Embryotoxicity in rats and rabbits from cutaneous application of amide-type solvents and substituted ureas

Stula, Edwin F.; Krauss, William C

doi:10.1016/0041-008x(77)90052-7

Cited by 73 publications

(19 citation statements)

References 13 publications

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“…in unverdünnter Form, sehr wahrscheinlich unter nichtokklusiven Bedingungen, aufgetragen. Dabei zeigten sich verminderte Körpergewichte bei den Muttertieren und leichte bis ausgeprägte Embryoletalität [103]. Nach Inhalation (vgl.…”

Section: Dermale Applikationunclassified

Dimethylformamid [MAK Value Documentation in German language, 1992]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 18. Lieferung, Ausgabe 1992 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Angaben zur Pharmakokinetik Erfahrungen beim Menschen Zusammenfassung Tierexperimentelle Befunde Akute und subakute Toxizität Subchronische und chronische Toxizität Reproduktions‐ und Teratogenitätsstudien Untersuchungen zur gentoxischen Wirkung Mikrobielle Testsysteme Säugerzellkulturen Untersuchung zur kanzerogenen Wirkung Sonstige Wirkungen Begründung des MAK‐Wertes

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Section: Dermale Applikationunclassified

Dimethylformamid [MAK Value Documentation in German language, 1992]

2012

The MAK‐Collection for Occupational Health and Safety

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“…Unfortunately, it is also a very hazardous chemical, causing both short term effects such as respiratory tract irritation, headache and nausea, and long term damages at the level of internal organs and on reproduction ( (Fail et al, 1998;George et al, 2002George et al, , 2000Gleich, 1974;Kennedy and Short, 1986;Merkle and Zeller, 1980;Stula and Krauss, 1977), see also Table1 for further details). It is rapidly absorbed orally, via inhalation or skin contact, and, given that in experimental animals it has been shown to have embryotoxic and teratogenic effects (Merkle and Zeller, 1980;George et al, 2002George et al, , 2000, pregnant women are considered to be particularly at risk (European Chemical Agency.…”

Section: Introductionmentioning

confidence: 99%

A safer, urea-based in situ hybridization method improves detection of gene expression in diverse animal species

Sinigaglia

Thiel

Hejnol

et al. 2018

Developmental Biology

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In situ hybridization is a widely employed technique allowing spatial visualization of gene expression in fixed specimens. It has proven to be essential to our understanding of biological processes, including developmental regulation. In situ protocols are today routine in numerous laboratories, and although details might change, they all include a hybridization step, where specific antisense RNA or DNA probes anneal to the target nucleic acids strand. This step, in general, is carried out at high temperatures and in a denaturing solution, the hybridization buffer, commonly containing 50% (v/v) formamide. An important drawback is that hot formamide poses a significant health risk and so must be handled with great care.We were prompted to test alternative hybridization solutions for in situ detection of gene expression in the medusa of the hydrozoan Clytia hemisphaerica, where traditional protocols caused extensive deterioration of the morphology and texture during hybridization, hindering observation and interpretation of results. Inspired by optimized protocols for Northern and Southern blot analysis, we substituted the 50% formamide with an equal volume of 8 M urea solution in the hybridization buffer. The new protocol yielded better morphologies and consistency of tissues, and also notably improved the resolution of the signal, allowing more precise localization of gene expression, as well as reduced staining at non-specific sites. Given the improved results using a less toxic hybridization solution, we tested the urea protocol on a number of other metazoans: two brachiopod species (Novocrania anomala and Terebratalia transversa) and the worm Priapulus caudatus, obtaining a similar reduction of aspecific probe binding. Overall, substitution of formamide by urea in in situ hybridization offers safer alternative protocols, potentially useful in research, medical and teaching contexts. We encourage other workers to test this approach on their study organisms, and hope that they will also obtain better sample preservation, more precise expression patterns and fewer problems due to aspecific staining, as we report here for Clytia medusae and Novocrania and Terebratalia developing larvae.

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“…There was a time when it was believed that dimethylformamide is metabolized to monomethylformamide (Barnes and Ranta 1972, Kimmerle and Eben 1975a, 1975b; the latter substance is clearly teratogenic in animal studies (Oettel and Frohberg 1964, Roll and Bar 1967, Stula and Krauss 1977 so that for this reason alone it was expected that dimethylformamide would have embryotoxic and/or teratogenic effects. More recent data indicate that hydroxydimethylformamide is the main metabolite of dimethylformamide, not monomethylformamide, and that the monomethylformamide found in the early studies was an artefact produced during processing and analysis of the samples (Section 1.1) .…”

Section: Reproductive and Developmental Toxicitymentioning

confidence: 99%

“…In a study with rabbits, dimethylformamide doses of 200 mg/kg and day, undiluted and very probably applied under non-occlusive conditions, caused some prenatal deaths (Stula and Krauss 1977). In another study (Gelbke 1984), dimethylformamide doses of 0, 100, 200 and 400 mg/kg *** and day were applied undiluted and under semi-occlusive conditions to groups of 15 animals from day 6 to day 18 post coitum; in the 200 mg/kg dose group, as in the control group, no effects were seen.…”

Section: Dermal Applicationmentioning

confidence: 99%

Dimethylformamide [MAK Value Documentation, 1997]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 8 (1997) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute and subacute toxicity Subchronic and chronic toxicity Reproductive and Developmental Toxicity Genotoxicity Microbial test systems Mammalian cell cultures In vivo Carcinogenicity Other Effects Manifesto (MAK value, classification)

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Embryotoxicity in rats and rabbits from cutaneous application of amide-type solvents and substituted ureas

Cited by 73 publications

References 13 publications

Dimethylformamid [MAK Value Documentation in German language, 1992]

Dimethylformamid [MAK Value Documentation in German language, 1992]

A safer, urea-based in situ hybridization method improves detection of gene expression in diverse animal species

Dimethylformamide [MAK Value Documentation, 1997]

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