The penetration of rat skin by some nitrosamines of environmental importance

N-Nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA) were applied to the clipped dorsal skin (about 3.5 X 3.5 cm) of adult male Fischer 344 rats. NDELA was applied undiluted, dissolved in water and dissolved in cutting oil; NMOR was applied dissolved in water and in ethyl acetate. To compare the extent of absorption through the skin with that from the stomach, aqueous solutions of the nitrosamines were used for gavage. Blood and urine samples were analysed for nitrosamines, using GC-TEA or HPLC-TEA. Maximum skin penetration observed with NMOR was 56%, following application of 5 mg, whereas a similar proportion of the dose was regularly present after gavage of 5 mg. Less than 1% was recovered from the urine. Skin painting of NDELA in water (20 mg in 100 microliter) and in cutting oil (25 mg in 25 microliter) yielded small concentrations of NDELA in the blood; less than 25 mg/l in all cases. However, when 50 mg NDELA was painted on the skin undiluted, from 130 to 220 mg/l of blood were recovered after one hour. fifty mg NDELA in water yielded similar blood concentrations when administered by gavage. From 20 to 30% of the NDELA applied undiluted and by gavage were recovered in the urine. It is concluded that, although there are differences between animals, exposure to NMOR or NDELA represents a risk due to absorption through the skin.