Developmental toxicity of diesel exhaust: a review of studies in experimental animals.

Diesel exhaust (DE) is a complex mixture of combustion products of diesel fuel, including gases and diesel exhaust particles (DEPs), commonly known as soot, that contains many toxic air contaminants. Studies of pre- and postnatal exposure to DE or DEPs have revealed changes in growth, sexual development, hormone levels, spermatogenesis, weights of the reproductive and accessory organs, behavior, monoaminergic system, expression of immune-related genes, histopathology of the testes and brain, susceptibility to allergies, and inflammatory and genotoxic endpoints in rodent offspring. Changes in gene expression for gonadal development were also observed after exposure to DE. As for the causative agent for the developmental toxicity of DE, DEPs and the gaseous phase, conflicting findings were reported. Although this paper provides initial information on the potential developmental toxicity of DE including the gaseous phase and DEPs, further studies using relevant concentrations closely reflecting expected levels of human exposure are needed.

Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats.

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM) with greater than 100-fold selectivity against all other steroid receptors and is a potentially superior treatment for postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of lasofoxifene on male reproduction in rats in light of the known effects of estrogen modulating compounds on male reproductive ability. METHODS: Lasofoxifene was administered to adult male rats at doses of 0.1, 1, 10, and 100 mg/kg for 66-70 consecutive days. After 28 days of dosing, male rats were cohabited with untreated female rats. Female rats were euthanized on gestation day 14 and a uterine examination was carried out for evaluation of reproductive parameters and embryo viability. Male rats were euthanized after 66-70 days of dosing and epididymal sperm motility and concentration were assayed. The testes, epididymides, prostate, and seminal vesicles were weighed and microscopically examined. RESULTS: The duration of cohabitation was increased for 100 mg/kg males by 0.7 days. The number of males copulating and the number of implantation sites produced per copulation were reduced in the 10 and 100 mg/kg groups. Weights of the seminal vesicles and epididymides were reduced for all groups, although the testes weight and epididymal sperm motility and concentration were not affected by treatment. There were no microscopic findings in the male reproductive tissues. CONCLUSION: The changes in male fertility and reproductive tissue weights after exposure to lasofoxifene are consistent with those previously described for estrogen receptor-modulating compounds.