Lead, sublethal toxicity

Sublethal toxicity tests that use species of relatively low sensitivity (z. e., fathead minnow) reduce the usefulness of both EEM Hazard Assessment Schemes to estimate potential effects observed in the field. Insensitive laboratory measurements can lead to an underestimation of potential field effects and reduce the strength of laboratory toxicity tests as good estimators of effects. 

Discharges of contaminant lead have resulted in increases in organism and human lead levels comparable to increases documented in environmental matrices, as indicated by a recent estimate of the natural level of lead in blood of preindustrial humans (0.016 fxg/dL or 0.8 n. This estimate is 175-fold lower than average blood lead levels in the United States (2.8 /ig/ dL or 140 nl and 600-fold lower than the recently (1991) revised Centers for Disease Control (CDC) action level of concern for early toxic effects in children (10 fig/dh or 480 n. The significance of these comparisons to public health is corroborated by numerous studies suggesting that there may be no lower threshold for sublethal toxicity in contemporary (i.e., lead-contaminated) humans. Those data also indicate that environmental lead concentrations that were previously considered innocuous may be deleterious to human health. 

No data were available on toxic or sublethal effects of lead to reptiles under controlled conditions. 

As mentioned previously, maternal and/or fetal stress associated with sublethal exposures to OP insecticides could lead to an increased incidence of abortions or pre-term births in intoxicated pregnant women and animals. Because of lower levels of detoxifying enzymes (i.e. paraoxonase), the fetus appears to be more susceptible to OP intoxication than adults, and developmental neurotoxicity and growth retardation have been associated with low-level, prenatal exposures of humans to OP insecticides (Desaiah, 1998 Eskanazi et ah, 2008 Peiris-John and Wickremasinghe, 2008). In addition to the maternal and fetal effects, OP insecticides can also have direct toxic effects on the placenta, possibly involving (depending on the species) AChE inhibition within the placental cholinergic system (Pelkonen et ah, 2006). 

It has been shown that T lymphocytes have AChE located on the plasma membrane, while B cells are esterase negative (Szelenyi et al, 1982). Thus, AChE inhibition by toxic agents in sublethal doses may play an important role in immunodeficiency following exposure to nerve gases. Zabrodskii et al (2003) showed inhibition of AChE in T cells and the decrease in the number of esterase-positive T lymphocytes (and, to a certain extent, in monocytes and macrophages) directly correlated with suppression of T cell-dependent antibody production and to the degree of DTH reduction, on exposure to dimethyl dichlorovinyl phosphate, sarin, VX, lewisite, tetraethyl lead, and dichloroethane. This presumably involves the loss of some functions by T... 

Daily exposure of rats, mice, or guinea pigs to certain organophosphates with sublethal doses can lead to severe toxicity during the first few days, but further exposure for 7-14 days can lead to development of tolerance. For example, daily dosing of DFP (0.5 mg kg s.c.) produces severe anticholines-... 

Five amides, 50(n=4,6), 55, 5 and 6(n=6), isolated from P. guineense were investigated by Candy and co-workers [10] with respect to their knockdown and lethal activity against adult houseflies, as well as the rates of recovery of M. domestica from the effects of sublethal doses of the amides. As with other insecticides, rapid and potent knockdown activity on topical application of the amides depends, apart from the intrinsic toxicities of the individual compounds, on their ability to penetrate the cuticle and relevant membranes en route to the site of action. Attempts to correlate knockdown activity in the P. guineense amide series with polarity on this basis seemed to show some inconsistencies, perhaps as a result of steric factors [10,102]. The rate of recovery from the effects of sub-lethal doses of insecticides is associated, inter alia, with processes that lead to removal of the toxicant, so that recovery from treatment with Piper amides embodying the methylenedioxyphenyl group, which retards the action of mixed function oxidases, is slower than recovery from the effects of the less stable aliphatic amides. 

Toxic and sublethal effects of lead and its compounds on birds held under controlled conditions vary widely with species, with age and sex, and with form and dose of administered lead. Several generalizations are possible decreased blood ALAD and increased protoporphyrin IX activity levels are useful early indicators of lead exposure lead shot and certain organolead compounds are the most toxic forms of lead nestlings are more sensitive than older stages and tissue lead concentrations and pathology both increase in birds given multiple doses over extended periods. Blood lead concentrations of lead-poisoned waterfowl may be reduced with initiation of disodium calcium ethylenediamine tetraacetate therapy however, ALAD levels remained depressed. 

In acute toxicity tests, the test organisms are exposed for a relatively short period in relation to their generation time. The acute effects recorded with such tests usually concern the survival of the test species, regardless of how mortality is evoked. In chronic tests, the test organisms are exposed for a significant part of their life cycle or the entire life cycle of one to several generations. The (sub)chronic effects primarily concern sublethal impacts such as reduced reproduction or growth, altered behaviour or development, which ultimately may also lead to increased mortality. 

The effect which originally defined the compound is the "shock which AT produces on i.v. injections into guinea pigs. Of activated, AT-containing rat plasma 3 ml/kg may be lethal. Purified hog AT is lethal at doses of 25 - 5o wg/kg (Bodammer, 1967). It is thus more toxic than histamine, even on a weight basis. The main adverse effect is bronchospasm which leads to asphyxia. When an animal has recovered from a sublethal dose a second injection of AT will have a much less severe or no bronchoconstrictor effect, i.e. the action on the bronchi is tachyphylactic. The constrictor action is preceded by a short period of respiratory stimulation which effect is not tachyphylactic (Bodammer and Vogt, 1967). 

As the global magnitude of lead contamination has been realized, it has raised new concerns about the chronic toxicity and sublethal effects of human lead exposures (NRC 1993 Smith and Flegal 1992b USEPA 1986). These concerns are substantiated by studies that have shown that there may be no lower threshold concentration for lead toxicity in contemporary humans (Bellinger et al. 1987, 1991 Dietrich et al. 1992, 1993a,b McMi-chael et al. 1988 Needleman et al. 1979, 1990 Schwartz 1994 Schwartz and Otto 1987 Wasserman et al. 1994). It should also be recognized that these concerns, while now well justified, were initially raised by C.C. Patterson three decades ago (Patterson 1965). 

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