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Young children may be more susceptible to environmental chemicals that are toxic because their organs are not fully developed and their skin is more permeable to substances which are absorbed by the body. This includes agents that are applied directly to the skin, such as over-the-counter skin care products. A study was conducted to determine mothers' practices for bathing their newborn infants (45 infants were included) and to determine the amount of chemical exposure from over-the-counter skin care products. The average one-month-old baby was bathed four times a week, and its hair was shampooed three times a week. The average newborn had eight skin care products applied, resulting in exposure to an average of 48 chemicals. Forty-seven percent of mothers used baby powder, which the authors discourage because ingestion of it by infants can be fatal. Seventy-eight percent of the babies developed a rash, but only 45 percent of the mothers sought medical advice. Thirty-seven percent of the mothers reported the rash to be the result of a change in bathing practice or product use. Therefore, the study shows that newborns are exposed to a large number of products. Twelve percent of the chemicals found in over-the-counter skin care products for newborns have toxicity ratings that are considered moderately or very toxic, if ingested. Information is not available on the toxicity from absorption through the skin. Also, toxicity information was not available for 64 percent of the chemicals present in over-the-counter skin care products for newborns. The level of absorption and possible toxicity of these products in infants should be examined. (Consumer Summary produced by Reliance Medical Information, Inc.)

Despite a wide interindividual variation of cytochrome P-450 1A2 (CYP1A2) activity, genetic polymorphism of CYP1A2 has not been reported. By amplification of exons of CYP1A2 by polymerase chain reaction in eight Chinese subjects, the polymerase chain reaction products were directly sequenced. One subject showed heterozygous C2866→G (Phe21→Leu) polymorphism. DNA from 157 Chinese subjects (104 polychlorinated biphenyl-exposed subjects and 53 control subjects) was screened for polymorphism by single-strand conformation polymorphism method and MboII endonuclease digestion. Only 1 of 157 samples showed another heterozygous C2866→G mutation. The subject was previously exposed to polychlorinated biphenyl and showed a value of 3.5% in the caffeine breath test. The value is not significantly higher than the mean value of polychlorinated biphenyl-exposed subjects (3.12 ± 0.29%, mean ± S.E.M.). The incidence of the point mutation in these Chinese subjects is less than 1%. The prevalence of the F21L mutation in other ethnic groups and its effect on the metabolic activity of CYP1A2 remain to be further evaluated.

The optimal conditions for performing the caffeine CO2breath test (CBT) were investigated in smokers and nonsmokers. Caffeine labeled with13C or 14C in all three (1, 3, and 7) methyl groups or specifically in the 1-, 3-, or 7-methyl groups were orally administered to healthy adults and the expiration of labeled CO2was measured for 8 or 24 hr. The absolute rate of labeled CO2excretion from trilabeled caffeine was proportional to the dose up to 3 mg/kg in all subjects. In smokers, the rate of labeled CO2excretion averaged twice that in nonsmokers at all doses. A correlation was observed between the 2-hr cumulative CO2excretion from trilabeled caffeine and the apparent oral metabolic clearance rate (MCR) of caffeine (r = 0.90). Monolabeled CBTs in smokers and nonsmokers demonstrated that 80% ± 4% of labeled CO2expired in the breath during the first 2 hr of a trilabeled CBT was derived from the 3 position; at 6 to 8 hr equal amounts were derived from the 3 and 7 positions. Little N-demethylation was observed from the 1 position at any time during the 8-hr test. The results indicate that the 2-hr cumulative excretion of labeled CO2could be used to accurately predict the metabolic clearance rate of caffeine and is the best CBT parameter for detecting the effect of smoking on caffeine N-demethylation. The data suggest that the primary routes of caffeine metabolism are 3-N-demethylation and ring hydroxylation and confirm that caffeine metabolites are N-demethylated primarily in the 3 and 7 positions.Clinical Pharmacology and Therapeutics (1982) 32, 261–269; doi:10.1038/clpt.1982.157