Hypophagia-Induced Weight Loss in Mice, Rats, and Guinea Pigs Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Hypophagia-lnduced Weight Loss in Mice, Rats, and Guinea PigsTreated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin. KELLING, C.K, CHRISTIAN, B. J., INHORN, S. L., AND PETERSON, R. E. (1985).Fundam. Appl. Toxicol. 5, 700–712. C57BL/6 mice treatedwith 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 360 µ/kg)displayed a significant reduction in feed intake and body weightuntil just before death, when they developed ascites and subcutaneousedema. This caused body weight of the mice that died to suddenlyincrease during the terminal stage of toxicity. TCDD-treatedmice that survived did not develop ascites or edema, and maintaineda body weight that was slightly less than that of pair-fed mice.Cumulative lethality in TCDD-treated mice (69%) was greaterthan that of pair-fed controls (14%). In guinea pigs treatedwith TCDD (2 µ/kg) both the time course and magnitudeof hypophagja were closely associated with weight loss. Pair-fedguinea pigs did not lose quite as much weight as TCDD-treatedanimals because their total body water content was higher. Waterintake in pair-fed guinea pigs was greater than that of TCDD-treatedanimals. The time course and magnitude of lethality tended tobe similar in TCDD-treated guinea pigs (81%) and pair-fed controls(64%). In Fischer F-344 rats treated with TCDD (100 µg/kg)body weight loss was associated with a reduction in both feedand water intake. The time course and magnitude of weight lossin TCDD-treated and pair-fed rats was essentially identical.Lethality was higher in TCDD-treated rats (95%) than pair-fedcontrol animals (48%). Taken together, these findings suggestthat hypophagia is responsible for the loss of adipose and leantissue in mice, guinea pigs, and rats treated with a LD70–95dose of TCDD. Under these dosage conditions, weight loss contributesmore to the lethality of guinea pigs than to that of FischerF-344 rats or C57BL/6 mice     

Percutaneous Penetration of N-Nitrosodiethanolamine through Human Skin (in Vitro): Comparison of Finite and Infinite Dose Applications from Cosmetic Vehicles

N-Nitroso compounds (nitrosamines) have been detected at theparts per billion level in a wide variety of matrices includingindustrial chemicals, pharmaceuticals, and food. Although N-nitrosodiethanolamine(NDELA) may be detected as an impurity in some cosmetic products,studies on NDELA absorption through human skin have been limited.A study to determine the extent of NDELA absorption followingtopical application was therefore undertaken to assist in theproper assessment of risk following unintended exposure. NDELAabsorption was measured in vitro through human cadaver skinusing isopropyl myristate (IPM) and generic prototype personal-careformulations (sunscreen and shampoo) spiked with [¹⁴C]NDELA.When applied as a finite dose at a concentration of 0.06% orlower, NDELA absorption was found to be a linear function ofconcentration. Total absorption at 48 hr ranged from approximately35 to 65% of the dose and was formulation dependent (IPM>shampoosunscreen).Absorption occurred relatively rapidly from all formulationsand peak rates of absorption were seen within the first 5 hrfrom the IPM and shampoo formulations. When applied as an infinitedose, total NDELA absorption followed a different rank order(shampoo IPM>sunscreen) and evidence of barrier damage wasseen with the shampoo formulation.