Uptake of pyrene in a breast-fed child of a mother treated with coal tar.

A woman was treated for atopic dermatitis with coal tar containing ointments. Coal tar containing ointments contain genotoxic polycyclic aromatic hydrocarbons. Over a period of 50 days the accumulated dose of different coal tar containing ointments treatments corresponded to 993 mg of pyrene and 464 mg of benz[a]pyrene. During this treatment she gave breast milk to her 3-month-old daughter. Analysis of urine samples from the breast-fed child showed elevated levels of urinary excretion of a metabolite of pyrene (1-hydroxypyrene, 1-OHP). These levels were in the same range as urinary excretion levels of this metabolite observed in the mother's urine. As no pyrene was observed in breast milk at a limit of determination of 0.0035 micromol/L, transfer of pyrene from mother to child via breast milk is not likely. Also, a low level of 1-hydroxypyrene observed in the mother's milk did not account for the observed urinary excretion levels in the child. It must therefore be assumed that pyrene was transferred from mother to child via another route, presumably direct skin-to-skin or skin-to-mouth contact. Dermatologists should inform their patients who receive treatment with coal tar containing ointments of the risk of transfer of polycyclic aromatic hydrocarbons by skin-to-skin or skin-to-mouth contact.

The occupational exposure of dermatology nurses to polycyclic aromatic hydrocarbons - evaluating the effectiveness of better skin protection.

OBJECTIVES: We studied the uptake of polycyclic aromatic hydrocarbons (PAH) in nurses who apply ointments containing coal tar to patients and investigated the effectiveness of skin protection methods. METHODS: We determined gas-phase PAH on XAD-2 and particle-associated PAH on filters. We also used pads to determine PAH on the skin. Pyrene and benzo(a)pyrene were analyzed by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry; their respective urinary metabolites 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene were analyzed using high performance liquid chromatography with fluorescence detection. RESULTS: We ruled out the inhalation of airborne pyrene and benzo(a)pyrene as the sources of PAH exposure. However, substantial amounts of pyrene and benzo(a)pyrene were observed on the hands of the nurses (median 33.0 and 16.4 ng/cm (2), respectively). Excretion of urinary 1-hydroxypyrene indicated an increased uptake of pyrene in 8 out of 12 nurses. We asked 35 nurses to perform a treatment with gloves followed by a second treatment without gloves. The use of gloves changed the excretion of 1-hydroxypyrene by -0.58 mumol (range -5.1-1.0 mumol), corresponding to a median reduction of 51.5% (P<0.001). Based on this finding, a new protocol was adopted, involving the permanent use of vinyl gloves and Tyvek sleeves. The effectiveness of this protocol was tested against pre-existing work practices and showed a 97% reduction in skin contamination with pyrene and benzo(a)pyrene, and a lowering in urinary excretion of 1-hydroxypyrene of 57%. CONCLUSION: Protecting the skin more stringently reduced pyrene and benzo(a)pyrene contamination of the hands, and lowered urinary excretion of 1-hydroxypyrene.

Highly increased urinary 1-hydroxypyrene excretion rate in patients with atopic dermatitis treated with topical coal tar.

Coal tar preparations, as used in dermatological practice, contain numerous polycyclic aromatic hydrocarbons of which many are proven animal carcinogens. Increased urinary 1-hydroxypyrene excretion in patients with atopic dermatitis treated with topical coal tar preparations has been demonstrated. Little is known about the relationship between the dermal uptake of polycyclic aromatic hydrocarbons on the one hand and the amount of tar applied to the skin, the total body area affected, the condition of the epidermal barrier and the severity of the dermatitis on the other. We compared urinary 1-hydroxypyrene excretion rate with these variables. The urinary 1-hydroxypyrene excretion rate was highly dependent on the total amount of tar applied to the skin and the total body area affected, and less on the severity of the atopic dermatitis or the condition of the epidermal barrier. Exposure to therapeutic doses of coal tar leads to much higher rates of urinary 1-hydroxypyrene excretion than occupational exposure. Because of the potential carcinogenicity of coal tar, as clearly demonstrated both in animal studies and from occupational exposure, careful consideration should be given to the use of coal tar preparations in dermatological practice. However, the risk of short-term high exposure is unknown. Restriction of the use of coal tar should be based on epidemiological studies and/or appropriate risk models taking into account its relative safety established over many years of clinical use.

Urothelial cell DNA adducts in rubber workers.

Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing (P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas.