Commentary: Update on Animal Models for NTP Studies

King-Herbert, Angela; Sills, Robert C.; Bucher, John R.

doi:10.1177/0192623309356450

Cited by 46 publications

(35 citation statements)

References 5 publications

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“…Department of Health and Human Services uses this strain in its 2-year studies, after in-depth discussions on the suitability and advantages of the SD rat over previously used strains [23].…”

Section: The National Toxicology Program Of the Usmentioning

confidence: 99%

Rat feeding studies with genetically modified maize - a comparative evaluation of applied methods and risk assessment standards

Meyer¹,

Hilbeck²

2013

Environ Sci Eur

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A 2-year rat feeding study with genetically modified NK603 maize sparked an international scientific and public debate as well as policy responses by the European Commission. The European Food Safety Authority (EFSA) evaluated the study as defective based on conceptual and methodological shortcomings by retroactive application of the recommendations of its recent guidance on 90-day feeding studies. Our comparative analysis of the three relevant NK603 publications, including a 90-day feeding study of Monsanto, showed that all of them satisfy or fail to satisfy the EFSA evaluation criteria to a comparable extent; the rejection of only one of the papers is, thus, not scientifically justified. We also show that EFSA's criteria are not standard practice in 21 other rat feeding studies lasting at a minimum of 12 months. The review reveals critical double standards in the evaluation of feeding studies submitted as proof of safety for regulatory approval to EFSA. We specifically argue that the current approach to declare statistically significant differences between genetically modified organisms and its parents as 'biologically irrelevant' based on additional reference controls lacks scientific rigor and legal justification in the European Union (EU) system. Only recently, the EU authorities started building up an implementing system based on its own legislation and supportive of the EU approach to risk assessment in the context of technology assessment. Until these issues are resolved, we do not expect that neither the public nor the scientific debate will subside.

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Section: The National Toxicology Program Of the Usmentioning

confidence: 99%

Rat feeding studies with genetically modified maize - a comparative evaluation of applied methods and risk assessment standards

Meyer¹,

Hilbeck²

2013

Environ Sci Eur

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“…Consequently, the NTP decided to switch to the Harlan Sprague Dawley (Hsd:Sprague Dawley SD) rat for future bioassays (King-Herbert et al, 2009). Nine previous NTP bioassays had been performed using female Harlan SD rats to evaluate the chronic toxicity and carcinogenicity of dioxins and dioxin-like compounds.…”

Section: Introductionmentioning

confidence: 99%

Comparison of NTP Historical Control Tumor Incidence Rates in Female Harlan Sprague Dawley and Fischer 344/N Rats

et al. 2010

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The National Toxicology Program (NTP) has historically used Fischer 344/N (F344/N) rats for the majority of its bioassays. In 2008 the NTP switched rat strains and began using Harlan Sprague Dawley (SD) rats. The NTP had previously used female SD rats in nine bioassays. This article compares historical control (HC) tumor incidence rates from these nine SD rat studies with HC tumor rates from matched NTP F344/N rat bioassays to identify similarities and differences. Matching on sex, laboratory, diet, and route led to nine comparable F344/N rat studies. Our analyses revealed statistically significant strain differences in incidence rates for clitoral gland adenoma, mammary gland fibroadenoma, mammary gland carcinoma, thyroid gland C cell adenoma, and mononuclear cell leukemia. These represent five of the seven most common tumor types among female SD and F344/N rats in the NTP HC database. When vehicle was included as an additional matching criterion, the number of comparable F344/N rat studies dropped to four, but similar results were obtained. Among female F344/N rats, the incidence of pituitary gland pars distalis adenoma was significantly higher when the vehicle was corn oil as compared to water, suggesting a possible vehicle effect.

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“…For reproductive toxicity studies in rats, at least 10 live pups per litter is desirable in order to evaluate any adverse effects on fetal development appropriately and therefore the litter size produced by the 8-weekold males was considered inadequate. King-Herbert et al (2010) reported that Wistar Han rats that were time-mated at the animal supplier and then shipped into the National Toxicology Program facility produced small litter sizes (8.2 pups/litter). In the current study, 12-week-old males produced litter sizes >10 pups/litter and there are no concerns for evaluation for the adverse effects on fetuses.…”

Section: Discussionmentioning

confidence: 99%

Effects of male sexual maturity of reproductive endpoints relevant to DART studies in Wistar Hannover rats

et al. 2014

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-Wistar Hannover rats have been utilized as one of major strains in regulatory toxicology studies. This study was performed to verify the appropriate age of male sexual maturity in the development and reproductive toxicity (DART) study in Wistar Hannover rats (RccHan:WIST) by comparing reproductive endpoints between 8, 10 and 12 weeks of ages. Although fertility showed a tendency toward decrease in 8-week-old males, copulation index was not different among three ages. Testis weights reached a plateau at 10 weeks of age, whereas weights of other reproductive organs developed until 12 weeks of age. Indices of spermatogenesis (sperm motility, number of sperm in the epididymis and testis and contents of morphologically abnormal sperm) showed age-related progress and did not fully develop except for 12-week-old. For histology, epididymal tubules in 8-week-old animals showed immaturity with tall epithelium. At cesarean section, dams mated with 8-week-old males showed high incidence of preimplantation loss and the number of live fetuses was less than 10. In conclusion, although reproductive performance attained maturity by age of 10 weeks, spermatogenesis was not fully established at 10-weekold, which could result in a low fertility index. Therefore, we recommend that Wistar Hannover male rats at 12-week-old or older are used to conduct DART study properly and evaluate any adverse effects on dams and embryo-fetal development.

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Commentary: Update on Animal Models for NTP Studies

Cited by 46 publications

References 5 publications

Rat feeding studies with genetically modified maize - a comparative evaluation of applied methods and risk assessment standards

Rat feeding studies with genetically modified maize - a comparative evaluation of applied methods and risk assessment standards

Comparison of NTP Historical Control Tumor Incidence Rates in Female Harlan Sprague Dawley and Fischer 344/N Rats

Effects of male sexual maturity of reproductive endpoints relevant to DART studies in Wistar Hannover rats

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