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- Acute toxicity
- Irritation/Corrosivity
- Sensory irritation
Human Health EffectsThis chapter is a summary of the health effects of formaldehyde. It is mainly based on the Concise International Chemical Assessment Document (IPCS, 2002), the Toxicological Profile (ATSDR, 1999) and the SIDS Initial Assessment Report (OECD, 2002). Articles published post 1998 are summarised in this chapter.
There are no reports in the literature of human deaths following acute dermal or inhalation exposure to formaldehyde. Human deaths following ingestion of formaldehyde have been reported (Kline, 1925; Levison, 1904). However, the data are from very old case reports (1899-1919) whose reliability cannot be determined. Information is available from more recent cases, which report ulceration and damage along the aero-digestive tract following ingestion of formaldehyde (Allen et al., 1970; Kochhar et al., 1986). Though these cases did not result in death, significant toxicity was observed, requiring drastic medical procedures to be undertaken. In the case reported by Kochhar et al. (1986), a 26 year old woman who accidentally ingested 45 ml (42.5 grams) 37% formaldehyde solution (equivalent to approximately 700 mg/kg assuming the woman weighed 60 kg) vomited streaks of blood immediately following ingestion. Examination 4 days later showed severe to moderate ulceration of the oesophagus and stomach that resulted in a feeding jejunostomy being performed. In the case reported by Allen et al. (1970) a tracheostomy was conducted on a 14 year old boy following ingestion of approximately 120 ml formaldehyde solution (concentration not reported, nor whether ingestion was accidental or deliberate). Six days later a laparotomy revealed multiple areas of gastric necrosis and, hence, a total gastrectomy and a feeding jejunostomy were performed.
The skin irritation potential of formaldehyde solution has been evaluated in a number of international reviews (IPCS, 1989; IARC, 1995; IPCS, 2002; OECD, 2002) and all report formaldehyde solution to be a skin irritant in humans. However, this conclusion is based on anecdotal evidence, with a review of the effects of formaldehyde in solutions on human skin by Maibach (1983) sometimes cited. This review reported that though formaldehyde solution is said to have irritant potential based on human experience, little quantitative data exists. This review also makes the point that since formaldehyde solution is known to cause skin sensitisation, reported irritant effects may be sensitisation effects. Skin rashes were reported by embalmers in the NICNAS survey. Acute controlled exposure studies of volunteers exposed to airborne formaldehyde at concentrations up to 3 ppm have not found increased reporting of skin irritation symptoms (ATSDR 1999). Sensory irritation is the result of the chemical stimulating the trigeminal nerve endings in the cornea and nasal mucosa, which evokes a stinging or burning sensation in the eyes and upper respiratory tract (nose and throat). This is a receptor mediated mode of action and occurs at relatively low concentrations. Sensory irritation is different to eye and skin irritation/corrosivity used for hazard classification (Section 12.2) and also different from the irritation leading to cytoxicity, hyperplasia and nasal tumours (Section 10.4.1). These latter examples are a result of physical damage to the cells, whereas sensory irritation is a nerve response. Formaldehyde exposure has long been associated with irritation to the eyes and upper respiratory tract. Repeated complaints, such as sore eyes and throat by embalmers were reported in the NICNAS survey. In more recent years, chamber studies have investigated sensory irritation following short-term exposures to known low levels of gaseous formaldehyde. In chamber studies in healthy and asthmatic volunteers, mild to moderate eye irritation was self-reported following exposure to formaldehyde levels ranging from 0.25 to 3 ppm (0.3 to 3.6 mg/m3) for up to 5 hours, though exposures were generally < 3 hours. Overall, the data from these studies indicate that eye irritation is a more sensitive parameter than nose and throat irritation which was generally self-reported at concentrations > 1 ppm (Weber-Tscopp et al., 1977; Andersen & Molhave, 1983; Bender et al., 1983; Day et al., 1984; Schachter et al., 1986; 1987; Sauder et al., 1986; 1987; Green et al., 1987; 1989; Kulle et al., 1987; Kulle, 1993; Witek et al., 1987). A summary of these studies can be found in Table 11.1. It should be noted that a study by Pazdrak et al. (1993) is not included in Table 11.1 because of major methodological shortcomings (e.g. exposures could not be verified as information was not provided regarding the techniques used to generate the aerosol or the methods used to measure formaldehyde). A study by Krakowiak et al. (1998) also has methodological shortcomings and is also not included. Sensory irritation due to exposure to formaldehyde has rapid onset (Sauder et al. 1987, Yang et al. 2001) and the intensity of effect does not appear to significantly increase with longer exposures (Sauder et al. 1987). This is in accord with the theoretical considerations of sensory irritation where the intensity of response is dependent on the concentration of the substance and not the duration of exposure. A study is available where exposure to formaldehyde was through modified eye goggles (Yang et al., 2001). Eight volunteers were exposed to 0, 1.65, 2.99 or 4.31 ppm formaldehyde for 5 minutes and eye irritation was self-reported. Individual scores were not reported. Although the higher formaldehyde concentrations resulted in greater eye irritation scores, compared to control exposures irritancy scores were only statistically significant at 1.65 and 4.31 ppm, and only 1.5, 2.5 and 3.0 minutes after the onset of exposure. A study is available where exposure was via a facemask (Reed & Frigas, 1984). Thirteen subjects who had reported respiratory symptoms to previous exposures of formaldehyde were exposed for 20 minutes to concentrations up to 3 ppm (3.6 mg/m3) formaldehyde. No significant effect was seen on pulmonary function, while self-reports of eye, nose and throat irritation occurred as frequently with clean air as with formaldehyde. A summary of these studies is included in Table 11.1. With the exception of Weber-Tschopp et al. (1977), Bender et al. (1983), Pazdrak et al. (1993) and Yang et al. (2001), the studies in Table 11.1 also determined the effect of formaldehyde exposure on pulmonary functions. No statistically significant exposure-related effect was seen on forced vital capacity (FVC), forced expiratory volume in 1.0 second (FEV1.0), peak expiratory flow rate (PEFR), or the maximal flow at 50% of the vital capacity (MEF50%) in healthy and asthmatic subjects exposed up to 2.0 ppm (2.4 mg/m3) for up to 3 hours. In contrast, small but statistically significant decreases were seen in FEV1.0 (2 %) and FEFR (7%) in 9 healthy volunteers after 30 minutes exposure to 3 ppm (3.6 mg/m3) formaldehyde but not after 1 or 3 hour exposure periods (Sauder et al., 1986). In a further study by this project team, using the same exposure level and duration, no effects were observed in asthmatics (Sauder et al., 1987). In a study by Green et al. (1987), exposure to 3 ppm formaldehyde for approximately 1-2 hours resulted in small but statistically significant decreases (2% to 3%) in FEV1.0 and FVC in 22 healthy volunteers. Conversely, no significant deficits in pulmonary function were seen in 16 asthmatic subjects similarly exposed. In a further study by Green et al. (1989), although there was no effect on FVC, a small (6%) decrease in forced expiratory flow rate between 25% and 75% FVC (FEFR25-75) was seen in 24 healthy volunteers exposed to 3 ppm formaldehyde for approximately 2 hours. Overall, the weight of evidence indicates there is no effect on pulmonary function at concentrations up to 3 ppm, the highest exposure level tested. A study is available investigating mucous flow rate in the nasal cavity of 16 volunteers exposed to 0.25, 0.4, 0.8 or 1.7 ppm (0.3, 0.48, 0.96 or 2.0 mg/m3) formaldehyde for 4-5 hours (Andersen & Molhave, 1983). Compared to control values, the mucous flow rate was reduced at 0.25 ppm and above. However, the response did not increase at concentrations above 0.4 ppm. The relevance of this finding to human health is unclear. Data are available from community (Ritchie & Lehnen, 1987; Broder et al., 1988) and workplace studies (Alexandersson & Hedenstierna, 1988; 1989; Holmstrom & Wilhelmsson, 1988; Horvath et al., 1988; Holness & Nethercott, 1989; Uba et al., 1989). However, for determining the irritant potency of formaldehyde, the data from these uncontrolled environments are not considered as reliable as data from controlled chamber studies, due primarily to the unknown contribution of other substances. The workplace and community studies are summarised in Section 11.4. An extensive review of chamber, community and workplace studies to formaldehyde was recently conducted (Bender, 2002). Overall, this review concluded that it is not possible to identify a specific threshold for irritation, due primarily to the self-reporting of irritation that has no diagnostic accuracy. This is demonstrated by reports of irritation with placebo (zero) exposures in chamber (see Table 11.1) and workplace studies (Holness & Nethercott, 1989). However, Bender (2002) went on to state that using chamber studies, which provide the highest quality data, some individuals (5% to 20%) begin to sense irritation from 0.5 to 1 ppm (0.6 to 1.2 mg/m3), though the reported response rate is often similar in controls (i.e. a response rate of 20% to 30% is not unusual). At levels of 1 ppm (1.2 mg/m3) and greater, one can attribute responses to formaldehyde with greater certainty. Furthermore, although asthmatics are thought to be more sensitive to irritants, studies by Green et al. (1987), Sauder et al. (1986; 1987) and Witek et al. (1987) have demonstrated that at concentrations of 2 - 3 ppm (2.4 - 3.6 mg/m3) for up to 3 hours, asthmatics were no more sensitive to formaldehyde than non- asthmatics. Therefore, although formaldehyde is a known eye and upper respiratory tract irritant in humans, the limitations of the available data and subjective nature of sensory irritation do not allow identification of a definitive no-observed-effect level (NOEL). The data from chamber studies demonstrate that the sensory irritation responses at levels of ≥1 ppm (1.2 mg/m3) can definitely be attributed to formaldehyde. Some individuals begin to sense irritation from 0.5 ppm (0.6 mg/m3), although the response rate is often similar to that reported in controls. Although there is limited evidence that some individuals report sensory irritation at concentrations as low as 0.25 ppm (0.3 mg/m3) the data are very unreliable. Therefore, the LOEL is considered to be 0.5 ppm. The odour threshold of gaseous formaldehyde varies widely ranging from 0.05 to 1.0 ppm. However, for most people the odour threshold is in the 0.5 to 1.0 ppm range (OECD, 2002).
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