Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The EU RAR summarises and discusses the results of a number of studies of different designs and reliability.

Data source

Reference
Reference Type:
review article or handbook
Title:
European Union Risk Assessment Report: chromium trioxide, sodium chromate, sodium dichromate, ammonium dichromate and potassium dichromate
Author:
European Chemicals Bureau
Year:
2005
Bibliographic source:
3rd. Priority List; Volume 53

Materials and methods

Type of study / information:
The EU RAR discusses the available data relating to human occupational exposure to the water-soluble Cr (VI) compounds. Data relating to carcinogenicity, irritation/corrosion, dermal and respiratory sensitisation are discussed elsewhere in the dossier.
Endpoint addressed:
repeated dose toxicity: inhalation
genetic toxicity
toxicity to reproduction / fertility
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Epidemiological studies of exposed workers of various designs.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The studies investigate health effects in workers exposed to various water-soluble hexavalent chromium compounds.

Method

Details on study design:
The studies discussed are of various designs.

Results and discussion

Results:
The results of the various studies, when considered as a whole, do not provide any strong evidence for genotoxic effects in occupationally exposed workers. Similarly, there is no convincing evidence of any adverse effects on reproduction. In addition to the local irritant corrosive effects seen for this group of compounds (and discussed elsewhere), there is also some evidence for effects on renal function at similar exposure levels.

Any other information on results incl. tables

Genotoxicity

Few studies of genotoxic potential in humans are available. No evidence of genotoxic activity has been found in adequately-conducted studies in circulating lymphocytes from chromium-exposed workers. In contrast, there is a vast array of genotoxicity data in vitro and less extensive testing in animals available. The evidence clearly indicates that highly water-soluble Cr (VI) compounds can produce significant mutagenic activity in vitro and in vivo. The Cr (VI) compounds under consideration are therefore regarded as in vivo somatic cell mutagens. In addition, toxicokinetic and dominant lethal data suggest that water-soluble Cr (VI) has the potential to be an in vivo germ cell mutagen.

Repeated exposure toxicity

All the human information on the toxic effects arising from repeated exposure to highly watersoluble 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.

Applicant's summary and conclusion

Conclusions:
The studies indicate a possible link between occupational exposure to irriant levels of chromium (VI) compounds and advese effects on renal function. The availbale studies do not provide any convincing evidence for gentoxicity or reproductive effects of this group of compounds.
Executive summary:

Genotoxicity

A few studies have been conducted in which circulating lymphocytes have been isolated from chromium-exposed workers and examined for chromosome aberrations, micronuclei, SCE and changes in chromosome numbers. In general, the results from better-conducted and reported studies including chromium plating workers in Japan and SS-MMA welders in Scandinavia have been negative. Evidence of genotoxicity has been reported in several other studies of chromate production workers in Eastern Europe and chromium plating workers in Italy. However the manner in which these were conducted and reported precludes full assessment of the significance of the findings.

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. The main effects reported are irritant and corrosive responses in relation to inhalation and dermal exposure. These include inflammation in the lower respiratory tract, and nasal septum perforation in the upper respiratory tract; findings are discussed elsewhere in the dossier. It is not possible to relate 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. Some evidence of kidney damage has also been found among chromate production and chromium plating workers. No exposure-response data or no-effect levels are available. However, it appears that the exposure levels at which kidney toxicity occurs overlaps with the atmospheric concentrations at which respiratory tract effects have been reported.

Reproductive toxicity

A poorly reported study of the course of pregnancy and childbirth in a group of women employed in a chromate production plant produced inconclusive results. Another study claimed that a group of women engaged in the production of “chromium compounds” showed a much greater incidence of pregnancy complications in comparison with a control group without occupational exposure to chromium. The type of exposure to chromium was not specified and the study is of poor quality. No conclusions can be drawn regarding any potential effects of chromium on reproduction in humans due to the poor quality of the investigations conducted.

Overall, it is concluded that the human data relating to effects on reproduction are limited to poorly reported studies of female workers from which no conclusions can be drawn.