24. Health and environmental consequences of the chromates

F. Health, regulation, open questions and conclusion

The reaction products are not only chemically relevant. The calcium and sodium chromates considered here are carcinogenic; skin contact, local effects on the skin and possible uptake must be assessed in addition to inhalation. In the case of injuries, individual Cr(VI) compounds can cause severe skin ulcers. [2, 3]

Uptake into the cell: the Trojan horse

Water-soluble chromates are structurally analogous to sulphate and phosphate ions. The cell therefore takes them up via its sulphate and phosphate transport pathways as if they were an ordinary nutrient anion. Chromium(VI) thus enters the cell interior unhindered, whereas trivalent chromium barely passes through the cell membrane. [53]

Reduction inside the cell: DNA damage and oxidative stress

Inside the cell, chromium(VI) is reduced stepwise by ascorbate, glutathione and cysteine via the reactive intermediates chromium(V) and chromium(IV) to stable chromium(III). According to the evaluation of the International Agency for Research on Cancer (IARC), this produces chromium(III)-DNA adducts, DNA-protein and DNA-DNA cross-links, DNA strand breaks including double-strand breaks, and oxidative base damage. The predominant form is ternary adducts, in which chromium(III) links the DNA with small molecules such as cysteine, histidine, glutathione or ascorbate. The reactive intermediates of the reduction additionally generate oxidative stress. [53]

In the cell nucleus, it is thus trivalent chromium that damages the DNA. The widespread equation of chromium(III) with harmlessness therefore falls short: what matters is whether chromium enters the cell.

Epidemiological basis: the chromate industry cohorts

The carcinogenic effect is not only derived from animal experiments but has been demonstrated in workers in the chromate industry. The US occupational safety agency OSHA based its limit value of 5 µg/m³, issued in 2006, primarily on two cohorts from chromate production: the workers at the Baltimore plant (Gibb et al. 2000; 2,357 men, observed from 1950 to 1992) and those at the plant in Painesville, Ohio (Luippold et al. 2003). The IARC classifies chromium(VI) compounds as carcinogenic to humans (Group 1), with an established effect on the lung and observed associations with cancer of the nose and paranasal sinuses. [53, 54]

Classification of the target chromates

Under the harmonised European classification, calcium chromate is classified as carcinogenic category 1B (H350) and as very toxic to aquatic life with long-lasting effects (H400, H410). Sodium chromate is additionally classified as mutagenic, toxic to reproduction, skin sensitising and corrosive. [3]

Skin contact

Skin contact must be assessed in its own right. Prolonged contact can lead to dermatitis and skin ulcers; some of those exposed develop allergic sensitisation, in which even small quantities trigger severe skin reactions. Contaminated components, insulation materials, tools and gloves therefore remain a hazard even when air measurements are unremarkable. The German TRGS 561 (Technical Rule for Hazardous Substances) requires special protective measures in the event of skin contact with chromium(VI) compounds. [19, 56]

Not all chromium(VI) is the same: the individual chromates

In practice, people usually speak of “chromium(VI)” across the board. This generalisation is harmful because it loses sight of the individual chromates. Solubility, particle behaviour, residence time in the lung and classification differ considerably. In a British comparative study in rat lungs (Levy et al. 1986), poorly soluble chromates caused lung tumours significantly: strontium chromate in 43 and 62 of 99 animals, calcium chromate as a positive control in 25 of 100, zinc chromate, by contrast, in only 5 and 3 of 100 respectively. [55]

Calcium chromate, the main product of in-situ formation on calcium-containing insulation materials and in ashes, is thus among the most potent chromates in animal experiments. An assessment that only records “chromium(VI)” and does not name the compound conceals these differences.

All exposure routes must be assessed individually

Article 3(2) and (3) of the European Directive 2004/37/EC requires the assessment of possible exposures, including other routes of exposure, in particular absorption into or through the skin. For these activities, the following routes must each be taken into account individually and then in the overall assessment: [18]

• Inhalation: release and inhalation of chromate dusts during maintenance, opening, dismantling, cleaning or handling; activity-related air measurements assess this route.

• Dermal: contact with contaminated components, insulation materials, tools, gloves or liquids; skin exposure, possible uptake and local effects must be assessed separately.

• Oral: hand-to-mouth transfer via contaminated hands, objects, food or drinks; work processes, hygiene and spreading of contamination must be taken into account.

A low air concentration is not a general exoneration criterion. It does not answer the questions of skin contact, oral uptake or surface contamination. The German TRGS 561 requires, in section 3.3.4, special protective measures in the event of skin contact with Cr(VI) compounds. [19]

Environment

For the target compounds likely here, the environmental hazard is also significant. Calcium chromate and sodium chromate are to be classified as very toxic to aquatic life with long-lasting effects (H410). The formation of these chromates therefore concerns occupational safety and health, waste and residue management and water protection at the same time.

The fact that the starting product is sold as an insulation material does not change the hazardous substance relevance of the reaction products formed under intended thermal stress.

How far chromium(VI) can spread in the environment is shown by the case of Hinkley in California, known from the film Erin Brockovich (2000): between 1952 and 1966, the US energy company PG&E used chromium(VI) as a corrosion inhibitor in the cooling tower water of a compressor station. The wastewater entered the groundwater via unlined ponds and contaminated an area around three kilometres long and one and a half kilometres wide. [57]

In-depth look at inhalation health risks: Speer et al. (2022)

The American study submitted examines particulate zinc chromate (ZnCrO₄) in non-malignant, immortalised human bronchial fibroblasts. Exposure was at 0.1, 0.2 and 0.3 µg/cm² over 24, 72 and 120 hours. The authors record changes in microRNA expression by means of sequencing and additionally verify selected findings with qPCR. The compound investigated is zinc chromate, not calcium or sodium chromate. [39]

According to the bioinformatic target and signalling pathway analysis, the altered microRNAs concern central areas of carcinogenesis: chromosomal instability, inflammation, oxidative stress, evasion of cell death and cellular transformation. The changes in expression were measured; not every gene or signalling pathway effect derived from them was directly tested as a functional endpoint. The study thus deepens the mechanistic understanding of particulate Cr(VI) exposure in human lung cells. [39]

For the assessment of chromate dusts, this is a relevant biological reference: cellular regulatory and repair processes may be affected even if a later routine examination does not reconstruct earlier exposure. However, the cell culture dose in µg/cm² is not an air concentration in µg/m³; the series of experiments is neither an inhalation cohort study nor a measurement of the disease risk at a specific plant. Compound, solubility, particle behaviour and the dose actually taken up must still be taken into account when transferring the findings to other chromates. [39]

Air measurement, biomonitoring and long-term effects are different levels

A workplace air measurement describes the activity and time period sampled. Urinary chromium serves to assess an absorbed chromium burden; the British EH40 lists the biological guidance value as chromium in urine, not as a direct Cr(VI) speciation measurement. Such a value reliably reconstructs neither exposure that lies far in the past nor genotoxic changes that have already occurred. The three levels must therefore not be used as substitute evidence for one another. [39, 42]

In British occupational safety and health, the British authority HSE likewise requires consideration of all routes of uptake, including the skin and ingestion; for carcinogenic substances, exposure must be reduced as far as is reasonably practicable. The British practical case is therefore listed as a separate European application example, not as evidence of currently applicable EU law or of a common European limit value. [41]