Food additives and contaminants-Fd Chem. Toxic. Vol. 20, No. 1 147

In laboratory experiments on eight test materials, nestling gulls were given a single intubated dose of a test crude oil (1 ml) or of an aromatic or aliphatic fraction (the amount present in 1 ml of crude oil) in corn oil (total volume 1 ml). Blood samples were taken at intervals for hormone analysis. Some of the oil samples had significant effects on the hormone levels while others had none. The effective samples raised plasma corticosterone levels with a day of dos- ing and thyroxine levels after 6 days. The former reached a peak (50% above the levels in controls intu- bated with corn oil) after 4 days and returned to con- trol levels by day 14, at which time the thyroxine levels were still raised. Increases in ACTH levels were also demonstrated. A weathered oil, which increased hormone levels in the laboratory gulls. was used in field studies on the three species, and in spite of the necessarily restricted blood sampling, the results obtained supported the laboratory findings.

All the test materials that increased plasma-hor- mone levels had been shown in previous studies to reduce growth rates in gulls and guillemots. The other test oils and fractions affected neither hormone levels nor growth. The authors suggest that these findings and the other effects shown to follow ingestion of the ‘active’ types of oil appear to be consistent with the following sequence of interactions; changes in the intestinal mucosa affect both osmotic balance and nutrient uptake, while direct effects of the oil on the nasal salt gland impose additional stress on the osmoregulatory system; the resulting rise in blood sodium triggers an adrenocortical response and the rise in blood corticosterone leads to proliferation of the nasal salt gland and depresses the growth rate, probably (in view of demonstrated increases in plasma uric acid) by stimulating protein catabolism; salt-gland hypertrophy restores osmotic balance within a few days and corticosterone levels return to normal; the subsequent rise in thyroxine levels is probably a compensatory attempt to increase overall metabolic processes.

Through the skin barrier with NDELA

Bronaugh, R. L., Congdon, E. R. & Scheuplein, R. J. (1981). The effect of cosmetic vehicles on the pen- etration of N-nitrosodiethanolamine through excised human skin. J. invest. Derm. 76, 94.

There have been various reports of contamination of cosmetic products and toilet preparations with N-nitrosodiethanolamine (NDELA) at levels ranging up to about 50ppm (Cited in F.C.T.. 1977, 15, 423) and even in some cases up to 130 ppm (ibid 1981, 19, 137). Following earlier studies demonstrating tumour induction in rats and hamsters treated with high total doses of NDELA, a recent study in F344 rats has confirmed the compound’s potent carcinogenicity in that species, although it appears the B6C3Ft mice similarly given NDELA in the drinking-water were less susceptible to its carcinogenic activity (ibid 1981, 19, 799).

Since some cosmetics may remain in contact with considerable areas of the body surface for fairly long

periods, the carcinogenic potential of NDELA, a non- volatile material, makes its capacity to penetrate the skin barrier a question of major importance. Studies (Federal Register 1979, 44, 21365) have shown NDELA to penetrate excised human skin from an aqueous vehicle and to be aborbed through monkey skin in uiuo. In an in uiuo human experiment, another group demonstrated the urinary excretion of NDELA following application of a cream-type facial founda- tion containing 77ppm NDELA to the chest and back of a male volunteer (Cited in F.C.T. 1981, 19, 137).

Continuing their in vitro studies, the group cited above has now compared the absorption of t4C-labelled NDELA through excised human epi- dermis following application in three different vehic- les-water, propylene glycol and isopropyl myrista- te-all commonly used in cosmetics. Epidermal samples were removed from human abdominal skin taken at autopsy and the integrity of the epidermal barrier was confirmed by measuring the permeability of the skin to tritiated water. The diffusion cells were designed to reflect in viuo conditions as far as possible, and [14CJNDELA was applied to the test membrane in a large excess over that liable to be absorbed, to avoid any significant change in concentration during the exposure.

The permeability constants for NDELA in water and in propylene glycol were both small (55 x 10m6 and 3.2 x 10m6 cm/hr respectively) but that for NDELA in isopropyl myristate was some 250 times higher (1.1 x 10e3 cm/hr). The increased rate of pen- :tration in the lipoidal vehicle was probably due to a more favourable partitioning into the membrane since the partition coefficients (the ratios of NDELA con- centration in the stratum corneum to that in the ve- hicle) showed a similar pattern-approximately 1.8, 1.0 and 228 for water, propylene glycol and isopropyl myristate respectively.

The authors anticipate that other lipoidal vehicles may also enhance percutaneous absorption of NDELA, and they report a permeability constant of 6.2 x 10m5 cm@ for NDELA in a popular lotion (oil-in-water emulsion), a value somewhere between those for the water ,and the isopropyl myristate ve- .-_ -. has. They point out, however, that some formula- tion ingredients may affect.skin penetration in ways not directly related to their effects on the solubility properties of the vehicle. Using an equation taking into account the concentration of NDELA in a given formulation, the area of application, the skin-contact time and the permeability constant determined for NDELA in that formulation, the amount of NDELA likely to penetrate the skin under the given conditions of use can be estimated. The authors acknowledge that the calculation tends to overestimate the amount absorbed, because it assumes that the surface concen- tration remains undepleted and disregards any lag time in the penetration rate. However they claim that application of this calculation to the conditions used in the in uiuo human experiment mentioned above (ibid 1981, 19, 137) using the permeability constant that they had obtained with the popular lotion gave a value for skin absorption of the same order of magni- tude as that derived in practice from the urinary excretion of the NDELA.