Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Chemical sensitisation has not been demonstrated in persons exposed to insoluble forms of beryllium either in massive or particulate forms. The study by Curtis, the only human study looking for evidence of a physical beryllium sensitisation reaction occurring through intact human skin, found no sensitisation reaction using insoluble forms of beryllium. The Curtis human study found 8 of 16 controls (not occupationally exposed to beryllium), who had been skin patch tested, developed an allergic-eczematous dermatitis (sensitisation) using soluble beryllium salts. Curtis ruled out anions, acidity and primary irritancy of beryllium salts as direct factors in causing allergic dermatitis. He also found examples of patients who had acute pneumonitis from exposure to airborne beryllium salts without skin sensitisation. Curtis concluded that there was no sensitisation as the result of applying insoluble beryllium in the forms of beryllium oxide powder, beryllium metal powder and disks of metallic beryllium to the skin. Curtis did find two cases of skin sensitisation handling metallic beryllium powder, but concluded that they were the result of residual beryllium fluoride (soluble beryllium salt) in the powder. The problem of residual beryllium fluoride in metallic beryllium powder was resolved in the early 1950s when the additional purification step of vacuum casting was added to the processing methodology in manufacturing beryllium metal.

 [1]Curtis G.H. Cutaneous Hypersensitivity Due to Beryllium: A Study of 13 Cases. AMA Arch Dermatol Syph 64: 470–482 (1951).


Migrated from Short description of key information:
A guinea pig maximization test is available. Furthermore, relevant publications are included considered to add to the information.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Beryllium metal does not cause respiratory sensitisation as defined by the Globally Harmonized System that defines a sensitiser as a chemical that causes a substantial proportion of exposed people or animals todevelop anallergic reaction in normal tissue after repeated exposureto the chemical. Achemical allergyis an adverse reaction to a chemical resulting from previous sensitisation to that chemical or to one that is structurally similar. A chemical allergy is initiated by the immune system and expressed as hypersensitivity; after an initial allergic reaction to a chemical, very small subsequent exposures can evoke a severe response. The range of chemical sensitisation response is broad and can manifest itself in forms such as a skin rash, eye irritation, allergic asthma, or even anaphylactic shock. Beryllium sensitisation refers to immunological response by persons whose immune system is genetically susceptible to recognizing the presence of beryllium. Occupational exposure to insoluble forms of beryllium is not at all associated within the above generally accepted concepts of a chemical sensitiser. Chemical sensitisation has not been demonstrated in persons exposed to insoluble forms of beryllium either in massive or particulate. Furthermore, Chapter 3.4 of Global Harmonized System (GHS) Purple Book[i]states the following:

“A respiratory sensitiser is a substance that will lead to hypersensitivity of the airways following inhalation of the substance.

“A skin sensitiser is a substance that will lead to an allergic response followed by skin contact.

“For the purpose of this chapter, sensitisation includes two phases: the first phase is the induction of specialized immunological memory in an individual by exposure to an allergen. The second phase is the elicitation, i.e. production of a cell-mediated or antibody-mediated allergic response by exposure of a sensitized individual to an allergen.

“For respiratory sensitisation the pattern of induction followed by elicitation phases is shared in common with skin sensitisation.

“Usually, for both skin and respiratory sensitisation, lower levels are necessary for elicitation than are required for induction.

“Evidence that a substance can induce specific hypersensitivity will normally be based on human experience. In this context, hypersensitivity is normally seen as asthma, but other reactions such as rhinitis/conjunctivitis and alveolitis are also considered. The condition will have the clinical character of an allergic reaction.”

In summary, occupational exposure to insoluble forms of beryllium is not associated within the above generally accepted concepts of a chemical sensitiser. There is no dermal sensitisation reaction, such as skin rash, hives, and irritation of the nose, throat, skin or eye, associated with dermal exposures to insoluble forms of beryllium. There is no short-term respiratory reaction, such as allergy or asthma involving shortness of breath, chest tightness, wheeze, cough and irritation, associated with airborne exposures to insoluble forms of beryllium. 

For insoluble forms of beryllium to be considered a respiratory sensitiser, observations of the exposed population would indicate that a sub-group of short-term workers exposed to low concentrations of airborne beryllium would suddenly start to develop strong respiratory symptoms upon each entry of the facility (asthma-like crisis, shortness of breath, etc.). This has not been the case, even in primary beryllium production operations. 

 

[1]United Nations, Globally Harmonized System of Classification and Labelling of Chemicals 147-155 (2007)


 



Migrated from Short description of key information:
Statement from occupational health surveillance.

Justification for classification or non-classification

Chemical sensitisation has not been demonstrated in persons exposed to insoluble forms of beryllium either in massive or particulate forms. 

Beryllium metal does not cause respiratory sensitisation as defined by the Globally Harmonized System. Occupational health surveillance of beryllium metal production workers has indicated that exposure to beryllium metal is not associated with the development of respiratory allergic reactions such as asthma and rhinitis.