The effect of seed orientation deviations on the quality of 125I prostate implants.

We quantified the effect of seed orientation deviations on five prostate seed implant cases at our institution. While keeping their positions fixed, the iodine-125 seeds were assigned orientations sampled from a realistic probability distribution derived from the post-implant radiographs of ten patients. Dose distributions were calculated with both a model that explicitly includes anisotropy (TG43 anisotropy function) and a point source model (TG43 anisotropy factor). Orientation deviations had only a small influence on prostate dose-volume histograms: the 95% confidence intervals on the volumes receiving 100%, 150% and 200% dose were at most +/-0.8%, +/-1.1% and +/-0.6% of the prostate volume, respectively. The dose-volume histograms of anisotropic seed distributions were marginally better than those with isotropic point-source seeds. Anisotropy caused a displacement of cold spots (regions receiving <100% of the prescribed dose) in <1% of the prostate volume. Our results indicate no net benefit to prostate dosimetry in using more isotropic seeds. Furthermore, we propose a new 'weighted anisotropy function' to better account for the effects of anisotropy when seed orientation is unknown. Conceptually, the TG43 anisotropy factor described in AAPM TG43 averages the effect of anisotropy over all solid angles, with the implicit assumption that all seed orientations are equally probable. In prostate implants, however, seeds are preferentially oriented parallel to the needle axis. The proposed weighted anisotropy function incorporates this non-uniform probability.

Beard dermatitis due to para-phenylenediamine use in Arabic men.

The most common active ingredient in hair coloring is para-phenylenediamine (PPDA), which can produce contact dermatitis, particularly in persons who dye their scalp hair and in hairdressers. We have identified another group of patients also at risk, namely men from Arab countries, who commonly grow beards and dye them. We searched the computerized patient database at the Mayo Clinic for patients with beard dermatitis associated with dye use. Eight Arabic men presented to the Mayo Clinic between 1994 and 1999 with beard dermatitis and a positive patch test to PPDA. The lesions were described as pruritic, erythematous, papular eruptions that developed in the jaw area after each application of beard dye. The symptoms subsided after the patients discontinued use of the PPDA-containing dye and received treatment with topical corticosteroids. Allergic contact dermatitis in the beard area due to PPDA occurs in Arabic men as a result of their propensity to dye their beards.

Carcinogenicity of N1-[tris(hydroxymethyl)]methyl-4-nitro-o-phenylenediamine fed to mated and non-mated Sprague-Dawley rats.

N1(-)[tris(hydroxymethyl)]methyl-4-nitro-o-phenylenediamine was fed in the diet to groups of 30 male and 55 female Sprague-Dawley rats at levels of 0.2, 0.6 and 2.0% for up to 6 months. One mid-dose and two high-dose females developed palpable mammary masses that were subsequently diagnosed as mammary adenocarcinomas at a 13-wk interim kill involving 10 rats/sex/group. After 14 wk, 25 females per group with no apparent masses were mated in a reproduction/teratology study. Mammary tumours developed in a dose-related fashion both in the pregnant rats and in the remaining 20 females/group that continued on treatment for 6 months. On gestation day 20 (wk 17-18) the final incidences of mammary adenocarcinomas in the low-, mid- and high-dose mated dose groups were 20, 60 and 84%, respectively, while the corresponding incidences in the non-mated females at 6 months were 5, 40 and 85%. Most mammary tumours were encapsulated but, at 6 months, lung metastases were noted in four rats, and four females also had Zymbal's gland tumours. Non-neoplastic changes in male and female rats considered to be related to treatment included increases in thyroid follicular cell size accompanied by an accumulation of golden-brown pigment, multifocal hepatic necrosis with non-suppurative inflammation, and renal tubular pigmentation. Increases in foetal variations in the mid- and high-dose groups were considered to be related non-specifically to retarded growth. Malformations observed in the high-dose group were found primarily in single foetuses and were not considered to be treatment related. Although the mean numbers of micronucleated polychromatic erythrocytes in bone marrow obtained from high-dose treated females after 13 wk slightly exceeded historical negative control values, the data were not considered indicative of a genotoxic effect because of the absence of either a dose relationship or a substantive increase in the frequency of micronucleated cells.

Failure of short-term in vitro mutagenicity tests to predict the animal carcinogenicity of hair dyes.

A number of hair-dye chemicals that have given positive results in various short-term mutagenicity tests have shown no clear evidence of carcinogenicity in animal bioassays. Commercial HC Blue No. 1 and its analogues HC Red No. 3 and HC Blue No. 2 are all mutagenic in the Ames test but only the HC Blue No. 1 is carcinogenic in animals. A carcinogenicity study in mice was carried out on both a commercial sample of HC Blue No. 1 and a highly purified sample which was negative in a battery of short-term tests for mutagenic activity. Both samples, administered at 0.3% in the diet for up to 24 months, were carcinogenic to mice, inducing hepatocellular carcinomas in greater than or equal to 89% of the mice examined. Therefore the presence of mutagenic impurities is not responsible for the carcinogenicity of commercial HC Blue No. 1. Discrepancies between the results of mutagenicity and carcinogenicity tests on hair dyes and other chemicals are discussed, and the value of short-term mutagenicity tests for assessing chemical safety is questioned.

Evaluation of the teratological and dominant lethal potential of N,N-bis-(2-hydroxyethyl)-p-phenylenediamine sulphate in a 6-month feeding study in rats.

N,N-Bis-(2-hydroxyethyl)-p-phenylenediamine sulphate (N,N-Bis) was administered to 40 male and 45 female Sprague-Dawley rats per group by admixture with their diets at levels of 0.03, 0.1 and 0.3% for periods up to 6 months. Methaemoglobin levels were determined at wk 6. After 90 days ten animals/sex/group were killed for studies of possible target organs, haematology and blood chemistry. After 90 days, 25 females in each group were mated to untreated males in a teratology study. At wk 20, 20 males in each group were transferred from the test diets containing N,N-Bis to the control diet and were mated to untreated females in a dominant lethal study. The remaining animals were killed after 6 months for terminal studies (gross examination of organs, haematology and blood chemistry). The males used in the dominant lethal study were also killed at month 6, to serve as a comparison recovery group (gross examination of organs). Feeding of N,N-Bis at levels up to 0.3% in the diet caused a significant reduction in the body weight of male rats. The only signs of gross pathology after either 3 or 6 months of N,N-Bis feeding were darkened thyroids. This effect was noted in the high-dose group at both time intervals and, to a lesser extent, in the mid-dose group at month 6, and it was also seen in most of the high-dose recovery males and in a small number of mid-dose recovery males. No pathological effects were detected microscopically after the feeding of N,N-Bis for 90 days. N,N-Bis was not teratogenic, nor did it induce a dominant lethal effect in this study when administered to rats at levels including those causing borderline toxicity.

Mutagenicity studies on urine concentrates from female users of dark hair color products.

Urines from women, collected before and after hair dyeing, were evaluated for mutagenic activity in the Ames Salmonella-Microsome Test. Thirty (30) sets of samples were tested as concentrates following removal of histidine on an XAD-2 resin column. None of the samples taken following the use of various Clairol products containing high levels of dyes gave any indication of increased mutagenic activity when compared to samples taken before hair dyeing. These results indicate that the use of hair dyes does not result in exposure of the urinary system to mutagens detectable in a sensitive microbial system, and thus suggest the absence of significant biological effects among users of hair dyes and persons occupationally exposed.

Hair dyes and aplastic anemia.

Reports linking the use of hair dyes with bone marrow suppression and aplastic anemia have appeared sporadically over the past 45 years. For the most part these clinical cases are difficult to evaluate but appear to rely heavily for support on a single report in 1935. The infrequency of these reports and the wide-spread use of hair color products argue strongly against a primary toxic action on bone marrow in humans. The results of studies in three species of animals support this conclusion, giving no indication that chronic exposure to hair dyes causes adverse effects on hematopoiesis. Although it cannot be dismissed as a possibility, invoking idiosyncrasy seems on equally shaky grounds since any rational basis for continued association of a substance with individual sensitivity should find increasing numbers of cases with increasing population exposure. Clearly this has not been the case.