Final Report on the Safety Assessment of 4-Methoxy-m-Phenylenediamine, 4-Methoxy-m-Phenylenediamine Sulfate, and 4-Methoxy-m-Phenylenediamine-HCl

Abstract

The hair dye ingredient 4-Methoxy-m-Phenylenediamine Sulfate (4-MMPDS) prior to 1978 was used extensively used in the United States. Concerns raised because of studies which showed the hair dye to be an animal carcinogen prompted the voluntary reformulation and deletion of 4-MMPD in hair dyes containing this ingredient. No reports were made on the use of this ingredient until 1989 when 17 uses were reported. Assays on volunteers indicate that less than 0.2% of the dye penetrates the scalp and that about 3.9% is absorbed through the skin of the forearm. The dye is metabolized and excreted in the urine; a major metabolic product was 4-acetylamino-2-aminoanisole. The LD50 range in rats of aqueous solutions of 4-MMPD was 400–500 mg/kg. No gross tissue abnormalities were reported in subchronic feeding or dermal studies. 4-MMPD was not an ocular irritant when tested at 2.5%, but was a mild skin irritant when tested at the same concentration. The dermal application of hair dye formulations containing up to 4.0% 4-MMPD were negative for both embryotonic toxicity and teratogenic effects. The results of numerous mutagenic studies vary between the assay system used. 4-MMPD was noncarcinogenic in four dermal carcinogenic studies, but was carcinogenic to both rats and mice in feeding studies. On the basis of the information included in this report, it is concluded that 4-Methoxy-m-Phenylenediamine, 4-Methoxy-m-Phenylenediamine Sulfate, and 4-Methoxy-m-Phenylenediamine HCl are unsafe for use in cosmetic products.