Comparison of maternal and fetal toxic dose responses in mammals

Rogers, John M.

doi:10.1002/tcm.1770070310

Cited by 17 publications

(2 citation statements)

References 52 publications

(16 reference statements)

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“…The experimental designs of these studies were quite inadequate to the stated goal of examining the predictability of A/D ratios across mammalian species because of the selection of submammalian endpoints. Other studies (Rogers, 1987;Rogers et al, 1988) reported that in response to the fungicide dinocap, the mouse had an A/D ratio of -16, whereas the rat and hamster had A/D ratios of 1 .…”

Section: ;mentioning

confidence: 98%

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Developmental Toxicity: Extrapolation Across Species

Hoar

1995

Journal of the American College of Toxicology

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There is a pervasive lack of understanding about the definition of a developmental toxicant and the experimental design necessary to differentiate between maternal toxicants and those uniquely, i.e., selectively, hazardous to the conceptus. Thus, the acceptance of the adult-to-developmental (A1D) ratio and its ability to identify those compounds uniquely hazardous to the conceptus has been compromised, as has the extrapolation of hazard across species. The failure to establish a shared understanding is discussed, together with the role of an in vitro screen for determining the A/D ratio. The addition of an environmental exposure factor permitting the extrapolation of hazard assessment across species and the estimation of potential human developmental toxicity is detailed.

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Section: ;mentioning

confidence: 98%

“…It is not surprising that doubts have been expressed concerning the constancy of the A/D ratio calculated across species (Daston and D'Amato, 1989;Daston et al, , 1991Rogers, 1987;Rogers et al, 1988;Schardein, 1987). However, good examples of different ratios for the same chemicals tested in standard evaluations are rare or nonexistent.…”

Section: ;mentioning

confidence: 99%

Developmental Toxicity: Extrapolation Across Species

Hoar

1995

Journal of the American College of Toxicology

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The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster

et al. 1988

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The fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD-1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague-Dawley rat and Syrian golden hamster, and adult-to-developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was administered by gavage to pregnant rats on gestation days 7-20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7-14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)

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Examination of a rodent limb bud micromass assay as a prescreen for developmental toxicity

Wise

Clark

Rundell³

et al. 1990

Teratology

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The mouse limb bud micromass assay is one of many short-term tests proposed as preliminary screens for potential developmental toxicity. Previous efforts to validate this assay have used too few "nonteratogens." The purpose of this study was to examine additional compounds, most of which, based on the literature, were perceived to have low potential for developmental toxicity in vivo. In addition, a method of data analysis was sought that would identify selective developmental toxins in the micromass assay, i.e., those that are effective at dosages not maternally toxic. The concentration of each of 23 compounds that produced a 50% inhibition (IC50) of radiolabeled thymidine (T) and sulfate (S) incorporation was determined and used to calculate a T/S ratio. The T/S ratio may be a useful measure of developmental hazard, since T incorporation measures toxicity toward a general cell function (DNA synthesis) and S incorporation measures mainly toxicity toward a developmentally specific cell activity (chondroitin sulfate synthesis). All compounds tested produced T/S ratios of less than 2.0. Since 22 of these 23 compounds are classified as "nonteratogens" or nonselective developmental toxins in vivo, a low T/S ratio in this in vitro assay system may be capable of discriminating potential for developmental hazard in vivo.

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Comparison of maternal and fetal toxic dose responses in mammals

Cited by 17 publications

References 52 publications

Developmental Toxicity: Extrapolation Across Species

Developmental Toxicity: Extrapolation Across Species

The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster

Examination of a rodent limb bud micromass assay as a prescreen for developmental toxicity

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