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Biomedical subjects

P F Infante

Publications and source records attributed to P F Infante.

At least 37 records · Page 2Linked to original sources

Projections of leukemia risk associated with occupational exposure to benzene.

In 1982, White et al published an assessment of quantitative leukemia risk associated with lifetime occupational exposure to benzene. At about the same time, IARC (1982) published estimates of quantitative cancer risk associated with industrial chemicals. Benzene was one of the two chemicals selected by IARC for its risk estimation. This paper presents a summary of these assessments along with new study results demonstrating adverse effects on bone marrow and peripheral blood cells as a result of low-level benzene exposure. Mathematical extrapolations based on epidemiologic studies are consistent with a finding of significant risk of dying from leukemia under the current occupational permissible exposure limit of 10 ppm. Although a significant reduction of risk could be expected to be achieved by reducing exposure to 1 ppm, a significant risk may still remain. The uncertainty of the dose-response projections rests on the underlying estimates of relative risk of death from leukemia, the estimates of benzene exposure (dose), and the appropriateness of the mathematical model. Recent findings in experimental animals demonstrate chromosomal damage to bone marrow cells, significant depression of the bone marrow, and disturbances of immune system function as a result of less than 1 week of exposure to the current permissible benzene exposure limit of 10 ppm. This was the lowest dose tested. These experimental findings provide further evidence of a potentially significant risk of bone marrow proliferative cancer (leukemia) as a result of low-dose benzene exposure.

Air Pollutants, Occupational↗

Benzene: epidemiologic observations of leukemia by cell type and adverse health effects associated with low-level exposure.

Benzene has been known to be a bone marrow poison for almost a century. However, it was not until the last decade that benzene's carcinogenic potential was demonstrated by epidemiologic studies. The proposed regulation by the Occupational Safety and Health Administration (OSHA) to lower exposure levels of benzene in the workplace, and the court challenges that followed, have made the evidence of benzene toxicity a frequent topic of discussion and analysis. Epidemiologic evidence of leukemia risk associated with benzene exposure is summarized, including a discussion of certain contentions raised during the OSHA hearing. Special attention is given to information on specific cell types of leukemia associated with benzene and to qualitative and quantitative assessments of health risks associated with low-level benzene exposure.

Adult↗

Occupational reproductive hazards: necessary steps to prevention.

Although some attention has recently been given to the study of occupational reproductive hazards, little is known about measures being taken to prevent exposure to substances having the potential to cause such problems. In the past, OSHA has promulgated a standard to lower the permissible exposure level to a reproductive toxin as the major focus only after experimental evidence was confirmed in humans. The method of selection of appropriate substitutes is also cause for concern. A chemical known to cause testicular atrophy, cancer, and gene mutations in subhuman test systems and to cause sterility in male workers was replaced with a substance known from experimental studies to cause testicular toxicity, cancer of multiple sites, and gene mutations. Experimental test results need to be addressed from the standpoint of determining presumptive risk to humans. A scheme for setting priorities for reduction of exposure or for consideration of regulation of occupational reproductive hazards also needs to be developed. A policy addressing occupational reproductive hazards may serve as a stimulus for protecting workers from these hazards and for improving scientific research protocols.

Ethylene Dibromide↗

Review of epidemiologic study results of vinyl chloride-related compounds.

Epidemiologic study results addressing the carcinogenicity of six compounds related to vinyl chloride (vinylidene chloride, trichloroethylene, perchloroethylene, carbon tetrachloride, ethylene dibromide and epichlorohydrin) are reviewed. The study results suggest an increased carcinogenic risk among workers exposed to epichlorohydrin and to dry cleaning and degreasing solvents. Although several studies report no significant excess of cancer mortality, an evaluation of the design of these investigations demonstrates that these negative cohort studies consisted of populations of insufficient sample size and latency to permit any meaningful conclusions regarding carcinogenic risk. Therefore, experimental studies must be relied upon to determine whether several of these substances pose a potential carcinogenic risk to humans. Available evidence indicates that all of these substances have demonstrated a carcinogenic response in experimental animals and most are mutagenic in experimental test systems.

Epidemiologic Methods↗

Observations of the site-specific carcinogenicity of vinyl chloride to humans.

A review of epidemiologic studies of workers exposed to vinyl chloride (VC) was conducted. Some of these studies comprised small cohorts and thus were insensitive in the evaluation of carcinogenic response for sites that do not demonstrate a high relative risk. Other larger studies used methodology and design that precluded an interpretation of the results. Such limitations were acknowledged by some authors. Use of restrictive disease rubrics also lead to the submerging of sites that would have demonstrated significant excesses. For example, some investigators analyzed data for liver cancer deaths with the board category of digestive system cancer deaths, while others combined data for CNS cancer deaths with the broad category of "other and unspecified cancer," and most studies analyzed information for lymphatic and hematopoietic system cancer deaths with all data combined. Only four of eight studies reviewed could demonstrate a significant excess of liver cancer among VC-exposed workers--a site confirmed in humans by 1974. In contrast, five of eight studies appear to demonstrate a significant excess of CNS cancer mortality. Workers exposed to VC also demonstrate a significant excess of mortality for lung cancer, while the data for lymphatic and hematopoietic system cancer are suggestive. Interpretation of cancer of the latter systems may have been clarified if investigators had not analyzed their data by broad disease classifications.

Adenocarcinoma↗

Leukaemia in benzene workers.

Workers occupationally exposed to benzene in 1940-49 were followed for vital status up to 1975. In comparison with two control populations, a significant (P less than 0-002) excess of leukaemia was observed. A five-old excessive risk of all leukaemias and a ten-fold excess of deaths from myeloid and monocytic leukaemias combined are demonstrated in the study population compared with controls. These figures under-estimate the true leukaemia risk to benzene-exposed workers, because follow-up is only 75% complete and the untraced 25% of the study population were all regarded, in the statistical analysis, as being alive at the end of the study period. The environment of the workers in the study population was not contaminated with solvents other than benzene, and existing records indicate that the benzene levels themselves were generally below the limits recommended at the time of their measurement.

Adult↗

Enamel hypoplasia in relation to caries in Guatemalan children.

Guatemalan children with anterior linear enamel hypoplasia (LEH) had a significantly greater caries experience in posterior dentition than their peers who did not have anterior LEH. The findings suggest that the synergistic mechanism of undernutrition and infection, which may underlie the occurrence of anterior LEH, may also predispose clinically normal appearing deciduous molars to an excessive caries attack equal to that observed in the grossly hypoplastic anterior teeth. The nutritional implications merit further investigation.

Child↗

Mutagenic and carcinogenic risks associated with halogenated olefins.

Recent experimental evidence indicates that structural analogs of vinyl chloride namely, vinylidene chloride and trichloroethylene, are mutagenic. Carcinogenic response also has been observed in experimental animals following exposure to vinylidene chloride, trichloroethylene, and perchloroethylene. More recent observations demonstrate low-level vinyl chloride-induced mammary carcinoma. An additional chlorinated olefin, chloroprene, has demonstrated a mutagenic response in several test systems. Likewise, several studies have indicated significant excesses of chromosomal aberrations as well as adverse effects on reproductive function following male exposure to chloroprene. Although reports have indicated an increased incidence of lung and skin cancer among workers occupationally exposed to chloroprene, adequately designed studies have not been carried out which would allow the development of valid inferences regarding its carcinogenicity. The question facing the scientific community and society is whether observations in subhuman species are adequate to institute prudent public health practice by controlling these agents as carcinogens or mutagens or whether, once again, epidemiologic enumeration of the toll will be required.

Animals↗

Carcinogenic, mutagenic and teratogenic risks associated with vinyl chloride.

The data presented demonstrate clearly that vinyl chloride (VC) is related to a significant excess of mortality from cancer of the liver, lung and brain among workers occupationally exposed to VC. The risk of dying from cancer of the lymphatic and hematopoietic system also appears to increase with an increase in latency. These cancer sites could have been predicted by the animal bioassay conducted by Maltoni. With regard to the liver, even the histophthologic type of cancer (angiosarcoma) was observed first in experimental animals. A study of cancer mortality among populations residing proximate to VC polymerization facilities also demonstrated an increased risk of dying from CNS and lymphatic cancer. These latter findings raise cause for concern about out-plant emmissions of VC, but without further study these cancers obviously cannot be interpreted as being related to out-plant exposure to VC. Various test systems now have elicited a positive mutagenic response to VC. Thus, our observations of a significant excess of fetal mortality among the wives of males, who were occupationally exposed to VC, raise public health concern that VC may be mutagenic in humans. With regard to the teratogenicity of VC, observations of a significant excess of children born with birth defects were reported among populations residing proximate to VC polymerization facilities. Additional epidemiologic study is needed to determine whether a repeated pattern of excessive numbers of children born with birth defects can be observed in other communities with VC polymerization facilities.

Abnormalities, Multiple↗