ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01144.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01145.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01146.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01147.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01148.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The qualitative and quantitative evaluation of risk in developmental toxicology has been discussed in several recent publications.(1–3) A number of issues still are to be resolved in this area. The qualitative evaluation and interpretation of end points in developmental toxicology depends on an understanding of the biological events leading to the end points observed, the relationships among end points, and their relationship to dose and to maternal toxicity. The interpretation of these end points is also affected by the statistical power of the experiments used for detecting the various end points observed. The quantitative risk assessment attempts to estimate human risk for developmental toxicity as a function of dose. The current approach is to apply safety (uncertainty) factors to die no observed effect level (NOEL). An alternative presented and discussed here is to model the experimental data and apply a safety factor to an estimated risk level to achieve an “acceptable” level of risk. In cases where the dose‐response curves upward, this approach provides a conservative estimate of risk. This procedure does not preclude the existence of a threshold dose. More research is needed to develop appropriate dose‐response models that can provide better estimates for low‐dose extrapolation of developmen

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01149.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Longitudinal data were analyzed for seminal characteristics of rhesus monkeys and beagles. The monkeys were exposed to DBCP; the beagles were exposed to acute or chronic whole body gamma irradiation. The semen was analyzed for volume and sperm concentration. Sperm were measured for percent motility, swimming speed, and head dimensions. Abnormalities of the sperm tail were also noted. All treatments resulted in measurable effects on the semen parameters. Sperm production, as evaluated by seminal sperm concentration or total sperm numbers in the ejaculate, was as informative of testicular toxicity as any other parameter or combination of parameters. A consistent finding was that changes in sperm output occurred concomitantly with changes in sperm motility.

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01150.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The problem of extrapolating effects of reproductive toxins on experimental animals to predict the doses that would produce infertility in human males is discussed using published data on effects of testosterone and estradiol on sperm production in the rat, rabbit, rhesus monkey, ram, stallion, and humans. This analysis indicates that calculation of the dose of testosterone that reduces human sperm counts by a given percentage is best done using the dose administered to laboratory animals expressed on the basis of body weight, as opposed to some other parameter such as body surface area. A survey of the available data in the literature indicates the incompleteness of the data set and the specific information needed to improve the basis for extrapolation. Nevertheless, we can predict from studies on laboratory animals the dose of testosterone necessary to reduce sperm counts in humans within a factor of 2.

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01151.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Exogenous agents may perturb development during the embryonic period and adversely affect the formation of organs. However, adverse effects on development are not limited to the embryonic period nor are the manifestations restricted solely to outright gross structural malformation, but may instead be expressed as a decrement or aibberration of postnatal function. Susceptibility to altered development may extend well into the postnatal period. Studies of functional parameters in several organ systems have demonstrated the broad‐based susceptibility, subtlety of expression and potential of long‐lasting effects of altered development assessed by physiologic assays. Adverse effects on functional development, whether in the CNS, reproductive, gastrointestinal, genitourinary, respiratory, or immune systems, etc., merit continuing investigation. From the viewpoint of risk estimation and hazard detection, evaluations of postnatal functional parameters may be relevant for several reasons. First, such parameters may serve as low‐dose triggers. Second, they may be useful as a focal point for epidemiological studies. Finally, a more thorough understanding of the degree and magnitude of such postnatal functional deficits is needed since an adverse maternal effect may be transient, considered acceptable, or unperceived, but the effect on the conceptus may be permanent and severe. The immune and respiratory systems are discussed as two examples of how subtle and protean adverse effects on functional development m

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01152.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Screening methods are used for hazard identification. Assays for heritable mutations in mammals are used for the confirmation of short‐term test results and for the quantification of the genetic risk. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of the expected frequency of genetic changes induced per unit dose. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The indirect method uses experimental data only for the calculation of the doubling dose. The quality of the risk estimation depends on the assumption of persistence of the induced mutations and the ability to determine the current incidence of genetic diseases. The difficulties of improving the estimates of current incidences of genetic diseases or the persistence of the genes in the population led us to the development of an alternative method, the direct estimation of the genetic risk. The direct estimation uses experimental data for the induced frequency for dominant mutations in mice. For the verification of these quantifications one can use the data of Hiroshima and Nagasaki. According to the estimation with the direct method, one would expect less than 1 radiation‐induced dominant cataract in 19,000 children with one or both parents exposed. The expected overall frequency of dominant mutations in the first generation would be 20–25, based on radiation‐induced dominant cataract mutations. It is estimated that 10 times more recessive than dominant mutations are induced. The same approaches can be used to determine the impact of chemical m

ISSN:0272-4332    

DOI:10.1111/j.1539-6924.1988.tb01153.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY