B. Dwight Culver

Erythrocyte lead-binding protein after occupational exposure: I. Relationship to lead toxicity

Abstract Lead content was determined in various fractions of red blood cell (RBC) hemolysates from normal controls and from three groups of lead-exposed workers: without toxicity, toxicity associated with high blood lead levels, and toxicity associated with low blood lead levels. The most significant finding was a decrease in the lead bound to a 10,000 molecular weight protein in the group of workers with toxicity at low blood lead levels (43 to 54 μg%). These results suggest that workers who have diminished capacity for synthesizing this low-molecular-weight lead-binding protein are at increased risk for developing lead toxicity at relatively low blood lead levels.

An overview of male reproductive studies of boron with an emphasis on studies of highly exposed Chinese workers.

Boron treatment of rats, mice, and dogs has been associated with testicular toxicity, characterized by inhibited spermiation at lower dose levels and a reduction in epididymal sperm count at higher dose levels. The no-adverse-effect level for reproductive effects in male rats is 17.5mg B/kg bw/day. Earlier studies in human workers and populations have not identified adverse effects of boron exposure on fertility, but outcome measures in these studies were relatively insensitive, based mainly on family size and did not include an evaluation of semen end points. A recent study of nearly 1000 men working in boron (B) mining or processing in Liaoning province in northeast China has been published in several Chinese and a few English language papers. This study included individual assessment of boron exposure, interview data on reproductive experience and semen analysis. Employed men living in the same community and in a remote community were used as controls. Boron workers (n=75) had a mean daily boron intake of 31.3mg B/day, and a subset of 16 of these men, employed at a plant where there was heavy boron contamination of the water supply, had an estimated mean daily boron intake of 125 mg B/day. Estimates of mean daily boron intake in local community and remote background controls were 4.25mg B/day and 1.40 mg/day, respectively. Reproductive outcomes in the wives of 945 boron workers were not significantly different from outcomes in the wives of 249 background control men after adjustment for potential confounders. There were no statistically significant differences in semen characteristics between exposure groups, including in the highly exposed subset, except that sperm Y:X ratio was reduced in boron workers. Within exposure groups the Y:X ratio did not correlate with the boron concentration in blood, semen and urine. In conclusion, while boron has been shown to adversely affect male reproduction in laboratory animals, there is no clear evidence of male reproductive effects attributable to boron in studies of highly exposed workers.

Erythrocyte lead‐binding protein after occupational exposure. II. Influence on lead inhibition of membrane Na+,K+‐adenosinetriphosphatase

Membrane Na+,K+-adenosinetriphosphatase in erythrocytes from three groups of industrially exposed Pb workers (without toxicity, with toxicity associated with high blood Pb levels, and with toxicity associated with low blood Pb levels) was inversely correlated with Pb in the membrane fraction but not significantly correlated with total erythrocyte Pb. This difference was attributable to the proportion of erythrocyte Pb bound to hemoglobin and a Pb-binding protein of molecular weight 10,000.

Sensory and Associated Reactions to Mineral Dusts: Sodium Borate, Calcium Oxide, and Calcium Sulfate

Occupational exposure limits (OELs) for irritant dusts have had no quantifiable bases. This study (1) charted chemosensory feel, denoted chemesthesis here, to dusts of calcium oxide (1 to 5 mg/m3), sodium tetraborate pentahydrate [sodium borate] (5 to 40 mg/m3), and calcium sulfate (10 to 40 mg/m3); (2) examined correlates of the chemesthetic sensations; and (3) sought to illuminate the basis for potency. Twelve screened men exercised against a light load while they breathed air in a dome fed with controlled levels of dust for 20 min. Measured parameters included nasal resistance, nasal secretion, minute ventilation, heart rate, blood oxygenation, mucociliary transport time, and chemesthetic magnitude, calibrated to pungency of carbon dioxide. Subjects registered time-dependent feel from exposures principally in the nose, secondarily in the throat, and hardly in the eyes. Calcium oxide had the greatest potency, followed by sodium borate, with calcium sulfate a distant third. Of the physiological parameters, amount of secretion showed the best association with chemesthetic potency. That measure, as well as mucociliary transport time and minute ventilation, went into calculation of mass of dust dissolved into mucus. The calculations indicated that the two alkaline dusts increased in equal molar amounts with time. At equal molar concentrations, they had, to a first approximation, equal chemesthetic magnitude. On the basis of mass concentration in air or dissolved into mucus, calcium oxide and sodium borate differed in potency by a factor just above five, equal to the difference in their molecular weights. This relationship could inform the setting of OELs for a critical effect of irritation.

Inorganic boron health effects in humans: An aid to risk assessment and clinical judgment

This is a review of human response to elevated levels of boron containing compounds with emphasis on studies containing sufficient detail for evaluation of dose-response relationships. Qualitative information is also included where it will assist assessment of risk or contribute to clinical judgment. Skin absorption and dermatitis is also reviewed. Quantitative data are sparse, especially for infants and children. For acute oral doses in children, there are only two data points where dose and temporal relationships have been estimated with some care and where recovery was uneventful; these come from a single paper. Doses were 94.7 mg B/kg in a 24-day infant and 30.4 mg B/kg in a 14-month infant. Effects were irritability, mild diarrhea with vomiting, marked erythema in the diaper area at 94.7 mg, and sparse, mildly erythematous macular rashes on the face and neck at 30.4 mg. Adults given intravenous doses averaging 25 mg 10B/kg (range 19–46 mg 10B/kg) over a 75-second period responded within 2 minutes with nausea followed by vomiting, excitation, and subsequent mild depression. No-effect levels for humans can be established at about 1 g of boric acid per day (2.5 mg B/kg/day). The chronic adverse effect level is 5.0 mg B/kg/day. Infant response at high levels is similar enough to adult responses that it is reasonable to assume that the infant is not more sensitive than the human adult. Non-systemic effects of boron are minor. Respiratory exposure in industry has not caused chronic pulmonary effects. Skin exposure does not cause dermatitis.

In vitro percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in human skin: a summary.

Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry, which now allows quantitation of percutaneous absorption of10B in10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10% in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption.Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percent dose, with flux and permeability constant (Kp) calculated at 0.009 μg/cm2/h and 1.9 x 10-7 cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percent dose, with flux andKp calculated at 0.009 μg/cm2/h and 1.8 x 10-7 cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percent, with flux andKp calculated at 0.01 μg/cm2/h and 1.0 x 10-7 cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption.These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.

Anti‐HTLV III ELISA and Western Blot Testing in a Blood Donor Population: Implications for Donor Notification

Abstract. We have evaluated the western blot (WB) test for distinguishing anti‐HTLV III ELISA‐positive donors who have likely been exposed to HTLV III from those that are false positives. Of 1,955 donors, 26 were positive for anti‐HTLV III by ELISA testing. Only 6 (23%) were positive by WB: 5 of these 6 were male homosexuals with multiple partners and 5 of 6 had low Th/Ts ratios. The WB‐positive donors gave the highest absorbance values in the anti‐HTLV III ELISA assay. The immunologic abnormalities in the WB‐positive donors suggest that they should be notified of their test results. We conclude that basing a donor notification policy on WB results is the optimum public health strategy for blood banks at the present time.

Detection of airborne industrial papain by a radioimmunoassay

A method for measuring papain, an extract of Carica papaya, in the ambient air of an industrial setting was developed using a modified radioallergosorbent test. Papain in air samples was collected and insolubilized by coupling with cyanogen bromide activated cellulose particles. The coval-ently bound papain was measured by incubating the conjugate with anti-papain antibodies of the immunoglobulin E class (IgE) and anti-IgE-I125. Binding of the radiolabel was directly proportional to the concentration of papain in the conjugate. The sensitivity of the test was such that a minimum of 5 nanograms of papain was reliably measured. Based on sampling conditions, the procedure was capable of measuring concentrations of papain as low as 5 pico-grams per cubic meter of air without dependence on the enzymatic properties of the protease.

Summary of research needs

ConclusionA symposium such as this shows how much we know about this element, boron, and also how little we know. Sufficient evidence has been presented to convince some attendees that boron is essential for successful reproduction in some species. Others exhibit healthy skepticism and want further convincing. Most importantly, we need to know if boron is essential for human health and well-being, and if so, how much is required. Much has been accomplished by the extremely generous collaboration between individual researchers in this field of boron research, and there is still room for many more collaborators to join in this exciting search. A review of the articles presented will identify quickly fruitful areas for future research.