A developmental toxicity and psychotoxicity evaluation of FD and C Red Dye #3 (erythrosine) in rats

Abstract

Two experiments were conducted to evaluate FD and C Red Dye #3 for its developmental toxicity and psychotoxicity. Adult Sprague-Dawley rats were fed diets containing the dye for 2 weeks and were then bred. The diets were continued for the females throughout gestation and lactation and were provided continuously to their offspring thereafter. The treatment groups for Experiment 1 were Red Dye #3 as 0.0, 0.25, 0.5, or 1.0% of the diet (w/w), and a positive control group treated with the toxin hydroxyurea on days 2-10 of life (50 mg/kg/day, s.c.); Experiment 2 was a replication of Experiment 1 with the same dose groups, but without the positive control group. Parental animals were evaluated for weight and food consumption, and females for reproductive success. The offspring were assessed on a series of tests using the Cincinnati Psychoteratogenicity Screening Test Battery, plus weight, food consumption, physical landmarks of development, and brain weight. Red-3 produced no reductions in parental or offspring weight or food consumption. Red-3 significantly increased preweaning offspring mortality in the first experiment, but not in the second. Behaviorally, Red-3 produced no dose-dependent effects that replicated across the two experiments. It was concluded that no evidence was obtained that dietary exposure to FD and C Red Dye #3 (erythrosine) is psychotoxic to developing rats.

Toxicity of food colours and additives: A review

“…A number of studies have also failed to establish significant dose-related adverse effects in the reproductive toxicity and post-partum development of F0 and F1 generation of rats that received erythrosine (Vorhees et al, 1983;JECFA, 1986;Tanaka, 2001). Erythrosine has also been discovered to possess no psychotoxic potential in developing rats (Vorhees et al, 1983).…”

“…A number of studies have also failed to establish significant dose-related adverse effects in the reproductive toxicity and post-partum development of F0 and F1 generation of rats that received erythrosine (Vorhees et al, 1983;JECFA, 1986;Tanaka, 2001). Erythrosine has also been discovered to possess no psychotoxic potential in developing rats (Vorhees et al, 1983). Erythrosine, however, was adjudged to have potential toxic effects on the reproductive process in male adult mice causing a decrease in the epididymal sperm count and motility as well as an increased frequency in sperm abnormalities (Abdel-Aziz et al, 1997;Vivekanandhi et al, 2006 …”

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

“…Vorhees et'al. ( 1983a ) , supported in part by FDA, used hydroxyurea as a positive control in a study to evaluate postnatal developmental toxicity induced by FD&C Red Dye #3 in rats. The experiment for FD&C Red Dye #3 will not be discussed here.…”

“…Most of these studies involved administration on a single day of gestation or on a restricted number of days (e.g., GD 9–12), limiting their utility for an evaluation of the entire gestational period. There are two studies (Vorhees et al, 1983a, b) involving postnatal administration of hydroxyurea to developing experimental animals. There are experimental animal studies addressing mechanism of action.…”

Scientific Opinion on the re-evaluation of Erythrosine (E 127) as a food additive

“…In developmental toxicity studies, Erythrosine does not adversely affect development of young animals at dose levels up to 500 mg/kg bw/day, which is the highest dose level tested for this endpoint. There are no indications, based on the studies evaluated by JECFA and SCF, that Erythrosine can adversely affect male fertility at dose levels up to 2000 mg/kg bw/day, which is the highest dose levels tested (Albridge et al, 1981;Vorhees et al, 1983). Two more recent studies have however indicated that Erythrosine may affect testicular function.…”