Bis(2-ethylhexyl) phthalate

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Adequacy of study:

other information

Data source

Reference

Title:

No information

Author:

World Health Organization, International Agency for Research|on Cancer: IARC Monographs on the Evaluation of the|Carcinogenic Risk of Chemicals to Humans; DEHP; 77, 41-148|(2000)

Materials and methods

Type of study / information:

Type: other: Review (WHO; carcinogenicity, reproductive toxicity)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) phthalate

EC Number:

204-211-0

EC Name:

Bis(2-ethylhexyl) phthalate

Cas Number:

117-81-7

Molecular formula:

C24H38O4

IUPAC Name:

1,2-bis(2-ethylhexyl) benzene-1,2-dicarboxylate

Results and discussion

Any other information on results incl. tables

RS-Freetext:
DEHP is ubiquitous in the general environment. Occupational
exposure is usually <1mg/m³, concentration in ambient air is
usually <0.1 mg/m³. Highest levels are found in foods rich
in fat, e.g. milk, where concentrations up to 10 mg/kg were
found. Large exposure may result from DEHP leaching out of
medical devices, e.g. during dialysis.

Human carcinogenicity data: one small (limited power) study
failed to show excess cancer mortality.
Animal carcinogenicity data: carcinogenic in rodents.
Considerable amount of information is available that
carcinogenicity is related to peroxisome proliferation via
binding an activation of the nuclear peroxisome proliferator
receptor a. This phenomenon is given in rodents, but not in
man.

Exposure during of rat and mice during organogenesis caused
malformations and fetal death. One study in knock-out mice
suggested that this was not mediated by the peroxisome
proliferator receptor a. No human reproductive and
developmental effect data were available. Exposure of rats
and mice to DEHP impaired fertility and damaged testes.
Young animals were much more susceptible. This effect was
independent from peroxisome proliferator receptor a as
evidenced in studies using knock-out animals. Sertoli cells
were the main target in the testes.

DEHP was extensively examined for genotoxic effects in vivo
and in vitro. However, the vast majority of results was
negative. No DNA-binding was found nor were DNA-strand
breaks.

Applicant's summary and conclusion

Conclusions:

CL-Freetext:
Evaluation:
There is adequate evidence of carcinogenicity in
experimental animals, and inadequate evidence of
carcinogenicity in humans.

Overall evaluation: DEHP is not classifiable as to its
carcinogenicity in humans (Group 3).

The overall evaluation takes into account:
a) carcinogenicity in rodents was not dependant on
DNA-binding but involved peroxisome proliferation
b) peroxisome proliferation and hepatocellular proliferation
were noted in rodents during carcinogenicity studies
c) peroxisome proliferation has not been demonstrated in
humans

It was therefore concluded that the mechanism of
carcinogenicity in rodents is not relevant to humans.