marrow cells in a single study or micronuclei in mouse bonemarrow cells in four studies..
reverse mutation SA0. Salmonella typhimurium TA100. Salmonella typhimurium TA100. reverse mutation SA0. (1981a) MacDonald (1981) Nagao & Takahashi (1981) Richold & Jones (1981) Rowland & Severn (1981) Simmon & Shepherd (1981) Trueman (1981) Venitt & Crofton-Sleigh (1981) Antoine et al. (1978) Baker & Bonin (1981) Brooks & Dean (1981) Hubbard et al. reverse mutation – – – – – – NT NT – – – – – – – – – – – – With exogenous metabolic system – – – NT – – – – – – ? NT – – – – – – – – 32 2300 NG NG NG 19000 1000 1250 500 1000 500 NG 2500 NG 5000 1000 NG 1250 250 94 Nakamura et al. differential toxicity ERD. Bacillus subtilis rec strains. reverse mutation SA0. Salmonella typhimurium TA100. Salmonella typhimurium TA100. Salmonella typhimurium TA100.Table 1. Escherichia coli pol A/W3110-P3478. Salmonella typhimurium TA100. reverse mutation SA0. reverse mutation SA0. (1981) Ichinotsubo et al. differential toxicity SAF. reverse mutation SA0. Escherichia coli DNA-repair deficient strains. Salmonella typhimurium TA100. forward mutation SA0. (1981) Purchase et al. Salmonella typhimurium TA100. Salmonella typhimurium TA100. (1987) Rosenkranz et al. Escherichia coli DNA-repair deficient strains. Salmonella typhimurium. Salmonella typhimurium TA100. (1981) Doseb (LED or HID) Reference DIMETHYLFORMAMIDE Tweats (1981) Ichinotsubo et al. reverse mutation SA0. differential toxicity (liquid suspension test) ERD. (1983) 557 . SOS repair test. differential toxicity BSD. reverse mutation SA0. Genetic and related effects of N. (1981b) Green (1981) Kada (1981) Skopek et al.N-dimethylformamide Test system Resulta Without exogenous metabolic system PRB. reverse mutation SA0. Escherichia coli DNA-repair deficient strains. Salmonella typhimurium TA100. reverse mutation SA0. Salmonella typhimurium TA100. differential toxicity ERD. Salmonella typhimurium TA100. reverse mutation SA0. reverse mutation SA0. Salmonella typhimurium TA1535/pSK1002 ECL.
Salmonella typhimurium TA1535. reverse mutation SA5. Salmonella typhimurium TA1535. Salmonella typhimurium TA1537. Salmonella typhimurium TA1537. Salmonella typhimurium TA1535. reverse mutation SA5. Salmonella typhimurium TA1537. Salmonella typhimurium TA1537. reverse mutation SA5. reverse mutation SA7. Salmonella typhimurium TA1537. reverse mutation SA7. (1985) Mortelmans et al. (1986) Purchase et al. (1985) Mortelmans et al. reverse mutation SA7.558 Table 1 (cond) Test system Resulta Without exogenous metabolic system SA0. (1983) Falck et al. Salmonella typhimurium TA1537. (1986) Baker & Bonin (1981) Brooks & Dean (1981) Gatehouse (1981) MacDonald (1981) Nagao & Takahashi (1981) Richold & Jones (1981) Rowland & Severn (1981) Simmon & Shepherd (1981) Trueman (1981) Antoine et al. reverse mutation SA7. Salmonella typhimurium TA1535. reverse mutation SA5. (1986) Doseb (LED or HID) Reference IARC MONOGRAPHS VOLUME 71 . reverse mutation SA7. reverse mutation SA7. Salmonella typhimurium TA1535. reverse mutation SA7. (1978) Baker & Bonin (1981) Brooks & Dean (1981) Gatehouse (1981) Richold & Jones (1981) Rowland & Severn (1981) Simmon & Shepherd (1981) Trueman (1981) Antoine et al. (1983) Falck et al. Salmonella typhimurium TA1535. Salmonella typhimurium TA1537. reverse mutation SA7. reverse mutation SA7. Salmonella typhimurium TA1535. reverse mutation SA5. Salmonella typhimurium TA1537. reverse mutation SA5. reverse mutation SA5. Salmonella typhimurium TA1535. reverse mutation SA7. reverse mutation SA0. reverse mutation NT – NT – – – – – – – – NT – – – – – – – – – – – NT – With exogenous metabolic system – – – – – – – – – – – – – – – – – – – – – – – – – 1000 5000 1250 500 1000 1000 5000 1000 NG 1250 94 1000 5000 500 1000 1000 5000 NG 5000 1000 NG 1250 94 500 5000 Falck et al. Salmonella typhimurium TA1535. reverse mutation SA5. Salmonella typhimurium TA100. Salmonella typhimurium TA1537. (1985) Mortelmans et al. Salmonella typhimurium TA100. Salmonella typhimurium TA1537. Salmonella typhimurium TA1535. reverse mutation SA5. reverse mutation SA5. reverse mutation SA7. reverse mutation SA5. Salmonella typhimurium TA1537. Salmonella typhimurium TA1537. Salmonella typhimurium TA1535. reverse mutation SA7.
Salmonella typhimurium TA98. Salmonella typhimurium TA98. Salmonella typhimurium TA98. Salmonella typhimurium TA98. reverse mutation SA8. reverse mutation SA9. reverse mutation SA9. reverse mutation SA8. reverse mutation SA8. reverse mutation SA9. (1978) Baker & Bonin (1981) Brooks & Dean (1981) Gatehouse (1981) Hubbard et al. Salmonella typhimurium TA98. reverse mutation SA8. Salmonella typhimurium TA1538. reverse mutation SA9. Salmonella typhimurium TA1538. reverse mutation SA9. reverse mutation SA8. Salmonella typhimurium TA98. Salmonella typhimurium TA1538. Salmonella typhimurium TA98. Salmonella typhimurium TA98. reverse mutation SA9. reverse mutation SA8. reverse mutation SA9. Salmonella typhimurium TA98. reverse mutation SA8. reverse mutation SA9. Salmonella typhimurium TA1538. Salmonella typhimurium TA98. Salmonella typhimurium TA98. reverse mutation SA8. (1985) Purchase et al. reverse mutation SA9. Salmonella typhimurium TA1538. Salmonella typhimurium TA1538. reverse mutation SA9. Salmonella typhimurium TA98. (1981a) MacDonald (1981) Nagao & Takahashi (1981) Richold & Jones (1981) Rowland & Severn (1981) Simmon & Shepherd (1981) Trueman (1981) Venitt & Crofton-Sleigh (1981) Antoine et al. (1978) Baker & Bonin (1981) Brooks & Dean (1981) Richold & Jones (1981) Rowland & Severn (1981) Simmon & Shepherd (1981) Trueman (1981) Antoine et al. (1981) Ichinotsubo et al. reverse mutation SA9. Salmonella typhimurium TA1538. reverse mutation SA9. reverse mutation SA9. (1983) Falck et al.Table 1 (cond) Test system Resulta Without exogenous metabolic system SA8. reverse mutation NT – – – – – – – NT NT – – – – – – – – – – – – – NT With exogenous metabolic system – – – – – – + – – – – – ? NT – – – – – + – – – 1250 500 1000 5000 1000 NG NG 94 1000 1250 500 1000 1000 500 NG 5000 NG 5000 1000 NG 250 250 94 1000 Purchase et al. Salmonella typhimurium TA1538. Salmonella typhimurium TA98. reverse mutation SA9. (1985) Doseb (LED or HID) Reference DIMETHYLFORMAMIDE 559 . Salmonella typhimurium TA98. Salmonella typhimurium TA98. (1983) Falck et al. Salmonella typhimurium TA1538. reverse mutation SA9.
homozygosis by mitotic recombination or gene conversion – NT – NT – – – – – NT – + – – + – With exogenous metabolic system – – – – – – – – – – – + – – + – 5000 73000 1000 4000 500 NG NG 250 250 1000 1000 500 1000 167 4700 500 Mortelmans et al. (1981) Zimmermann & Scheel (1981) Sharp & Parry (1981b) Doseb (LED or HID) Reference IARC MONOGRAPHS VOLUME 71 . Salmonella typhimurium TA98.560 Table 1 (cond) Test system Resulta Without exogenous metabolic system SA9. Escherichia coli WP2 uvrA. TA92. homozygosis by mitotic recombination or gene conversion SCH. reverse mutation ECW. Escherichia coli K-122/343/113 forward or reverse mutation ECW. Escherichia coli WP2 uvrA. homozygosis by mitotic recombination or gene conversion SCH. reverse mutation SAS. reverse mutation ECW. reverse mutation ECW. (1981) Jagannath et al. ‘race XII’. Saccharomyces cerevisiae JD1. reverse mutation SSB. Salmonella typhimurium (other miscellaneous strains). DNA damage in DNA-repair strains SSD. Saccharomyces cerevisiae ‘race XII’. (1986) Green & Savage (1978) Brooks & Dean (1981) Mohn et al. Escherichia coli WP2 uvrApKM101. (1981) Matsushima et al. reverse mutation ECW. Escherichia coli WP2 uvrApKM101. Escherichia coli WP2 uvrA. (1981) Sharp & Parry (1981a) Kassinova et al. reverse mutation ECW. Salmonella typhimurium. differential toxicity in DNA repair-deficient strains SCH. (1981) Venitt & Crofton-Sleigh (1981) Venitt & Crofton-Sleigh (1981) Falck et al. reverse mutation ECF. Saccharomyces cerevisiae rad strains. homozygosis by mitotic recombination or gene conversion SCH. (1981) Gatehouse (1981) Matsushima et al. Escherichia coli WP2 uvrA. (1985) Kassinova et al. Saccharomyces cerevisiae. reverse mutation SAS. Saccharomyces cerevisiae D7. Saccharomyces cerevisiae D4.
mouse lymphoma L5178Y cells. mouse and hamster hepatocytes in vitro UIA. tk locus in vitro – – + – – – – (+) – – – – – (+) NT NT NT NT NT – – With exogenous metabolic system – – + NT 800 20 100 300000 900 40 000 ppm feed 40 000 ppm inj 700 7300 70 700 70 3000 5000 Mehta & von Borstel (1981) Loprieno (1981) Parry & Sharp (1981) Gichner & Veleminsky (1987) Wurgler & Graf (1981) Foureman et al. Drosophila melanogaster. mouse hepatocytes in vitro G5T. mutation DMX. forward mutation SZF.Table 1 (cond) Test system Resulta Without exogenous metabolic system SCF. rat primary hepatocytes in vitro URP. sex-linked recessive lethal mutations URP. Drosophila melanogaster. (1994) Williams (1977) Williams & Laspia (1979) Ito (1982) McQueen et al. sex-linked recessive lethal mutations DMX. (1983) Klaunig et al. Unscheduled DNA synthesis. Fischer 344 rat primary hepatocytes in vitro URP. Unscheduled DNA synthesis. sex-linked recessive lethal mutations DMX. Schizosaccharomyces pombe. tk locus in vitro G5T Gene mutation. aneuploidy ASM. Unscheduled DNA synthesis. Saccharomyces cerevisiae D6. rat primary hepatocytes in vitro UIA. mouse lymphoma L5178Y cells. Saccharomyces cerevisiae XV185-14C. Arabidopsis species. Drosophila melanogaster. Unscheduled DNA synthesis. Gene mutation. forward mutation SCN. (1994) Foureman et al. (1984) Jotz & Mitchell (1981) McGregor et al. Unscheduled DNA synthesis. (1988) Doseb (LED or HID) Reference DIMETHYLFORMAMIDE 561 .
Gene mutation. B6C3F1 mice in vivo MVM. Sister chromatid exchange. Micronucleus test. human lymphocytes in vitro CHL. Sister chromatid exchange. human lymphocytes in vitro SVA. Sister chromatid exchange. Chinese hamster ovary CHO cells in vitro SIC. Chinese hamster ovary CHO cells in vitro SIC. Gene mutation.007 80000 2500 ip × 1 1600 ip × 1 2. Chromosomal aberrations. ICR mice in vivo MVM. Syrian hamster embryo cells. (1983) Koudela & Spazier (1979) Antoine et al. Chinese hamster ovary CHO cells in vitro CIC. Sister chromatid exchange. (1981) Kirkhart (1981) Salamone et al. CD mice in vivo – – – – – – – – – – + – – – – – With exogenous metabolic system – – – – – – NT NT – NT NT NT 4700 4700 900 6300 100 6300 300 10 000 500 80000 0. human fibroblasts in vitro SHL. (1988) Myhr & Caspary (1988) Evans & Mitchell (1981) Natarajan & van Kesterenvan Leeuwen (1981) Perry & Thomson (1981) Natarajan & van Kesterenvan Leeuwen (1981) Dean (1981) Pienta et al. Cell transformation.562 Table 1 (cond) Test system Resulta Without exogenous metabolic system G5T Gene mutation. Chromosomal aberrations. tk locus in vitro G5T. Sister chromatid exchange. rat liver RL1 cells in vitro TCS. human lymphocytes in vitro CHL. (1981) Tsuchimoto & Matter (1981) Doseb (LED or HID) Reference IARC MONOGRAPHS VOLUME 71 . mouse lymphoma L5178Y cells. Micronucleus test. CBA/J mouse bone-marrow cells in vivo MVM. (1983) Paika et al. Micronucleus test. (1977) Gupta & Goldstein (1981) Antoine et al. Chinese hamster ovary CHO cells in vitro CIR.5 ip × 1 1500 ip × 2 Mitchell et al. mouse lymphoma L5178Y cells. Chromosomal aberrations. tk locus in vitro SIC. Chromosomal aberrations. diphtheria toxin HF Dipr. clonal assay GIH.
Micronucleus test. (1979) Chen et al. (1983) +. mg/kg bw/day. HID. (1983) Ye (1987) Quarles et al. weak positive. BALB/c mice in vivo MVM. ?. (CBA × BALB/c) F1 mice in vivo SPM. BALB/c mice in vivo a Doseb (LED or HID) With exogenous metabolic system 2000 ip × 1 1 ip × 1 3 ip × 1 NT 3800 900 ip × 5 667 ip × 1 Reference DIMETHYLFORMAMIDE – + – + – – Antoine et al. negative. Syrian hamster embryo cells treated in vivo ICR. highest ineffective dose. Sperm morphology. not given.Table 1 (cond) Test system Resulta Without exogenous metabolic system MVM. Inhibition of intercellular communication. positive. lowest effective dose. Chinese hamster lung V79 fibroblasts in vitro SPM. inconclusive LED. NG. mice in vivo TVI. intraperitoneal b 563 . not tested. μg/mL. ip. NT. –. injection. Micronucleus test. Cell transformation. in-vivo tests. (+). (1984) Topham (1981) Antoine et al. inj. Sperm morphology. in-vitro tests.
5.1 Summary of Data Reported and Evaluation Exposure data Exposures to dimethylformamide occur during its production and during the production of inks. Mortality and cancer incidence studies and nested case–control investigations of testicular cancer and several other anatomical sites at several facilities with exposure to dimethylformamide noted no convincing associations. and its use as a purification or separation solvent in organic synthesis. 5. for 7 h per day for five days in a rat bone-marrow cell cytogenetic study. fibres. All results were negative. 5. 4. It has been detected in ambient air and water. where a cancer cluster had been noted.2 . The positive data for cytogenetic damage in humans occupationally exposed to it are not very convincing. No morphologically transformed colonies were observed in Syrian hamster embryo cell cultures. If dimethylformamide is carcinogenic.3 Mechanistic considerations Dimethylformamide does not appear to be genotoxic as judged from results of a variety of in-vitro and in-vivo assays. resins. The Working Group was also aware of inhalation studies with dimethylformamide conducted for the United States National Institute of Occupational Health. Further research has failed to confirm this relationship. identified no additional cases. No increase in tumours was found. 1979).3 5. pharmaceuticals. These involved exposure to 400 ppm [1200 mg/m3] for 7 h in a rat bone-marrow cell cytogenetic study. Animal carcinogenicity data Dimethylformamide was adequately tested for carcinogenicity by inhalation in one study in mice and one study in rats.564 IARC MONOGRAPHS VOLUME 71 As reported in an abstract. no dominant-lethal effect was observed in groups of ten Sprague-Dawley rats exposed by inhalation to 300 ppm [900 mg/m3] dimethylformamide for 6 h per day for five consecutive days (Lewis. A screening effort at a leather tannery. synthetic leather. Human carcinogenicity data Case reports of testicular cancer in aircraft repair and leather tannery facilities suggested possible association with dimethylformamide.25 h in a Drosophila melanogaster sex-linked recessive lethal assay.4. Dimethylformamide inhibited intercellular communication (as measured by metabolic co-operation) between Chinese hamster V79 hprt +/– cells. either after treatment in vitro or after exposure of the dams to dimethylformamide (3 mL/kg bw) by intraperitoneal injection. a male rat dominant lethal assay and a mouse sperm morphology assay and for 2. adhesives. it is extremely unlikely that it owes its carcinogenicity to a genotoxic mechanism.
5. J. G. Vol. & Ashby. S. 5. & Bittersohl. 207–212 Arimoto. 55–57 (in Russian) Brooks. Report of the International Collaborative Program (Progress in Mutation Research. B. Whitehouse Station. Henrotte. (1981) Mutagenic activity of 42 coded compounds in the Salmonella/ mammalian microsome assay with preincubation. F. Haber. A. 26.. H.. Cincinnati. Dimethylformamide has been extensively tested in a broad range of in-vitro and in-vivo genotoxicity assays. 1). Nakano. Jenar-Dubuisson. Reports on chromosomal damage in workers exposed to dimethylformamide either failed to take into account smoking as a bias factor or were documented incompletely. eds. S. Toxicology. & Ashby. 102. (1996) The Merck Index. S. OH.S. 488– |490 American Conference of Governmental Industrial Hygienists (1997) 1997 TLVs® and BEIs®. Leonard.. pp. pp.L. & Hayatsu. Gig.M. OH. 1. & Decat. Wunscher. 249–260 Berger.J. F. Results have been consistently negative in well controlled studies..4 Overall evaluation Dimethylformamide is not classifiable as to its carcinogenicity to humans (Group 3). Y. J. G.. 366–368 (in German) Bortsevich. 31. Amsterdam. N.J. & Bonin. pp. Elsevier.M. Vol. 105–112 Baker. (1982) A solvent effect on the mutagenicity of tryptophan-pyrolysate mutagens in the Salmonella/mammalian microsome assay. Ohara. Tanaka. There is evidence suggesting lack of carcinogenicity of dimethylformamide in experimental animals. Vol.. References American Conference of Governmental Industrial Hygienists (1991) Documentation of the Threshold Limit Values and Biological Exposure Indices. Nov..DIMETHYLFORMAMIDE 565 Other relevant data Acute exposure of humans or experimental animals to relatively high concentrations of dimethylformamide causes hepatotoxicity as a major toxic effect. Evaluation of Short-Term Tests for Carcinogens. (1985) Epidemiologic studies of the exposure to dimethylformamide. I. Mutat. Merck & Co.. 1). ed. R. A. H.. 6. NJ. Tr. T. 459 . 12th Ed.. Cincinnati.V..J. Report of the International Collaborative Program (Progress in Mutation Research. Res. 23 Antoine. p. Evaluation of Short-Term Tests for Carcinogens. (1983) Lack of mutagenic activity of dimethylformamide. In: de Serres. Arany.. Elsevier.U.. Z.5 Evaluation There is inadequate evidence in humans for the carcinogenicity of dimethylformamide... G. (1984) Hygienic significance of dimethylformamide penetration through the skin. Amsterdam. J. In: de Serres. 261–270 Budavari. G. Zabol. J. Hyg. (1981) Study of 42 coded compounds with the Salmonella/mammalian microsome assay. K.. p. prof.. eds. J. ges.. & Dean. 6th ed..
Med. 30. (1990) N-Alkylformamides are metabolized to Nalkylcarbamoylating species by hepatic microsomes from rodents and humans. Elsevier... L. J. Dallas. J. Toxicol.. D.. B. G. & Ashby. Dimethylformamide and its metabolites in the urine of exposed workers. M. C. A. M.J. Saviozzi. Evaluation of Short-Term Tests for Carcinogens.. S. 16. R.. S. W. occup. 1.. C. (1995) Hepatotoxicity and P4502E1-dependent metabolic oxidation of N. Vol. occup.P. E. Urol.L.. Hyland. Shalat..M. Xi. Conwill. J. 289–292 . O. J. & Redlich. D. Work Environ. Health effects of dimethylformamide after occupational exposure at low concentrations. Fayerweather. Huang. 570–579 Ducatman. Arch. R.N-dimethylformamide in rats and mice. 3.. pp. environ.-B. Qu. Vol. Health. Chem. A.. 1).-X.J. Partanen. (1981) Effects of 20 coded chemicals on sister chromatid exchange frequencies in cultured Chinese hamster cells. & Mustchin. 47–52 Chemical Information Services (1995) Directory of World Chemical Producers 1995/96 Edition. (1988b) Mortality study of workers exposed to dimethylformamide and/or acrylonitrile. 1253–1254 Casal Lareo. & Ashby.L..E. Toxicol. Toxicol. (1986) Germ cell tumors of the testicle among aircraft repairmen. an automated bacterial mutagenicity assay. H. (1995) Biological monitoring of workers exposed to N. Report of the International Collaborative Program (Progress in Mutation Research... T. (1991) Prolonged spontaneous and alcohol-induced flushing due to the solvent dimethylformamide. Menicagli. A. Evaluation of Short-Term Tests for Carcinogens.E. 67. Res. J. Branca. pp. J.. & Halperin.. A. 155–171 Chen. Amsterdam.. eds. Health. L.-L. Report of the International Collaborative Program (Progress in Mutation Research.. Int. & Vainio.E. In: de Serres. F..H. Sorsa. T... P. Kavanagh.J. K. J.. & Mitchell. Elsevier. Yasugi. environ. M. Y. Scand.E. W. (1985) Mutascreen. & Pell..-Q. H.. Li. J. W.. and leather tanneries. J.-Y. T. T. (1992) Occupational dimethylformamide exposure. Amsterdam. In: de Serres. 336. Suovaniemi. Lancet. Mizunuma. J. Health. Kawai. 165–170 Cox.. 834–836 Evans. Dayal. Chang. 119–125 Fleming. Fajen. occup. TX Chen. 461–468 Calvert. S.. 538–550 Falck. (1981) Activity of 27 coded compounds in the RL1 chromosome assay.E. 69–70 Cross. 150. K. Hills. E.. & Gervasi.. & Perbellini. 1). (1990) Testicular cancer. L. 30.A.G.C. S. (1990) Liver injury in workers exposed to dimethylformamide. Mutat Res. N.M. F. J. M. C. 819–818 Chieli. (1988a) Cancer incidence of workers exposed to dimethylformamide and/or acrylonitrile. Fayerweather. S. 24. Cell Biol.W.. 136..N-dimethylformamide II. T. 357–362 Dean. Contact Derm.L.M. & Ikeda. Med.566 IARC MONOGRAPHS VOLUME 71 Cai. occup. J. 69. & Crawl. B.H. J.. 63. & Gescher. L.. 813–818 Chen.E. eds. 3. Int. (1984) Inhibition of metabolic cooperation in Chinese hamster V79 cells by various organic solvents and simple compounds. & Pell. & Trosko. Arch. P. Arch. dimethylformamide.
Amsterdam.N-dimethylformamide: key to the understanding of its toxicity. 376–386 Gescher. Elsevier. Report of the International Collaborative Program (Progress in Mutation Research. 151. pp. pp. A.. M.. 192. M. D. X. Report of the International Collaborative Program (Progress in Mutation Research. McKnight. & Ashby... (1990) Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF). (1988a) Comparison of the effects of transforming growth factor β. & Savage. & Ashby. & Veleminsky..J. 1). A. & Valette. & Bridges. F. eds. N. 145.J. Somay. & Meyer. 162–172 Gupta. Vol... M. J... C. Elsevier. M.. their ninhydrin positive metabolites and selected secondary amines for potential mutagenicity. A. 10. C. F. 208–227 Gatehouse. F. J. Amsterdam.R. S. Green. appl. Res.W..J. 219–232 Hubbard.. 13–22 Guilbaud. (1992) The differential effects of N. & Ashby. eugenol. T.N-dimethylformamide... Cell Res. M. Valencia. Dittrich.. 125–135 Hoosein. 245–251 Gichner. Res. T. eds.J.. M. 614–625 Hansen.K.DIMETHYLFORMAMIDE 567 Foureman. McKnight..G. Cancer Lett. J. 1). but have no effect on the mutagenic potential of N-methyl-N-nitrosourea. S. Mason.H. Vol. S.L. 23. In: de Serres. Childress.. Amsterdam. Mutat. Report of the International Collaborative Program (Progress in Mutation Research.A. D. (1981) Mutagen testing in the human fibroblast diphtheria toxin toxin resistance (HF Dipr) system.. Pavelka. & Dittrich. S. 31–35 Green. J.F.. Vol. N. (1990) Effects of differentiation-inducing agents on maturation of human MCF-7 breast cancer cells. (1987) The organic solvents acetone. Results of 70 coded chemicals tested for the National Toxicology Program. Toxicol. B.E. 57. Bridges.. In: de Serres.A. N.N-dimethylformamide and transforming growth factor-β1 on a human ovarian cancer cell line (HOC-7).W. & Zimmering. J. Brattain. Evaluation of Short-Term Tests for Carcinogens. Mutag.H. (1981) Fluctuation test with S9 and hepatocyte activation. Evaluation of ShortTerm Tests for Carcinogens. 40. 1). Ellinger..E. 361–370 . J. & Brattain. (1981) Mutagenic activity of 42 coded compounds in the ‘Microtiter’ fluctuation test. Chakrabarty..G. N. eds.M. E. P. pp. Toxicol. 6.. & Brattain. M. Physiol.. Gas. (1988b) Comparison of the antiproliferative effects of transforming growth factor-β. D. Wain. Amsterdam. J. J.R. 115–121 Grunt. E. 183–194 Green. Physiol. N.M. (1993) Metabolism of N.K. N. Res. J.J. 333–338 Hoosein. O. F. cell. and retinoic acid on transformed and nontransformed fibroblasts. Brattain. K. (1994) Chemical mutagenesis testing in Drosophila. pp. Elsevier. Elsevier. 1). Evaluation of Short-Term Tests for Carcinogens. M.S.E.N-dimethylformamide and retinoic acid on a human colon carcinoma cell line.. ethanol and dimethylformamide potentiate the mutagenic activity of N-methyl-N′-nitro-N-nitrosoguanidine. Environ. J. & Goldstein. A. Report of the International Collaborative Program (Progress in Mutation Research.. In: de Serres. mol.M. Mutat. Vol. eds.. & Ashby..L. (1981) A differential killing test using an improved repair-deficient strain of Escherichia coli.. N.A. (1978) Screening of safrole. Evaluation of Short-Term Tests for Carcinogens. cell. Chem. R. R. J. In: de Serres. 175. Exp. Dupont.
(Occupational Safety and Health Series No. J. Evaluation of Short-Term Tests for Carcinogens. pp... J..J. Vultaggio. 596–601 IARC (1989) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. McCooey..M. 32. pp.R. Mower. Some Organic Solvents. N. & Ashby. eds. K.J. J. G.E. pp. Lyon. G. 21–52 Hundley. 1). 456–467 Jotz. Amsterdam.J. Vol.. M. 298–301 Ichinotsubo.E..T.L.. Singer. Vol. & Mandel. In: de Serres. 72.L. H. Placke. eds.T. & Brusick. coli strains. Amsterdam. Elsevier. J. Amsterdam. 229–237 Hurtt.. Report of the International Collaborative Program (Progress in Mutation Research. appl.. 580–593 . D. pp.. Jr (1992) 13-Week inhalation toxicity study of dimethylformamide (DMF) in cynomolgus monkeys.. Amsterdam. Evaluation of Short-Term Tests for Carcinogens. Lieder. Lieder.W. Report of the International Collaborative Program (Progress in Mutation Research.. pp. pp. Jr (1993b) Dimethylformamide pharmacokinetics following inhalation exposure in monkeys. A. 1). & Kennedy. M.D. 53–79 Hurtt. Vol. Drug chem.E. (1981) Effects of 20 coded chemicals on the forward mutation frequency at the thymidine linase locus in L5178Y mouse lymphoma cells... 16. D. Fundam. Elsevier. Malley. Jr (1993a) Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice. Valentine.L. Drug chem. & Kennedy.. H. 15..H. M.. Mower. Lett. 3rd Ed. M. eds. & Mandel. Elsevier. 53–60 Jagannath. J.. P. 18. 195–198 Imazu.M.. Hurtt. R. (1982) Unscheduled DNA synthesis induced by chemical carcinogens in primary cultures of adult rat hepatocytes. M. Killinger. (1992) Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats. P. F.. Evaluation of Short-Term Tests for Carcinogens. G. 37). (1981a) Mutagen testing of a series of paired compounds with the Ames Salmonella testing system. 1). & Mitchell. L.E. Vol. Report of the International Collaborative Program (Progress in Mutation Research. In: de Serres. D. A..J. F. J. Evaluation of Short-Term Tests for Carcinogens. 168–169 Ito. Resin Monomers and Related Compounds. McCooey. 171–197 Ichinotsubo. M. Toxicol. S..A. Vol. 1). F. D. Toxicol. (1981b) Testing of a series of paired compounds (carcinogen and noncarcinogen structural analog) by DNA repair-deficient E. Toxicol. Mie med.. M. K.. Report of the International Collaborative Program (Progress in Mutation Research. & Ashby.. & Inoue.E. Geneva. Placke. In: de Serres. D. (1981) Genetic activity of 42 coded compounds in the mitotic gene conversion assay using Saccharomyces cerevisiae strain D4. S. F. Toxicol.568 IARC MONOGRAPHS VOLUME 71 Hundley. K. Toxicology.L. & Ashby. 47. eds. N. 59.G. 41–50 International Labour Office (1991) Occupational Exposure Limits for Airborne Toxic Substances. Fujishiro. K. J. Pigments and Occupational Exposures in Paint Manufacture and Painting. & Kennedy.M. G. Elsevier.G.. (1991) Ten-day repeated-exposure inhalation study of dimethylformamide (DMF) in cynomolgus monkeys. & Kennedy.. M. & Ashby.H. In: de Serres.
3-166 Loprieno. Baker.B. Hinton. Vol. Int. eds. D. In: de Serres. J. Report of the International Collaborative Program (Progress in Mutation Research. (1979) Dominant lethal mutagenic bioassay of dimethylformamide (DMF) (Abstract No. F. Amsterdam. J. Vol. (1981) Results of cytogenetic examination of persons working in an environment of increased concentration of dimethylformamide vapours in the atmosphere. pp. E. Frumin. 1). W. Evaluation of Short-Term Tests for Carcinogens. & Spazier. New York.. Monoghan. S. Kovaltsova. Jr (1993) Hawley’s Condensed Chemical Dictionary. In: de Serres. Cai. (1984) Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes. 698–704 Klaunig. S. K. (1979) Effect of dimethylformamide on human peripheral lymphocytes. S. Physiol. Evaluation of Short-Term Tests for Carcinogens. Int.. 166 Lewis. K.E. ed. 459–466 Lewis.J.. & Towne. p. B. Elsevier. B. K. Yasugi. J. 1). pp..J.. Elsevier.N-dimethylformamide and extracellular matrix on transforming growth factor-β binding to a human colon carcinoma cell line. cell. ii. P.. (1989) Effects of N. 653–658 Levine. A.. R. Arch. P.. Boca Raton.E. N. & Ikeda. J. and Ashby. J..-Q. 63.M.. Report of the International Collaborative Program (Progress in Mutation Research. CRC Press. & Zakharov.A. Toxicol. Goldblatt. Braithwaite. (1997) CRC Handbook of Chemistry and Physics.E. & Chakrabarty. & Spazier. (1981) The DNA-damaging activity of 42 coded compounds in the Rec-assay. A. 434–455 Kawai. 119–125 Koudela.-Y. 455–460 Kirkhart. M. 1. & Ashby. T.. Yao. 1153 Levine.F. 175–182 Kassinova. K. Watanabe.. 1). eds. B. D. Elsevier. 50. Csk. Report of the International Collaborative Program (Progress in Mutation Research. Elsevier.N-dimethylformamide. 121–123 (in Czech) Levin. F... Mutag. FL. eds.J.. (1981) Micronucleus test on 21 compounds. Lipsky. Xi. Pathol. F. Lancet. Environ. 2. Prak. Lék.V. & Ashby. Huang. In: de Serres. Black. M... 138.V.. J. 24..DIMETHYLFORMAMIDE 569 Kada.. S.. T.V. In: de Serres. & Brattain.-Z.J. D. 12. environ. Amsterdam. & Ashby. Marfin... Evaluation of Short-Term Tests for Carcinogens... M.V.J. (1992) Occupational dimethyl formamide exposure. I. (1987) Testicular cancer in leather tanners exposed to dimethylformamide. Landrigan.G. 12th Ed. J. Health. 1). Ea-7).R. J. S. eds. 432–436 (in Czech) Koudela. Amsterdam. Evaluation of Short-Term Tests for Carcinogens.C. Amsterdam. T. L. B..B. M. T. S. Mizunuma. Vol. (1981) Screening of coded carcinogenic/noncarcinogenic chemicals by a forwardmutation system with the yeast Schizosaccharomyces pombe. Vol. Monomethylformamide excretion in urine after occupational dimethylformamide exposure. p. Report of the International Collaborative Program (Progress in Mutation Research.. M. pp. Cancer. occup. Van Nostrand Reinhold. Hyg.. F. Qu. S.J.-X. (1981) Activity of 40 coded compounds in differential inhibition and mitotic crossing-over assays in yeast. (1992) Response of FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene to differentiation induction by N. G. 78th Ed. & Trump. pp. 424–433 . 33.M. J. K.E... 416 Lide...
1). In: de Serres. D. Toxicol. eds.A.M.N-dimethylformamide in humans. & Sugimura. J. J... Threadgill. Health. C. Environ. (1983) The hepatocyte primary culture/DNA repair assay using mouse or hamster hepatocytes. Kreiser. A. Cattanach. 1).570 IARC MONOGRAPHS VOLUME 71 MacDonald. & Flek. Int. I. Amsterdam. F. R. B. J. H. environ. Arch.. R.. (1986) Salmonella mutagenicity tests: II. Health.I. occup. Haworth.. 967–976 Matsushima. H. pp. eds. Cross..D. Brown. Y.J. T.. appl.. & Nohová.. 268–279 Marsella. Van Pelt. (1981) Salmonella/microsome tests on 42 coded chemicals.. 1). 64. Mutag. New York. J. M. (1994) Formic acid and derivatives. appl. pp..S. & Zeiger. II: 18 coded chemicals.. M. & Kennedy. (1992b) Absorption. mol.J. environ. Report of the International Collaborative Program (Progress in Mutation Research. Mutag. In: de Serres.. G. J. 285–297 Malley.J.. Sawamura. Slone. Ross. Evaluation of Short-Term Tests for Carcinogens. Elsevier. & Caspary. 64. P. K. J. F. 37–101 Mohn. Mutag. Elsevier. E. mol. 98. metabolism. Vol. Stadler. T. 85–92 Mráz. 507–516 . W.N-dimethylformamide in humans. (1981) Reverse mutation test on 42 coded compounds with the E. Shirai. T.C.. C. Speck. (1981) Studies on the mutagenic activity of 20 coded compounds in liquid tests using the multipurpose strain Escherichia coli K-122/343/113 and derivatives.D. Pharmacol.J. Elsevier. 11. (1988) Responses of the L5178Y tk+/tk– mouse lymphoma cell forward mutation assay. Rudd.. coli WP2 system. T. (1981) Mutagenic activity of 42 encoded compounds in the haploid yeast reversion assay. 1–8 Mehta. J.D.. Amsterdam.. 7). & Ashby. (1988) Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: intralaboratory results for sixty-three coded chemicals tested at SRI International. Results from the testing of 270 chemicals.. In: Kroschwitz. Vol.N-dimethylformamide. R. 4th Ed. Report of the International Collaborative Program (Progress in Mutation Research. & van der Horst-van der Zon. 387–395 McGregor.J. Takamoto. Vol. 414–423 Mitchell. Report of the International Collaborative Program (Progress in Mutation Research.. F.. J.. Environ.C. G. In: de Serres. A. Evaluation of Short-Term Tests for Carcinogens. & Howe-Grant. F. Evaluation of Short-Term Tests for Carcinogens.L. 12 (Suppl. Jr (1994) Chronic toxicity/oncogenicity of dimethylformamide in rats and mice following inhalation exposure. Edwards. eds. G. J. pp.. G. Toxicol.J. & Ashby. Mutag. H. Report of the International Collaborative Program (Progress in Mutation Research. McBride. P. (1989) Differences between rodents and humans in the metabolic toxification of N... W.J. pp.J. A. Arch.. strain XV-14C. S. eds. 23. 5. C. & Williams. Environ. J. eds. Vol. and elimination of N.. Jr.. & von Borstel. M. Kirk-Othmer Encyclopedia of Chemical Technology. 1–119 Mráz. Tainer. Vogels-Bouter. (1992a) Percutaneous absorption of N. Fundam.B... L. A. occup.. Amsterdam. D. J. 1).. 8 (Suppl.M.. & Ashby. Amsterdam. & Nohová. John Wiley.E. W. pp. 91–118 McQueen.A. Evaluation of Short-Term Tests for Carcinogens. D. 11.W.. 79–83 Mráz. 396–413 Mortelmans. S. Elsevier. Vol. D. Lawlor. Gescher.. Environ. J. In: de Serres. & Caspary. & Ashby. 13). Int. Elliott.
Thummel.. J.. & Westwood. Report of the International Collaborative Program (Progress in Mutation Research. Shimada.. Chem.J.R. Longstaff. (1981) Mutagenic activity of 20 coded compounds in chromosome aberrations/sister chromatid exchanges assay using Chinese hamster ovary (CHO) cells. 873–903 . J.. Elsevier. Randall. Vol.. 192.C.T. eds. Evaluation of Short-Term Tests for Carcinogens.. 49.. 1). J. & Ashby. W. J. 6. (1993) Investigation of the mechanistic basis of N. 673–681 Parry. M.. & van Kesteren-van Leeuwen. Styles. Ashby. Schreck. S. Vol. Elsevier. I. In: de Serres. & Ashby. eds. National Institute for Occupational Safety and Health Paika. J. Mutag. Vol.. & Thomson. Inc. (1981) In vivo SCE analysis of 20 coded compounds.. & Sharp.J.. 1). E. 19. M. & Sugimoto. R. Metabolism of N. W. (1981) Induction of mitotic aneuploidy in the yeast strain D6 by 42 coded compounds. Poiley. OH. Lefevre. M... (1988) Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: intralaboratory results for sixty-three coded chemicals tested at Litton Bionetics. F.A. pp..R. P. J. Environ.J. pp. K.-I.C. J. Amsterdam. (1981) Evaluation of the sister chromatid exchange method in mammalian cells as a screening system for carcinogens. F. 37. Beauchesne. & Hinshaw. (1989) Up-regulation of c-myc in a transformed cell line approaching stationary phase growth in culture. Evaluation of Short-Term Tests for Carcinogens. Cancer Res. Br. 2320–2326 Myhr. A. Cancer. I. Public Health Service. Amsterdam.J.Ndimethylformamide and its deuterated isotopomers by cytochrome P450 2E1. Anderson. & Ashby. D. & Lebherz... A. E. S. 239–246 Natarajan. Toxicol. mol.. A.J.. K.J. 1).M. eds. Report of the International Collaborative Program (Progress in Mutation Research.B. F. 103–194 Nagao. Report of the International Collaborative Program (Progress in Mutation Research. Res. J. Amsterdam. Res.J.E. Y. F. J. Gescher. Int. & Threadgill. eds. 197–207 Mulder. 642–655 Purchase. Unpublished data as of November 1997. X..H. Jheeta. (1981) Mutagenic activity of 42 coded compounds in the Salmonella/ microsome assay.. pp.E. In: de Serres. Evaluation of Short-Term Tests for Carcinogens. Vol.D. Elsevier. J. F. Vol. K. eds. In: de Serres.A.. In: de Serres. Oki.N-dimethylformamide toxicity.C.DIMETHYLFORMAMIDE 571 Mráz. T. J. P. Hyland. Mutat.F. Cincinnati. 1).J. 551–559 NOES (1997) National Occupational Exposure Survey 1981-83. III (1977) Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. In: de Serres.J. & Caspary. pp. Oda. 302–313 Nakamura. Evaluation of Short-Term Tests for Carcinogens.. J. I. R. (1978) An evaluation of 6 short-term tests for detecting organic chemical carcinogens. (1987) SOS-inducing activity of chemical carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002: examination with 151 chemicals. 560–569 Pienta. Elsevier.A. 468–480 Perry. 12 (Suppl 13).T. Levine. & Ashby.M. P.. Amsterdam. Report of the International Collaborative Program (Progress in Mutation Research. 1). D. Evaluation of ShortTerm Tests for Carcinogens.A.. pp. A. Amsterdam.. Elsevier. Report of the International Collaborative Program (Progress in Mutation Research. B.. R. M.. Cancer. & Latt. Y. F. & Takahashi. United States Department of Health and Human Services. & Ashby.
Schenley.A. pp. J. Med. D. J. eds. J.. 748–757 Richold. 491–501 .. K. T. O. 1). In: de Serres. 615.A.M. J. 65–67 Sharp. Evaluation of Short-Term Tests for Carcinogens. F. Z.. M. N. C. F. W. B.. Y.. M. & Ashby. C.L. (1992) Increase in sister chromatid exchange rates in association with occupational exposure to N. 210– 218 Rosseel. Elsevier. Int. & Cullen. Vol. 1). & Lijinsky.B. J. Health.. 686–697 Seiji. Report of the International Collaborative Program (Progress in Mutation Research.W.F. Sega. & Ashby. Vol. intern.. 314–322 Rosenkranz.R. Vol.N-dimethylformamide. Araki. Report of the International Collaborative Program (Progress in Mutation Research. eds. Kuribayashi. Kageyama. Report of the International Collaborative Program (Progress in Mutation Research.C. Fleming. (1979) Transformation of hamster fetal cells by nitrosated pesticides in a transplacental assay. Evaluation of Short-Term Tests for Carcinogens. In: de Serres. Report of the International Collaborative Program (Progress in Mutation Research. & Ashby. Report of the International Collaborative Program (Progress in Mutation Research. K.J.. & Leifer. J. Arch.W. Kawai. P. M. Evaluation of Short-Term Tests for Carcinogens.. 1). pp.. Sigal. Amsterdam... Beckett. chromatogr. F. In: de Serres. S. L. H. M... eds. Miller. Arch. Evaluation of Short-Term Tests for Carcinogens. T. (1993) Simultaneous determination of N. pp. environ. Cai. Report of the International Collaborative Program (Progress in Mutation Research. West. Gastroenterology. Int. C. T.572 IARC MONOGRAPHS VOLUME 71 Quarles.J. Amsterdam. Evaluation of Short-Term Tests for Carcinogens. 39. A. Inoue.S. Amsterdam. S. W. pp. biomed. H. D. (1981) Mutagenicity of carcinogens and noncarcinogens in the Salmonella/microsome test. Hyman. (1981b) Induction of mitotic gene conversion by 41 coded compounds using the yeast culture JD1. 323–332 Sakai. M.T. & Severn. Elsevier.. I. Amsterdam. T & Masuyama. C. Elsevier. (1981) Mutagenic activity of 41 compounds in the in vivo micronucleus assay. Belpaire.. Vol. (1981a) Use of repair-deficient strains of yeast to assay the activity of 40 coded compounds. Elsevier. F.M. 1).L. Elsevier. N-monomethylformamide and N-hydroxymethyl-N-methylformamide in rat plasma by capillary gas chromatography. J.. In: de Serres. E.. J. & Jones.J.J. Sparer.. J. environ. J..-X. Vol. & Parry. 1). Amsterdam. T. eds.. Appl. F. M. occup. & Wijnant... M. (1981) DNA polymerase deficient assay. 108.A. Shalat. & Ashby. & Ashby.N-dimethylformamide and N-acetyl-S-(N-methylcarbamoyl) cysteine. Ann. occup. T.. True. Barwick. eds. 1). A.N-dimethylformamide. & Ikeda. C.M. Samijn. S.. 502–516 Sharp. J. H.. 125–129 Salamone. Vol. (1990) Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide. Yosida. J.. pp. In: de Serres. M. L.K. & Riely. Riely.. In: de Serres.. Cancer Res. Evaluation of Short-Term Tests for Carcinogens. (1988) Liver disease associated with occupational exposure to the solvent dimethylformamide. Cullen. 64. eds. 4525–4533 Redlich. 67. (1981) Mutagenic activity of 42 coded compounds in the Salmonella/ microsome assay. Heddle. Health.... Amsterdam. & Katz. F. pp. F. (1995) Biological monitoring of workers exposed to N. 99. & Parry.M. 680–686 Redlich.A.J.. Watanabe.D.J.R.S.C. J. 154– 158 Rowland. Elsevier.. & Ashby.
& Matter.G. & Crofton-Sleigh.J. W. T.J.N-dimethylformamide.J.T. New York. & Ashby.. F. Vol.E.J. T. (1981) Activity of coded compounds in the micronucleus test. F.J.. & Belpaire. Arch. and N-methylformamide in the rat. pp. eds. (1989) A case-control study of cancer among Du Pont employees with potential for exposure to dimethylformamide. Report of the International Collaborative Program (Progress in Mutation Research. Elsevier. Report of the International Collaborative Program (Progress in Mutation Research.A. D. F.. Report of the International Collaborative Program (Progress in Mutation Research. Report of the International Collaborative Program (Progress in Mutation Research. Amsterdam. (1996) Handbook of Environmental Data on Organic Chemicals. eds.. Evaluation of Short-Term Tests for Carcinogens. (1994) Metabolism and hepatotoxicity of N. M. Med. Elsevier. J. R. & Ashby.J. K. 1).. & Ashby. Vol. 31. & Pell. pp. W. B. M. & Ashby.DIMETHYLFORMAMIDE 573 Simmon. In: de Serres. C. Vol. (1981) Mutagenic activity of 42 coded compounds using 8-azaguanine resistance as a genetic marker in Salmonella typhimurium.... Elsevier. Evaluation of Short-Term Tests for Carcinogens. N-hydroxymethyl-N-methylformamide. D. Amsterdam. eds. Amsterdam. MD [Record No. Vol. (1981) Mutagenic activity of 42 coded compounds in the Salmonella/microsome assay.E. P. Elsevier. I. & Roznícková. & Ashby. 705–711 Tweats. Kaden. eds. N. F. 1). 1).G. Amsterdam.J. F. J. pp.. S. pp. Evaluation of Short-Term Tests for Carcinogens. Vol. Report of the International Collaborative Program (Progress in Mutation Research.C. Rosseel. 291–295 Venitt. Evaluation of Short-Term Tests for Carcinogens. 371–375 Šrám. Vol..R. Bethesda. occup. Res. 147. 818–820 Walrath. G.. 1). Amsterdam. Report of the International Collaborative Program (Progress in Mutation Research. Elsevier. and CM871 (uvrA lexA recA). Vol. Holá. P. pp. 322 Topham. eds. Van Nostrand Reinhold. Evaluation of Short-Term Tests for Carcinogens. Wijnants. & Thilly. (1985) The use of the cytogenetic analysis of peripheral lymphocytes as a method for checking the level of MAC in Czechoslovakia (Abstract No. J. R. (1981) Evaluation of some chemicals by the sperm morphology assay. J. V. J. & Ashby. In: de Serres. In: de Serres. WP67 (uvrA polA). K. 1). F.F.J. Landa. 68.J. F. Elsevier.. & Ashby. 351–360 Verschueren. (1981) Mutagenicity of 42 coded compounds in a bacterial assay using Escherichia coli and Salmonella typhimurium. 3rd Ed. Amsterdam. eds. In: de Serres. 333–342 Skopek. pp. S. & Shepherd. J. Toxicol. Evaluation of Short-Term Tests for Carcinogens. Report of the International Collaborative Program (Progress in Mutation Research.M.. W. J. Evaluation of Short-Term Tests for Carcinogens. 199–209 United States National Library of Medicine (1997) Hazardous Substances Data Bank (HSDB). F.. In: de Serres. Gilby.W.. (1981) Activity of 42 coded compounds in a differential killing test using Escherichia coli strains WP2. In: de Serres.. J. 78] Van den Bulcke.. Mutat. 87). Fayerweather.F. 343–350 Tsuchimoto. J. 432–438 . J. pp.. Andon. Elsevier.M. Amsterdam. 1).. 1). B. 718–720 Trueman. In: de Serres. (1981) Activity of 42 coded compounds in the Salmonella reverse mutation test.. pp. eds. Buylaert.
Cancer Lett. W. 46. environ.K.-S..J. Shiau. G. In: de Serres. Geneva Williams. Vol. 6.-J. U.-D. eds. F. M. Recommendations.. 2nd Ed. 1). (1977) Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures. 199–206 Williams. 1). Cancer Res. (1991) Dimethylformamide-induced liver damage among synthetic leather workers... 37. Lin. Res.). J. Arch. & Ashby.N-dimethylformamide on the frequency of micronuclei in bone marrow polychromatic erythrocytes of mice (Chin. Evaluation of ShortTerm Tests for Carcinogens.J. (1981) Mutagenic activity of 10 coded compounds in the Drosophila sex-linked recessive lethal assay. & Scheel. M.. Chiang. & Chang. Report of the International Collaborative Program (Progress in Mutation Research. 161–166 WHO (1991) Dimethylformamide (Environmental Health Criteria No. 481–490 . J. G.F. Chen. F. J. In: de Serres. J.M. (1981) Induction of mitotic gene conversion in strain D7 of Saccharomyces cerevisiae by 42 coded chemicals.574 IARC MONOGRAPHS VOLUME 71 Wang. Amsterdam.E. Elsevier. pp.. eds. (1987) The effect of N. J. I.. Vol. pp. 27–32 Zimmermann. F. & Laspia. Zool.M. Report of the International Collaborative Program (Progress in Mutation Research. Lai. G.. 114). Vol.. S. International Programme on Chemical Safety WHO (1993) Guidelines for Drinking Water Quality. 8. Geneva. J. 1.-S.-Y. Evaluation of Short-Term Tests for Carcinogens.-R. & Ashby.. F.. (1979) The detection of various nitrosamines in the hepatocyte primary culture/DNA repair test.-M. 1845–1851 Wurgler. Health. 666–672 Ye. Amsterdam. & Graf. Elsevier.