In adults

C-6 Hydroyylation. This biotransformation is more predominant in infants than in adults, and can prevent other metabohc transformations. 

Infants maybe sensitive to doses of vitamin A [11103-57-4] in the range of 75,000—200,000 lU (22.5—60 mg), although the toxic dose in adults is probably 2—5 million lU (90.6—1.5 g). Intakes in this range from normal food suppHes without oral supplements are simply beyond imagination (79). Vitamin D [1406-16-2] toxicity is much more difficult to substantiate clinically. Humans can synthesize active forms of the vitamin in the skin upon irradiation of 7-dehydrocholesterol. Toxic symptoms are relatively nonspecific, and dangerous doses seem to He in the range of 1000—3000 lU/kg body wt (25—75 flg/kg body wt) (80). Cases of toxicity of both vitamins E and K have been reported, but under ordinary circumstances these vitamins are considered relatively innocuous (81). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

Mepivacaine hydrochloride [1722-62-9] similar in profile to Hdocaine, is used for infiltration, peripheral nerve blocks, and extradural anesthesia. It appears to be less toxic than Hdocaine in adults but more toxic in newborns. The duration of action is longer than that of Hdocaine because of its lower vasodilator activity. Mepivacaine has Htde topical activity. 

In humans, vitamin A deficiency manifests itself in the following ways night blindness, xerophthalmia, Bitot s spots, and corneal involvement and ulceration. Changes in the skin have also been observed. Although vitamin A deficiency is seen in adults, the condition is particularly harmful in the very young. Often, this results from malnutrition (56). 

The symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

The threshold of a toxic dose in adult humans is about 0.2—0.5 g Ba the lethal dose in untreated cases is 3—4 g Ba, LD q about 66 mg/kg (47). The fatal dose of barium chloride for humans is reported to be between 0.8 and 0.9 g (0.55—0.60 g of Ba) (50). However, for most of the acid-soluble salts of barium, doses greater than 1 g have been tolerated (51). Lethal doses are summarized in Table 5. Dusts of barium oxide are considered potential dermal and nasal irritants (52). 

An average of about 7 ppm of bromine is found ia terrestrial plants, and edible foods contain up to 20 ppm. Among animals the highest bromide contents are found ia sea life, such as fish, sponges, and cmstaceans (44). Animal tissues contain 1—9 ppm of bromide and blood 5—15 ppm. The World Health Organization has set a maximum acceptable bromide iatake for humans at 1 mg/kg of body weight per day. In adult males the bromine content ia semm has been found to be 3.2—5.6 p.g/mL, ia urine 0.3—7.0 p.g/mL, and ia hair 1.1—49.0 p.g/mL. Bromine may be an essential trace element as are the other hahdes (45). 

Environmental exposures to PCBs are significantly lower than those reported in the workplace and are therefore unlikely to cause adverse human health effects in adults. However, it is apparent from the results of several recent studies on children that there was a correlation between in utero exposure to PCBs, eg, cord blood levels, and developmental deficits (65—68) including reduced bkth weight, neonatal behavior anomaUes, and poorer recognition memories. At four years of age, there was stiU a correlation between prenatal PCB exposure levels and short-term memory function (verbal and quantitative). In these studies the children were all exposed to relatively low environmental levels of PCBs. Although these effects may be related to other contaminants, it is clear that this is an area of concern regarding the potential adverse human health impacts of PCBs. 

In adults, a few areas may require further study. For example, there is a report of soya consumption causing an increased incidence of hyperplastic epithelial cells in the nipple aspirate fluid of pre- and postmenopausal women.This could constitute a risk factor for breast cancer. Also, the use in herbal medicine of particular plants emphasises that these species have the potential to cause physiological changes. Consequently, the increasing public interest in the use of herbal medicines could lead to unintended (adverse) effects, particularly as most... 

Nitrate is not a new problem. Excessive concentrations were recorded in many domestic wells in a survey conducted 100 years ago. What is new is the public concern about nitrate. This arises from two medical conditions that have been linked to nitrate methaemoglobinaemia ( bine-baby syndrome ) in infants, and stomach cancer in adults. Both are serious conditions, so we need to examine possible links carefully, but we need to note that these conditions are not caused by nitrate but by the nitrite to which it may be reduced. Nitrate itself is harmless and is most notable from a medical standpoint as a treatment for phosphatic kidney stones. 

Summary of Lowest Observed Effect Levels for Key Lead-Induced Health Effects in Adults... 

BENZENESULFONIC ACID DERIVATIVES As has been discussed previously, substituted -alkylbenzene-sulfonylureas often possess the property of releasing bound insulin, thus sparing the requirement for insulin injections in adult-onset diabetes. A pyrimidine moiety, interestingly, can serve as a surrogate for the urea function. 

High concentrations of SO, can produce tempo-rai y breathing difficulties in asthmatic children and in adults who are active outdoors. Sulfur dioxide also can directly damage plants and has been shown to decrease crop yields. In addition, sulfur oxides can be converted to sulfuric acid and lead to acid rain. Acid rain can harm ecosystems by increasing the acidity of soils as well as surface waters such as rivers, lakes, and streams. Sulfur dioxide levels fell, on average, by 39 percent between 1989 and 1998. 

The plasma half-life of 6-MP after intravenous bolus injection is 21 min in children and is twofold greater in adults. After oral intake peak levels are attained within 2 h. 6-MP is used for the treatment of ALL and has shown certain activity in chronic myelogenous leukemia. The major side effects involve myelosuppression, nausea, vomiting, and hepatic injury. 

---