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M D Whorton

Publications and source records attributed to M D Whorton.

34 records · Page 2Linked to original sources
PubMed1983

An evaluation of the mouse sperm morphology test and other sperm tests in nonhuman mammals. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The literature on the mouse sperm morphology test and on other sperm tests in nonhuman mammals was reviewed (a) to evaluate the relationship of these tests to chemically induced spermatogenic dysfunction, germ-cell mutagenicity, and carcinogenicity, and (b) to make an interspecies comparison to chemicals. A total of 71 papers were reviewed. The mouse sperm morphology test was used to assess the effects of 154 of the 182 chemical agents covered. 4 other murine sperm tests were also used: the induction of acrosomal abnormalities (4 agents), reduction in sperm counts, (6 agents), motility (5 agents), and F1 sperm morphology (7 agents)). In addition, sperm tests for the spermatogenic effects of 35 agents were done in 9 nonmurine mammalian species; these included analyses for sperm count, motility, and morphology, using a large variety of study designs. For the mouse sperm morphology test, 41 agents were judged by the reviewing committee to be positive inducers of sperm-head shape abnormalities, 103 were negative, and 10 were inconclusive. To evaluate the relationship between changes in sperm morphology and germ cell mutagenicity, the effects of 41 agents on mouse sperm shape were compared to available data from 3 different mammalian germ-cell mutational tests (specific locus, heritable translocation, and dominant lethal). The mouse sperm morphology test was found to be highly sensitive to germ-cell mutagens; 100% of the known mutagens were correctly identified as positives in the sperm morphology test. Data are insufficient at present to access the rate of false positives. Although it is biologically unclear why one might expect changes in sperm morphology to be related to carcinogenesis, we found that (a) a positive response in the mouse sperm morphology test is highly specific for carcinogenic potential (100% for the agents surveyed), and (b) overall, only 50% of carcinogens were positive in the test (i.e., sensitivity approximately equal to 50%). Since many carcinogens do not produce abnormally shaped sperm even at lethal doses, negative findings with the sperm test cannot be used to classify agents as noncarcinogens. We conclude that the mouse sperm morphology test has potential use for identifying chemicals that induce spermatogenic dysfunction and perhaps heritable mutations. Insufficient numbers of chemicals agents have been studied by the other sperm tests to permit similar comparisons. A comparison of 25 chemicals tested with sperm counts, motility, and morphology in at least 2 species (including man, mouse and 9 other mammals) demonstrated good agreement in response among species. With further study, interspecies comparisons of chemically induced sperm changes may be useful for predicting and evaluating human effects.

Animals↗
PubMed1983

An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

To evaluate the utility of sperm tests as indicators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count (for 87 of the 89 exposures reviewed). Sperm motility was evaluated for 59 exposures, morphology for 44, and double Y-bodies for only 4. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm tests (52); those suggestive of improving semen quality (11); those showing inconclusive evidence of adverse effects from exposure (14); and those showing no significant changes (12). Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen; thus sperm tests in mice and other laboratory mammals may have a potential role in hazard identification. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another; all of them may thus be needed when testing for chemically induced changes from agents of unknown activity. This review also gives evidence that sperm tests can be used to assess the extent and the potential reversibility of induced spermatogenic damage. The reviewing committee recommends further studies to determine (a) the dose-response characteristics of the human sperm tests, (b) details of the reversibility of induced changes with time after exposure, (c) the relative responses in the 4 sperm tests in exposed individuals, (d) the mechanism of action, (e) the biological and genetic implications of chemically induced effects, and (f) the comparison of responses among different species for risk assessment. The reviewing committee outlines specific considerations for planning new sperm studies on chemically exposed men.

Animals↗
PubMed1983

Mutagenicity, carcinogenicity and reproductive effects of dibromochloropropane (DBCP).

Dibromochloropropane (DBCP), a brominated organochlorine nematocide, has been used since the mid-1950s. Its primary value was its effectiveness on perennial crops without damaging the plants. DBCP also had less acute toxicity than earlier soil fumigants such as ethylene dibromide. DBCP became widely used on citrus, grapes, peaches, pineapple, soybeans and tomatoes. In Central America and Israel, banana trees were treated with DBCP. By 1975, 25 million pounds were being produced in the U.S. per year. The majority of U.S. production was applied in the Pacific Coast states, particularly California's San Joaquin Valley, and the Southern Atlantic Coast states. Animal studies in the early 1960s revealed hepatic and renal effects and testicular atrophy in DBCP-treated rates. Testicular atrophy was noted at the lowest exposure level tested (5 ppm). In 1973, DBCP was found to cause gastric carcinoma in mice and rats, and mammary adenocarcinoma in rats. A later study linked DBCP to nasal cavity tumors in rats. DBCP is an in vitro mutagen after activation with microsomal enzymes. A dominant lethal effect has been observed in rats. DBCP also induces increases in sister-chromatid exchanges and chromosomal aberrations. Mean fetal weight and maternal weight gain is decreased in pregnant rats exposed to DBCP. In mid-1977, employees in a California pesticide formulation plant were discovered to be infertile. Further investigations documented azoospermia and oligospermia among many of the workers handling DBCP. These findings were duplicated in other DBCP production plants. In the United States, the Occupational Safety and Health Administration (OSHA) and the Environmental Protection Agency (EPA) rapidly restricted the use of DBCP. The application of DBCP to all but pineapples in Hawaii was banned by the EPA in 1979. In 1982, the EPA exempted the peach crop in the Southern Atlantic coast states from the ban on DBCP use. Prior to the 1977 events, no such agent in workplace concentrations had been shown to produce infertility and sterility in otherwise healthy men. Subsequently, the interest in DBCP had led to many other studies, and has contributed to a heightened awareness about workplace hazards to both the male and female reproductive systems. This article will review the current state of knowledge of the in vitro, animal, and human toxicology of DBCP.

Animals↗
PubMed1983

Persistence of symptoms after mild to moderate acute organophosphate poisoning among 19 farm field workers.

Exposure to 2 organophosphate pesticides occurred when entry into a cauliflower field was permitted 4 h after application of highly toxic chemicals. It resulted in acute illness of mild to moderate degree in 19 farm workers, including 3 children and 1 pregnant woman. There were no fatalities. Two to three months were required for recovery from major symptoms and return to normal acetylcholinesterase levels. An exception was the persistence of eye symptoms in the majority 4 mo after the day of exposure.

Adolescent↗
PubMed1983

Feasibility of identifying high-risk occupations through tumor registries.

The primary objective of this study was to assess the feasibility of using a population-based tumor registry to identify occupational groups at high risk of developing cancer. The study group comprised 6,424 union members residing in the San Francisco/Oakland Standard Metropolitan Statistical Area (SMSA) who represent six occupations: asbestos workers, bakers, painters, plasterers, plumbers and roofers. Computer linkage of union rosters to the California Tumor Registry (CTR) file identified incident cases of cancer. The CTR's age-sex-year-specific incidence rates were used to calculate the expected number of cancer cases, and estimated standardized incidence ratios (SIRs). The results demonstrate, as expected, increased cancer incidence (SIR = 498) for trachea, bronchus, lung and pleura among asbestos workers, a group widely recognized as having high risk for respiratory cancers, and among painters (SIR = 199). Strengths and weaknesses of such an approach are discussed.

Asbestos↗
PubMed1982

Male occupational reproductive hazards.

Studies assessing reproductive function among male workers were rare in the United States before the discovery of sterility and infertility in 1977 among employees of a pesticide formulating plant in central California. Subsequently, the etiologic agent, dibromochloropropane (DBCP), has been shown in numerous studies of humans and animals to produce similar effects. While studies on the influence of workplace exposures to various chemicals on reproductive function have proliferated during the past five years, no other single agent has approached the dramatic effects exhibited by DBCP. Other agents that have been evaluated and have shown some adverse effects are reviewed critically. Studies of spontaneous abortion or congenital abnormalities in children of wives of men exposed to anesthetic gases and DBCP indicate that pregnancy outcome, as well as infertility and sterility, is an important outcome measure.

Chemical Industry↗
PubMed1981

Testicular function among epichlorohydrin workers.

Epichlorohydrin (1,2-epoxy-3-chloropropane) (ECH) is a colourless liquid used in the production of insecticides, agricultural chemicals, epoxy resins, and many other productions. It is highly reactive and an alkylating agent suspected of possessing carcinogenic properties in man. The results of a clinical-epidemiological investigation to ascertain whether exposure to ECH may be associated with sperm count suppression among ECH production workers at two chemical plants are presented. Medical histories and physical examinations with special emphasis on the genitourinary tract were completed on each participant. Blood samples and three semen specimens were also obtained. Since no internal control group were available, the data arising from this effort were analysed for each plant (plant A, 44 men; plant B, 84 men) using a control group of 90 chemical plants workers unexposed to any agents known to be toxic to the tests who were included in previous studies. This study provides no evidence that exposure to ECH at the concentrations existing at the two plants studied is responsible for sperm count suppression.

Chemical Industry↗
PubMed1981

A method for monitoring the fertility of workers. 2. Validation of the method among workers exposed to dibromochloropropane.

A method has been developed for monitoring industrial workers and others exposed to environmental agents which may impair fertility. National birth probabilities specific for maternal birth cohort, age, parity, and race are used to derive expected fertility. Observed fertility is obtained by questionnaire. Standardized fertility ratios are computed for exposure and non-exposure periods and compared. The analytic techniques have been validated by applying the method to a group of 36 male factory employees working in an agricultural chemical division (ACD) where pesticides including the nematocide dibromochloropropane were formulated. Twelve of these employees in mid-1977 had been discovered to have severely depressed sperm counts related to occupational exposure. The standardized fertility ratio (SFR) computed from data available in mid-1977 for the period at risk from employment in the ACD (SFR = 0.75) was significantly lower than those derived for the entire not-at-risk period (SFR = 1.88) and the portion related to employment in other areas of the factory (SFR = 2.16). Similar differences also were evident from data available several years earlier, demonstrating that the surveillance technique would have been capable of detecting occupationally induced infertility among these workers in advance of the actual discovery date.

Antinematodal Agents↗
PubMed1980

Recovery of testicular function among DBCP workers.

Twenty-one men with DBCP-related sperm count suppression were re-examined one year after termination of exposure in July 1977. When examined initially, 12 of these men were azoospermic and nine oligospermic. By October 1978 the sperm count of eight of the nine oligospermic men had improved considerably, six having recovered to a normospermic state. None of the 12 azoospermic men had improved by August 1978. Eleven of the 12 men exposed for more than four years were azoospermic. Serum follicle-stimulating hormone (FSH) for these 11 men increased significantly between assessments. Four children were born to the wives of the nine oligospermic men; three of the children were normal and one had several defects. The significance of this observation cannot be interpreted in terms of DBCP exposure, since this study was not designed to examine pregnancy outcome.

Chemical Industry↗
PubMed1979

Testicular function among carbaryl-exposed exployees.

A cohort of 101 male carbaryl production workers with at least 1 yr experience in the carbaryl area was selected from employment records. Of these individuals, 47 provided satifactory semen samples for analysis; 36 of the 47 provided blood for hormone assay. There were no major age or employment-status differences between those who agreed to participate and those who did not. In the absence of sufficiently detailed industrial hygiene exposure data, a subjective exposure classification was developed. No apparent relationships were found between sperm count and exposure category or years worked in classifications based on carbaryl exposure. Also, no relationship was found between fathering children and exposure to carbaryl. When the sperm-count distribution of the carbaryl-exposed workers was compared with a distribution of sperm counts representing a nonexposed (control) population, no overall differences were observed that could be related to carbaryl exposure. There was a small excess in the number of sperm counts less than 20 million per milliliter among the carbaryl-exposed men, but the excess was not significant at alpha = 0.05.

Adult↗
PubMed1976

Carbon monoxide intoxication: a review of 14 patients.

In 14 cases of carbon monoxide poisoning, medical records were available for retrospective review in which blood samples for carboxyhemoglobin (COHgb) were obtained. Twelve victims (86%) were overcome while at work. Correlation of the clinical picture and COHgb saturation was not always possible although hypertension was not uncommon initially. On follow-up only three patients were mildly hypertensive. Skin or mucous membrane color changes were difficult to detect. Three cases are presented to illustrate factors in the diagnosis and possible sequelae.

Adult↗
PubMedDate not supplied

Male reproductive hazards.

Studies of adverse reproductive effects on male workers have only become prominent in the last 10 years and have used a variety of approaches to evaluate male reproductive function. This article focuses on studies that utilize semen analysis.

Abnormalities, Drug-Induced↗