Chronic toxicity study on formaldehyde administered orally to rats

Tobe, Masuo; Naito, Katsushi; Kurokawa, Yuji

doi:10.1016/0300-483x(89)90213-8

Cited by 51 publications

(16 citation statements)

References 4 publications

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“…For example, the studies by Appelman et al (1988), Johannsen et al (1986), and Til et al (1988, 1989) did not find any changes in hematology with exposure. Tobe et al (1989) reported statistically significant lowered RBC counts and Hb concentrations, but these changes were not exposure-concentration dependent. The results by Tobe et al (1989) were contradicted by Vargova et al (1993), who reported increased hematocrit (Hct) and Hb concentrations and RBC counts in blood.…”

Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 79%

“…Tobe et al (1989) reported statistically significant lowered RBC counts and Hb concentrations, but these changes were not exposure-concentration dependent. The results by Tobe et al (1989) were contradicted by Vargova et al (1993), who reported increased hematocrit (Hct) and Hb concentrations and RBC counts in blood. Furthermore, statistically significant changes in WBC counts following oral exposure to formaldehyde were found by Vargova et al (1993) as increased monocyte counts and decreased lymphocyte counts only following exposure to very high doses (as high as 80mg/kg for 4 weeks, equivalent to ∼800 ppm in drinking water).…”

Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 79%

“…As shown in Table 14, these studies ranged from subacute to chronic in duration (4 weeks to 24 months) and used a wide range of exposure concentrations; the highest was 5000 ppm in drinking water (Tobe et al, 1989) and 20 ppm in air (Woutersen et al, 1987). …”

Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 99%

“…Studies have been conducted to examine the potential for formaldehyde in air to induce hematotoxicity in animals and humans and leukemia in animals. The animal studies generally reported neither hematotoxicity (Monticello et al, 1989; Appelman et al, 1988; Holmstrom et al, 1989; Kerns et al, 1983; Kamata et al, 1997; Woutersen et al, 1987; Til et al, 1988, 1989; Johannsen et al, 1986) nor leukemia (Albert et al, 1982; Kerns et al, 1983; Sellakumar et al, 1985; Kamata et al, 1997; Feron et al, 1988; Til et al, 1989; Tobe et al, 1989; Takahashi et al, 1986) associated with formaldehyde exposure. Although a few animal studies reported changes in one or more hematology parameters (Dean et al, 1984; Tobe et al, 1989; Vargova et al, 1993), two animal studies reported leukemias (Soffritti et al, 1989, 2002), and a few human study findings were consistent with hematotoxicity from exposure to formaldehyde (Tang et al, 2009; Zhang et al, 2010b), these studies were inconsistent with other study findings and/or plagued by possible confounding.…”

Section: Introductionmentioning

confidence: 99%

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Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Rhomberg

Bailey

Goodman

et al. 2011

Critical Reviews in Toxicology

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Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding.

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Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 79%

Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 79%

Section: Weight Of Evidence Regarding Hematotoxicity From Formaldementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Rhomberg

Bailey

Goodman

et al. 2011

Critical Reviews in Toxicology

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“…In another study (Tobe et al 1989), FA was administered for up to 24 months in Wistar rats. Exposure levels were 0, 10, 50 or 300 mg kg −1 day −1 .…”

Section: Exposure–response Relationships For Lymphohematopoietic Malimentioning

confidence: 99%

Cancer effects of formaldehyde: a proposal for an indoor air guideline value

2010

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Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings.

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Formaldehyd [MAK Value Documentation in German language, 2000]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 31. Lieferung, Ausgabe 2000 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Histopathologische Veränderungen Zellproliferation Mechanismen der Inaktivierung von Formaldehyd Genotoxizität Schlussfolgerungen Toxikokinetik und Metabolismus Erfahrungen beim Menschen Einmalige und wiederholte Exposition Probanden‐Studien Studien mit Exposition am Arbeitsplatz Studien zur Irritationswirkung und zur Veränderung von Atemwegsparametern Studien mit histologischer Untersuchung der Nasenschleimhaut Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Lokale Effekte Systemische Effekte Genotoxizität In vitro In vivo DNA‐Protein‐Crosslinks (DPX) p53‐Mutationen Keimzellschädigende Wirkung Kanzerogenität Inhalation Orale Verabreichung Bewertung

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Chronic toxicity study on formaldehyde administered orally to rats

Cited by 51 publications

References 4 publications

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Cancer effects of formaldehyde: a proposal for an indoor air guideline value

Formaldehyd [MAK Value Documentation in German language, 2000]

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