Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No hematology, urinalysis or clinical chemistry analyses were performed.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Phthalate esters carcinogenicity in F344/N rats and B6C3F1 mice
Author:
Huff JE, Kluwe WM
Year:
1984
Bibliographic source:
Ind. Hazards Plastics Synthetic Elastomers, 137-154.
Reference Type:
publication
Title:
Carcinogenic potential of phtahlic acid esters and related compounds: structure-activity relationships
Author:
Kluwe WM (1986). Carcionogenic potential of phtahlic acid esters and related compounds: structure-activity relationships. Environ. Health Perspect 65, 271-278.
Year:
1986
Bibliographic source:
Environ. Health Perspect 65, 271-278.
Reference Type:
study report
Title:
Unnamed
Year:
1979
Title:
No information
Author:
U.S. EPA Integrated Risk Information System (IRIS)
Year:
2004
Bibliographic source:
http://www.epa.gov/IRIS/subst/0308.htm (December 15, 2004).
Report Date:
2004

Materials and methods

Principles of method if other than guideline:
50 male and female rats each (20 male and 20 female rats as control) were fed doses of the test substance of 0, 7.500, or 15.000 ppm (ca. 0, 500, 1000 mg/kg bw/d for 102-106 consecutive weeks, followed by sacrifice, necropsy and histopathological examination of major organs and tissues.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: purity 98.8 %

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: diet
Duration of treatment / exposure:
105 week
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
7500, 15000 ppm = ca. 500, 1000 mg/kg bw/d
Basis:

No. of animals per sex per dose:
50 male and 50 female rats
Control animals:
yes, concurrent no treatment
Details on study design:
Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

F344 rats (50/sex/group) were fed diets containting 7500 or 15,000 ppm  phthalic anhydride for 105 weeks (approx. 500 and 1,000 mg/kg bw/day).  The observation that the testcompound is unstable (2.59% loss of activity  per day at room temperature) has to be noted, although this is of minor  relevance because the diet was prepared fresh every 1 to 1-1/2 weeks and  the diet was stored at 5 degree Celsius, consequently the hydrolysis is  assumed to be lower than 26%.

Body Weights and Clinical Signs
The mean body weights of the high-dose males were lower than the controls
from week 13 to the end of the study, but the decrease was never more than 10%. Mean body weights of the low-dose males and both the low- and high-dose females were essentially unaffected by the test compound.

Survival
No statistical significant difference in mortality was observed in any group.
Survival male rats: high-dose group 36/50 (72 %) low-dose group 44/50 (88),
control group 14/20 (70 %)
Survival female rats: high-dose group 41/50 (82 %), low-dose group 42/50 (84 %),
control group 17/20 (85 %)

Pathology
Severe chronic inflammatory, degenerative, or proliferative lesions frequently
seen in aged rats occurred with approx. equal frequency and severity in the dosed and control groups of animals.

Based on the reduced body-weight gain (<10 %) the NOAEL in this study was 500 mg/kg/day.

Applicant's summary and conclusion

Executive summary:

50 male and female rats each (20 male and 20 female rats as control) were fed daily doses of the test substance of 0, 7.500, or 15.000 ppm (ca. 0, 500, 1000 mg/kg bw/d for 102-106 consecutive weeks, followed by sacrifice, necropsy and histopathological examination of major organs and tissues.

The NOAEL = 500 mg/kg/day, based on the reduced body-weight gain (<10%)

reference: Huff, 1984; Kluwe, 1986; NCI, 1979