The Role of Pathology in Evaluation of Reproductive, Developmental, and Juvenile Toxicity

Bowman, Christopher J.; Halpern, Wendy G.

doi:10.1016/b978-0-12-821044-4.00031-5

Cited by 2 publications

(2 citation statements)

References 279 publications

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“…Presence of a single embryo or visible former implantation site is considered evidence of pregnancy. If no visible signs of pregnancy, the uterus is further examined by staining with 10% ammonium sulfide to visualize former implantation sites (Bowman & Halpern, 2022). However, compounds that inhibit implantation may do so prior to a decidualization reaction and therefore do not stain for implantation sites even though fertilization and blastocyst formation occur normally (Beltrame et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor

Bowman,

Campion,

Catlin

et al. 2024

Birth Defects Research

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BackgroundAbrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery.MethodsThis second study had 4 groups of 20 females each administered abrocitinib (0, 3, 10, or 70 mg/kg/day) 2 weeks prior to cohabitation through gestation day (GD) 7. In addition, 2 groups of 20 rats (0 or 70 mg/kg/day) were dosed for 3 weeks followed by a 4‐week recovery period before mating. All mated females were evaluated on GD 14.ResultsNo effects were observed at ≤10 mg/kg/day. At 70 mg/kg/day (29x human exposure), decreased pregnancy rate, implantation sites, and viable embryos were observed. All these effects reversed 4 weeks after the last dose.ConclusionsBased on these data and literature on the potential role of JAK signaling in implantation, we hypothesize that these effects may be related to JAK1 inhibition and, generally, that peri‐implantation effects such as these, in the absence of cycling or microscopic changes in nonpregnant female reproductive tissues, are anticipated to be reversible.

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Section: Discussionmentioning

confidence: 99%

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor

Bowman,

Campion,

Catlin

et al. 2024

Birth Defects Research

Self Cite

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“…70 % of cough symptoms mostly subside within 24 -48 h after medication. In recent years, FGLOL has been found to be effective in the treatment of coughvariant asthma, and is intended to be used for symptomatic treatment of asthma indications in children [8,9]. The clinical medication cycle is relatively short, but it covers a wide range in children, from 1 year old to 12 years old.…”

Section: Discussionmentioning

confidence: 99%

Toxicological testing of Fuganlin Oral Liquid on young Sprague Dawley rats

Guo¹,

Huang²,

Lei³

et al. 2023

Trop. J. Pharm Res

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Purpose: To further evaluate the safety of Fuganlin Oral Liquid (FGLOL) for clinical application by conducting toxicological tests in young rats. Methods: Based on the clinical dose for infants aged less than 1 year, 4-day-old Sprague-Dawley (SD) rats were orally administered FGLOL3.88, 11.64 and 38.75 g crude drug/kg for 18 days, followed by a 3-week withdrawal. This was followed by evaluating the effect of FGLOL on various growth and development indicators, nerve reflex function and spontaneous behavior of the rats. Based on the clinical dose for children aged 1 - 6 years, 15-day-old rats were orally administered FGLOL3.88, 11.64 and 38.75 g crude drug/kg for 31 days, followed by a 3-week withdrawal in order to evaluate the impact of the FGLOL on the development of reproductive organs and nervous systems in young rats. The effects of FGLOL on the safety of young rats were judged based on ophthalmic examination, physical examination, spontaneous behavior and other developmental effects. Results: FGLOL did not cause animal death, and no significant toxicological changes were observed in the body weight, growth and development, and behavior of the young rats (p < 0.05). No observed adverse effect level (NOAEL) even after administering the higher dose at each stage. However, the results at each stage showed that oral administration of a large amount of FGLOL had a greater effect on normal food consumption of the rats (p < 0.05). Conclusion: The findings indicate that Fuganlin Oral Liquid, a traditional Chinese medicine formulation, is safe in rats. However, clinical trials are required to acertain its safety in humans.

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The Role of Pathology in Evaluation of Reproductive, Developmental, and Juvenile Toxicity

Cited by 2 publications

References 279 publications

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor

Toxicological testing of Fuganlin Oral Liquid on young Sprague Dawley rats

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