Formaldehyde

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation, other

Type of information:

other: Review

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

review article or handbook

Title:

Lowest adverse effects concentrations (LOAECs) for formaldehyde exposure

Author:

Gelbke HP, Gröters S, Morfeld P

Year:

2014

Bibliographic source:

Regulatory Toxicology and Pharmacology 70 (2014) 340–348

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The authors discuss the scientific literature available for cell replication, histopathological alterations and tumour response (polypoid adenomas) and present new statistical analyses for cell replication and tumour response (polypoid adenomas). Data is discussed in relation to the conclusion of the Committee for Risk Assessment (RAC) of the European Chemicals Agency which concluded that 2 ppm formaldehyde represent a Lowest Observed Adverse Effect Concentration (LOAEC) for polypoid adenomas, histopathological lesions and cell proliferation.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Formaldehyde

EC Number:

200-001-8

EC Name:

Formaldehyde

Cas Number:

50-00-0

Molecular formula:

CH2O

IUPAC Name:

formaldehyde

Details on test material:

- Name of test material (as cited in study report): formaldehyde

Test animals

Species:

other: mammals

Administration / exposure

Route of administration:

inhalation

Results and discussion

Results of examinations

Details on results:

In this review the assessments of RAC is assessed and the following conclusions are drawn:
- PA (papillomas, polypoid adenomas) are not related to development of squamous cell carcinomas (SCC) and the data do not allow to define a LOAEC or NOAEC.
- For histopathological alterations a NOAEC of 1 ppm can be derived and lesions at 2 ppm are not related to SCC development.
- For cell replication the total database clearly justifies a NOAEC of 2 ppm and LOAECs of 3 ppm to 4 ppm.

Effect levels

Basis for effect level:

other: Reviewing the available data NOAECs for histopathological lesions and cell proliferation of 1 ppm and 2 ppm, respectively, are clearly indicated

Remarks on result:

not measured/tested

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

This reassessment of the extremely broad database does not support the assessments of RAC (2012) that 2 ppm FA represent a LOAEC for tumour development, histopathological lesions and cell proliferation. Rather, the available data clearly indicate NOAECs for histopathological lesions and cell proliferation of 1 ppm and 2 ppm, respectively.

Executive summary:

In this reliable review the authors discuss the scientific literature available for cell replication, histopathological alterations and tumour response (polypoid adenomas).

In 2012 the Committee for Risk Assessment (RAC) of the European Chemicals Agency concluded that 2ppm formaldehyde represent a Lowest Observed Adverse Effect Concentration (LOAEC) for polypoid adenomas, histopathological lesions and cell proliferation. An analysis of all data shows that a LOAEC of 2ppm it is not justified for cell proliferation and polypoid adenomas. Higher values are also supported by a new statistical analysis. For histopathological lesions a NOAEC of 1ppm may be defined but the lesions at 2ppm cannot be regarded as pre-stages for tumour development. One major uncertainty exists: the description of polypoid adenomas and the lesions at 2ppm often is insufficient and diagnostic uncertainties can only be resolved by a re-evaluation according to modern histomorphological standards. Although the discrepancy between our assessment and that of RAC may seem rather small we feel the LOAECs proposed by RAC must be challenged taking into consideration the broad data base for formaldehyde and the potential impact of any published RAC opinion on the present discussions about appropriate occupational and indoor exposure limits.