NTP technical report on the toxicity studies of Black Newsprint Inks Administered Topically to F344/N Rats and C3H Mice.

Abstract

Toxicity studies were conducted by applying black newsprint inks or mineral oils to clipped skin of the dorsal interscapular area of C3H mice and F344/N rats of both sexes, to determine systemic and local effects. Four lots of both letterpress and offset types of newsprint ink were studied, either as composite mixtures or as individual lots. An industrial grade mineral oil, used as an extender for newsprint ink formulation, and USP medicinal grade mineral oil also were studied. Analyses for the presence of polycyclic aromatic hydrocarbons (PAHs) were conducted on composite ink mixtures and mineral oils; letterpress and offset ink mixtures were found to have cumulative concentrations of 206 and 105 ppm, respectively; the concentration of PAHs in the printing ink mineral oil sample was 208 ppm, while none were detected in the USP grade mineral oil. In genetic toxicity studies, letterpress and offset newsprint ink composite mixtures were each mutagenic in Salmonella typhimurium strains TA98 and TA100 when tested in a preincubation protocol with added hamster liver S9. With rat liver S9, results for both inks were positive in strain TA98 and negative in strain TA100. Neither type of ink was mutagenic in the absence of S9 activation. In 30-day studies, 5 rats and mice per sex were given single, daily dermal applications of letterpress or offset newsprint inks, 5 days per week, for a total of 21 - 22 applications. Dose groups for each type of ink received either the neat (undiluted) composite ink mixture, or the 3:1, 1:1, or 1:3 dilutions (ink:USP mineral oil), with a total dose volume of 100 (mice) or 250 (rats) &mgr;l. All animals survived until the end of the studies. Toxicity attributed to ink administration was limited to decreased body weight gains in female rats treated with neat and the 3:1 dilution of letterpress ink, and to scaliness at the site of application in 1 or more mice in each letterpress ink treatment group. As a result of grooming activity and the large amount of test chemical applied, chemicals were spread over the body, and there was evidence that some oral ingestion had occurred. In 13-week studies, various ink and mineral oil formulations were administered dermally to 10 rats and mice per sex. To prevent accumulation of inks and distribution over the body as seen in the 30-day studies, the frequency of application was reduced to twice weekly and the total dose volume was decreased to 20 microliters for mice and 50 microliters for rats. Treatment groups for rats consisted of letterpress ink mixture, offset ink mixture, printing ink mineral oil, USP mineral oil, and clipped, untreated controls. Groups of mice were administered each of the 4 individual lots of both letterpress and offset inks, the composite mixtures of each, and printing ink and USP mineral oils; clipped, untreated groups served as controls. All rats, all male mice, and all female mice except one administered offset ink-lot E survived to the end of the studies. Effects attributable to compound administration in rats were limited to decreased body weight gains in females treated with printing ink mineral oil and letterpress ink mixture, and increased liver and kidney weights in both males and females exposed to USP mineral oil; there were no local toxic effects at the site of application. In mice, there were no body weight effects, but liver weights were increased in most ink and mineral oil treatment groups of both sexes. Dermal toxicity was evidenced in mice by scaliness and irritation at the site of application of both sexes treated with USP mineral oil and letterpress ink-lot C. Microscopically, local toxicity at the site of application was observed in mice of all treatment groups and was characterized by acanthosis and inflammation. In summary, results of these studies indicate that topical administration of black newsprint inks and mineral oils produces local toxicity at the site of application in mice; toxic effects on the skin in this species are consistent with those of a primary cutaneous irritant. In rats, possible evidence for toxicity was limited to decreased body weight gains in females treated with letterpress ink formulations.