Downloaded from www.sjweh.fi on June 27, 2013

Original article Scand J Work Environ Health 1990;16(6):381-393 doi:10.5271/sjweh.1767 Epidemiologic evidence on the relationship between formaldehyde exposure and cancer. by Blair A, Saracci R, Stewart PA, Hayes RB, Shy C

Affiliation: National Cancer Institute, Occupational Studies Section, Rockville, MD 20892.

This article in PubMed: www.ncbi.nlm.nih.gov/pubmed/2284588

Print ISSN: 0355-3140 Electronic ISSN: 1795-990X Copyright (c) Scandinavian Journal of Work, Environment & Health

REVIEWS Scand J Work En viron Health 1990;16:381-93

Epidemiologic evidence on the relationship between formaldehyde exposure and cancer by Aaron Blair , PhD,1 Rodolfo Saracci , MD,2 Patricia A Stewart, MS,1 Richard B Hayes, DDS, PhD,1 Carl Shy, MD3 BLAIR A, SARACCI R, STEWART PA, HAYES RB, SHY C. Epidemiologic evidence on the relationship between formaldehyde exposure and cancer. Scand J Work Env iron H ealth 1990;16:381- 93. Over 30 epidemiologic studies have evaluated cancer risks associated with formaldehyde exposure. Excesses were reported for several sites, leukemia and cancers of the nasal cavities, nasopharynx, lung, and brain generating the greatest interest. The excesses of leukemia and brain and colon cancer found among professionals may not be related to formaldehyde exposure, since similar excesses were not observed among industrial workers. Inconsistencies among and within studies impede assigning formaldehyde a convincing causal role for the excesses of lung cancer found among industrial workers. A causal role for formaldehyde is the most probable for cancers of the nasopharynx and, to a less extent, the nasal cavities. Evidence of exposure-response relationships, the fact that direct contact with formaldehyde may occur at these upper respiratory sites, and the consistency of these findings with experimental studies make this assumption highly probable. Key terms: lung, meta-analysis, nasal, nasopharynx, review.

An imal bio assays (I , 2) indicate that formaldeh yde ca uses nasal tumors in rats. The wide spread use of for maldehyde in ind ustry a nd in commercial products ha s heightened public health co ncern s regarding this chemical. In the United States, the National Oc cupational Ha zards Survey (3) of the National Institute for Occupational Safet y and Health indicates that 1.6 million wor kers may be expo sed to formaldehyde during the manu facture o f formaldeh yde resins, textiles, ga rments, particle bo ard and plywood, insulating materials, dinnerware, and paper a nd in health-related pro fession s. In addition , off-ga ssing of formaldehyde fro m certain co nsumer products may lead to expo sure of large numbers of th e ge neral public. The results of animal expe riments led to ep idem iologic studies on a variety of formaldehyde-exposed populations. Previous reviews of these studies have pr imarily focu sed on asses sin g th e weight of evid ence co ncern ing fo rma ldehyde as a human carcinogen witho ut a det ailed presentation of the stu dy result s. In one such review the International Agenc y for Research on Ca ncer (l ARC) concluded that th ere is sufficien t eviden ce fo r th e carcinoge nic ity of form ald eh yde in

1

2 .1

National Cancer Institute, Rockville, Maryland, United States. Internatio nal Agency for Research on Cancer, Lyon, France. University of North Carolina, Chapel Hill, North Carolina, United States.

Reprint requests to: Dr A Blair, National Cancer Institute, Occupational Studies Section, Executive Plaza North, Room 418, Rockville, MD 20892, USA.

animals, but limited evidence for humans (4). Another group co ncluded that th e evidence fo r the carcinogenicity of formaldeh yde in humans was less per suasive th an did IARC (5). In our review of th e epidemiologic literature we hav e summarized results on a site-by-site basis and have focu sed on potential expo sures to form aldehyde and other expo sures that the study populations ma y ha ve experienced to eva luate the strength o f th e evidence regarding fo rmalde hyde and human ca ncer.

Study designs Over 30 reports fro m epidemiologic studies on form ald ehyde have been published (table I) . These reports hav e focused on professional groups such as funeral directors and embalmers, anatomists, pathologists, and workers in formaldeh yde facilities producing formaldeh yde , resins, plastic molding, decorative laminates , plywood , particle bo ard , and apparel. These studies, as well as relevant broad surveys of cancer risk by occupation in the United States, Canada, a nd Swed en, a re included in thi s review. The studies ha ve been conducted in eight countries (United States, Canada, Great Britain , Denmark, The Netherlands, Finland, Sweden , and Italy) and ha ve emplo yed standardized mortal ity ratio (SMR), proportionate mortality ratio (PMR), standardized incidence ratio (SIR), and case-referent des ign s. The total number of cancer cases with potential exp osur e to formald eh yde in thes e studies is now large enough to provide considerable statistical po wer for evalu ating the ca rci nogenicity o f formaldeh yde in humans for all but rare sites. 38 1

Table 1. Des c ri p t ion o f th e epidem io log ic s tu dies on formald eh yde. (PMR i n ci d e n c e ra ti o, SMR stand a rdized mortali ty rat io)

=

Author

Study des ign

Populat ion stu died

Time period

=p ro portionate mort a li t y ra t io, SIR =stan dardized

Exposu re evaluation

Diseases report ed

1959- 1961

Number of subjec ts

. Contr ol of Compar.'son smoking populat ion

Professiona l and nonoccupational exposures Peter sen & Milham (6)

PMR

None

All

No

Cali fornia

Jensen & Andersen (7)

Physicians Casereferent SIR Pharmacy users

t 943-1 976

Specialty

Lung cancer

84 cases , 252 referents

No

Ot her cancers

1969-1978

None

Lung All cancer

557

No

All pharmacy users

Friedman & Ury (8)

Funerai direc to rs

Milham (9)

PMR

Funeral directors

1959-1979

None

All

333

No

Washington

Walrath & Fraumeni (48)

PMR

Funeral directors, embalmers

1925- 1980

Type of lice nse

All

1132

No

United States

Harringt on & Shannon (65)

SMR

Pat hologists

1955- 1973

None

2079

No

United Kingdom

Harringto n & Oakes (64)

SMR

Patholo gist s

1974- 1980

None

13 selec ted causes 13 selected

2307

No

Unit ed King dom

causes

Levine et al (47)

SMR

Undertakers

1928- 1977

Latency

All

1477

No

Ontario

Walrat h & Fraumeni (10)

PMR

Embalmers

1925- 1980

Duratio n

All

1007

No

United St ates

Gallagher et al (11)

PMR

Funeral directors

1950-1978

None

All

No

British Columb ia

Logue et al (12)

SMR

Path ologi sts

1962- 1977

None

Selected

St roup et a! (49)

SMR

Anato mis ts

1888-1 979

All

No No

United States

Walrath et al (67)

SM R

Funeral directors,

1954- 1970

Speci alty, durati on None

5585 2317

All

408

No

Other vete rans

Funera l direct ors

1975- 1985

None

All

4046

No

United States

Chemic al workers Casereferent

1957- 1979

Level, duration

All cancer

Yes

Oth er wo rkers

emba lmers

Hayes et al (63)

PMR

Industrial workers Fayerwe ather et al (40)

481 cases 481 referents

Marsh (35)

PMR

Chemic al worker s

1950-1976

Duration

32 cause s

603

No

United Stat es

Wong (36)

SMR

Chemical work ers

1940- 1977

Durat ion

23 causes

2026

No

United States

9 ca uses All

24 256

No No

Unit ed States Unite d States

13 causes

7680

No

United Kingdom, local

Lung, bladder

889 cases 1758 refere nts

No

Oth er death s

Nasal,

839 cases 2465 ref erent s

No

Oth er cancers

No

Sweden

Yes

Other workers

1332

No

Italy

26561

No

Unite d Stat es, unexposed

Liebli ng et al (37)

PMR

Chemical workers

1976- 1980

None

Stayner et al (33)

PMR

Garment workers

1959- 1980

Durati on, latency

Acheson et al (23, 68)

SMR

Chemic al workers

1937- 1981

Coggon et al (41)

Brit ish de aths Casereferen t Danish Cancer Casereferent Registry

1975-1979

Level, dura tio n Level

1970-1982

Duration

Ol sen et al (44)

Malke r & Weiner (13)

Partanen et al (31)

SIR

Nested case-

Swedis h CancerEnvironment Regist ry Finnis h woodworkers

naso1961- 1979

None

pharynx 6 cancers

1957-1 980

Level, duration

Respiratory cancer

67378

60 cases 171 referents

referent

Bert azzi et al (30, 50)

SMR

Resin workers

1959- 1986

Duration

14 cau ses

Blair et al (24- 28)

SMR

10 plant s

1934-1 980

Level,

All

duration

Bond et al (43)

Nest ed Chemical worker s

1940-1980

Latency

Lung

308 cases 588 referents

Yes

Oth er workers

1978- 1981

Level

Nasal cancer

91 cases 195 referents

Yes

Populat ion referents

1979- 1983

Levell duration

Nasa l,

285 cases, 552 referents

Yes

pharyn x

Populat ion referents

Probability of expo sure

Nasal, nasopharyn x

371 cases, 605 referents

No

Othe r deaths

casereferent

Hayes et al (42) Vaughan et al (45, 62)

The Netherland's Casereferent hosp ita ls Washington Casereferent Tumor Regis try

Rou sh et al (59)

Connec tic ut Casereferent Tumor Registry

1935- 1975

Stayner et al (34)

SMR

1959--1982

Duration

All

Gerin et al (39)

Mont real Caserefere nt

1979- 1985

Level, duration

19 cancers

Garment worker s

Exposure information

Formaldehyde is ubiquitous in the environment. For th e assessment of can cer risk s asso ciated with form aldehyde exposure, it is of paramount importance that the level of expos ure o f study subjects be determined.

382

11030

No

United Stat es

4259

Yes

Populat ion and other cance r

In epidemiologic studies of forma ldehyde exposure and cancer risk variou s ap proaches to exposure assessment have been taken, largely dict ated by th e cons traints of the study design. Mortality surveys, such as of profe ssional groups, have relied upo n quali tat ive assessme nt

of exposure based upon job title or similar designations. Mortality studies of individual industrial facilities have generally provided more-detailed exposure estimates based on industrial exposure measurements and ancillary information. Case-referent studies composed of persons from a variety of occupations have generally relied on indirect exposure assessment based on knowledge of work practices and exposures in formaldehyde-related jobs .

Study groups

Professionals Embalmers may come in contact with a variety of chemicals, including formaldehyde, pheno l, dyes and stains, glutaraldehyde, glycol, glycerol, xylene, alcohols, and particulates, and also with biologic material and gamma radiation (14). Levels of 2.0

35 % > 2.0 ppm

Asb estos

Dust in all plants

< 0.1- >2.0, peaks > 4.0

3 % > 2.0 ppm

Alcohol , ureas, anti oxidants, plast iciz ers, dyes , asbes tos , wood dust , pheno l, stearat es, amides , and others

Dust in many plants

None

Higher in past

Blai r et al (24-27)

Stayner et al (34)

3 garment manufactur ing plants

Partanen et al (31) and Kauppi nen & Niem ela (32)

19 particleboard , ply wood, glue , sawm ill plants

Bertazzi et al (30)

1 resin pla nt

Current geometric mean=0.14 -0.17, no peaks measure d 9 % > 1.5 (average expo sure)

1974- 1979 mean levels = 0.2-3.8

Wood dust, glues , pesticides, pheno l, te rpenes, solvents, exhaust gases, molds Urea, melamine, styrene, expo xy resins, solvents , epic hlorhydrin

Past levels higher

383

data available since 1970 and interviews with management and long-term employees about process changes and controls were used to estimate the exposure levels. Twenty-five percent of the subjects were unexposed. Among those holding jobs where exposure occurred, 35 070 had their highest exposed job in the low-exposure category, 14 0J0 had their highest exposed job in the moderate category, and 51 0J0 had their highest exposed job in the high category (> 2.0 ppm). The authors specifically mentioned the presence of only one other substance, asbestos, but we assume that many of the chemicals identified in the formaldehyde and resin plants studied by Blair et al (24-27), such as wood dust, phenol, melamine, and urea, may have also been present in the formaldehyde and resin plants in this study. Blair et al (24-29) studied IO plants producing a variety of products, including formaldehyde, formaldehyde resins and molding compounds, decorative laminates, photographic film, and plywood. The estimates of formaldehyde levels for each unique combination of job, department, plant, and calendar-year combination were based on the results of monitoring conducted by the investigators (about 2000 full-shift personal samples) (27), company monitoring results (over 4500 results dating back to the 1960s for some plants), plant visits, job descriptions, and interviews with management and long-term employees regarding changes in the process, controls, work practices, and sensory perceptions (26). With the use of these estimates jobs were assigned to categories of trace, ~ 0.1, 0.1- 1.00 and total number of studies 6/9 7/9 Professionals 0/3 1/4 Industrial wor kers

2/5 1/4

9

0.8

14

10 1.4

7.9 1.1 8 16.0 0.5

122 114.4 1.1

22 26.0 0.8

11/13 2/3

1/6 1/2

a Data in italics are included in the summary stat istics.

Colon and rectal cancer. Melanoma. , P 0- 5.5 ppm-years , hi gh level 2:5.5 ppm-yea rs. b Lower level = all exp osed , high er leve l = p robab ly exposed t o high leve ls for at least one year. C On a scal e of 1- 9, lower level = 1-2 and higher level = 2:3 (all among th ose exposed to lower levels of wood dusts) . d Exposu re esti mat es fr om industrial hyg ienist A. e Ex pos ure es ti mates from industrt at hygienist B. f Lower level ver sus me diu m to high level s. 9 Usin g data f rom in d ustr ial hyg ienist B for H ayes et al (42). , P ,;0.05.

Table 6. Rel at ive risks fo r naso pha ryn geal ca ncer by level or duration of exposure to form alde hyde . (0 cases, E expected number of cases , RR relative risk)

=

=

Un exposed

Lower level/d ur at ion

=o bserv ed num ber o f

Hi gher level/du rat io n

Au tho r

0

E

RR

0

E

RR

Blair et al (28)" Roush et al (59)b Vaug han et al (45)C

1 126 16

0.5 126 16

2.0 1.0 1.0

2 21 7

0.5 21 5.8

4.0 1.0 1.2

Tot al

143

142.5

1.0

30

27.3

1,1

0

X for t rend

E

RR

2 7 4

0.3 3.1 2.9

7.5 2.3 * 1.4

0.83 1.29 0.65

13

6.3

2.1 '

2.02'

a Unexposed =

Epidemiologic evidence on the relationship between formaldehyde exposure and cancer.

Over 30 epidemiologic studies have evaluated cancer risks associated with formaldehyde exposure. Excesses were reported for several sites, leukemia an...
9MB Sizes 0 Downloads 0 Views