Assessment of haematological and clinical pathology effects of blood microsampling in suckling and weaned juvenile rats.

UNLABELLED: Tail vein microsampling in juvenile rats for toxicokinetic assessment has the potential to significantly reduce satellite animal use. This paper explores the toxicological consequences of microsampling at various post natal day (PND) ages. METHODS: Microsamples were taken as follows: suckling pups, 10 pups/sex, 3×32µL samples on PND19, euthanased PND20; weaned pups, 10 pups/sex, 6×32µL samples on PND23 and PND37, euthanased PND38; and satellite pups, 3 pups/sex, 5×32µL samples on PND14 and PND35, euthanased on PND36. At termination on PND20 or PND38, clinical pathology samples were obtained and spleen, liver and bone marrow were examined. There were 10 unsampled concurrent control animals for each experiment. RESULTS: Suckling animals: females showed a slight, statistically significant decrease in red blood cell count (0.94× of control; p<0.05) with slight decreases in haemoglobin and haematocrit. The suckling males showed a slight increase in reticulocyte counts (1.05× of control) plus a statistically significant, slight increase in relative splenic weight. Weanling animals: the only effect was decreased liver weight in the microsampled females. In both suckling and weanling experiments, all clinical pathology values were within the age control range. In the satellite pups microsampled on PND14, there was a statistically significant transient increase in bodyweight gain between PND17 and PND21. CONCLUSION: The nature of the toxicological effects of microsampling was as expected. The magnitude of effects does not preclude microsampling main test pups provided care is taken over study design and blood volume loss.

Toxicological evaluation of peroxy sulfonated oleic acid (PSOA) in subacute and developmental toxicity studies.

Peroxy sulfonated oleic acid (PSOA) is a new coupler used in sanitizing solutions primarily for the food and beverage industry. The toxicity of PSOA was evaluated in a 28-day repeat dose study according to OECD 407 guidelines with a 14-day recovery period and a developmental toxicity study according to OECD 414 guidelines. In both studies, PSOA was administered once daily via gavage at 0, 5, 15 and 50 mg/kg/day to Sprague-Dawley rats. Due to its corrosive properties, the highest test concentration was restricted to 0.5%. No findings related to PSOA administration were observed for the 28-day repeat-dose study and the NOEL is 50 mg/kg/day. Additionally, no impairment of the mucous membranes of the gastrointestinal tract was observed up to 0.5%, which is considered the NOEC in terms of local toxicity. For the developmental study, an embryo-fetal NOEL of 50 mg/kg/day was identified and the maternal NOEL is considered to be 15 mg/kg/day, based on slight reductions in maternal body weight and food consumption, as well as a modest increase in the incidence of clinical observations at the high dose. These findings demonstrate that PSOA appears to have minimal potential to induce toxicity associated with repeat-dose or developmental exposures.