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In an in vitro dermal penetration assay, excised skin from male C3H mice, 4-10 weeks old was used to determine the penetration of polynuclear aromatic compounds (PACs) (Roy et al., 1996). Skin from untreated mice was slightly shaved after asphyxiation with carbon dioxide. The shaved dorsal section of the skin was excised along with the adhering viscera. One skin specimen per mouse was covered with saline-moistened gauze and used within two hours following removal in the in vitro assay. Franz diffusion cells were used in the absorption assay. Excised skin specimens were placed between two halves of Franz cells. The polynuclear aromatic compounds (PACs) fortified with3H-BaP (benzo-a-pyrene) were administered to the skin on the donor side (n=5) in 70 µL of dosing solution. After dosing, the receptor fluid in each cell was sampled every 24 hours for four days.3H radioactivity in the test material before dosing and radioactivity in the receptor fluid after dosing was determined using a Beckman LS 5801 counter. The penetration rate of the PACs, measured by the diffusion of the PACs fortified with3H-BaP, ranged between 7% (of the applied dose absorbed in 48 hours) to 48%.

In a read-across placental bio-availability study with distillate aromatic extract, three presumed-pregnant Sprague Dawley rats were clipped free of dorsal hair on gestation day 10 and were treated with a protective device (details not specified) to contain the test material (Kerstetter, 1989). The test material, 318 Isthumus Furfural extract containing two radiolabelled surrogates (14C-carbazole [≤0.01%] and3H-benzo(a)pyrene [(≤0.01%]) was applied to the clipped skin at 1000 mg/kg-body weight using a digital 250µl Gilson Microman Model M250 micropipette on gestation days 10, 11, and 12. Following treatment, each animal was fitted with an Elizabethan collar to minimize disturbance of the treated site. Every 24 hours urine and faeces along with cage rinse were collected for analysis. All animals were sacrificed on day 13 and necropsied.

 

The study authors reported that though the radiolabelled surrogates14C-carbazole (≤0.01% and3H-benzo(a)pyrene (≤0.01%) penetrated the skin of the treated dams, very little of the material reached the embryos. Less than 0.01% of14C-carbazole or3H-benzo(a)pyrene was detected in the embryos on gestation day 13. Based on these results, the study authors concluded that the placenta served as an effective barrier against the transport of14C-carbazole or3H-benzo(a)pyrene to the embryo.

The relationship between exposure dose (dermal) and the dose reaching a critical target was assessed in a mouse skin painting study and human tissue in vitro using viscous oil products including RAE samples. The relative bioavailability of PAC was compared by measuring the interaction of the marker PAC ([14C]Ba-P and [3H]Ba-P) with skin DNA and/or blood following cutaneous exposures to test materials. Adduct concentration in blood and skin DNA as measured by radioactivity was inversely proportional to the viscosity of the test material. More specifically, the amounts of radioactivity in mice treated with the RAEs was five times lower in blood and three times lower in skin DNA than the amounts measured in mice treated with lower viscosity oils. This trend in bioavailability was also observed in human skin tissue tests in vitro (Potter et al., 1999).

 

The flux of a representative PAC from more viscous oil products including RAEs and subsequent DNA and blood adduct formation was mathematically modelled. Adduct formation was found to be a function of oil product viscosity and aromaticity. These data were modelled to develop a carcinogenic potency index (Brandt, 1999), which was a function of not only PAC content but was also a function of these physical-chemical properties as well.