The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the mechanism of action, the effects after inhalation, the toxicity to fertility, the genotoxicity and carcinogenicity of di(2‐ethylhexyl) phthalate (DEHP). The literature has been searched for new studies relevant to the evaluation of these endpoints. Prenatal toxicity is not included in this evaluation.
A MAK value of 2 mg/m3 for the inhalable fraction has been calculated by toxicokinetic extrapolation from the lowest oral NOAEL of 3.7 mg DEHP/kg body weight and day (90‐day rat study). At the LOAEL (38 mg/kg body weight and day) vacuolization of Sertoli cells was observed. The MAK value is markedly below the NOAEC of 50 mg/m3 in a 28‐day rat inhalation study. The larynx was not investigated in this study. Although it might have been a possible target organ, because the structurally related dibutyl phthalate caused low grade squamous metaplasia in the larynx, this effect is regarded as adaptive.
As systemic toxicity is critical, DEHP is classified in Peak Limitation Category II. The effects are more likely attributable to monoethylhexyl phthalate (MEHP) or its further metabolites. As the initial half‐life of MEHP of 1.9 hours is decisive for the peak concentrations in the blood, an excursion factor of 2 has been established.
DEHP induced hepatocellular adenomas and carcinomas in rats and mice, as well as tumours originating from the enterochromaffin cells of the stomach and from the acinar and islet cells of the pancreas. A new long term study with male rats confirms the data. Since the documentation from 2002 no new mechanistic data or genotoxicity studies have become available which call into question the previous carcinogenicity evaluation. The classification in Carcinogen Category 4 is therefore retained.
As available data for DEHP and its metabolites in vitro and in vivo do not provide any clear evidence of genotoxic effects, DEHP is not classified in one of the categories for germ cell mutagens.
Dermal absorption can provide a relevant contribution to systemic toxicity. DEHP is therefore designated with an “H”. The substance is not sensitising to skin or airways.