Adverse Effects in Humans and Animals of Prenatal Exposure to Selected Therapeutic Drugs and Estimation of Embryo-Fetal Sensitivity of Animals for Human Risk Assessment

Khera, K. S.

doi:10.1007/978-1-4615-7314-2_10

Cited by 12 publications

(2 citation statements)

References 411 publications

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“…For both reproductive and developmental effects, animals prove to be highly relevant surrogates for humans (Clements Associates, 1981). Although a few exceptions have been reported, generally the types of effects found in animals are similar to those reported in exposed humans (Khera, 1984). For instance, chlordecone produced reduced litter size in mice (Huber, 1965) and reduced normal sperm counts in men (Cohn et al, 1978).…”

Section: The Concept Of Targetmentioning

confidence: 79%

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Perspectives On Reproductive and Developmental Toxicity

1986

Toxicol Ind Health

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Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents. Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproductive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposure and the stage of the cycle at which it occurs. Signs of reproductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction (Amann, 1982) and/or development (Johnson, 1984). Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any aspect of reproduction and development. Data currently available establish that these state-of-the-art tests conducted in laboratory animals are often highly predictive of the type of adverse effect a particular chemical will have in humans, as well as the exposure level at which it will occur. By adding a modest safety factor to the no-observed-effect-level of well-executed animal studies, safe human exposure levels can be established. Responsibility for determining the intrinsic hazard potential and the risk estimate of exposure rests with manufacturers and major users of occupational and other environmental chemicals. As public awareness of reproductive and developmental hazards has increased in recent years, it has come to be understood that some chemicals have a predilection for causing reproductive impairment and/or disrupting development in the absence of other toxicity. Such substances must be identified to establish safe exposure levels and to determine the types of effects to be expected, should excessive human exposure occur. The setting of safe exposure levels is necessary both from the standpoints of ensuring public safety and avoiding product liability.

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Section: The Concept Of Targetmentioning

confidence: 79%

“…Similarities in the types of effects produced by chemicals on in utero development exist also, but perhaps not quite as consistently. About 80-85% of the agents known to perturb human embryonic development also have been demonstrated to produce similar defects in animal embryos (Khera, 1984).…”

Section: The Concept Of Targetmentioning

confidence: 99%

Perspectives On Reproductive and Developmental Toxicity

1986

Toxicol Ind Health

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A population-based case-control teratologic study of acetylsalicylic acid treatments during pregnancy

Czeizel

Rockenbauer

Mosonyi

2000

Pharmacoepidem. Drug Safe.

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Developmental Toxicology

DeSesso¹,

Willhite²

2009

General, Applied and Systems Toxicology

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The full range of development that is subject to injury—be it a consequence of maternal disease, nutritional excess or deficiency, xenobiotic or radiation exposure or as a result of infectious agents ‐ begins with the primordial germ cells of the individual's parents, proceeds through gametogenesis and concludes at the end of a person's natural life. The present chapter is focused upon understanding adverse reproductive outcome as a result of embryonic exposure to selected environmental chemicals and therapeutic drugs. The chapter begins with examples from ancient history and contemporary motion pictures, from the scientific literature and from the popular press. The text explains some of the fundamental steps taken and the genes involved in establishment of the vertebrate body plan. Examples are provided to illustrate how failure of proper gene expression and coordination at precise embryonic stages is responsible for the pathogenesis of specific congenital malformations. Consolidated presentations of experimental teratology and developmental toxicity studies are provided, along with the steps required to interpret the results of those studies in the context of human health risk assessment. The chapter contrasts the risks associated with misdirected speculation, irrational public fear and chemical rumors compared to the real public health consequences associated with maternal disease (e.g., alcoholism, diabetes, obesity) and nutritional deficiency (e.g., vitamin A, folates). The chapter concludes with the fundamental role of inappropriate embryonic gene expression in carcinogenesis. Increased understanding of genomic regulatory circuits in embryos has contributed to increased understanding of normal cell regeneration and turnover and how disturbances in those circuits lead to neoplasia and other degenerative diseases in children and adults.

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Adverse Effects in Humans and Animals of Prenatal Exposure to Selected Therapeutic Drugs and Estimation of Embryo-Fetal Sensitivity of Animals for Human Risk Assessment

Cited by 12 publications

References 411 publications

Perspectives On Reproductive and Developmental Toxicity

Perspectives On Reproductive and Developmental Toxicity

A population-based case-control teratologic study of acetylsalicylic acid treatments during pregnancy

Developmental Toxicology

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