Collaborative work on evaluation of ovarian toxicity 16) Effects of 2 or 4 weeks repeated dose studies and fertility study of Chlorpromazine hydrochloride in rats

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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“… 10 Berger et al (2005), 84 Izumi et al (2009), 164 Rehm et al (2007), 208 Westwood (2008), 214 Yuan and Foley (2002)…”

Section: Morphologymentioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Alison²,

et al. 2014

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“…Of note, the prevalence of hematological disorders, such as impairments in platelet, white blood cell functions, hemoglobin levels, and coagulation/fibrinolytic activity, has progressively increased due to the toxic effects of existing drugs developed from obsolete animal models [26] , [38] . Accordingly, some first- and second-generation antipsychotic medications such as chlorpromazine (CPZ) and clozapine respectively, used in the treatment of different psychotic disorders such as schizophrenia and bipolar disorder, have been associated with several adverse effects, notably promoting hematological disorders [37] , [43] , [49] , [50] . Hematological perturbations including any changes in the normal functioning of blood cells, including alterations in their numbers, size, or function, have been linked to chemical exposure and long-term use of some drugs [14] , [22] , [31] .…”

Section: Introductionmentioning

confidence: 99%

Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10

Obukohwo,

Ben-Azu,

Nwangwa

et al. 2024

Toxicology Reports

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“…Administration of an estrogen analogue ethinylestradiol or estradiol benzoate to young adult rats resulted in estrogenic effects on the vagina and uterus and increases in early stage follicles along with apoptotic corpora lutea or large basophilic corpora lutea in the ovary (Andrews et al 2002; Ferre et al 2013), the ovarian features of which do not match those of early reproductive senescence. Finally, administration of centrally acting agents such as chlorpromazine and sulpiride to young adult rats has been shown to produce not only increased large follicles in the ovary but also epithelial mucification and/or atrophy in the vagina (Ishii et al 2009; Izumi et al 2009). These vaginal patterns of change are inconsistent with the state of persistent estrus.…”

mentioning

confidence: 99%

Using Histopathologic Evidence to Differentiate Reproductive Senescence from Xenobiotic Effects in Middle-aged Female Sprague-Dawley Rats

2015

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The female reproductive cycle is orchestrated by cyclical and coordinated hormonal changes under the direction of the hypothalamic-pituitary-gonadal (HPG) axis. Any disruption of the HPG axis may lead to functional and structural alterations in the female reproductive system. Test article-related disturbances in the estrous cycle can be recognized in nonclinical toxicity studies by staging the cycle based on microscopic evaluation of female reproductive organs. In chronic rat toxicity studies, an additional complication is the development of reproductive senescence, which is associated with natural alterations in the reproductive cycle leading to changes in the female reproductive system that can potentially be confused with test article effects. The current article describes the features of persistent estrus, one stage of reproductive senescence, in middle-aged Sprague-Dawley rats and discusses elements to help differentiate senescence from induced effects.

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Collaborative work on evaluation of ovarian toxicity 16) Effects of 2 or 4 weeks repeated dose studies and fertility study of Chlorpromazine hydrochloride in rats

Cited by 11 publications

References 12 publications

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Nonproliferative and Proliferative Lesions of the Rat and Mouse Female Reproductive System

Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10

Using Histopathologic Evidence to Differentiate Reproductive Senescence from Xenobiotic Effects in Middle-aged Female Sprague-Dawley Rats

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