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Reference Dose for Chronic Oral Exposure (RfD)

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[UPDATE] The (inhaltion) portion of this assessment is currently under development and the latest

draft can be found at, IRIS Toxicological Review of Formaldehyde (Inhalation) (External Review

Draft)

0419

Formaldehyde; CASRN 50-00-0

Human health assessment information on a chemical substance is included in the IRIS

database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment

development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and

II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were

reached during the assessment development process. Supporting information and explanations

of the methods used to derive the values given in IRIS are provided in the guidance documents

located on the IRIS website.

STATUS OF DATA FOR Formaldehyde

File First On-Line 10/01/1989

Oral RfD Assessment (I.A.) on-line 09/01/1990

Inhalation RfC Assessment (I.B.) no data

Carcinogenicity Assessment (II.) on-line 05/01/1991

_I. Chronic Health Hazard Assessments for Noncarcinogenic

Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Formaldehyde

CASRN — 50-00-0

Last Revised — 09/01/1990

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain

toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. In general, the

RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily

exposure to the human population (including sensitive subgroups) that is likely to be without

an appreciable risk of deleterious effects during a lifetime. Please refer to the Background

IRIS Home

Chronic Health

Hazards for NonCarcinogenic Effects

Reference Dose for

Chronic Oral Exposure

(RfD)

Oral RfD Summary

Principal and

Supporting Studies

Uncertainty and

Modifying Factors

Additional

Studies/Comments

Confidence in the

Oral RfD

EPA Documentation

and Review

Reference

Concentration for

Chronic Inhalation

Exposure (RfC)

Inhalation RfC

Summary

Principal and

Supporting Studies

Uncertainty and

Modifying Factors

Additional

Studies/Comments

Confidence in the

Inhalation RfC

EPA Documentation

and Review

Carcinogenicity

Assessment for

Lifetime Exposure

Evidence for Human

Carcinogenicity

Weight-of-Evidence

Characterization

Human

Carcinogenicity

Data

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Critical Effect Experimental Doses*

Document for an elaboration of these concepts. RfDs can also be derived for the

noncarcinogenic health effects of substances that are also carcinogens. Therefore, it is essential

to refer to other sources of information concerning the carcinogenicity of this substance. If the

U.S. EPA has evaluated this substance for potential human carcinogenicity, a summary of that

evaluation will be contained in Section II of this file.

__I.A.1. Oral RfD Summary

UF MF RfD

Reduced weight gain,

histopathology in rats

Rat 2-Year Bioassay

Til et al., 1989

NOAEL: 15 mg/kg/day

LOAEL: 82 mg/kg/day 

100

 

1

 

2E-1

mg/kg/day

 

* Conversion Factors: none

__I.A.2. Principal and Supporting Studies (Oral RfD)

Til, H.P., R.A. Woutersen, V.J. Feron, V.H.M. Hollanders, H.E. Falke and J.J. Clary. 1989. Twoyear drinking water study of formaldehyde in rats. Food Chem. Toxicol. 27: 77-87.

Formaldehyde was administered daily in drinking water to Wistar rats (70/sex/dose) for up to

24 months at mean doses of 0, 1.2, 15, or 82 mg/kg/day for males and 0, 1.8, 21, or 109

mg/kg/day for females. Up to 10 rats/sex/dose were sacrificed and examined after 12 months

and 18 months of treatment; the remainder was sacrificed and examined at 24 months. Mean

body weights of the high-dose group were decreased in males from week 1 and in females

from week 24 through termination. Food intake was significantly decreased in all high-dose

males with females showing a similar but less consistent decrease in food intake. A 40%

decrease in drinking water intake was reported in all high-dose animals while those rats

receiving the middle dose showed a slight but generally insignificant decrease in liquid intake.

Changes in urinalyses, and hematological and clinical chemistry parameters, were not doserelated, so were not considered to be related to formaldehyde intake. Among the high-dose

males, significant decreases were seen in the absolute heart and liver weights at 18 months

and at termination; in testes weights at 18 months; and in kidney weights at termination.

High-dose females showed significant increases in the relative kidney weights at 12 and 24

months. Relative brain weights were significantly increased in high-dose males at all three

examination periods and in females at termination only. Relative testes weights were

significantly increased in high-dose males at termination. These relative organ weight increases

were generally ascribed to the decreased body weights observed. A significant increase in

mortality among males receiving the 15 mg/kg/day dose was not considered toxicologically

significant.

Gross examination at 12, 18, and 24 months revealed a raised, thickening of the limiting ridge

of the forestomach in most high-dose rats and in some rats of both sexes from other groups.

Irregular mucosal thickening of the forestomach and glandular stomach were seen in several

rats of the high-dose group and in occasional rats of other groups. The incidence of

discoloration and irregularity of the kidney surface and atrophy of the testes was lower in the

high-dose group as compared with controls.

Significant histopathological changes of the gastrointestinal tract were found in high-dose

males and females and included chronic atrophic gastritis of the glandular stomach from week

53 on, as well as focal ulceration and glandular hyperplasia at the terminal examination. The

incidence of focal papillary epithelial hyperplasia and focal hyperkeratosis of the forestomach

was significantly increased in both sexes at the terminal examination. These effects of

formaldehyde on the gastric mucosa were considered cytotoxic in nature. A significant increase

in the incidence of papillary necrosis of the kidneys was reported in both sexes of high-dose

rats at the terminal examination. No treatment-related gastric tumors were observed in this

study. The incidence and type of tumors observed in other organ systems were common to this

Animal

Carcinogenicity

Data

Supporting Data

for Carcinogenicity

Quantitative Estimate

of Carcinogenic Risk

from Oral Exposure

Summary of Risk

Estimates

Dose-Response

Data

Additional

Comments

Discussion of

Confidence

Quantitative Estimate

of Carcinogenic Risk

from Inhalation

Exposure

Summary of Risk

Estimates

Dose-Response

Data

Additional

Comments

Discussion of

Confidence

EPA

Documentation,

Review and,

Contacts

Bibliography

Revision History

Synonyms
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strain and similar to those found in aging rats, 30 were not considered toxicologically

significant. A NOAEL of 15 mg/kg/day in male rats was indicated in this study.

Formaldehyde was administered daily in the drinking water of Sprague-Dawley rats

(15/sex/dose) at doses equivalent to 0, 50, 100, or 150 mg/kg/day for 90 days (Johannsen et

al., 1986). Male and female high-dose rats (150 mg/kg/day) and male rats receiving the 100

mg/kg/day dose showed a significant decrease in body weight gain. A dose-related decrease in

the intake of drinking water was reported in both sexes of treated rats. Food intake and feed

efficiency was comparable among all groups. No statistically significant differences were seen in

urinalyses, or hematological and blood chemistry parameters. No treatment-related

histopathological findings were observed. A NOAEL of 50 mg/kg/day was indicated for rats.

Similarly, formaldehyde was administered in the diet of pure-bred beagle dogs (4/sex/dose) at

doses of 0, 50, 75, or 100 mg/kg/day for 90 days. A significant decrease in body weight gain

was reported in the high-dose dogs of both sexes with no effect on weight gain at the two

lower dose levels. A reduced food consumption and feed efficiency was observed in dogs at all

treatment levels. No treatment-related effects were seen on hematological, blood chemistry, or

urinalysis parameters, nor were any treatment-related lesions observed. The gastrointestinal

mucosa was not affected by formaldehyde intake. A NOAEL of 75 mg/kg/day was indicated.

Marks et al. (1980) administered formaldehyde as an aqueous solution to pregnant CD-1 mice

at oral doses of 74, 148, and 185 mg/kg on days 6 to 15 of gestation. The high dose was

lethal to most of the treated mice by day 18. Mortality was 1/35 and 22/34 among dams

treated at 148 and 185 mg/kg/day, respectively. In the high-dose group, the number of

resorption sites was increased and mean litter size was slightly decreased. No effects on fetus

size, and no gross or microscopic skeletal or soft tissue abnormalities were observed.

Hurni and Ohder (1973) exposed pregnant beagle dogs (9 to 11/group) to formaldehyde in the

diet at levels of 125 or 375 ppm from 4 days after mating through day 56. Assuming that 1

ppm in the diet of a 10-kg dog consuming 250 g of dry chow/day equals 0.025 mg/kg/day

(Lehman, 1959), this would correspond to doses of 3 or 9 mg/kg/day. The dogs were weighed

weekly, and the pups were weighed at birth and twice weekly thereafter. Feeding of

formaldehyde had no effect on pregnancy rate, maternal body weight, or duration of gestation.

Mean litter sizes were within normal ranges. No effects were reported on growth or mortality.

All pups were inspected for defects at birth and at 8 weeks postpartum. Stillborns, as well as

pups dying before weaning, were autopsied and examined for internal and skeletal anomalies.

Normal behavior, appearance, mobility and muscular coordination were reported for all dogs

observed for up to 9 months.

Seidenberg et al. (1987) evaluated formaldehyde in the Chernoff/Kavlock developmental

toxicity screen. Formaldehyde was administered by gavage at 540 mg/kg/day to pregnant

ICR/SIM mice on gestation days 8 through 12. The mice were allowed to deliver, then several

neonatal growth and viability parameters were measured in the offspring. Comparative

statistical analysis of these parameters between treated animals and concurrent (vehicletreated) controls revealed no significant effect on any perinatal parameter examined.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — An uncertainty factor of 100 was used to account for the inter- and intraspecies

differences.

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

Based on this 2-year study in rats in which a NOAEL is identified, the uncertainty factor of 100

is considered appropriate for extrapolating results to humans. This study consisted of adequate

numbers of animals of both sexes as well as a thorough examination of toxicological and

histological parameters.

Takahashi et al. (1986) conducted a two-stage carcinogenesis bioassay in male Wistar rats.

The animals were administered N-methyl-N'-nitro-N- nitrosoguanidine (MNNG) at 100 mg/L in

the drinking water for the first 8 weeks of the study, followed by administration of 0.5%
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formalin (dose not specified) in the drinking water during weeks 8 through 40. Other groups of

animals received just MNNG or formalin (dose not specified). The animals were sacrificed at the

termination of dosing and the stomachs were examined grossly and microscopically. The actual

doses of formaldehyde received by the test animals is not known, because dose concentrations

were not reported, and drinking water consumption was not measured. Formalin did not

produce malignant tumors when given alone. In animals receiving just formalin, forestomach

papillomas occurred in 8/10 animals. In rats given MNNG alone, adenocarcinoma of the pylorus

occurred in 1/30 rats, preneoplastic hyperplasia of the pylorus occurred in 7/30 rats, and

adenocarcinoma of the duodenum occurred in 3/30 rats. In the group administered both MNG

and formalin, forestomach papillomas occurred in 15/17 animals, adenocarcinoma of the

pylorus in 4/17, preneoplastic hyperplasia of the pylorus in 7/17, and adenocarcinoma of the

duodenum in 1/17.

__I.A.5. Confidence in the Oral RfD

Study — High

Database — Medium

RfD — Medium

Confidence in the critical study is high since it consisted of adequate numbers of animals of

both sexes, as well as a thorough examination of toxicological and histological parameters.

Confidence in the database is medium as several additional chronic bioassays and reproductive

and developmental stuides support the critical effect and study. Medium confidence in the RfD

follows.

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 1989

Other EPA Documentation — None

Agency Work Group Review — 11/17/1989, 05/17/1990, 06/20/1990

Verification Date — 06/20/1990

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general,

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

Top of page

_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Formaldehyde

CASRN — 50-00-0

Not available at this time.

Top of page

_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Formaldehyde

CASRN — 50-00-0

Last Revised — 05/01/1991

Section II provides information on three aspects of the carcinogenic assessment for the

substance in question; the weight-of-evidence judgment of the likelihood that the substance is

a human carcinogen, and quantitative estimates of risk from oral exposure and from inhalation

exposure. The quantitative risk estimates are presented in three ways. The slope factor is the
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result of application of a low-dose extrapolation procedure and is presented as the risk per

(mg/kg)/day. The unit risk is the quantitative estimate in terms of either risk per ug/L drinking

water or risk per ug/cu.m air breathed. The third form in which risk is presented is a drinking

water or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1 in

1,000,000. The rationale and methods used to develop the carcinogenicity information in IRIS

are described in The Risk Assessment Guidelines of 1986 (EPA/600/8-87/045) and in the IRIS

Background Document. IRIS summaries developed since the publication of EPA's more recent

Proposed Guidelines for Carcinogen Risk Assessment also utilize those Guidelines where

indicated (Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to Section

I of this IRIS file for information on long-term toxic effects other than carcinogenicity.

_II.A. Evidence for Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Classification — B1; probable human carcinogen, based on limited evidence in humans, and

sufficient evidence in animals. Human data include nine studies that show statistically

significant associations between site-specific respiratory neoplasms and exposure to

formaldehyde or formaldehyde-containing products. An increased incidence of nasal squamous

cell carcinomas was observed in long-term inhalation studies in rats and in mice. The

classification is supported by in vitro genotoxicity data and formaldehyde's structural

relationships to other carcinogenic aldehydes such as acetaldehyde.

__II.A.2. Human Carcinogenicity Data

Limited. At least 28 relevant epidemiologic studies have been conducted. Among these, two

cohort studies (Blair et al., 1986, 1987; Stayner et al., 1988) and one case-control study

(Vaughan et al., 1986a,b) were well-conducted and specifically designed to detect small to

moderate increases in formaldehyde-associated human risks. Blair et al. studied workers at 10

plants who were in some way exposed to formaldehyde (largely through resin formation) and

observed significant excesses in lung and nasopharyngeal cancer deaths. Despite a lack of

significant trends with increasing concentration or cumulative formaldehyde exposure, lung

cancer mortality was significantly elevated in analyses with or without a 20-year latency

allowance. No explicit control was made for smoking status. Stayner et al. reported statistically

significant excesses in mortality from buccal cavity tumors among formaldehyde-exposed

garment workers. The highest SMR was for workers with long employment duration (exposure)

and follow-up period (latency). The Vaughan et al. nasal and pharyngeal cancer case-control

study examined occupational and residential exposures, controlling for smoking and alcohol

consumption. It showed a significant association between nasopharyngeal cancer and having

lived 10 or more years in a mobile home, especially for mobile homes built in the 1950s to

1970s, a period of increasing formaldehyde- resin usage. No exposure measurements were

available.

The 25 other reviewed studies had limited ability to detect small to moderate increases in

formaldehyde risks owing to small sample sizes, small numbers of observed site-specific

deaths, and insufficient follow-up. Even with these potential limitations, 6 of the 25 studies

(Acheson et al., 1984; Hardell et al., 1982; Hayes et al., 1986; Liebling et al., 1984; Olsen et

al., 1984; Stayner et al., 1985) reported significant associations between excess site-specific

respiratory (lung, buccal cavity, and pharyngeal) cancers and exposure to formaldehyde. Some

of these studies looked at potential confounders (such as wood-dust exposure) in greater

detail; they did not discern sinonasal cancer incidence excesses of the size predicted. Others

(Liebling et al., 1984; Stayner et al., 1985) overlapped the Acheson et al. (1984), Hardell et al.

(1982) and Hayes et al. (1986) studies; the improved design and nonoverlapping portions of

the later studies (Blair et al., 1986; Stayner et al., 1988) reinforce the conclusions of the

earlier studies. Analysis of the remaining 19 studies indicate that leukemia and neoplasms of

the brain and colon may be associated with formaldehyde exposure. The biological support for

such postulates, however, has not yet been demonstrated. Although the common exposure in

all of these studies was formaldehyde, the epidemiologic evidence is categorized as "limited"

primarily because of the possible exposures to other agents. Such exposures could have

contributed to the findings of excess cancers.

__II.A.3. Animal Carcinogenicity Data
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Sufficient. Consequences of inhalation exposure to formaldehyde have been studied in rats,

mice, hamsters and monkeys. The principal evidence comes from positive studies in both sexes

of two strains of rats (Kerns et al., 1983; Albert et al., 1982; Tobe et al., 1985) and males of

one strain of mice (Kerns et al., 1983), all showing squamous cell carcinomas.

For the CIIT, Kerns et al. (1983) exposed about 120 animals/sex/species (Fischer 344 rats and

B6C3F1 mice) to 0, 2, 5.6 or 14.3 ppm, 6 hours/day, 5 days/week for 24 months. Five animals

per group were sacrificed at 6 and 12 months and 20 per group were killed at 18 months. At

24 and 27 months the number sacrificed is unclear. The studies were terminated at 30 months.

From the 12th month on, male and female rats in the highest dose group (14.3 ppm) showed

significantly increased mortality compared with controls. In the 5.6- ppm group, male rats

showed a significant increase in mortality from 17 months on. Female mice showed generally

comparable survival across dose groups, as did male mice, but the male mice as a whole

showed increased mortality because of housing problems. Squamous cell carcinomas were

seen in the nasal cavities of 51/117 male rats and 52/115 female rats at 14.3 ppm (HDT) by

experiment's end (as many as 35 carcinomas had been identified in males by month 18 based

on EPA analysis notes and Kerns (Chart 8). At 5.6 ppm, 1/119 male rats and 1/116 female rats

showed squamous cell carcinomas of the nasal cavity. No such tumors were seen at 0 or 2

ppm. Polypoid adenomas of the nasal mucosa were seen in rats at all doses (0 ppm: 1/118 M,

0/114 F; 2 ppm: 4/118 M, 4/118 F; 5.6 ppm: 6/119 M, 0/116 F; 14.3 ppm: 4/117 M, 1/115 F)

in a significant dose-related trend, albeit one that falls off after a peak. Among the mice,

squamous cell carcinomas were seen in two males at 14.3 ppm. No other lesions were

noteworthy.

Sellakumar et al. (1985) exposed male Sprague-Dawley rats, 100/group, 6 hours/day, 5

days/week for lifetime to 10 ppm HCl and to 14 ppm formaldehyde. This was a combined

exposure HCl and formaldehyde were administered simultaneously, and each was administered

separately. An equal number of rats received an air control. HCl was administered to determine

if tumor response was enhanced by an additional irritant effect or by the combining of

formaldehyde and HCl to form bis-(chloromethyl)ether (BCME). Groups receiving formaldehyde

alone or with HCl showed an increase in nasal squamous cell carcinomas; those without

formaldehyde were free of carcinomas and other tumors (0/99 in each group), although rhinitis

and hyperplasia were of comparable incidence.

Tobe et al. (1985) conducted a 28-month study of male Fischer 344 rats (about 2 weeks

younger than those in Kerns et al., 1983). Groups of 32 rats were exposed 6 hours/day, 5

days/week to 0, 0.3, 2.0, 3,3, or 15 ppm formaldehyde in aqueous solution methanol; another

group of 32 was exposed to methanol only (vehicle control). Animals were sacrificed at 12, 18,

and 24 months. Exposure to 15 ppm ended at 24 months; at that point, mortality was 88%. At

28 months mortality was 60% in the control group and 32% in the 0.3 dose group. Squamous

cell carcinomas were seen at 15 ppm in 14/27 rats surviving past 12 months, compared with

0/27 in the controls. No polypoid adenomas were observed; the increased incidences of rhinitis

and hyperplasia were dose-related.

While these three rodent studies are principal in the weight-of-evidence, inhalation studies

have been carried out in other strains and species. Dalbey (1982), as part of a promotion

experiment, exposed male Syrian golden hamsters to 10 ppm formaldehyde 5 times/week, 5

hours/day throughout their lifetimes, 132 animals were untreated controls. Although survival

time was significantly reduced in the treated group, no tumors were observed in either treated

or control groups. Rusch et al. (1983) carried out a 6-month toxicity study in 6 male

cynomolgus monkeys, 40 F344 rats (20M, 20F), and 20 Syrian golden hamsters (10M, 10F)

with 22 hours/day, 7 days/week exposure to three levels of formaldehyde with corresponding

controls. The highest dose tested was 2.95 ppm. The short duration of the assay, the small

sample sizes, and, possibly, the low concentrations tested, limited the sensitivity of the assay

to detect tumors. In the highest dose group in both rats and monkeys, incidences of squamous

metaplasia/hyperplasia of the nasal turbinates were significantly elevated.

__II.A.4. Supporting Data for Carcinogenicity

Mutagenic activity of formaldehyde has been demonstrated in viruses, Escherichia coli,

Pseudomonas fluorescens, Salmonella typhimurium and certain strains of yeast, fungi,

Drosophila, grasshopper and mammalian cells (Ulsamer et al., 1984). Formaldehyde has been

shown to cause gene mutations, single strand breaks in DNA, DNA-protein crosslinks, sister

chromatid exchanges and chromosomal aberrations. Formaldehyde produces in vitro
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transformation in BALB/c 3T3 mouse cells, BHK21 hamster cells and C3H-10Tl/2 mouse cells,

enhances the transformation of Syrian hamster embryo cells by SA7 adenovirus, and inhibits

DNA repair (Consensus Workshop on Formaldehyde, 1984).

When inhaled, acetaldehyde, the closest aldehyde to formaldehyde in structure, causes cancers

in the nose and trachea of hamsters, and nasal cancers in rats.

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_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure

None.

Top of page

_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation

Exposure

Inhalation Unit Risk — 1.3E-5 per (ug/cu.m)

Extrapolation Method — Linearized multistage procedure, additional risk

Air Concentrations at Specified Risk Levels:

Risk Level Concentration

E-4 (1 in 10,000) 8E+0 ug/cu.m

E-5 (1 in 100,000) 8E-1 ug/cu.m

E-6 (1 in 1,000,000) 8E-2 ug/cu.m

__II.C.2. Dose-Response Data for Carcinogenicity, Inhalation Exposure

Tumor Type — squamous cell carcinoma

Test Animals — Rat/F344, males

Route — inhalation

Reference — Kerns et al., 1983

----------- Dose -----------

Administered

(ppm)

Human Equivalent

(mg/kg)/day

Tumor

Incidence

0 0 0/156

2 2 0/159

5.6 5.6 2/153

14.3 14.3 94/140

__II.C.3. Additional Comments (Carcinogenicity, Inhalation Exposure)

In the Kerns et al. (1983) study, rats that died at 11 months (prior to appearance of the first

squamous cell carcinoma) were not considered at risk. Those sacrificed at 12 and 18 months

were treated as though they would have responded in the same proportion as rats remaining

alive at the respective sacrifice times and those living beyond 24 months were included with

animals sacrificed at 24 months. From the estimates of the probability of death with tumor

within 24 months and its variance, the number of animals at risk and the number with tumors
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were derived for a 24-month study with no 12- or 18-month kills. These rounded numbers are

shown above and were used for significance tests and modeling.

The unit risk should not be used if the air concentration exceeds 8E+2 ug/cu.m, since above

this concentration the unit risk may not be appropriate.

__II.C.4. Discussion of Confidence (Carcinogenicity, Inhalation

Exposure)

The experimental range is close to expected human exposures. Estimated lifetime excess risks

from six epidemiologic studies are close to upper bound risks based on animal data (usually

within 1 order of magnitude for four types of estimated occupational and residential exposure).

Animal-based estimates derived using time in the model were similar but would have required

the use of more assumptions in the calculations. Three non-zero doses were used in addition to

controls in the study on which calculations are based, with a large number of animals per

group. Male and female incidences were close throughout the exposure groups.

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_II.D. EPA Documentation, Review, and Contacts (Carcinogenicity

Assessment)

__II.D.1. EPA Documentation

Source Document — U.S. EPA, 1987

The OTS Assessment of Health Risk has received wide internal and external review.

__II.D.2. EPA Review (Carcinogenicity Assessment)

Agency Work Group Review — 02/03/1988

Verification Date — 02/03/1988

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general,

at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

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_III. [reserved]

_IV. [reserved] 

_V. [reserved]

_VI. Bibliography

Substance Name — Formaldehyde

CASRN — 50-00-0

Last Revised — 08/01/1991

_VI.A. Oral RfD References

Hurni, H. and H. Ohder. 1973. Reproduction study with formaldehyde and

hexamethylenetetramine in beagle dogs. Food Cosmet. Toxicol. 11: 459-462.

Johannsen, F.R., G.J. Levinskas and A.S. Tegeris. 1986. Effects of formaldehyde in the rat and

dog following oral exposure. Toxicol. Lett. 30: 1-6.
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Marks, T.A., W.C. Worthy and R.E. Staples. 1980. Influence of formaldehyde and sonacide

(potentiated acid glutaraldehyde) on embryo and fetal development in mice. Teratology. 22:

51-58.

Seidenberg, J.M., D.G. Anderson and R.A. Becker. 1986. Validation of an in vivo developmental

toxicity screen in the mouse. Teratol. Carcinogen. Mutagen. 6: 361-374.

Takahashi, M., R. Hasegawa, F. Furukawa, K. Toyoda, H. Sato and Y. Hayashi. 1986. Effects of

ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric

carcinogenesis in rats after initiation with N-methyl- N'nitro-N'nitrosoguanidine. Jap. J. Cancer

Res. 77: 118-124.

Til, H.P., R.A. Woutersen, V.J. Feron, V.H.M. Hollanders, H.E. Falke and J.J. Clary. 1989. Twoyear drinking water study of formaldehyde in rats. Food Chem. Toxicol. 27(2): 77-87.

U.S. EPA. 1989. Draft Drinking Water Health Advisory for Formaldehyde. Office of Drinking

Water, Washington, DC.

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_VI.B. Inhalation RfC References

None

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_VI.C. Carcinogenicity Assessment References

Acheson, E.D., M.J. Gardner, B. Pannett, H.R. Barnes, C. Osmond and C.P. Taylor. 1984.

Formaldehyde in the British Chemical Industry. The Lancet. p. 611-615.

Albert, R.E., A.R. Sellakumar, S. Laskin, M. Kuschner, N. Nelson and C.A. Snyder. Gaseous

formaldehyde and hydrogen chloride induction of nasal cancer in the rat. J. Natl. Cancer Inst.

68(4): 597-603.

Blair, A., P.A. Stewart, R.N. Hoover, et al. 1986. Mortality among industrial workers exposed to

formaldehyde. J. Natl. Cancer Inst. 76(6): 1071-1084.

Blair, A., P. Stewart, P.A. Hoover, et al. 1987. Cancers of the nasopharynx and oropharynx and

formaldehyde exposure. J. Natl. Cancer Inst. 78(1): 191-193.

Consensus Workshop on Formaldehyde. 1984. Deliberations of the Consensus Workshop on

Formaldehyde, October 3-6, 1983. Little Rock, AK. (Final report)

Dalbey, W.E. 1982. Formaldehyde and tumors in hamster respiratory tract. Toxicology. 24: 9-

14.

Hardell, L., B. Johansson and O. Axelson. 1982. Epidemiological study of nasal and

nasopharyngeal cancer and their relation to phenoxy acid or chlorophenol exposure. Am. J.

Ind. Med. 3: 247-257.

Hayes, R.B., J.W. Raatgever, A. de Bruyn and M. Gerin. 1986. Cancer of the nasal cavity and

paranasal sinuses, and formaldehyde exposure. Int. J. Cancer. 37: 487-492.

Kerns, W.D., K.L. Pavkov, D.J. Donofrio, E.J. Gralla and J.A. Swenberg. 1983. Carcinogenicity

of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res. 43: 4382-

4392.

Liebling, T., K.D. Rosenman, H. Pastides, R.G. Griffith and S. Lemeshow. 1984. Cancer

mortality among workers exposed to formaldehyde. Am. J. Ind. Med. 5: 423-428.

Olsen, J.H., S.P. Jensen, M. Hink, K. Faurbo, N.O. Breum and O.M. Jensen. 1984. Occupational
Formaldehyde (CASRN 50-00-0) | IRIS | US EPA

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Date Section Description

formaldehyde exposure and increased nasal cancer risk in man. Int. J. Cancer. 34: 639-644.

Rusch, G.M., J.J. Clary, W.E. Rinehart and H.F. Bolte. 1983. A 26-week inhalation toxicity

study with formaldehyde in the monkey, rat and hamster. Toxicol. Appl. Pharmacol. 68: 329-

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from Exposure to Formaldehyde. Office of Toxic Substances, Washington, DC.

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_VII. Revision History

Substance Name — Formaldehyde

CASRN — 50-00-0

10/01/1989 II. Carcinogen summary on-line

10/01/1989 VI. Bibliography on-line

12/01/1989 I.A. Oral RfD now under review

02/01/1990 VI. Supplementary data on-line

09/01/1990 I.A. Oral RfD summary on-line

09/01/1990 II. Text edited

09/01/1990 VI.A. Oral RfD references added

01/01/1991 II. Text edited

01/01/1991 II.C.1. Inhalation slope factor removed (global change)

05/01/1991 II.C.1. Corrected units in risk level concentrations

08/01/1991 VI.A.&C. Citations clarified

01/01/1992 IV. Regulatory Action section on-line

04/01/1997 III., IV.,

V.

Drinking Water Health Advisories, EPA Regulatory Actions, and

Supplementary Data were removed from IRIS on or before April 1997.

IRIS users were directed to the appropriate EPA Program Offices for
Formaldehyde (CASRN 50-00-0) | IRIS | US EPA

http://www.epa.gov/iris/subst/0419.htm[3/27/2012 4:12:35 PM]

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this information.

01/02/1998 I., II. This chemical is being reassessed under the IRIS Program.

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_VIII. Synonyms

Substance Name — Formaldehyde

CASRN — 50-00-0

Last Revised — 10/01/1989

50-00-0

ALDEHYDE FORMIQUE (FRENCH)

ALDEHYD MRAVENCI (CZECH)

ALDEIDE FORMICA (ITALIAN)

BFV

FA

FORMALDEHYD (CZECH, POLISH)

FORMALDEHYDE

FORMALDEHYDE SOLUTION (DOT)

FORMALIN

FORMALITH

FORMIC ALDEHYDE

FORMOL

FYDE

HOCH

IVALON

KARSAN

LYSOFORM

METHANAL

METHYL ALDEHYDE

METHYLENE GLYCOL

METHYLENE OXIDE

MORBICID

NCI-C02799

OPLOSSINGEN (DUTCH)

OXOMETHANE

OXYMETHYLENE

PARAFORM

POLYOXYMETHYLENE GLYCOLS

RCRA WASTE NUMBER U122

SUPERLYSOFORM

UN 1198 (DOT)

UN 2209 (DOT)

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