Reproductive toxicity defined

Reproduction toxicity. Reproduction toxicity defined in the EC classification embraces two independent properties ... 

A slight toxic effect ( toxic defined as negative effects on health, growth, and reproduction) of the treated receiving water on the green alga Spiropyra species as a typical representative of the P-mesosaprobic zone was observed, when the test unit was subjected to the impact of 40 ppm secondary alkanesulfonates. 

Reproductive Toxicity. No information was located regarding reproductive effects in humans. Intermediate-duration inhalation studies in animals (Eustis et al. 1988 Kato et al. 1986) indicate that the testes may undergo degeneration and atrophy at high exposure levels, but the dose- response curve is not well defined. Further studies in animals to identify the threshold for this end point would... 

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). 

In the OECD Draft Guidance Document on Reproductive Toxicity Testing and Assessment (OECD 2004d), the term endocrine disruption is defined as above. 

The second objective of the hazard assessment concerns characterization of the identified hazards of a particular substance. Under REACH this means that the registrant must define so-called derived no-effect levels., abbreviated DNELs. With respect to human health, these values constitute exposure levels above which humans should not be exposed and below which risks for humans are considered controlled. The DNEL derivation is a complex process which comprises several conversion steps and the application of different assessment factors. In the case of reproductive toxicity, the registrant derives separate DNELs with respect to developmental toxicity on the one hand and to impairment of sexual function and fertility on the other hand. 

The health risk cannot be well defined because very little information is available on the toxicity of most commercial chemicals (Postel, 1987). According to the data published in 1984 by the National Research Council (National Research Council, 1984), very little is known about the toxicity of approximately 79% of commercial chemicals. Fewer than 10% were examined for carcinogenicity, mutagenicity, and reproductive toxicity (National Research Council, 1984). Obviously, nothing is known about pollutants that are byproducts of industrial processes and were never intended for commercial use. 

The chemical should not contain any chemicals that are a carcinogen or that are known to cause reproductive toxicity. Carcinogens are defined as those chemicals listed in the current edition of the Annual Report on Carcinogens, U.S. Department of Health and Human Services, National Toxicology Program. Chemicals known to cause reproductive toxicity, for example, are defined as those hsted by the state of California under the Safe Drinking Water and Toxic Enforcement Act of 1986 (Cah-fomia Code of Regulations, Title 22, Division 2, Subdivision 1, Chapter 3, Sections 1200, et seq.)... 

Numerous diagnostic methods have been developed to evaluate female reproductive dysfunction. Although these methods have rarely been used for occupational or environmental toxicological evaluations, they may be helpful in defining biological parameters and mechanisms related to female reproductive toxicity. If clinical observations link exposure to the reproductive effect of concern, these data will aid the assessment of adverse female reproductive toxicity. The following clinical observations include end-points that may be reported in case reports or epidemiological research studies. 

The RACB studies were designed by NTP to test chemicals for potential reproductive toxicity in males and females. In addition, this two-generation study design can be used to characterize the toxicity and to define the dose-response relationship for each chemical. 

Reproductive failure can be induced by environmental hazards at any level, although most types of infertility have not been linked to environmental factors. Since it is not ethically possible to observe or impose reproductive toxic exposures on human subjects, much of what we believe about the effects of putative toxins are based on the assumption that well-defined spontaneous reproductive failures are accurate surrogates for environmentally induced defects. Spontaneous reproductive failures, together with results from animal experiments, are used as models to predict or to understand the impact of reproductive toxicants on the human system. 

Many compounds have been implicated as male reproductive toxicants, but their sites and mechanisms of action are not well understood. The classification of male reproductive toxicants as direct or indirect is useful to help define the primary site of toxicity (Figure 6). A direct toxicant would primarily target the testicular cells, the excurrent duct system of the male reproductive tract, or mature spermatozoa. An indirect toxicant would cause reproductive toxicity by acting on hypothalamic/pituitary neuroendocrine controls or on extragonadal systems. Since the testis is subject to hormonal control and feedback loops, the action of indirect toxicants on endocrine homeostasis can ultimately damage testicular cell types. 

It is currently estimated that 15% of couples are clinically infertile (no conception after 1 year of unprotected intercourse) 30% of the infertility is attributable to the male partner, 20% to the female partner, 20% to a combination of problems in both partners, and another 30% is not explained by diagnosis of adverse conditions in either partner. Once conception has occurred, up to 80% of human pregnancies may be lost, most in the first trimester. Reproductive toxicity may be defined as an adverse effect on any aspect of male or female reproductive... 

The list of alternative tests for reproductive toxicity, at variable stage of development, is fairly long given the complexity of the reproductive cycle and the multiple cell types and functions involved. An official source of information on alternative test development is the website of the European Centre for the Validation of Alternative Methods (ECVAM) (http //ecvam-dbalm.jrc.ec. europa.eu/ updated to 15 June 2013). Forty methods are listed for the area of reproductive toxicity. They are split into four categories effects on female fertility (n = 8), effects on male fertility n= 10), developmental toxicity (n = 21), and genotoxicity-mutagenicity (n= 1). Only eight of these methods have been developed up to fully defined protocols that can be downloaded from the same website ... 

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