Studies on the prenatal toxicity of N,N-dimethylformamide in mice, rats and rabbits

Hellwig, J.; Merkle, J.; Klimisch, H.-J.; Jäckh, Rudolf

doi:10.1016/0278-6915(91)90037-8

Cited by 35 publications

(25 citation statements)

References 13 publications

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“…Inhalation developmental toxicity studies reported reduced maternal body weight. Developmental effects included reduced fetal weight; increases in the litter incidence of total external, skeletal, and visceral malformations and skeletal variations; and increased number and percentage of dead implants (BASF 1974a,b,c;Kimmerle and Machemer 1975;BASF 1989;Hellwig et al 1991;Lewis et al 1992). Genotoxicity testing of DMF has generally been negative (Antoine et al 1983;NTP 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The AEGL-2 derivation was based on the study in which groups of 15 pregnant Himalayan rabbits were exposed to DMF at 0, 50, 150, or 450 ppm for 6 h/day on gestation days (GD) 7-19 (Hellwig et al 1991). Over GD 7-19, mean maternal body-weight gain was reduced in dams exposed to DMF at 150 ppm compared with controls, while dams in the 450-ppm group lost weight; mean maternal body-weight gain over the entire study period of GD 0-29 was also decreased in dams from the 150-and 450-ppm DMF groups compared with controls.…”

Section: Discussionmentioning

confidence: 99%

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Acute Exposure Guideline Levels for Selected Airborne Chemicals

2013

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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acute Exposure Guideline Levels for Selected Airborne Chemicals

2013

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“…7 8 In addition to liver toxicity, DMF is also known to be embryotoxic and teratogenic in animal experiments at concentrations >100 mg/kg/day 9 or >150 ppm. 10 DMF is categorised in ''pregnancy group B'' by the German MAK and BAT commission (human fetal toxicity cannot be ruled out even at a MAK level of 10 ppm or lower at the workplace, exposure of pregnant women to DMF should be avoided). Case-control studies in humans also suggested a relation between exposure to DMF and the formation of germinal cell testicular cancer.…”

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confidence: 99%

The use of biomarkers of exposure ofN,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry

Käfferlein

Ferstl²,

Burkhart-Reichl³

et al. 2005

Occup Environ Med

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Background: N,N-dimethylformamide (DMF) was recently prioritised for field studies by the National Toxicology Program based on the potency of its reproductive toxic effects. Aims: To measure accurately exposure to DMF in occupational settings. Methods: In 35 healthy workers employed in the polyacrylic fibre industry, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine, and N-methylcarbamoylated haemoglobin (NMHb) in blood were measured. Workplace documentation and questionnaire information were used to categorise workers in groups exposed to low, medium, and high concentrations of DMF. Results: All three biomarkers can be used to identify occupational exposure to DMF. However, only the analysis of NMHb could accurately distinguish between workers exposed to different concentrations of DMF. The median concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. It was possible by the use of NMHb to identify all working tasks with increased exposure to DMF. While fibre crimpers were found to be least exposed to DMF, persons washing, dyeing, or towing the fibres were found to be highly exposed to DMF. In addition, NMHb measurements were capable of uncovering working tasks, which previously were not associated with increased exposure to DMF; for example, the person preparing the fibre forming solution. Conclusions: Measurement of NMHb in blood is recommended rather than measurement of NMF and AMCC in urine to accurately assess exposure to DMF in health risk assessment. However, NMF and AMCC are useful biomarkers for occupational hygiene intervention. Further investigations regarding toxicity of DMF should focus on highly exposed persons in the polyacrylic fibre industry. Additional measurements in occupational settings other than the polyacrylic fibre industry are also recommended, since the population at risk and the production volume of DMF are high.

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“…Embryotoxic effects, including teratogenicity, were reported in rabbits (Merkle and Zeller, 1980;Hellwig et al, 1991), mice (Scheufler and Freye, 1975;Hellwig et al, 1991), and rats (Hellwig et al, 1991). Hellwig et al (1991) administered DMF to pregnant Sprague-Dawley rats by gavage at dose levels of 166, 503, and 1510 mg/kg/day on Gestation Days 6-15. Rat dams receiving dosages of 503 and 1510 mg/kg/ day showed a dose-dependent decrease in body weight gain.…”

mentioning

confidence: 99%

“…The developmental toxicity of DMF has been examined in several experimental species following different routes of exposure (for review see Barlow and Sullivan, 1982;Kennedy, 1986). Embryotoxic effects, including teratogenicity, were reported in rabbits (Merkle and Zeller, 1980;Hellwig et al, 1991), mice (Scheufler and Freye, 1975;Hellwig et al, 1991), and rats (Hellwig et al, 1991). Hellwig et al (1991) administered DMF to pregnant Sprague-Dawley rats by gavage at dose levels of 166, 503, and 1510 mg/kg/day on Gestation Days 6-15.…”

mentioning

confidence: 99%