Características del municipio de Ortigueira

Exposures of concern at the Huntsville facilities were identified based on interviews with

former workers and published news articles describing soil contamination at Plant 2. Information

obtained from these sources was corroborated using results from the NIOSH exposure

assessment at the IBM electronics plant in New York State. These exposures are briefly

reviewed for their associations with specific diseases. Causes of death of a priori interest based on the exposures of concern at the Huntsville facilities are summarized in Table 2.1.

22

Lead

Lead is a systemic toxicant affecting all major organ systems. Chronic exposure to

elevated doses of lead in adults is primarily associated with chronic kidney disease, including

impaired renal function or kidney failure, and diseases of the central nervous system, including

neurodegenerative diseases and cognitive impairment 18,19. A large body of evidence has also

established a positive association between blood lead levels and various cardiovascular disease

endpoints, with the strongest evidence indicating increased risk of hypertension and

cerebrovascular disease 20-22. Defects in cardiac conduction and rhythm have also been

documented in populations chronically exposed to lead at low doses 23-25.

In occupational settings, several studies have described mortality risks among males with

elevated lead exposure through employment at lead smelter and battery manufacturing plants.

These studies have consistently reported associations between employment and elevated risk of

non-malignant kidney disease, cerebrovascular disease, and ischemic heart disease mortality 26-

31_{. A study of 1,990 workers at a U.S. lead smelting plant with extended follow-up and}

quantitative exposure ascertainment reported an elevated association between cumulative lead

exposure and ischemic heart, cerebrovascular, and chronic kidney disease mortality 32. An

external comparison also indicated excess mortality due to amyotrophic lateral sclerosis (ALS),

although the estimate was imprecise due to the rarity of the disease. However, a meta-analysis of

nine case-control studies of ALS reported a positive association between ALS incidence and

prior occupational exposure to lead 33. Some studies of workers occupationally exposed to lead

have reported elevated risk of stomach, lung, or kidney cancer, although these findings may be

confounded by exposure to other heavy metals, such as arsenic and cadmium 26,28,34,35_{. Overall,}

23

Chlorinated organic solvents

Trichloroethylene has been widely studied with respect to its cancer and non-cancer

toxicity. A re-evaluation of trichloroethylene by IARC in 2012 resulted in its classification as

carcinogenic to humans (Group 1) based on strong epidemiological and animal evidence for

kidney cancer and limited evidence for liver cancer and non-Hodgkin’s lymphoma 38. A meta-

analysis of epidemiological studies investigating trichloroethylene exposure and cancer risk

reported an elevated association for kidney cancer, liver cancer, and non-Hodgkin’s lymphoma,

although estimates for the latter two cancer sites were subject to issues of study heterogeneity

and a weaker exposure-response relationship 39.

The non-cancer health effects of trichloroethylene include toxicity to several major organ

systems. An in-depth toxicological review by the U.S. Environmental Protection Agency (EPA)

concluded strong evidence that trichloroethylene exposure is toxic to the immune system, central

nervous system, reproductive system, kidney, and liver 40. Epidemiological and experimental

evidence indicated that exposure can cause autoimmune disease (particularly generalized skin

disorders), impairment of nerve function, tubular nephropathy, and toxicity to the liver and

testes.

Other chlorinated solvents of interest include 1,1,1-trichloroethane and dichloroethane.

Both chemicals were last reviewed by IARC in 1979 and classified in a monographs supplement

in 1987 41,42. 1,1,1-trichloroethane was classified as having inadequate evidence for carcinogenicity in humans and experimental animals (Group 3), and dichloroethane was

classified as having inadequate evidence in humans, but sufficient evidence in animals (Group

24

central nervous system43. Chlorinated solvents have been associated with non-malignant liver

and nervous system diseases, including neurobehavioral impairment 43-46_.

Asbestos

The health effects of asbestos exposure have been extensively studied. The latest

evaluation by IARC in 2012 classified asbestos as a human carcinogen due to strong evidence

for mesothelioma and cancer of the lung, larynx, and ovary (Group 1) 47. Much of the

epidemiological evidence of the cancer risk of asbestos exposure comes from occupational

studies of workers with long term or high exposure to asbestos, although there is evidence of

elevated risk of malignant lung disease even at low levels. Asbestos exposure also causes non-

malignant lung disease, including fibrosis of the lungs and asbestosis 48.

Fiberglass dust

Exposure to man-made vitreous fibers, including fiberglass, was last reviewed for its

carcinogenic potential by IARC in 2002. It was concluded that there was inadequate evidence in

humans and limited evidence in experimental animals for the carcinogenicity of glass wool fibers

49_{. A retrospective cohort study of 32,110 employees at several U.S. fiberglass manufacturing}

plants from 1945 to 1978 found no excess of mortality due to non-malignant respiratory disease

and a small excess of respiratory system cancer compared to national reference rates 50_{. There}

were no excesses observed for other non-malignant causes of death. Internal comparisons of

exposure showed little evidence of association with respiratory system cancer. A systematic

review of the association between fiber glass exposure and respiratory system cancer published

25

Cause of death Exposure

Malignant

Kidney cancer TCE

Non-Hodgkin’s lymphoma TCE

Respiratory system cancer Asbestos

Non-Malignant

Hypertension Lead

Cerebrovascular disease Lead

Ischemic heart disease Lead

Cardiac conductive/rhythm disease Lead Amyotrophic lateral sclerosis (ALS) Lead

Central nervous system disease Lead, TCE, other solvents

Chronic kidney disease Lead, TCE

Liver disease TCE, other solvents

Non-malignant lung disease Asbestos

Table 2.1. Causes of death of a priori interest based on suspected workplace exposures at Huntsville facilities

26

CHAPTER 3: MATERIALS AND METHODS