scholarly journals Postnatal Effects of Gestational and Lactational Gavage Exposure to Boric Acid in the Developing Sprague Dawley Rat

2020 ◽  
Vol 176 (1) ◽  
pp. 65-73
Author(s):  
AtLee T D Watson ◽  
Vicki L Sutherland ◽  
Helen Cunny ◽  
Lutfiya Miller-Pinsler ◽  
Johnathan Furr ◽  
...  
Keyword(s):  
Drinking Water ◽  
Boric Acid ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Clinical Findings ◽  
Feed Consumption ◽  
Sprague Dawley ◽  
Toxicological Effect ◽  
Sprague Dawley Rat ◽  
Boron Exposure

Abstract Human exposure to boron occurs primarily through diet and drinking water sources. Animal studies have found that reduced fetal weight following gestational exposure to boron (as boric acid) is the most sensitive toxicological effect. However, recent studies suggest that newborns in areas with elevated boron in drinking water may receive levels of exposure that exceed the U.S. EPA oral reference dose for B. Currently, there are no data to inform a boron risk assessment accounting for this developmental window. To address this knowledge gap, the National Toxicology Program evaluated developmental toxicity following pre- and postnatal boron exposure. Time-mated female Sprague Dawley (Hsd: Sprague Dawley SD) rats were administered 0–20 mg B/kg/day (as boric acid) via gavage from gestation day 6 to 21; offspring were dosed via gavage at the same respective dose level from postnatal day (PND) 1 to 28. There were no dose-related effects on dam bodyweight, bodyweight gain, or feed consumption. Clinical findings were limited to low incidences of umbilical hernia in the 20 mg B/kg pups which resolved by study completion. Pup plasma boron concentrations increased in dose-proportional manner and were similar between PND 4 and PND 28. Postnatal weight gain was significantly reduced at 20 mg B/kg, with male and female pups weighing 23% less than the controls on PND 28. These findings demonstrate that postnatal growth in the Sprague Dawley rat is sensitive to boron exposure and highlights the importance of evaluating the potential toxicity of agents with known human exposures during early life stages.

Developmental Toxicity of Orange B Given to Rats in Drinking Water

1995 ◽  
Vol 11 (4) ◽  
pp. 387-397 ◽  
Author(s):  
T.F.X. Collins ◽  
T.N. Black ◽  
D.I. Ruggles
Keyword(s):  
Drinking Water ◽  
Soft Tissue ◽  
Developmental Toxicity ◽  
Skeletal Development ◽  
Clinical Findings ◽  
Feed Consumption ◽  
Cesarean Sections ◽  
Maternal Weight ◽  
Fetal Size ◽  
Dose Levels

Orange B, a pyrazolone dye used to color frankfurter and sausage casings, was given in distilled drinking water to pregnant Osborne-Mendel rats throughout gestation. Assessed on the basis of fluid consumption, the dose levels of 0, 0.05, 0.1, 0.2, and 0.4% corresponded to daily Orange B consumption of 0, 67.5, 129.6, 266.6, and 532.3 mg/kg body weight, respectively. On gestation day 20, the females were euthanized and cesarean sections were performed. Throughout gestation, the treated animals consumed less fluid than did the controls, but the decreases were not dose-related. Feed consumption and maternal weight gain were not affected. No dose-related changes were seen in maternal clinical findings, implantations, fetal viability, or fetal size (weight and length). No compound-related effects were seen in sternebral development. Ossification of the interparietal bones was reduced at some dose levels, but the decreases were considered random because of absence of dose response. No dose-related effect was seen in the incidence of skeletal variations in fetuses or in the number of litters containing fetuses with skeletal variations. Skeletal development, as measured by the average number of ossified vertebrae, was similar in all groups. Soft-tissue development was not affected by dose levels of 0.05 to 0.2%. In animals treated with 0.4% Orange B, significant increases were seen in the incidence of hydroureters (severe and moderate), in the average numbers of fetuses with at least one and at least two soft-tissue variations per litter, and in the percentage of litters containing fetuses with at least two soft-tissue variations.

Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats

2003 ◽  
Vol 22 (6) ◽  
pp. 453-464 ◽  
Author(s):  
Raymond G. York ◽  
Kathleen A. Funk ◽  
Michael F. Girard ◽  
David Mattie ◽  
Joan E. Strawson
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Developmental Toxicity ◽  
Thyroid Stimulating Hormone ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Maternal Thyroid

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T3, and T4 (thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T4 was decreased at all levels, and T3 was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T4 was reduced at 30.0 mg/kg-day, and T3 was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T3 and T4 levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.

Evaluation of the Developmental Toxicity of Acetyl Cedrene

2006 ◽  
Vol 25 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Aurelia Lapczynski ◽  
Daniel A. Isola ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
Anne Marie Api
Keyword(s):  
Body Weight ◽  
Soft Tissue ◽  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Body Weights ◽  
Weight Gains

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages ±10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

Peri- and Postnatal Developmental Toxicity of Salcaprozate Sodium (SNAC) in Sprague-Dawley Rats

2009 ◽  
Vol 28 (4) ◽  
pp. 266-277 ◽  
Author(s):  
M. Gary I. Riley ◽  
Raymond G. York
Keyword(s):  
Oral Absorption ◽  
Developmental Toxicity ◽  
Late Gestation ◽  
Female Rats ◽  
Feed Consumption ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Body Weights ◽  
Behavioral Parameters ◽  
Absorption Promoter

Salcaprozate sodium (SNAC) (sodium 8-((2-hydroxybenzoyl) amino) octanoate, CAS RN 203787-91-1) is classified as an oral absorption promoter and may be a useful means for improving the absorption of certain nutrients and pharmaceutical agents. Presented herein is a subset of data from a larger study evaluating the potential effects of SNAC on the gestation, parturition, lactation, maternal behavior, and offspring development of rats. Pregnant Crl:CD BR VAF/Plus female rats (F0; n = 25) received SNAC at 1000 mg/kg/d orally (gavage) from implantation through lactation and weaning. F1 pups were exposed in utero and potentially through maternal milk; observations continued through sexual maturity. The study concluded with Caesarean sectioning of F1 dams for litter observations and fetal evaluations. No deaths, abortions, premature deliveries, or gross lesions occurred in (F0) dams. Excess salivation, red perivaginal substance, and slight reductions in body weights, body weight gains, and/or feed intake were noted in late gestation/early lactation. SNAC was associated with a prolonged gestation period, leading to a greater number of dams with stillborn pups, higher number of stillborn pups, and reduced live litter size. Offspring body weights/gains, feed consumption, age of sexual maturation, mating, fertility, behavioral parameters, and organ weights at necropsy were unaffected by SNAC. No gross external changes were observed in F1 or F2 pups. In summary, SNAC administered orally at 1000 mg/kg/d to pregnant rats from gestation to weaning resulted in a slight decrease in maternal body weights (−3.8%) and prolonged gestation, along with an increase in stillbirths, but had no effects on growth and development in surviving offspring.

Evaluation of the Developmental Toxicity of α-Methyl-3,4-Methylene-Dioxyhydrocinnamic Aldehyde in Rats

2006 ◽  
Vol 25 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Anne Marie Api ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Mildred S. Christian ◽  
Robert M. Diener
Keyword(s):  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Excessive Salivation ◽  
Sprague Dawley Rats ◽  
Body Weights

The developmental toxicity of α-methyl-3,4-methylene-dioxyhydrocinnamic aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated for developmental toxicity in Sprague-Dawley rats (25/group; cesarean-sectioning identified 21 to 25 pregnant rats/group). Oral dosages of 0 (corn oil), 62, 125, or 250 mg/kg/day were administered by gavage on days 7 through 17 of gestation (GDs 7 through 17). Rats were observed for viability, clinical signs, body weights, and feed consumption. Necropsy and cesarean sectioning occurred on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. Analysis of dosage preparations verified calculated dosages ±10%. No deaths occurred. Excessive salivation occurred in all groups, but the incidence was increased at 250 mg/kg/day. The 250 mg/kg/day dosage also was associated with a significant increase in the incidences of a clear, red or yellow perioral and/or red perivaginal substance and significant reductions in mean feed consumption and body weight gains (11.6% and 7.4%, respectively) during the entire dosage period. No gross changes attributable to MMDHCA were observed at necropsy. Cesarean section or litter parameters, as well as fetal alterations, were not affected by MMDHCA at 250 mg/kg/day or either of the lower dosages tested. Based on these data, maternal and developmental no-observable-effect levels (NOAELs) of 125 and >250 mg/kg/day, respectively, were established for MMDHCA. It is concluded that MMDHCA is not a developmental toxicant in rats under the conditions of this study and dosing regimen.

Subchronic Toxicity and Developmental Toxicity Studies in Rats With Aquateric® Aqueous Enteric Coating

1999 ◽  
Vol 18 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Lois A. Kotkoskie ◽  
Christine Freeman ◽  
Mark A. Palmieri
Keyword(s):  
Developmental Toxicity ◽  
Dose Range ◽  
Clinical Signs ◽  
Study Groups ◽  
Feed Consumption ◽  
Histological Evaluation ◽  
Sprague Dawley ◽  
Enteric Coating ◽  
Toxicological Effects ◽  
Sprague Dawley Rats

Studies were conducted to evaluate the subchronic and developmental toxicity of Aquateric® Aqueous Enteric Coating. Homogeneity and stability studies were conducted over a range of 5,000 to 50,000 ppm Aquateric in the diet. In the subchronic study, groups of Sprague-Dawley rats (20/sex/group) received 0 (control), 5,000, 25,000, or 50,000 ppm Aquateric in the diet for 90 consecutive days. No mortality, clinical signs of toxicity or adverse toxicological effects on hematology or serum chemistry parameters, body weights, feed consumption, ophthalmological examinations, or histological evaluation of tissues were noted in any treatment group. In the developmental toxicity study, groups of pregnant Sprague-Dawley rats (25/group) received 0 (control), 5,000, 25,000 or 50,000 ppm Aquateric in the diet on gestational days 6-15. No evidence of maternal toxicity or fetotoxicity or embryotoxicity was noted. The no observed adverse effect level (NOAEL) exceeds 50,000 ppm in the diet, which represents a dose range of approximately 3600 to 4100 mg/kg/day. The results of these studies demonstrate the low toxicity of Aquateric. The estimated human intake is approximately 4 mg/kg/day. Based on the NOAEL from the subchronic study of 3604 mg/kg/day, the margin of safety is 900.

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat

Teratology ◽  
2000 ◽  
Vol 62 (4) ◽  
pp. 205-213 ◽  
Author(s):  
A. Barry Astroff ◽  
David W. Sturdivant ◽  
Stephen G. Lake ◽  
Ronald N. Shiotsuka ◽  
Glenn S. Simon ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Hexamethylene Diisocyanate ◽  
Sprague Dawley ◽  
Sprague Dawley Rat

A Rat Neurodevelopmental Evaluation of Offspring, Including Evaluation of Adult and Neonatal Thyroid, from Mothers Treated with Ammonium Perchlorate in Drinking Water

2004 ◽  
Vol 23 (3) ◽  
pp. 191-214 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
W. Ray Brown ◽  
Robert H. Garman ◽  
David R. Mattie ◽  
...  
Keyword(s):  
Drinking Water ◽  
Motor Activity ◽  
Passive Avoidance ◽  
Ammonium Perchlorate ◽  
Thyroid Stimulating Hormone ◽  
Follicular Epithelium ◽  
Feed Consumption ◽  
Exposure Level ◽  
Exposure Group ◽  
Sprague Dawley

The purpose of this study was to evaluate the potential neurodevelopmental toxicity of perchlorate exposure during gestation and the first 10 days of lactation. Mated Sprague-Dawley rats (25/exposure group) were given continual access to 0, 0.1, 1.0, 3.0, or 10.0 mg/kg-day ammonium perchlorate (AP) in drinking water, starting gestation day 0 (mating) through lactation day 10 (DL 10). One pup/sex/litter/exposure group was assigned to (1) juvenile brain weights, morphometry, and neuropathology; (2) passive avoidance and watermaze testing; (3) motor activity and auditory startle habituation; and (4) adult regional brain weights, morphometry, and neuropathology. AP had no effect on body weights, feed consumption, clinical observations, or sexual maturation of pups at exposures as high as 10.0 mg/kg-day. There were no behavioral effects in the offspring exposed as high as 10.0 mg/kg-day as evaluated by passive avoidance, swimming watermaze, motor activity, and auditory startle. Increases in hypertrophy and hyperplasia of the thyroid follicular epithelium and a decrease in the thyroid follicle size were observed in culled male pups in the 10.0 mg/kg-day group on DL 5. The exposure level for effects on triiodothyroxine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels for pups were 0.1, 1.0, and 3.0 mg/kg-day, respectively. There was an apparent increase in the thickness of the corpus callosum of the 10 mg/kg-day group pups on DL 12. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was greater than 10.0 mg/kg-day. Based on the thyroid morphometric and histopathologic findings, the NOAEL for pup toxicity was 0.1 mg/kg-day.

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