Formaldehyde and methylene glycol equivalence: critical assessment of chemical and toxicological aspects.

Due largely to the controversy concerning the potential human health effects from exposure to formaldehyde gas in conjunction with the misunderstanding of the well-established equilibrium relationship with its hydrated reaction product, methylene glycol, the concept of chemical equivalence between these two distinctly different chemicals has been adopted by regulatory authorities. Chemical equivalence implies not only that any concentration of methylene glycol under some condition of use would be nearly or completely converted into formaldehyde gas, but also that these two substances would be toxicologically equivalent as well. A relatively simple worst case experiment using 37% formalin (i.e., concentrated methylene glycol) dispels the concept of chemical equivalence and a review of relevant literature demonstrates that methylene glycol has no inherent toxicity apart from whatever concentration of formaldehyde that might be present in equilibrium with such solutions.

An examination of the sensitivity of reported trends in childhood leukemia incidence rates to geographic location and diagnostic coding (United States).

BACKGROUND: There have been conflicting reports of increased incidence of childhood leukemia in the United States with some, but not other, registries reporting increasing rates over the past two decades. Because of the reported discrepancy in childhood leukemia incidence rates an analysis of the SEER database was undertaken. METHODS: The latest SEER data (1973-1995) were analyzed for trends in childhood (age 0-14) leukemia incidence rates by histologic group (all leukemia combined, acute lymphocytic leukemia (ALL), acute mylogenous leukemia (AML), and other acute leukemia) for each SEER reporting region. RESULTS: A significant increase in ALL during 1973-1995 was observed in the combined SEER data, but the increase was a function of whether the first 3 years, data from the SEER Detroit reporting region are included. For the years 1973-1975 the Detroit region reported to much lower rates for ALL and much higher rates for "other acute leukemias" relative to the other SEER regions, resulting in an exaggerated temporal increase in ALL. CONCLUSION: Excluding both the temporal variability, and coding differences for Detroit in the 1973-1975 time frame, there has been no significant increase in childhood leukemia of any histologic group or age category in the United States from the 1970s to 1990s.

Environmental endocrine modulators and human health: an assessment of the biological evidence.

Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.

Chloroform mode of action: implications for cancer risk assessment.

Risk assessment methodology, particularly pertaining to potential human carcinogenic risks from exposures to environmental chemicals, is undergoing intense scrutiny from scientists, regulators, and legislators. The current practice of estimating human cancer risk is based almost exclusively on extrapolating the results of chronic, high-dose studies in rodents to estimate potential risk in humans. However, many scientists are questioning whether the logic used in this current risk assessment methodology is the best way to safeguard public health. A major tool of human cancer risk assessment is the linearized multistage (LMS) model. The LMS model has been identified as an aspect of risk assessment that could be improved. One way to facilitate this improvement is by developing a way to incorporate a carefully derived, more biologically relevant mechanism of action data on carcinogenesis. Recent data on chloroform indicate that the dose-response relationship for chloroform-induced tumors in rats and mice is nonlinear, based upon events secondary to cell necrosis and subsequent regeneration as the likely mode of action for the carcinogenic effects of chloroform. In light of these data, there is a sound scientific basis for removing some of the uncertainty that accompanies current cancer risk assessments of chloroform. The following points summarize the critical data: (1) a substantial body of data demonstrates a lack of direct in vivo or in vitro genotoxicity of chloroform; (2) chloroform induces liver and kidney tumors in long-term rodent cancer bioassays only at doses that induce frank toxicity at these target sites; (3) the chloroform doses required to produce tumors in susceptible species exceed the MTD, often by a considerable margin; (4) cytotoxicity and compensatory cell proliferation are associated with the chloroform doses required to induce liver or kidney tumors in susceptible rodent species; (5) there are no instances of chloroform-induced tumors that are not preceded by this pattern of dose-dependent toxic responses; (6) it is biologically plausible that cytolethality leads to chronically stimulated cell proliferation and related events such as inflammation and growth stimulation which act to initiate and promote the carcinogenic process; and (7) the consistently linked cellular events of cytolethality and subsequent cell proliferation, for which doses of no adverse effect have been clearly shown to exist, are one of the biological prerequisites for chloroform-induced tumors in animals. Based on these data, it is inappropriate to extrapolate cancer risk from high doses that produce necrosis and regenerative cell proliferation to low doses that do not with a model that presumes genotoxicity and a linear dose-response relationship. The weight of the scientific evidence concerning chloroform-induced tumors in rodents is consistent with and supports a cancer risk assessment methodology based on mode of action as the basis for establishing regulatory standards for this compound.

Item bias in cognitive screening measures: comparisons of elderly white, Afro-American, Hispanic and high and low education subgroups.

A study of item bias in standard cognitive screening measures was conducted in a sample of Afro-American, Hispanic and non-Hispanic white elderly respondents who were part of a dementia case registry study. The methods of item-response theory were applied to identify biased items. Both cross-cultural and high and low education groups were examined to determine which items were biased. Out of 50 cognitive items examined from six widely used cognitive screening measures, 16 were identified as biased for either high and low education groups or ethnic/racial group membership.

The impact of the April 1992 civil unrest on the Los Angeles REI WIC program and its participants.

This paper discusses the findings of a study conducted in south central Los Angeles in August 1992 among women in the Special Supplemental Food Program for Women, Infants, and Children. The goals of the study were to determine the current demographics of WIC participants; examine the financial hardship, need for relief services, and extent of hunger resulting from the civil unrest of April 1992; look at the effects of the unrest on different ethnic groups; determine the unmet need for WIC services; and evaluate the State and local WIC responses to the unrest. The 1,189 respondents were approximately 77 percent Latina, 20 percent African American, and 3 percent white. Half or more were recent immigrants, 19 percent were pregnant and parenting adolescents, 74 percent were school dropouts, and 56 percent were single mothers. Only 1 percent had any problems using WIC vouchers after the unrest, although more than half of their grocery stores had closed. Thirty-five percent experienced food deficits in their households, and 33 percent of those who applied for emergency food stamps had trouble getting them. Four percent said their children had gone to bed hungry in the last week, and 9 percent said they, the respondents, had as well. Only 2 percent needed shelter, and 1 percent became homeless, but 6 percent had family members who lost jobs due to the unrest. This study suggests that the chronically substandard conditions under which many families in south central Los Angeles live affect them more profoundly than did the dramatic consequences of the civil unrest.

Central serotonergic changes following antidepressant treatment: a neuroendocrine assessment.

We employed a neuroendocrine challenge paradigm to study the effects of antidepressant treatment on serotonergic systems in depressed patients. We compared the maximum prolactin response to intravenous clomipramine (CMI) in depressed patients who responded to antidepressant treatment to that of nonresponders. Pretreatment baseline prolactin concentrations and pretreatment prolactin responses to clomipramine challenge were not different in responders compared to non-responders. However, following antidepressant treatment, the 6 responders demonstrated a significant change in their clomipramine challenge test results, as indicated by an increase in prolactin responses. In contrast, the 7 nonresponders did not demonstrate a change in their prolactin response to clomipramine challenge following treatment. These data support the hypothesis that serotonergic system dysfunction, as manifested by blunted prolactin response to clomipramine challenge, tends to normalize after successful treatment for depression, and that abnormal serotonergic function may be a state-dependent characteristic.

Dialysis adequacy versus metabolic factors in the clinical assessment of CAPD.

We performed a cross sectional study of our continuous ambulatory peritoneal dialysis (CAPD) patients (n = 98) to examine the relation between parameters of adequacy of dialysis [KT/V, weekly creatinine clearance (Ccr)], urea kinetics (PCR), biochemical parameters (serum albumin), and clinical status of these patients. We also investigated the predictive value of these parameters in the determination of clinical outcomes. The clinical status of each patient was assessed by patient self-assessment and objectively by physicians and nurses. On this basis a total clinical assessment score was assigned. Individuals with a score of 3 or less were judged to be clinically stable (group 1, n = 61), while a score of 4 or more was considered "not doing well" (group 2, n = 37). A good correlation (r = 0.7) between subjective and objective assessments was observed. No correlation between total clinical assessment score and KT/V, PCRN (normalized protein catabolic rate), or Ccr was obtained, while serum albumin levels correlated inversely (r = -0.30; p < 0.003), suggesting that parameters of dialysis adequacy (weekly KT/V, Ccr) and urea kinetics (PCRN) are not predictive of clinical outcome in CAPD patients, in contrast with hemodialysis (HD) patients. Serum albumin levels were observed to be correlated with clinical outcome in CAPD patients. Hypoalbuminemia was observed in group 2 patients, despite statistically insignificant different values of KT/V, Ccr, and PCRN in the two groups. Therefore, clinical assessment and parameters such as serum albumin must be considered when determining the total well-being of CAPD patients.

Depression in women treated for gynecological cancer: clinical and neuroendocrine assessment.

To determine the prevalence of major depression in cancer patients and assess the usefulness of the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test for diagnosing major depression in these patients, the authors studied 83 women hospitalized for gynecological cancer. Nineteen (23%) had major depression according to DSM-III criteria. The sensitivity and specificity of the DST were 40% and 88%, respectively. No relationship between DST and TRH test results was found. These findings indicate a high prevalence of depression in cancer patients, but further research on these tests in cancer patients is needed; their routine use with cancer patients is premature at this time.

Development of indicator scales for the Comprehensive Assessment and Referral Evaluation (CARE) interview schedule.

The objective of this research was to develop indicator scales for major health and social problems of individuals aged 65 or over who live in the community. A semistructured interview technique, the Comprehensive Assessment and Referral Evaluation (CARE), was used in two large surveys in London and New York City. Twenty-two indicator scales were developed by using items that met certain clinical and statistical criteria. These indicator scales are intended for use in developing a general taxonomy of the problems of older individuals, for clinical assessment and referral of such individuals, and for use in geriatric epidemiological research. The scales were developed to be comprehensive with regard to the CARE, to be relatively independent of one another, and to have satisfactory content, clinical, and face validities, and interrater and internal consistency reliabilities.

Construct validity of indicator-scales developed from the Comprehensive Assessment and Referral Evaluation interview schedule.

This paper is an assessment of the construct validity of the scales developed from the Comprehensive Assessment and Referral Evaluation (CARE). Data collected from 445 elderly adults residing in New York and 396 in London were used to develop scales to measure medical, psychiatric, and social problems. Diagnostic and global ratings made by psychiatrists and social scientists provided one source of corroborative information; scales developed from information obtained from a random subsample of 162 collateral sources were used as another method of determining validity. Evidence was provided for convergent and divergent validity using multitrait-multimethod matrices to represent the relationships among scales across methods. Convergent validity coefficients ranged from (.40 to .75) for the CARE scales with the diagnostic ratings and from (.30 to .70) for the informant scales. It is argued that most scales are valid by this criterion.

Concurrent and predictive validity of indicator scales developed for the Comprehensive Assessment and Referral Evaluation interview schedule.

Evidence for the concurrent and predictive validity of indicator scales developed to assess psychiatric, social, and medical conditions of elderly adults is presented. These scales were developed from the Comprehensive Assessment and Referral Evaluation (CARE) on probability samples of 445 elderly community residents in New York City and 396 in London, England. Corroborative information was also collected from key collaterals of a random subsample of 162 of the New York elderly adults. Concurrent validity of the cognitive impairment and activity limitation scales was tested in relation to family report of inconvenience and decision to institutionalize. Predictive validity of the scales was assessed using morbidity and mortality as outcome variables. Individuals classified as having medical and psychiatric disorders at Time 1 were significantly more likely to manifest such disorders 1 year later at Time 2 than were persons not so classified. In addition, the odds that individuals with cognitive impairment, somatic complaints, activity limitation, and difficulty ambulating at Time 1 would be dead within 1 year were two to three times greater than for those without the disorder, a result that provides support for the contention that these scales are useful predictors of outcomes.