Toxicity, reproductive

The reproductive toxicity is subdivided into two quite different properties  

substances which can damage the development of the unborn child 

substances which can impair fertihty = here the acronym Rp is used 

Substances are classified as toxic to reproduction if they can cause developmental damage under conditions where no maternal toxicity can be observed. In order to prevent abnormal animal experiments, no higher dosage than the limit threshold of 1000 mg kg (oral) should be tested. On the other hand classification has been done using dosages with a maternal toxicity, if the developmental effects were very severe and should be communicated. 

The graduation in the category one to three follows the usual system mentioned in Section 3.3.1. Background information is presented in Section 2.6. 

In this classification system, reproductive toxicity is subdivided under two main headings  

Some reproductive toxic effects cannot be clearly assigned to either impairment of sexual function and fertility or to developmental toxicity. Nonetheless, chemicals with these effects would be classified as reproductive toxicants with a general hazard statement. 

Any effect of chemicals that would interfere with sexual function and fertility. This may include, but not be limited to, alterations to the female and male reproductive system, adverse effects on onset of puberty, gamete production and transport, reproductive cycle normality, sexual behaviour, fertility, parturition, pregnancy outcomes, premature reproductive senescence, or modifications in other functions that are dependent on the integrity of the reproductive systems. 

Adverse effects on or via lactation are also included in reproductive toxicity, but for classification purposes, such effects are treated separately (see 3.7.2.1). This is because it is desirable to be able to classify chemicals specifically for an adverse effect on lactation so that a specific hazard warning about this effect can be provided for lactating mothers. 

For the purpose of classification for reproductive toxicity, chemical substances are allocated to one of two categories. Effects on sexual function and fertility, and on development, are considered. In addition, effects on lactation are allocated to a separate hazard category. 

Developmental toxicity, defined in its widest sense to include any adverse effect on normal development either before or after birth, has become of increasing concern in recent years. Developmental toxicity can result from exposure of either parent prior to conception, from exposure of the embryo or fetus in utero or from exposure of the progeny after birth. Adverse developmental effects may be detected at any point in the life span of the organism. In addition to stmcmral abnormalities, examples of manifestations of developmental toxicity include fetal loss, altered growth, functional defects, latent onset of adult disease, early reproductive senescence, and shortened life span (WHO/IPCS 2001b). 

The term reproductive toxicity is used to describe the adverse effects induced by a substance on any aspect of mammalian reproduction and covers all phases of the reproductive cycle, including impairment of male or female reproductive function or capacity and the induction of nonheritable adverse effects in the progeny such as death, growth retardation, structural and functional effects (EC 2003). 

The term reproductive toxicity is sometimes used exclusively to describe toxic effects on male and female sexual function and fertility. More commonly, and in this book, reproductive effects are considered to include adverse effects on sexual function and fertility in males and females as well as developmental toxicity. 

Human sexual function and fertility disorders include, e.g., spontaneous abortions, impaired spermatogenesis, menstrual disorders, impotence, and early menopause. 

Toxicological Risk Assessments of Chemicals A Practical Guide 

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The reproductive toxicity of some phthalate esters has been reviewed by the Commission of the European Communities (45). This review concludes that testicular atrophy is the most sensitive indicator of reproductive impairment and that the rat is the most sensitive species. 

F. M. Sullivan and co-workers. The Toxicology of Chemicals, Series Two Reproductive Toxicity, Vol. 1, Commission of the European Communities, Bmssels, Belgium, 1993. 

Reproductive Toxicity. No data are available that impHcate either hexavalent or trivalent chromium compounds as reproductive toxins, unless exposure is by way of injection. The observed teratogenic effects of sodium dichromate(VI), chromic acid, and chromium (HI) chloride, adininistered by injection, as measured by dose-response relationships are close to the amount that would be lethal to the embryo, a common trait of many compounds (111). Reported teratogenic studies on hamsters (117,118), the mouse (119—121), and rabbits (122) have shown increased incidence of cleft palate, no effect, and testicular degeneration, respectively. Although the exposures for these experiments were provided by injections, in the final study (122) oral, inhalation, and dermal routes were also tried, and no testicular degeneration was found by these paths. 

Two-generation mammalian reproductive toxicity study or a less comprehensive test. 

BASE SET Mutagenicity Toxicity to reproduction Toxicity to algae Acute daphnia and fish toxicity Abiotic and readily biotic degradability Additional physico-chemical properties 1 t/annum or 5 t cumulative... 

Reproductive toxicity Rats/mice/rabbits Several months Potential to affect reproduction... 

Toxicologists tend to focus their attention primarily on c.xtrapolations from cancer bioassays. However, tlicrc is also a need to evaluate the risks of lower doses to see how they affect the various organs and systems in the body. Many scientific papers focused on tlic use of a safety factor or uncertainty factor approach, since all adverse effects other than cancer and mutation-based dcvclopmcnUil effects are believed to have a tlu cshold i.e., a dose below which no adverse effect should occur. Several researchers have discussed various approaches to setting acceptable daily intakes or exposure limits for developmental and reproductive toxicants. It is Uiought Uiat an acceptable limit of exposure could be determined using cancer models, but today tliey arc considered inappropriate because of tlircsholds. ... 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this system. 

No studies were located regarding reproductive toxicity in humans after oral exposure to endosulfan. 

In summary, although the available reproductive studies indicate that endosulfan has no adverse effects on reproductive performance in animals, severe adverse effects on male reproductive organs have been seen in rats and mice. This apparent discrepancy needs to be resolved with further research. Endosulfan may potentially cause reproductive toxicity in humans. 

Garcia-Reyero, N. and Denslow, N.D. (2006). Applications of genomic technologies to the study of organochlorine pesticide-induced reproductive toxicity in fish. Journal of Pesticide Science 31, 252-262. 

Reproductive Toxicity. Increased miscarriages were reported in one study of nurse-anesthetists exposed to trichloroethylene and other solvents (Corbett et al. 1974). A retrospective case-control study has should an approximate 3-fold increase in spontaneous abortion in women exposed to trichloroethylene and other solvents (Windham et al. 1991). Significant effects on sperm parameters were not observed in men occupationally exposed to trichloroethylene (Rasmussen et al. 1988). Adverse reproductive effects were not noted in humans that ingested water contaminated with trichloroethylene and other solvents (Byers et al. 

MATTISON D R, PLOWCHALK D R, MEADOWS M J, AL-JUBURI A Z, GANDY J and MALEK A (1990) Reproductive toxicity male and female reproductive systems as targets for chemical injury. Med Clin North Am. 74 (2) 391-411. 

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