Notwithstanding the inability to detect 13CD2-formalde- hyde-DNA adducts in blood or bone marrow following 5 days’ exposure to 10 ppm formaldehyde, the preponder- ance of credible animal and human data indicates that hematotoxicity is not a consequence of formaldehyde exposure, even up to very high exposure concentrations. This is a keystone issue because hematotoxicity (i.e., pan- cytopenia), which is an indicator of myelotoxicity, has been associated with all known human leukemogenic chemicals and appears to be a necessary precursor for chemical leu- kemogenesis (Golden et al., 2006). Tang et al. (2009) briefly reviews and tabulates a number of studies (almost all of which are published in Chinese journals) that purport to demonstrate that exposure to formaldehyde is a cause of hematotoxicity. However, from the various studies cited, although some formaldehyde levels are listed, there is not enough information in the tabular summary of study results to understand exposure conditions or other experimental variables that were present in order to evaluate whether the reported results on white blood cell counts, platelet counts, or hemoglobin levels were valid or due to formaldehyde or another exposure. For example, Tang et al. (2009) cite only one study in English by Kuo et al. (1997) in support of adverse hematological effects. This study was conducted on 50 hemodialysis nurses and controls from four hospitals in Taiwan and concluded that the white blood cell (WBC) counts were significantly lower in the exposed group com- pared to controls. Although this study provided a matrix suggesting a negative correlation coefficient for WBC count and formaldehyde concentration, no actual blood count data are provided and no significant correlation with any other blood variables was reported. Therefore, it cannot be determined if the change in WBC count was outside the normal range. In addition, the correlation matrix suggested increased rather than decreased red blood cell counts. This study, however, is suspicious because the formaldehyde mean personal sampling concentrations are extremely low and basically at background levels (e.g., 0.015, 0.017, 0.033, and 0.054 ppm) in the four hospitals. Indeed, these levels are similar to the formaldehyde exposure levels of controls as reported in Zhang et al. (2010). The majority of the more carefully conducted studies show essentially no reported adverse hematological effects followingexposureofeitherhumansoranimalstoformalde- hyde. This finding has substantial implications with respect to any proposed mechanism for formaldehyde-induced myeloid leukemia. No matter how one might hypothesize that this occurs (e.g., formaldehyde-induced myelotoxic- ity or formaldehyde-induced mutations to stem cells with subsequent transport to the bone marrow), all mechanisms require pancytopenia as an early indicator of potential dis- ease. This relationship occurs because myeloid leukemia is a malignant disease of the bone marrow in which the ability to make normal amounts of blood cells (e.g., erythrocytes, leukocytes, and platelets) is compromised. This results in decreased numbers of red and white blood cells and plate- lets in the peripheral blood. There is no consistent evidence that formaldehyde produces similar effects. © 2011 Informa Healthcare USA, Inc. Indoor air exposure limit for formaldehyde 705 Although an accidental ingestion of a large quantity of formaldehyde was reported to cause an intravascu- lar coagulopathy (Burkhart et al., 1990), several reports of human ingestion of lower doses have not shown any effects on the blood or blood-forming organs (Eells et al., 1981; Freestone and Bentley, 1989; Koppel et al., 1990). In animal studies, neither inhalation exposure (Appelman et al., 1988; Kamata et al., 1997; Kerns et al., 1983; Woustersen et al., 1987) nor oral exposure (Johannsen et al., 1986; Til et al., 1989; Tobe et al., 1989) to high doses of formaldehyde has produced any evidence of adverse hematological effects. A single study in rats exposed to massive oral doses of formaldehyde (e.g., 80 mg/kg for 4 weeks) reported minor increases in erythrocyte count and hemoglobin values (Vargova et al., 1993). As noted in ATSDR (1999), the lack of hematopoietic toxicity in these studies is “likely related to rapid metabolism prior to the formaldehyde reaching the blood and blood-forming components (bone marrow).” These data are also sup- ported by the 2-year chronic inhalation study conducted by Battelle (1981) in male and female B6C3F1 mice and F344 rats following exposure to formaldehyde at 0, 2, 6, and 15 ppm, with blood collected for analysis at 6, 12, and 24 months. Although there were sporadic significant effects compared to controls on random hematologic parameters, e.g., decreased lymphocyte counts in male rats at 6 months, none of the abnormalities observed in treated groups at any observation period was consid- ered as related to formaldehyde exposure. Because of the absence of any trends or evidence of an exposure- response relationship in mice or rats, the findings were considered incidental. Finally, there is an historical aspect to consider per- taining to the issue of whether inhaled formaldehyde causes adverse effects on blood cell counts consis- tent with pancytopenia. The American Conference of Governmental Industrial Hygienists (ACGIH) thresh- old limit values (TLVs) for formaldehyde have steadily declined with maximum allowable concentrations (MACs) or time-weighted averages (TWAs), show- ing the following progression over time: 1946–1947 (10 ppm MAC-TWA), 1948–1962 (5 ppm TLV-TWA), 1963–1971 (5 ppm TLV-ceiling), 1972–1984 (2 ppm TLV-ceiling), 1985 (1 ppm TLV-TWA), 1992 (0.3 ppm ceiling) (Paustenbach et al., 1997). With allowable formaldehyde exposures of 2–10 ppm from 1946–1984, one might expect at least isolated case reports of work- ers with either decreased blood cell counts if not frank pancytopenia. While it is unlikely that workers could tolerate exposure at the upper end of this range, the lack of such reports suggests that even these formalde- hyde exposures do not lead to hematotoxic effects. D.Derivation of an indoor air level of formaldehyde for carcinogenic effects A particular challenge arises when attempting to synthesize from the data summarized in this review an exposure level that would be protective from any