Chromium trioxide

Endpoint summary

Description of key information

Association between occupational exposure to chromic acid mist (aqueous chromium (VI) trioxide) and lung cancer has been concluded. Also, there is evidence from various case reports and worker studies, that exposure to Cr(VI) is associated with skin and respiratory sensitiation as well as eye, skin, and respiratory tract irritation.

Additional information

Cancer

In addition to the epidemiological studies provided (Sorahan, 1998, 2000 and Kerger, 2009) the studies reviewed in the EU RAR (including those previously summarised in the UK HSE and IOH reviews) demonstrate an association between occupational exposure to chromic acid mist (aqueous chromium (VI) trioxide) and lung cancer. Studies of chrome plating workers (specifically exposed to chromic acid mists) in the US and UK show a clear association between exposure and increased mortality from lung cancer. Studies of occupational exposure to other Cr (VI) compounds have not shown a similar association. The EU RAR notes that the acidic and corrosive nature of chromium trioxide may be a significant contributory factor in the carcinogenesis of chromic acid (aqueous chromium (VI) trioxide), but that the Cr (VI) ion is likely to be the toxic moiety. It is considered that there is concern for the human carcinogenicity of the other water-soluble Cr (VI) compounds in this group (EU RAR 2005).

Skin irritation

Accidental and/or occupational exposure of humans to Cr (VI) compounds is known to cause skin irritation which may be severe in nature, particularly following repeated exposure.

Animal data are consistent with the observations made in humans. It is not possible to determine a clear concentration-response relationship for repeated-exposure human skin effects from the occupational data available and quantitative data could be misleading given the potential for severe effects resulting from repeated contamination of slightly damaged skin.

The EU RAR concluded, based on reports of accidental occupational exposure, that the highly water soluble Cr (VI) compounds are skin irritants. Chromium (VI) trioxide is corrosive as a consequence of its low pH and the development of 'chrome ulcers' in workers repeatedly exposed to other salts also indicate the potential for skin corrosivity.

Eye irritation

Accidental splashing of highly water-soluble Cr(VI) compounds in solution into the eye has resulted in damage to the human eye. A number of case reports have detailed both inflammation of the cornea and conjunctivae and in more severe cases, corneal erosion and ulceration.

The EU RAR concluded that, significant damage to the eye can occur upon accidental exposure to highly water-soluble Cr (VI) compounds.

Respiratory irritation

Symptoms of sensory irritation of the respiratory tract are known to occur among chrome plating workers exposed to a mist of aqueous chromium (VI) trioxide. No quantitative data on such irritation are available from studies of workers. No studies reporting symptoms of sensory irritation are available for the other Cr(VI) compounds. Overall, it is not possible to determine a reliable concentration-response relationship for respiratory tract irritation using the available data. Nevertheless, the EU RAR concluded that, inhaled chromium (VI) trioxide has the potential to cause respiratory irritation, probably as a consequence of its low pH. 

In this case report (Moller, 1986) a 29-year-old male welder reported systemic reactions after exposure to to chromium vapors from chromium trioxide baths and fumes from steel welding during both occupational and nonoccupational activities. Inhalation challenge testing to 29 µg/mg³of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A late onset reaction to a chemical known to cause allergic contact dermatitis and occupational asthma suggested that immunologic mechanisms could be implicated in this case.

Skin tests and in vitro studies did not support a role for a classic IgE-mediated response. The possibility that chromium salts could exert direct histamine releasing effects on basophils was excluded in vitro but a similar effect on tissue mast cells was not investigated. The positive direct LlF assay in this patient suggested that cell-mediated mechanisms may play a role in this hypersensitivity response.

A skin biopsy specimen obtained after subsidence of most of the angioedema and wheezing demonstrated findings consistent only with an urticarial eruption, and a specific diagnosis could not be assigned to the lesion.

This case documents the occurrence of a late onset anaphylactoid reaction after inhalation of hexavalent chromium compound.

 

Skin sensitisation

The potential of the water-soluble Cr (VI) compounds to cause delayed contact hypersensitivity was investigated in a number of studies in occupationally exposed workers and in the general population, using patch-testing.

Allergic contact dermatitis (skin sensitisation) resulting from occupational exposure to water soluble Cr (VI) compounds is commonly encountered in a number of different groups. The EU RAR has reviewed a number of published reports of patch testing in Cr (VI) sensitised humans; the studies report minimum eliciting concentrations as low as 0.09 µg Cr (VI) /cm². The majority of reported studies were performed using aqueous solutions of sodium or potassium dichromate; while similar effects can be assumed for other water-soluble Cr (VI) compounds, a similar concentration-response relationship cannot be assumed as this will also be influenced by the extent of dermal penetration.

 

Respiratory sensitisation

A number of case reports, mainly within the chrome plating industry, provide evidence that inhaled Cr (VI) can cause asthma, although the total number of reported cases is small in relation to the number of workers potentially exposed.

Overall, the available case reports and evidence from well-conducted bronchial challenge tests, show that inhalation of Cr (VI) compounds can cause occupational asthma. As with skin, Cr (VI)- sensitised subjects may react to Cr (III). It is not possible to determine a no-effect level or exposure-response relationship for the induction or elicitation of occupational asthma.

 

Exposure related observations in humans (repeated dose toxicity)

With respect to repeated exposure, a large number of studies are available relating to exposure of workers to highly water-soluble Cr (VI), specifically sodium or potassium chromate/dichromate and chromium (VI) trioxide. All the human information on the toxic effects arising from repeated exposure to highly water soluble Cr (VI) relates to workers in the chromate production and chromium plating industries. These workers were exposed to sodium and potassium chromates and dichromates either in solid form (dusts) or in aqueous solution or to airborne mists of chromium (VI) trioxide in aqueous solution (chromic acid). Some of the principal toxic effects produced in these workers reflect the irritant and (at low pH) corrosive action of Cr (VI) ion toward mucous membranes. Nasal septum ulceration and perforation, inflammation of the respiratory tract along much if not all of its length, lung fibrosis, emphysema and chronic obstructive bronchopneumopathy and inflammation and ulceration of the gastrointestinal tract from the buccal cavity to the intestines have been observed. Many of these effects were particularly predominant among workers in these industries in the past when atmospheric Cr (VI) levels were probably relatively high. However it is not possible, from the available information, to relate many of these effects to reliable measures of Cr (VI) exposure. Although in principle a threshold dose should be identifiable, in practice the location of such a threshold is not possible from the data available. There is some evidence that atrophy of the nasal mucosa occurs in chromium plating workers exposed to very low average levels (below 0.004 mg/m³ chromium (VI) trioxide, below 0.002 mg Cr(VI)/m³) in the atmosphere. An important confounding factor in the development of nasal lesions is the possible transfer of Cr (VI) in solution from fingers to the nose due to poor personal hygiene.

Some evidence of kidney damage, such as proteinuria, has also been found among chromate production and chromium plating workers. It is noted that kidney damage was also reported following single exposure. Although in principle a threshold dose should be identifiable, in practice the location of such a threshold is not possible from the data available.