Angle and McIntire Studied the Best Way to Test for Lead

In this study, which is dated two years after the previous “Air Lead” study, Dr. Carol Angle and Dr. Matilda McIntire continued to examine the differing methods of whole lead vs RBC lead testing as well as blood enzymes. In this second study, however, they looked at the RBC enzymes 2,3-diphosphoglycerate (2,3-DPG) and Na/K ATPase instead of G-6-PD. 2,3-DPG is a chemical that interacts with hemoglobin, which carries oxygen in the blood, causing the hemoglobin to release more oxygen in tissues that are more active and therefore in need of more oxygen (Davies and Moores, 2010, p. 105-106). Na/K ATPase is a common protein that maintains the gradient of sodium (Na) concentrated outside of cells and potassium (K) concentrated inside of cells using the cellular fuel ATP to keep the pattern. This gradient of concentration is the basis for many important cellular processes, particularly in neurons. Lowered levels of either protein correlating with higher lead levels would therefore represent a toxic condition for the RBCs. Angle and McIntire hypothesized that they would find a better correlation to enzyme activity with red cell lead than with plasma lead levels due to the majority of lead in the blood being located on red blood cells (1974, p. 133).

Angle and McIntire found in their examination of the blood of Omaha suburban and urban high school students, whom they separated into treatments of urban, suburban, and urban G-6-PD deficient, that their results were mixed between the two enzymes. The 2,3-DPG statistical analyses seemed to show a higher correlation between red blood cell lead and 2,3-DPG than plasma lead levels, but further analyses showed this to be conflated with hemoglobin (Angle and McIntire, 1974, p. 135). This makes sense with current knowledge of this protein which is that 2,3-DPG levels’ effect of causing oxygen unloading “is of little functional importance and this metabolic pathway remains a biochemical oddity” (Davies and Moores, 2010, p. 106). This enzyme’s activity therefore did not reflect their hypothesis. For Na/K ATPase, however, their results were more supportive.

Na/K ATPase depletion to just 60% of the membrane was found in samples above and below a red cell lead level threshold (Angle and McIntire, 1974, p. 136). Angle and McIntire said that this finding “suggests an enzymatic sensitivity even at normal urban levels of blood lead” (1974, p. 136). Their definition of normal was their threshold of 40 μg/dL or micrograms per deciliter. This supported their hypothesis that red blood cell lead levels are a better indicator than whole blood cell lead, and they concluded that “significant biologic effects relate to lead at normal urban blood levels of lead” (Angle and McIntire, 1974, p. 136). This conclusion supported a general trend that was occurring in the second half of the 20th century in which a growing understanding of lead’s negative effects on the body at lower and lower levels led to lowering the level of lead considered safe. 

Starting in the early 1970s, when Angle and McIntire created this study, it became clear that lead poisoning had effects at levels below 40 μg/dL, then in 1978 to 30 μg/dL, then in 1985 to 25 μg/dL, and lastly in 1991 to 10 μg/dL (Landrigan, 2000, p. 530). This lowering of lead levels did not occur purely because of scientific data, however, “the new definitions reflect the culture’s transformed attitude toward the built environment and a new, but deeply felt, cultural aversion to preventable risks” according to Christian Warren in his celebrated monograph Brush with Death: A Social History of Lead Poisoning (2001, p. 5-6). “Aversion to preventable risks” can also be termed as the ‘precautionary principle.’ In environmental justice circles, this principle is the idea that if something is potentially dangerous it should be determined safe first then used, not used until proven dangerous. This stems from the recognition that human life is more precious than the potential advancement associated with a new advancement. This seems as obvious as ‘innocent until proven guilty’ but, similar to that judicial saying, it is more difficult in practice. The difficulty is mainly due to industry interests that would prefer to start making profits off new discoveries immediately, as we shall discuss in the next section.

Angle, C. R., & McIntire, M. S. (1974). Red Cell Lead, Whole Blood Lead, and Red Cell Enzymes. Environmental Health Perspectives 7, 133-137.

Davies, A., & Moores, C. (2010). 8 - Carraige of Gases by the Blood and Acid/Base Balance. In A. Davies, & C. Moores (Eds.), The Respiratory System (Second Edition) (pp. 99-118). Churchill Livingstone.

Landrigan, P. J. (2000). Pediatric lead poisoning: is there a threshold? Public Health Reports, 115(6), 530.

Warren, C. (2001). Brush with Death: A Social History of Lead Poisoning. Baltimore: Johns Hopkins University Press.