ABSTRACT
Perfluoroalkyl carboxylic acids (PFCAs) are a series of environmental contaminants that have received attention because of their possible adverse effects on wildlife and human health. Although many toxicological studies have been performed on perfluorooctanoic acid with carbon chain length C8, available toxicity data on PFCAs with longer chains are still insufficient to evaluate their hazard. A combined repeated dose and reproductive/developmental toxicity screening study for perfluorododecanoic acid (PFDoA; C12) was conducted in accordance with OECD guideline 422 to fill these toxicity data gaps. PFDoA was administered by gavage to male and female rats at 0.1, 0.5, or 2.5 mg/kg/day. The administration of PFDoA at 0.5 and 2.5 mg/kg/day for 42-47 days mainly affected the liver, in which hypertrophy, necrosis, and inflammatory cholestasis were noted. Body weight gain was markedly inhibited in the 2.5 mg/kg/day group, and a decrease in hematopoiesis in the bone marrow and atrophic changes in the spleen, thymus, and adrenal gland were also observed. Regarding reproductive/developmental toxicity, various histopathological changes, including decreased spermatid and spermatozoa counts, were observed in the male reproductive organs, while continuous diestrous was observed in the females of the 2.5 mg/kg/day group. Seven of twelve females receiving 2.5 mg/kg/day died during late pregnancy while four other females in this group did not deliver live pups. No reproductive or developmental parameters changed at 0.1 or 0.5 mg/kg/day. Based on these results, the NOAELs of PFDoA were concluded to be 0.1 mg/kg/day for repeated dose toxicity and 0.5 mg/kg/day for reproductive/developmental toxicity.
Subject(s)
Environmental Pollutants/toxicity , Lauric Acids/toxicity , Liver/drug effects , Maternal Exposure/adverse effects , Paternal Exposure/adverse effects , Reproduction/drug effects , Animals , Dose-Response Relationship, Drug , Female , Fluorocarbons , Hypertrophy , Liver/pathology , Male , Necrosis , No-Observed-Adverse-Effect Level , Pregnancy , Rats , Spermatozoa/drug effectsABSTRACT
A 28-day repeated dose toxicity test and reproduction/developmental toxicity test for N,N'-diphenyl-p-phenylenediamine (DPPD) were conducted in [Crl:CD(SD)] SPF rats. Male and female rats were dosed with DPPD by gavage for 28 days at 0, 100, 300, or 1000 mg/kg bw/day or for a total of 42-46 days at 0, 8, 50, or 300 mg/kg bw/day. No significant adverse effects were observed in the repeated dose toxicity study up to 1000 mg/kg bw/day in both sexes. In the reproduction/developmental toxicity study, two females showed piloerection, hypothermia, and pale skin; one died and the other showed dystocia on day 23 of pregnancy at 300 mg/kg bw/day. Another female delivered only three live pups at 300 mg/kg bw/day. A significantly prolonged gestation period was observed at 50 and 300 mg/kg bw/day. The NOAELs of repeated dose toxicity and reproduction/developmental toxicity were considered to be 1000 and 8 mg/kg bw/day, respectively.
Subject(s)
Parturition/drug effects , Phenylenediamines/pharmacology , Pregnancy, Animal/drug effects , Toxicity Tests/methods , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Male , No-Observed-Adverse-Effect Level , Pregnancy , Rats , Rats, Sprague-DawleyABSTRACT
Crl:CD(SD)rats were given 3-cyanopyridine by gavage at 0, 5, 30 or 180 mg/kg/day. Males were dosed for 42 days beginning 14 days before mating, and females for 40-53 days beginning 14 days before mating to day 3 of lactation, including throughout the mating and gestation periods. General toxicity, mainly liver damage, was observed in males at ≥30 mg/kg/day and in females at ≥5 mg/kg/day. Sertoli cell vacuolation was observed at 180 mg/kg/day, and spermatocyte damages were observed at ≥30 mg/kg/day. Effects on estrous cycles, corpora lutea and implantations, and unsuccessfully mated females, despite additional mating, were observed at 180 mg/kg/day. Delayed initiation of delivery, dystocia, and deaths or moribundities of pregnant females were observed at 180 mg/kg/day, and only two pregnant rats delivered live pups at that dose. The NOAEL for reproductive/developmental toxicity was concluded to be 30 mg/kg/day.
Subject(s)
Pyridines/toxicity , Animals , Corpus Luteum/drug effects , Estrous Cycle/drug effects , Female , Liver/drug effects , Liver/growth & development , Male , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Pregnancy , Rats , Reproduction/drug effects , Spermatogenesis/drug effectsABSTRACT
Three female Crl:CD(SD) rats/group were dosed with single wall carbon nanotube (SWCNT) or multi wall carbon nanotube (MWCNT) four times by gavage at a total of 50 mg/kg bw or 200 mg/kg bw (four equally divided doses at one-hour intervals). Acute oral doses of SWCNT and MWCNT caused neither death nor toxicological effects, and thus the oral LD
Subject(s)
Nanotubes, Carbon/toxicity , Toxicity Tests, Acute/methods , Administration, Oral , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Lethal Dose 50 , Male , No-Observed-Adverse-Effect Level , Particle Size , Rats , Rats, Sprague-DawleyABSTRACT
To obtain initial information on the possible repeated-dose oral toxicity of fullerene C60, Crl:CD(SD) rats were administered fullerene C60 by gavage once daily at 0 (vehicle: corn oil), 1, 10, 100, or 1,000 mg/kg/day for 29 days, followed by a 14-day recovery period. No deaths occurred in any groups, and there were no changes from controls in detailed clinical observations, body weights, and food consumption in any treatment groups. Moreover, no treatment-related histopathological changes were found in any organs examined at the end of the administration period and at the end of the recovery period. Blackish feces and black contents of the stomach and large intestine were observed in males and females at 1,000 mg/kg/day in the treatment group. There were no changes from controls in the liver and spleen weights at the end of the administration period, but those weights in males in the 1,000 mg/kg/day group increased at the end of the recovery period. Using liquid chromatography-tandem mass spectrometry, fullerene C60 were not detected in the liver, spleen or kidney at the end of the administration period and also at the end of the recovery period. In conclusion, the present study revealed no toxicological effects of fullerene C60; however, the slight increases in liver and spleen weights after the 14-day recovery period may be because of the influence of fullerene C60 oral administration. In the future, it will be necessary to conduct a long-term examination because the effects of fullerene C60 cannot be ruled out.
