An overview of the current challenges when using rabbits for prenatal developmental toxicity studies with consideration of the impact on data interpretation.

The rabbit prenatal developmental toxicity study is an international testing requirement for the identification and characterisation of the potential hazards of chemicals to human health. The importance of the rabbit for the detection of chemical teratogens is without question. However, the rabbit when used as a laboratory test species presents unique challenges affecting data interpretation.

Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test.

Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4.

Subchronic feeding study of grain from herbicide-tolerant maize DP-Ø9814Ø-6 in Sprague-Dawley rats.

This 13-week feeding study conducted in Sprague-Dawley rats evaluated the potential health effects from long-term consumption of a rodent diet formulated with grain from genetically modified (GM), herbicide-tolerant maize DP-Ø9814Ø-6 (98140; trade name Optimum GAT (Optimum GAT is a registered trademark of Pioneer Hi-Bred)). Metabolic inactivation of the herbicidal active ingredient glyphosate was conferred by genomic integration and expression of a gene-shuffled acetylase coding sequence, gat4621, from Bacillus licheniformis; tolerance to acetolactate synthase (ALS) inhibiting herbicides was conferred by overexpression of a modified allele (zm-hra) of the endogenous maize ALS enzyme that is resilient to inactivation. Milled maize grain from untreated (98140) and herbicide-treated (98140+Gly/SU) plants, the conventional non-transgenic, near-isogenic control (091), and three commercial non-transgenic reference hybrids (33J56, 33P66, and 33R77) was substituted at concentrations of 35-38% w/w into a common rodent chow formula (PMI) Nutrition International, LLC Certified Rodent LabDiet 5002) and fed to rats (12/sex/group) for at least 91 consecutive days.

Subchronic feeding study with genetically modified stacked trait lepidopteran and coleopteran resistant (DAS-Ø15Ø7-1xDAS-59122-7) maize grain in Sprague-Dawley rats.

DAS-Ø15Ø7-1xDAS-59122-7 (1507x59122) is a genetically modified (GM) maize hybrid that was produced by crossing of two GM maize inbreds; DAS-Ø15Ø7-1 and DAS-59122-7. This hybrid cross expresses four transgenic proteins: Cry1F and PAT (from DAS-Ø15Ø7-1) and Cry34Ab1/Cry35Ab1 and PAT (from DAS-59122-7) that confer resistance to lepidopteran and coleopteran pests and tolerance to the herbicidal active ingredient glufosinate-ammonium. The current subchronic feeding study was conducted in Sprague-Dawley rats to evaluate the potential health effects of long-term consumption of a rodent diet containing 1507x59122 maize grain compared with a diet containing maize grain from its near-isogenic control (091).

Subchronic feeding study of high oleic acid soybeans (Event DP-3Ø5423-1) in Sprague-Dawley rats.

DP-3Ø5423-1 (305423) is a genetically-modified (GM) soybean that was produced by biolistic insertion of a gm-fad2-1 gene fragment and the gm-hra gene into the germline of soybean seeds. The gm-fad2-1 gene fragment cosuppresses expression of the endogenous FAD2-1 gene encoding the seed-specific omega-6 fatty acid desaturase resulting in higher concentrations of oleic acid (18:1) relative to linoleic acid (18:2). The gm-hra gene encoding a modified acetolactate synthase (ALS) enzyme was used as a selectable marker.

Subchronic, reproductive, and developmental toxicity of a fluorotelomer-based urethane polymeric product.

A commercial fluorotelomer-based urethane polymeric dispersion, consisting of polymer, surfactant, and water, was evaluated in subchronic, reproduction, and developmental toxicity studies. The dispersion was administered daily by gavage to rats at dosages of 0, 50, 250, or 1000 mg polymer/kg/day or with 70 mg/kg/day of the sulfonate surfactant. Dose levels of 0, 50, 250, or 1000 mg polymer/kg/day were also used for the reproductive and developmental studies.

Subchronic feeding study of herbicide-tolerant soybean DP-356Ø43-5 in Sprague-Dawley rats.

Optimum GAT1 soybean is a genetically modified (GM) soybean containing event DP-356Ø43-5 (356043) that was produced by integration of the coding sequences of the GAT4601 and GM-HRA proteins. In planta expression of these proteins confers tolerance to glyphosate and sulfonylurea/imidazolinone herbicides, respectively. This paper reports the results from a subchronic rat feeding study conducted with 356043 soybeans.

90-day oral gavage toxicity study of 8-2 fluorotelomer alcohol in rats.

8-2 fluorotelomer alcohol is a fluorinated chemical intermediate used to manufacture specialty polymers and surfactants. The potential subchronic toxicity and the reversibility of the effects of this chemical were evaluated following approximately 90 days of oral gavage dosing to Crl:CD(SD)IGS BR rats. A complete toxicological profile, including neurobehavioral assessments and hepatic beta-oxidation, were conducted at selected intervals and a group of rats was included for a 90-day postdosing recovery period.

Evaluation of effects from repeated inhalation exposure of F344 rats to high concentrations of propylene.

Chronic exposure to propylene does not result in any increased incidence of tumors, yet does increase N7-hydroxypropylguanine (N7-HPGua) adducts in tissue DNA. To investigate any potential for genotoxicity (mutagenicity or clastogenicity), male F344 rats were exposed via inhalation to up to 10,000 ppm propylene for 1, 3, or 20 days (6 h/day, 5 days/week). The endpoints examined included gene (Hprt, splenocytes) and chromosomal (bone marrow micronucleus [MN]) mutations, hemoglobin (hydroxypropylvaline, HPVal) adducts in systemic blood, and DNA adducts (N7-HPGua) in several tissues.

Subchronic feeding study of DAS-59122-7 maize grain in Sprague-Dawley rats.

59122 is a transgenic maize line containing event DAS-59122-7 that expresses the corn rootworm (CRW) specific pesticidal Cry34Ab1 and Cry35Ab1 proteins from Bacillus thuringiensis (Bt) Berliner strain PS149B1 and the phosphinothricin-N-acetyltransferase (PAT) protein from Streptomyces viridochromogenes for tolerance to the herbicidal ingredient glufosinate-ammonium. For the current study, 59122 maize grain, non-transgenic near-isogenic maize grain (091), and a commercially available non-transgenic reference maize grain (33R77) were grown under conditions simulating commercial farming practices. Adult Sprague-Dawley rats (12/sex/group) were fed diets formulated with 35% maize grain from either 59122, 091, or 33R77, or one of two separate lots of commercially available rodent chow prepared with commercially available corn (35%) in accordance with the standards of Purina Mills Labdiet 5002 for approximately 90 days.

Subchronic inhalation exposure to acetone vapor and scheduled controlled operant performance in male rats.

Groups of adult male rats (10/group) were used to assess whether subchronic inhalation exposure to 0, 1000, 2000, or 4000 ppm of acetone vapor altered schedule-controlled operant performance. Rats were exposed to acetone vapor for 6 h/day, 5 days/wk, for a 13-wk period. Extensive training prior to the exposure series established a stable baseline of lever-pressing on a multiple fixed-ratio-fixed-interval (FR 20-FI 120 s) schedule of food presentation.

4-week inhalation toxicity study with a mixture of dichloroethylene and perfluorobutylethylene in rats.

Inhalation studies were conducted to determine the potential subchronic toxicity of a mixture of trans-1,2-dichloroethylene (70%), cis-1,2-dichloroethylene (5%), and perfluorobutylethylene (25%). Groups of rats were exposed to 0, 400, 2000, or 8000 ppm concentrations of the mixture vapor 6 h/day, 5 days/wk, for a total of 20 exposures. Subgroups of rats were further observed during a 1-mo recovery period.

Reproductive and repeated dose toxicity of cyclododecatriene (CDDT) in rats following oral (gavage) treatment.

Cyclododecatriene (CDDT, CAS No. 4904-61-4) was administered daily by oral gavage to groups of Crl:CD (SD)IGS BR rats at dose levels of 0 (control), 30, 100, or 300 mg/kg/day. Female rats were dosed for four weeks premating, through mating, gestation, and lactation (a total of 55 to 63 days of treatment).