home edit2 whole TSD November 2002 PDF format - OEHHA

presented an extension of a previous study (Bertazzi et al., 1986) which had detected elevated lung
cancer among 1,332 workers in a resin manufacturing plant subject to formaldehyde exposure. In the
extended study with more accurate estimates of exposure, the lung cancer rate was not elevated above
expected for those exposed to formaldehyde (Bertazzi et al., 1989). Linos et al. (1990) reported
elevated rates of follicular non-Hodgkin’s lymphoma and of acute myeloid leukemia among embalmers
and funeral directors in a population-based case control study. The investigators did not attribute these
tumors to formaldehyde exposure. Malker et al. (1990) found significantly elevated rates of incidence
of nasopharyngeal cancer among workers in fiberboard plants and among book binders, both being
subject to formaldehyde exposure.
Four recent occupational studies have investigated the relationship of formaldehyde exposure to
histological changes, some of which are potentially precancerous lesions, in the nasal mucosa.
Holmstrom et al. (1989) found that workers exposed to well-defined levels of formaldehyde developed
significant changes in the middle turbinate, while those exposed to both formaldehyde and wood dust
did not. Boysen et al. (1990) found in nasal biopses that workers exposed to formaldehyde showed a
significantly higher degree of metaplastic alterations. Edling et al. (1988) found significant histological
differences in the nasal mucosa of formaldehyde workers compared to unexposed workers but found
no histological differences between those exposed to formaldehyde and those exposed to formaldehyde
and wood dust. Berke (1987) found no statistical relationship between exfoliated nasal cells in
formaldehyde-exposed workers and control groups. Thus, these studies provide some indication of
possible histologic change due to formaldehyde exposure in humans, consistent with results in animals.
Animal Studies
A study sponsored by the Chemical Industry Institute for Toxicology (CIIT) has provided the most
quantitatively useful evidence for the carcinogenicity of formaldehyde (Swenberg et al., 1980a, b;
Kerns et al., 1983). This study used 120 male and 120 female Fischer-344 rats in each dose group,
including a clean air group. The adjusted tumor incidences (adjusted for competing causes of death,
including scheduled interim sacrifices) for squamous cell carcinomas in the nasal passages of males and
females combined, when exposed to 0, 2.0, 5.6, or 14.3 ppm formaldehyde for 6 hours/day, 5
days/week for up to 24 months, were 0/156, 0/159, 2/153 and 94/140 (U.S. EPA, 1987). In an
analogous study on mice, two mice in the high dose group (14.3 ppm) developed squamous cell
carcinomas, a finding that was not statistically significant but was thought to be biologically significant
due to the absence of this tumor in control animals and to concurrence with rat studies. Kerns et al.
(1983) also reported benign tumors, including polypoid adenomas and squamous cell papillomas.
Swenberg et al. (1980a, b) described a number of additional lesions in the nasal turbinates of rats
exposed to formaldehyde for 18 months, including rhinitis, epithelial dysplasia and hyperplasia,
squamous hyperplasia, and cellular atypia that occurred in a dose-related manner. Other inhalation
studies (Albert et al., 1982; Tobe et al., 1985) have provided positive evidence for the carcinogenicity
of formaldehyde.
Recent investigations of chronic toxicity have shown formaldehyde administered orally for 24 months to
be carcinogenic in Sprague-Dawley rats but not in Wistar rats. Soffritti et al. (1989), using six
312