DINP Information Center

Endocrine disruption

Photo: Healthy babiesDINP is not an endocrine disruptor as defined by the internationally accepted definitions for endocrine disruption (the Weybridge definition and the International Programme for Chemical Safety (IPCS) definition) and it is not an endocrine disruptor according to the criteria in the EU REACH guidance1

In other words, DINP is not responsible for any adverse effects mediated via the endocrine system in humans, animals, fish or other species.

DINP has on occasion, been mistakenly referred to as being an endocrine disruptor. This is not correct. Confusion has arisen because some experiments suggested unexpectedly that DINP might affect the reproductive system via disrupted function of the hormones oestrogen and testosterone. More than 10 years ago, assessments of the oestrogenic potential of DINP using yeast cells and human cell models showed a weak response for DINP. The report authors warned that the relevance of these results to a whole animal was unclear and that further tests were recommended2. Additional tests were carried out in cells and in suitable whole-animal models and the original findings were not confirmed3. Additionally, proposed effects of DINP on testosterone from a screening study4 were not confirmed in the robust two-generation rodent study5.

The two-generation rodent study, is considered by the OECD as the most robust in confirming whether a substance is a potential endocrine disruptor of the reproductive system or not. DINP was found not to cause any adverse effects on reproduction in this study. The conduct of this study, and the overall potential of DINP to cause adverse health effects on the reproductive system via endocrine disruption, was carefully analysed as part of the EU risk assessment process. In this case, the EU risk assessment clearly concluded that DINP should not be classified as a reproductive agent. In addition DINP has shown no evidence of endocrine related effects in sub-chronic and chronic toxicology studies.

Additionally, the experts on the EU Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) agree with the conclusions of the risk assessment that the effects observed in the available studies do not justify classification for effects on fertility or development. Since then, limited studies have been conducted on the association between endocrine disruption and the presence of phthalate metabolite levels in human breast milk and urine. These studies support the lack of association between exposure to DINP and adverse changes in endocrine sensitive health effects.

DINP is included on List 2 (test tube evidence) of the DG Environment List of Potential Endocrine Substances for further evaluation. The basis for this listing is unclear but is possibly related to the studies in human and yeast cells which were not confirmed in additional tests. DINP has already been "further evaluated" in extensive tests and it is unclear at this stage what additional tests could be done to further evaluate DINP. Based on all the evidence DINP should be moved to List 3a (No scientific basis for inclusion).

With regard to effects on fish and aquatic organisms, the Oslo Paris Commission for the Protection of the Marine Environment concluded that DINP is not an endocrine disruptor and as a result removed DINP from the List of Chemicals for Priority Action and the List of Chemicals of Possible Concern. In addition, a multigeneration study in fish, and studies on invertebrates have shown no evidence of endocrine related effects.

The European Union has confirmed that DINP is safe in all its current uses and applications. The use of DINP is restricted for use in PVC toys which can be placed in the mouth based on the precautionary principle. These restrictions were first put in place in 1999, and were confirmed in 2005 prior to the publication of the European Union's Risk Assessment in 2006. These restrictions were not based on any concerns related to endocrine effects. DINP is one of the most widely studied and evaluated substances in the world and has been subject to intensive scrutiny over the last 30 years, with demonstrated safe use for over 40 years.

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  1. The definition for endocrine effects according to the Weybridge definition, International Programme for Chemical Safety (IPCS) and the REACH Guidance require evidence of adverse health effects in intact organisms, or progeny, or subpopulations mediated via an effect on functioning of the endocrine system.
  2. "The estrogenic activity of phthalate esters in vitro. " Harris CA, Henttu P, Parker MG, Sumpter JP. Environ Health Perspect. 1997 Aug; 105(8):802-11.
  3. "Examination of the in vitro and in vivo estrogenic activities of eight commercial phthalate esters." Zacharewski TR, Meek MD, Clemons JH, Wu ZF, Fielden MR, Matthews JB. Toxicol Sci. 1998 Dec; 46(2):282-93.
  4. Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats. Borch J, Ladefoged O, Hass U, Vinggaard AM. Reprod Toxicol. 2004 Jan-Feb; 18(1):53-61.
  5. Two-generation reproduction study in rats given di-isononyl phthalate in the diet. Waterman SJ, Keller LH, Trimmer GW, Freeman JJ, Nikiforov AI, Harris SB, Nicolich MJ, McKee RH. Reprod Toxicol. 2000 Jan-Feb; 14(1):21-36.