Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Due to several shortcomings, this study is not adequate for hasard assessment.

Data source

Reference
Reference Type:
publication
Title:
Electron microscopical and cytochemical observations of the mouse liver following the Administration of phthalate ester (DOP).
Author:
Watari N, Kanai M, Torizawa K
Year:
1978
Bibliographic source:
J. Clin. Electron Microscopy 11, 103-120

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
other: DDY
Sex:
not specified

Administration / exposure

Type of coverage:
not specified
Vehicle:
olive oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
no data
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0.2 ml of a 10, 30, 50, or 100% solution
Basis:

No. of animals per sex per dose:
3 animals per dose group in a first experiment and 2 per group in a second
Control animals:
yes, concurrent vehicle

Examinations

Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
Macroscopically, the liver was greatly enlarged, lacked elasticity, and had a dark brown colour. Inflammatory signs were observed in the peritoneum in the two highest dose groups.
Structural alterations of the liver tissues were observed by light and electron microscopy and by cytochemistry in all dosed groups. In hepatic cells, the nuclei were atrophied and frequently contained fat droplets. The smooth endoplasmic reticulum was proliferated and vesiculated.
Mitochondria were decreased in size and some were degenerated. An unusual proliferation of the microbodies and their morphological alterations were found.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

DEHP (purity not specified) was percutaneously administered to DDY-mice (3 animals per dose group in a first experiment and 2 per group in a second) as daily doses of 0.2 ml of a 10, 30, 50, or 100% solution in olive oil for one month. Macroscopically, the liver was greatly enlarged, lacked elasticity, and had a dark brown colour. Inflammatory signs were observed in the peritoneum in the two highest dose groups. Structural alterations of the liver tissues were observed by light and electron microscopy and by cytochemistry in all dosed groups. In hepatic cells, the nuclei were atrophied and frequently contained fat droplets. The smooth endoplasmic reticulum was proliferated and vesiculated. Mitochondria were decreased in size and some were degenerated. An unusual proliferation of the microbodies and their morphological alterations were found.

The authors concluded that the results showed that DEHP is absorbed percutaneously and accumulates in the mouse liver resulting in damage to the cellular organelles.