Bis(2-ethylhexyl) phthalate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

One Magnusson-Kligman guinea pig maximization test has been performed, in which female albino Dunkin-Hartley guinea pigs were used (Greenough, 1981). The maximisation test comprised two procedures. The induction procedure consisted of an intradermal injection of the test material into the skin of the shoulder region followed by a topical application 7 days later. The intradermal injection (actually 3 injections) consisted of 0.1 ml Freund’s adjuvant alone, 0.1 ml 10% DEHP in paraffin oil, and 0.05 ml 10% DEHP in paraffin oil emulsified with 0.05 ml Freund’s adjuvant. The control group received 2 injections of Freund’s adjuvant only. For the topical application, a 2.2 cm patch of filter paper was wetted with 50% DEHP in paraffin oil and applied for 48 hours to the pre-treated area. The control group was not subjected to topical application. The challenge procedure which consisted of a topical application was carried out 14 days after the completion of the induction period. In preliminary experiments, a solution of 50% DEHP was determined to be non-irritant; higher concentrations were not tested. A 2 x 2 cm patch wetted with 50% DEHP was applied to a challenge site (on the right flank) of all animals for 24 hours. The degree of response was assessed 24 hours after removal of the challenge patch and rated. Any animal showing erythema at the challenge site was considered to have shown a positive response. DEHP was unequivocally not sensitising in the guinea pig maximization test; there were no positive responses.

Migrated from Short description of key information:

DEHP has not been found to induce skin sensitisation in animals.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Di(2-ethylhexyl) phthalate (DEHP) was tested using for respiratory sensitization in B6C3F1 mice (Butala et al., 2004). This test involves topical application and challenge of DEHP to mice followed by measurements of serum IgE. 

In addition auricular lymph nodes were harvested for measurement of IL-4 and IL-13 proteins and their corresponding messenger RNAs. Liver weight increase, a measure of peroxisomal proliferation, was monitored to assure that internal dosing had been achieved. 

ELISA and RNAse protection assays demonstrated that DEHP treatment did not significantly affect IgE, IL-4 or IL-13 levels. Similarly IL-4 and IL-13 mRNA levels were not elevated. In contrast, all of these were significantly elevated by trimellitic anhydride (TMA), a respiratory sensitizer used as the positive control in this assay. Liver weights were significantly elevated by DEHP, providing evidence of sufficient percutaneous absorption to induce physiological responses.

Under these experimental conditions, DEHP is not considered as a respiratory sensitizer.

The PVC flooring material is an important source for phthalates, but several other sources contribute in indoor environment. PVC products indoors (different surface materials) have been associated with airway effects in epidemiological studies (Jaakkola et al. 2006) but only in one study has the concentrations of di(2-ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBP) been measured (Bornehag et al., 2004). In that study DEHP was associated with asthma and BBP with rhinitis in children at the highest exposure quartile (Bornehag et al., 2004). Long-term exposure to DEHP (Larsen et al 2007) and metabolite, mono-2-ethylhexyl phthalate (Hansen et al. 2007), together with a model allergen did not show promoting effects on the development of the allergen specific IgE antibodies. Phthalates are not skin sensitizers for humans and there is no evidence of respiratory sensitization. Based on the lack of mechanistic support and taking into account the low exposure level of phthalates by inhalation, the EUScientific Committee on Health and Environmental Risks (SCHER, 2007) does not find consistent scientific evidence which indicate that phthalates should be high concern chemicals in indoor air.

Migrated from Short description of key information:

DEHP is not considered as a respiratory sensitizer

Justification for classification or non-classification

According to the criteria edicted in REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008, no classification is warranted for skin and respiratory sensitization.