Man-made vitreous (silicate) fibres with random orientation with alkaline and alkali earth oxides (Na2O+K2O+CaO+ MgO+BaO) content greater than 18% by weight and fulfilling one of the CLP Regulation Annex VI Note Q conditions

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro, other

Type of information:

other: IARC monograph

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans - Volume 81 - Man-made Vitreous Fibres

Author:

World Health Organization - International Agency For Research on Cancer

Year:

2002

Bibliographic source:

IARC Press, Lyon, France

Materials and methods

Principles of method if other than guideline:

This publication evaluates the carcinogenic risks of man-made vitreous fibers in humans with the help of international working groups of experts prepared, critical reviews and evaluations of evidence on the carcinogenicity of a wide range of human exposures.

Test material

Test material information

Constituent 1

Reference substance name:

Man-made vitreous (silicate) fibres with random orientation with alkaline and alkali earth oxides (Na2O+K2O+CaO+MgO+BaO) content greater than 18% by weight and fulfilling one of the Nota Q conditions

EC Number:

926-099-9

Molecular formula:

Not applicable as UVCB

IUPAC Name:

Man-made vitreous (silicate) fibres with random orientation with alkaline and alkali earth oxides (Na2O+K2O+CaO+MgO+BaO) content greater than 18% by weight and fulfilling one of the Nota Q conditions

Test material form:

solid: fibres

Results and discussion

Any other information on results incl. tables

The IARC Monograph Working Group on man-made vitreous fibres (MMVFs) reviewed many in vitro genetic toxicity studies of MMVFs and reported that genotoxic effects of MMVFs have been demonstrated in several cultured cell types, including human cells, and in cell-free assays. However, several caveats can be raised about thein vitrostudies on genotoxicity: (i) these assays are short-term and do not address issues related to fibre dissolution or biopersistence; and (ii) relatively high levels of man-made vitreous fibres on a mass basis have been studied, and the relevance to in vivo exposure levels is questionable. Many of the reviewed in vitro studies do not specify whether the MMVFs fulfil the Note Q criteria.

It is important to appreciate the degree to which biopersistence plays a role in the different studies and end-points under review, as this property of fibres is thought to be critical in determining chronic toxicity and carcinogenic outcome in humans and in experimental animal systems. In vitro assays are invariably short-term (i.e. from hours to days), and the effect of fibre durability is unlikely to be detected in such assays. [The IARC Monograph Working Group on MMVFs noted that endotoxin is a potent environmental contaminant and its presence in fibre samples could enhance their ability to cause acute inflammation. The presence of endotoxin or the steps taken to inactivate it, were not always reported.] Therefore, short-term tests could give a misleading impression of possible long-term biological effects. This will most likely become manifest as a false-positive result in an in vitro assay for long, highly biosoluble fibres.

Applicant's summary and conclusion

Conclusions:

Genetic toxicity in vitro testing might not provide the most appropriate information for assessing the genetic toxicity potential of Note Q MMVFs due to limitations of in vitro studies regarding biopersistence of fibres, perhap resulting in false-positive results of long, highly biosoluble fibres.

Executive summary:

The IARC Monograph Working Group on man-made vitreous fibres (MMVFs) reviewed many in vitro genetic toxicity studies of MMVFs and reported that genotoxic effects of MMVFs have been demonstrated in several cultured cell types, including human cells, and in cell-free assays. However, several caveats can be raised about thein vitro studies on genotoxicity. In vitro assays are invariably short-term (i.e. from hours to days), and the effect of fibre durability is unlikely to be detected in such assays. Therefore, short-term tests could give a misleading impression of possible long-term biological effects. This will most likely become manifest as a false-positive result in an in vitro assay for long, highly biosoluble fibres.

Based on this conclusion from IARC, genetic toxicity in vitro testing might not provide the most appropriate information for assessing the genetic toxicity potential of Note Q MMVFs. In addition, there are available in vivo data on genetic toxicity on Note Q MMVFs.