Registration Dossier

Toxicological information


Currently viewing:

Administrative data

Description of key information

Key value for chemical safety assessment

Justification for classification or non-classification

Non-classification justified on the basis of lack of concern in structurally related phthalate esters that have been examined and subjected to formal risk assessment.

Additional information

Several phthalates ranging from C8-C11 have been tested for repeat-dose toxicity in studies ranging from 21 days to two years. (Barber, E.etal. Peroxisome induction studies on seven phthalate esters. Toxicology and Industrial Health 3: 7-22, 1987. Butala, J.etal. (1996). Oncogenicity study of di(isonony1)phthalate in rats. The Toxicologist 30: 202; Lington, al.Chronic toxicity and carcinogenic evaluation of diisononyl phthalate in rats. Fundamental and Applied Toxicology 36: 79-89, 1997;David, R.etal. Esters of aromatic mono-, di-, and tricarboxylic acids, aromatic diacids and di-, tri-, or polyalcohols.In:Patty's Toxicology, Fifth edition, Vol. 6, Bingham E., B. Cohrssen and C.H. Powell (eds.), John Wiley & Sons, Inc. pp. 635-932, 2001).The principal effects found in these studies were those associated with peroxisomal proliferation, including liver enlargement and induction of peroxisomal enzymes. The strongest inducers of peroxisomal proliferation were DEHP, DINP and DIDP with substances of shorter and longer ester side chains (C6-C10, C7-C11 and C11) showing less pronounced effects. It has been concluded that members of the category would show similar but not more pronounced effects than those associated with DINP and DIDP. The relevance of these findings to human health is regarded as questionable as it has been shown that such effects are mediated through the peroxisome proliferation-activated receptor alpha (PPARα); (Valles, E.etal.Role of PPAR alpha in response to diisononyl phthalate (DINP). The Toxicologist 54: 418, 2000 and Ward, J .etal.Receptor and nonreceptor-mediated, organ-specific toxicity ofdi(2-ethylhexy1)phthalate(DEHP) in peroxisome proliferator-activated receptor alpha-null mice. Toxicologic Pathology 26: 240-246, 1998) and that levels of PPARα are much higher in rodents than humans (Tugwood, J.etal.(1996). Peroxisome proliferator-activated receptors: Structure and Function. Annals of theof Sciences Vol. 804., pp. 252-265, 1996 andPalmer, C.etal.Peroxisome proliferator activated receptor alpha expression in human liver. Molecular Pharmacology 53: 14-22,1998). Humans are thus expected to be significantly less responsive than rodents to peroxisome proliferating agents.


This is reflected in EU assessment of a number of phthalates (Commission Communication on the results of the risk evaluation and the risk reduction strategies for the substances: Dibutylphthalate; 3,4-Dichloroaniline; Di-isodecyl phthalate; 1,2-Benzenedicarboxylic acid, di-C9-11-branched alkyl esters, C 10-rich; Di-isononyl phthalate; 1,2-Benzenedicarboxylic acid, di-C8-1O-branched alkyl esters, C9-rich; Ethylenediaminetetraacetate; Methyl acetate; Monochloroacetic acid; n-Pentane; Tetrasodium ethylenediaminetetraacetate. Official Journal of the European Union 13th April 2006, 2006/C 90/04). The risk evaluation activities with regard to man and the environment was conducted in accordance with Commission Regulation (EC) No. 1488/94 of 28th June 1994. Di-isononyl phthalate (a C9 phthalate), 1,2-benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich (a C8-C10 phthalate), di-isodecyl phthalate (a C10 phthalate) and 1,2-benzenedicarboxylic acid, di-C9-1 1-branched alkyl esters, C 10-rich (a C9-C11 phthalate) are all not classified and the conclusion of the assessment of the risks to workers, consumers and man exposed via the environment was that there is no need for further information and/or testing or for risk reduction measures beyond those already applied. This conclusion was reached because the risk assessments show that risks are not expected.