Biomedical subjects
S A Book
Publications and source records attributed to S A Book.
Regulation of priority carcinogens and reproductive or developmental toxicants.
In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.
Prioritizing candidate reproductive/developmental toxicants for evaluation.
To provide a rational method for the timely evaluation of possible reproductive/developmental toxicants, a prioritization scheme was developed by the California Department of Health Services to select chemicals for consideration by the Proposition 65 Scientific Advisory Panel. Initially, four ascertainment methods were used to identify and construct a master list of 164 candidate agents. Using two criteria, the potential for human exposure and the perceived reproductive/developmental hazard as judged by an ad hoc committee of experts, 42 candidates from the master list were identified as priority agents. For practical purposes, the 15 priority agents with the highest rankings will be given the highest priority in the review process. Limitations in the prioritization method used and refinements to be incorporated in an annual update are described.
Potential lead exposures from lead crystal decanters.
We measured the concentrations of lead leached into 4% acetic acid, white port, and a synthetic alcoholic beverage that were stored in lead crystal decanters for 1-, 2-, and 10-day periods at room temperature. In decanters from 14 different manufacturers, measured lead concentrations ranged from 100 to 1800 micrograms/L. The pH of the leaching medium is probably the dominant factor determining the extent of lead leached, with greater leaching occurring at lower pH values. The consumption of alcoholic beverages stored in lead crystal decanters is judged to pose a hazard.
Developmental toxicity of L-selenomethionine in Macaca fascicularis.
Forty pregnant long-tailed macaques were dosed via nasogastric intubation with 0, 25, 150, or 300 micrograms/kg of L-selenomethionine (Se) daily during organogenesis [Gestational Day (GD) 20-50]. Clinical examination of the dams, maternal body weights, sonographic evaluations, clinical chemistry screens, and measures of serum progesterone and urinary estrone conjugates were used as indicators of maternal and fetal status in all animals. The pregnancies of two to three dams from each dose group were followed until term (approximately GD 165); the remainder (N = 7/dose group) were scheduled for hysterotomy on GD 100 +/- 2. A standard teratologic evaluation was performed including visceral and skeletal examinations. Fetal liver, kidney, skin, and smooth, cardiac, and skeletal muscles were examined by light microscopy; heart muscle was also evaluated by transmission electron microscopy. Neonates delivered at term remained with the dams and were removed periodically for morphometric, neurologic, behavioral, and ophthalmologic assessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependent maternal toxicity as evidenced by anorexia, vomiting, and a significant reduction in body weight increased with increasing duration of Se exposure. One growth-retarded fetus was recovered on GD 131 from a compromised dam exposed to 25 micrograms/kg-day; one early embryonic death (GD 35) and two fetal deaths [GD 68 (followed by maternal death) and GD 123] occurred among animals dosed with 300 micrograms/kg-day. Pregnancy loss among treated animals was not significantly different from concurrent or historical controls. No statistically significant treatment-related effects were observed at necropsy on GD 100 +/- 2. One infant exposed to 150 micrograms/kg-day prenatally exhibited a unilateral cortical cataract, which may have been a spontaneous occurrence. The limited developmental effects observed and reported teratogenesis in nonmammalian species suggest that comparative pharmacokinetic studies are required before the full public health significance of elevated Se is understood.
Utility of disposition data in evaluating retinoid developmental toxicity.
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Embryotoxicity and dose-response relationships of selenium in hamsters.
Pregnant hamsters were treated with selenite, selenate, and selenomethionine during the critical stages of embryogenesis. The dosing regimens were oral, intravenous, and osmotic minipump infusion. Malformations, mainly encephaloceles, were noted with oral and intravenous selenite and selenate but were associated with maternal toxicity manifested by inanition and weight loss. Fetal body weights and lengths were reduced in a dose-dependent manner with the inorganic forms. Single oral doses of selenomethionine above 77 mumol/kg induced similar malformations but not when the dose was delivered orally over four days nor by minipump over several days. Fetal body weights and lengths were decreased by selenomethionine in a dose-dependent manner. Maternal toxicity was pronounced with the higher doses of selenomethionine. Assigning a specific teratogenic effect to selenium is confounded by maternal toxicity.
Benzene, benzo(a)pyrene, and lead in smoke from tobacco products other than cigarettes.
Benzene, benzo(a)pyrene (BaP), and lead in mainstream smoke from cigars, roll-your-own (RYO) cigarette and pipe tobaccos were sampled to evaluate their potential health significance. Results with reference cigarettes were consistent with published values, providing support for the methodology employed. The emissions of benzene and BaP, expressed as mass emitted per gram of tobacco consumed, were similar for all products evaluated; for benzene, the mean values for cigars, RYO cigarette and pipe tobaccos were 156 +/- 52, 68 +/- 11, and 242 +/- 126 micrograms/g, respectively. Mean values for BaP were 42 +/- 7 and 48 +/- 4 ng/g for cigars and RYO cigarette tobacco, respectively. Lead values were below the limit of reliable quantitation in all cases. The mean benzene concentrations in a puff ranged from 1 to 2 x 10(5) micrograms/m3 for cigars, RYO cigarette and pipe tobaccos. For BaP, the puff concentration averaged about 60 micrograms/m3 for cigars and RYO cigarette tobacco. The results suggest that smoking cigars, pipes or RYO cigarettes leads to potential exposures which exceed the No Significant Risk levels of benzene and BaP set pursuant to California's Proposition 65. These tobacco products are now required to bear a health hazard warning when sold in California. We recommend that this be adopted as national policy.
Primate micronucleus study of L-selenomethionine.
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30-day oral toxicity study of L-selenomethionine in female long-tailed macaques (Macaca fascicularis).
Twenty female long-tailed macaques received nasogastric intubation of 0-600 micrograms/kg-day L-selenomethionine for up to 30 consecutive days. Selenium ingestion was well tolerated at all dose levels until the second to third week of the study at which time two animals given 600 micrograms/kg-day died. One animal from the 300 micrograms/kg-day group was removed from study on Treatment Day 19 due to selenium-induced hypothermia. In some cases, administered doses were reduced at the 300 and 600 micrograms/kg-day levels such that the final time-weighted average doses were 0, 25, 62-117, 150, 188-203, and 300 micrograms/kg-day. Six animals at the 188 micrograms/kg-day level or greater required nonscheduled fruit and dietary supplementation to prevent their impending demise. As the dose and duration of exposure increased, the incidence of anorexia, gastrointestinal distress, mucocutaneous toxicity, and frequency of reduced body temperature also increased. A dose-dependent reduction in body weight was also observed. At the greater doses, disturbances in menstrual function were evident, and were accompanied by the absence of serum progesterone concentrations above 1.0 ng/ml, reduced luteal phase lengths, increased intermenstrual intervals, and lowered estrogen excretion. A maximum tolerated dose of 150 micrograms/kg-day L-selenomethionine for 30 days was identified based on mean body weight reduction, hypothermia, dermatitis, xerosis, cheilitis, disturbances in menstruation, and the necessity of dietary intervention to prevent death at doses of 188 micrograms/kg-day or greater.
Sound science in the implementation of public policy. A case report on California's Proposition 65.
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Warnings and the hazards of drinking alcoholic beverages during pregnancy.
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Selenium and human health implications in California's San Joaquin Valley.
An evaluation was conducted on the human health impacts of elevated levels of selenium in the Kesterson National Wildlife Refuge and its surroundings in Merced County, California. Investigative activities of various agencies were summarized and assessed. Agricultural waste water not intended for human use showed elevated selenium concentrations of up to 1400 ppb. Levels of selenium in fish (up to 96 ppm, wet weight), aquatic birds (up to 130 ppm in liver, dry weight), and waterfowl (up to 5.3 ppm flesh, wet weight) were unsafe for unrestricted human consumption. Data on selenium in drinking water (less than 10 ppb), animals (mean values: beef liver 0.3-0.35 ppm, wet weight; milk, 0.01-0.02 ppm), and air (particulate, 14.8 ng/m3; gaseous, less than 1080 ng/m3) did not suggest a high level of exposure. Selenium concentrations in soil were highly variable and suggested a potential source of high exposure. Selenium values in blood and urine of workers were within normal range. A community health survey did not show any trend of adverse health effects in the local population.
California's proposition 65: a reply.
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Evaluation of the nitrate drinking water standard with reference to infant methemoglobinemia and potential reproductive toxicity.
In view of published results of epidemiologic studies which suggested an association between nitrate in drinking water and human malformations, an assessment of the toxicology of nitrates and nitrites in relation to possible adverse effects on reproduction and development was performed. The current water standard for nitrate is based on protection from methemoglobinemia. A review of the animal data failed to provide evidence for teratogenic effects attributable to nitrate or nitrite ingestion. Adverse reproductive effects reported occurred at doses that were about one thousand times and higher than the estimated human intake. Neither nitrate nor nitrite in experimental animals concentrated in the mammary gland or milk. The present assessment concludes that the maximum contaminant level of 45 ppm nitrate ion, or 10 ppm nitrate-nitrogen, adequately protects the very young from nitrate-induced toxicity, both pre- and postnatally.
Occurrence and distribution of bone tumors in beagle dogs exposed to 90Sr.
Radiation-induced bone tumors in beagle dogs exposed to 90Sr have been evaluated in terms of their incidence, time of appearance, occurrence as multiple tumors, anatomic distribution, and the influence of sex on their development. Among dogs fed 90Sr during skeletal development, the incidence of bone tumors was dose dependent. Tumors thus appeared in 10 of 19 dogs receiving average skeletal doses of 130 Gy, 15 of 60 receiving 97 Gy, 5 of 61 receiving 61 Gy, 2 of 65 receiving 26 Gy, and 1 of 40 receiving 1.3 Gy. No tumors appeared among 66 dogs who received 8 Gy, 78 who received 0.3 Gy, and 80 non-irradiated controls, all of which have been observed for life. Among dogs given a single intravenous injection of 90Sr in early adulthood, tumor production was somewhat higher than among 90Sr-fed dogs at the same radiation dose: bone tumors were present in 6 of 25 dogs who received 62 Gy and 1 of 20 dogs who received 7.5 Gy. Bone tumors appeared sooner and were more often multiple in animals receiving the higher doses. Long bones were the sites of most of the tumors appearing after the highest dose level. Bones of the head, particularly the mandible, were the predominant site of tumors in the next highest dose level group.
Chemical contamination of California drinking water.
Drinking water contamination by toxic chemicals has become widely recognized as a public health concern since the discovery of 1,2-dibromo-3-chloropropane in California's Central Valley in 1979. Increased monitoring since then has shown that other pesticides and industrial chemicals are present in drinking water. Contaminants of drinking water also include naturally occurring substances such as asbestos and even the by-products of water chlorination. Public water systems, commercially bottled and vended water and mineral water are regulated, and California is also taking measures to prevent water pollution by chemicals through various new laws and programs.