Boron in drinking-water
Background document for development of WHO Guidelines for Drinking-water Quality
Effects on humans
Available human data on boron compounds for routes other than inhalation focus on boric acid and borax. According to Stokinger (1981), the lowest reported lethal doses of boric acid are 640 mg/kg of body weight (oral), 8600 mg/kg of body weight (dermal), and 29 mg/kg of body weight (intravenous injection). Stokinger (1981) stated that death has occurred at total doses of between 5 and 20 g of boric acid for adults and <5 g for infants. Litovitz et al. (1988) stated that potential lethal doses are usually cited as 3–6 g total for infants and 15–20 g total for adults. A case-series report of seven infants (aged 6–16 weeks) who used pacifiers coated with a borax and honey mixture for 4–10 weeks concluded that exposures ranged from 12 to 90 g, with a very crudely estimated average daily ingestion of 18–56 mg of boron per kg of body weight (OSullivan & Taylor, 1983). [Estimates given here are corrected values, as intakes reported in this publication were underestimated by a factor of 3 (M. Taylor, personal communication to M. Dourson, in a letter dated 28 August 1997).] Toxicity was manifested by generalized or alternating focal seizure disorders, irritability, and gastrointestinal disturbances. Although infants appear to be more sensitive than adults to boron compounds, lethal doses are not well documented in the literature.
Goldbloom & Goldbloom (1953) reported four cases of boric acid poisoning and reviewed an additional 109 cases in the literature. The four cases were infants exposed to boric acid by repeated topical applications of baby powder. Toxicity was manifested by cutaneous lesions (erythema over the entire body, excoriation of the buttocks, and desquamation), gastrointestinal disturbances, and seizures. Approximately 35% of the 109 other case reports of boric acid poisoning involved children <1 year of age. The mortality rate was 70.2% for children, compared with 55.0% for all cases combined. Death occurred in 53% of patients exposed by ingestion, 75% of patients subjected to gastric lavage with boric acid, 68% of patients exposed by dermal application for treating burns, wounds, and skin eruptions, and 54% of patients exposed by other routes. Information on signs and symptoms for 80 patients showed that gastrointestinal disturbances were prevalent (73%), followed by CNS effects (67%). Cutaneous lesions were prevalent in 76% of the cases and in 88% of cases involving children <2 years of age. Gross and microscopic findings were reported for 45% of fatal cases. In general, boric acid caused chemical irritation primarily at sites of application and excretion and in organs with maximum boron concentrations. The most common CNS findings were oedema and congestion of the brain and meninges. Other common findings included liver enlargement, vascular congestion, fatty changes, swelling, and granular degeneration.
In addition to case reports, poison centres have published case-series reports. Unlike the case reports reviewed by Goldbloom & Goldbloom (1953), more recent reports suggest that the oral toxicity of boron in humans is milder than previously thought. Litovitz et al. (1988) conducted a retrospective review of 784 cases of boric acid ingestion reported to the National Capital Poison Center in Washington, DC, USA, during 1981–1985 and the Maryland Poison Center in Baltimore, MD, USA, during 1984–1985; approximately 88.3% of the cases were asymptomatic. All but two of the cases had acute (single) ingestion, and 80.2% involved children <6 years of age. No severe toxicity or life-threatening effects were noted, although boric acid levels in blood serum ranged from 0 to 340 µg/ml. The most frequently occurring symptoms, which involved the gastrointestinal tract, included vomiting, abdominal pain, diarrhoea, and nausea. Other symptoms (primarily CNS and cutaneous) occurred in fewer cases: lethargy, rash, headache, light-headedness, fever, irritability, and muscle cramps. The average dose ingested was estimated at 1.4 g. According to Litovitz et al. (1988), 21 of the children <6 years of age, 15 of whom were <2 years of age, ingested the reported potential lethal dose of 3 g; eight adults ingested the reported potential lethal dose of 15 g without clinical evidence of lethal effects.
Linden et al. (1986) published a retrospective review of 364 cases of boric acid exposure reported to the Rocky Mountain Poison and Drug Center in Denver, CO, USA, between 1983 and 1984. Vomiting, diarrhoea, and abdominal pain were the most common symptoms given by the 276 cases exposed in 1983. Of the 72 cases reported in 1984 for whom medical records were complete, 79% were asymptomatic, whereas 20% noted mild gastrointestinal symptoms. One 2-year-old child died, presumably from repeated ingestion of an insecticide containing 99% boric acid.
Overall, owing to the wide variability of data collected from poisoning centres, the average dose of boric acid to produce clinical symptoms is still unclear, presumably in the range of 100 mg to 55.5 g, reported by Litovitz et al. (1988).
Findings from human experiments show that boron is a dynamic trace element that can affect the metabolism or utilization of numerous substances involved in life processes, including calcium, copper, magnesium, nitrogen, glucose, triglycerides, reactive oxygen, and estrogen. Although the first findings involving boron deprivation of humans appeared in 1987 (Nielsen et al., 1987), the most convincing findings have come mainly from two studies in which men over the age of 45, postmenopausal women, and postmenopausal women on estrogen therapy were fed a low-boron diet (0.25 mg/2000 kcal) for 63 days and then fed the same diet supplemented with 3 mg of boron per day for 49 days (Nielsen, 1989, 1994; Nielsen et al., 1990, 1991, 1992; Penland, 1994). These dietary intakes were near the low and high values in the range of usual dietary boron intakes. The major differences between the two studies were the intakes of copper and magnesium: in one experiment, they were marginal or inadequate; in the other, they were adequate. The marginal or inadequate copper and magnesium intakes caused apparent detrimental changes that were more marked during boron deprivation than during boron repletion. Although the function of boron remains undefined, boron is becoming recognized as an element of potential nutritional importance because of the findings from human and animal studies.