Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

Developmental effects of endocrine-disrupting chemicals in wildlife and humans

This public health statement tells you about chromium and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Chromium has been found in at least 1,127 of the 1,699 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which chromium is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may be harmful.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to chromium, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), the form (chromium VI as opposed to chromium III), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

Toxicological Profile for Chromium

Chromium was discovered in 1797 by Vauquelin. Numerous industrial applications raised chromium to a very important economic element. At the same time, with the development of its uses, the adverse effects of chromium compounds in human health were being defined. Trivalent chromium is an essential trace element in humans and in animals. Chromium as pure metal has no adverse effect. Little toxic effect is attributed to trivalent chromium when present in very large quantities. Both acute and chronic toxicity of chromium are mainly caused by hexavalent compounds. The most important toxic effects, after contact, inhalation, or ingestion of hexavalent chromium compounds are the following: dermatitis, allergic and eczematous skin reactions, skin and mucous membrane ulcerations, perforation of the nasal septum, allergic asthmatic reactions, bronchial carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric deficiency. Prevention of occupational risks, biological monitoring of workers, and treatment of poisoning are also reported.

Toxic effects of chromium and its compounds

Chromium is a transition element occurring in the environment (soil, rocks, plants, dust, and gases), primarily in the elemental, trivalent [Cr(III)], and hexavalent [Cr(VI)] oxidation states. Both Cr(III) and Cr(VI) are environmentally stable, and their toxicologic profiles are well known; Cr(III) has limited toxicologic properties [De Flora et al. 1990; International Agency for Research on Cancer (IARC) 1990] and is considered to be an essential trace metal in humans (Anderson 1981), whereas various Cr(VI) compounds are considered to be human carcinogens [Agency for Toxic Substances and Disease Registry (ATSDR) 2000; De Flora 2000; Ding and Shi 2002; IARC 1990; Kawanishi et al. 2002; O’Brien et al. 2003], are known to induce both acute and chronic toxic effects (ATSDR 2000), and are of the greatest occupational and environmental health concern.

The respiratory tract is the main target organ of Cr(VI) toxicity associated with both acute (short-term) and chronic (long-term) inhalation (ATSDR 2000; De Flora 2000): acute exposure may cause shortness of breath, coughing, and wheezing (Sobaszek et al. 2000). Chronic exposure leads to ulcerations and perforations of the nasal septum, chronic bronchitis, decreased pulmonary function, pneumonia, and other respiratory effects (Bradshaw et al. 1998). On the basis of experimental and epidemiologic evidence (De Flora 2000; Gibb et al. 2000; Luippold et al. 2005; Park et al. 2004), IARC has classified Cr(VI) as a class 1 carcinogen (recognized human carcinogen).

Cr(VI) compounds are used in several industrial applications (chrome plating, welding inox steel and other special steels, painting, leather tanning, and wood preserving). Occupational exposure mainly occurs by inhalation, but it may involve the gastrointestinal tract and skin (De Flora 2000). Therefore, the respiratory tract is the primary target organ for Cr(VI) compounds. Experimental work on the rat showed that lung accumulation of Cr(VI) can be observed even after intravenous administration (Mutti et al. 1979). The mechanism of Cr(VI) cytotoxicity is not completely understood, but several studies have shown that Cr(VI) compounds induce oxidative stress, DNA damage, apoptotic cell death, and altered gene expression (Bagchi et al. 2002; Wise et al. 2002; Zhitkovich 2005). The reduction in Cr(VI) levels induced by redox-active enzymes and small molecules generates intermediate unstable states, such as Cr(V) or Cr(IV), that may mediate the formation of free hydroxyl, thiyl, ascorbate, and carbon-based radicals (Ding and Shi 2002; Levina and Lay 2005; O’Brien et al. 2003) that are capable of damaging macromolecular targets, such as DNA (Stohs et al. 2001). Interestingly, although Cr(III) reacts with DNA and proteins, it is unable to cross cell membranes. The opposite occurs for Cr(VI) species, which do not react with nucleophilic targets but can easily cross cell membrane through anion channels. Once inside the cell, Cr(VI) is rapidly reduced to the trivalent state, and Cr(III) then interacts with cell proteins and DNA (Levina and Lay 2005).

Improved work areas, procedures, and hygiene measures have minimized occupational exposure to Cr(VI) compounds and led to a reduction in traditional adverse effects on the lung, such as tracheobronchitis or pneumonia; however, long-term Cr(VI) exposure may still cause airway disorders, including airway irritation, sensitization, and lung cancer. Sensitive tests are therefore needed to evaluate early biochemical changes that occur in the respiratory tract after Cr(VI) exposure. Furthermore, because the respiratory tract is the primary route of exposure to Cr(VI), the quantification of biomarkers of free radical production at the target organ level could improve the sensitivity and specificity of putative biomarkers.

We have recently shown that exhaled breath condensate (EBC), a fluid formed as a result of the cooling of expired air, is a suitable matrix not only for assessing the biomarkers of oxidative stress in exposed workers [malondialdehyde (MDA)] but also for quantifying the levels of some pneumotoxic substances in the lung, in particular, cobalt (Goldoni et al. 2004). The synergistic effect of tungsten to power the lipid peroxidation caused by cobalt has also been demonstrated (Goldoni et al. 2004).

The aim of the present study was to investigate Cr levels in the EBC of workers employed in the chrome-plating industry and to assess early biochemical changes in the airways by analyzing EBC biomarkers of oxidative stress, such as hydrogen peroxide (H2O2) and MDA.

The Effect of Inhaled Chromium on Different Exhaled Breath Condensate Biomarkers among Chrome-Plating Workers

Twenty-two welders working with high chromium alloyed electrodes have been examined. Biological monitoring of exposure was accompanied by measurement of the hydrosoluble fraction of chromium in the air. Several indices of early renal tubular damage were also determined. The close relationship between airborne and urinary chromium suggests that the urinary excretion of the metal at the end of exposure, and particularly its increase above baseline values, are reliable indicators of absorption rate. The measurement of the renal clearance of diffusible chromium—taken as an index of body burden-showed the influence of the lower exchange rate compartment on the relationship between environmental and urinary chromium. Although the degree of exposure was the same, the urinary excretion of chromium was higher in the workers with a greater chromium body burden. The evaluation of some early nephrotoxicity indicators yielded no dose-effect relationship, even if a more frequent pathological “response” was observed in the subjects with a higher degree of exposure to chromium.

The role of chromium accumulation in the relationship between airborne and urinary chromium in welders.

Impaired dopaminergic modulation of pituitary secretion in workers occupationally exposed to styrene: further evidence from PRL response to TRH stimulation.

C. Giaroli

Papers

The role of chromium accumulation in the relationship between airborne and urinary chromium in welders.

Impaired dopaminergic modulation of pituitary secretion in workers occupationally exposed to styrene: further evidence from PRL response to TRH stimulation.

Distribution and urinary excretion of chromium. Studies on rats after administration of single and repeated doses of potassium dichromate.