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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed by the US National Toxicology Program on the related substance tetrachlorophthalic anhydride.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Tetrachlorophthalic anhydride
EC Number:
204-171-4
EC Name:
Tetrachlorophthalic anhydride
Cas Number:
117-08-8
IUPAC Name:
4,5,6,7-tetrachloro-2-benzofuran-1,3-dione
Details on test material:
Obtained from Aldrich Chemical Company, Milwaukee, WI. 99% in purity.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
Obtained from Simonsen Laboratories, Gilroy, CA.
Acclimated ~14 prior to start of study.
Age at study inititation: Rats (6 wks), Mice (5 wks)
Assigned to groups randomlly.
Fed NIH-07 Open Formula Mash ad libitum
Rats house 5/cage; Mice individually
Temperature 67-77 degrees F
30-70% relative humidity
Minimum of 10 air changes/hr.
Lighting 12 hr/d.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Once daily, 5 d/wk, for 13 weeks.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 94, 187, 375, 750, 1500 mg/kg bw
Basis:
other:
No. of animals per sex per dose:
10M/10F/dose
Control animals:
yes, concurrent vehicle
Details on study design:
wieghed weekly. necropsies on all animals. Measured weight of brain, heart, right kidney, liver, lung, spleen, right testis, and thymus. Complete histopathology on controls, all animals in the highest dose group with at least 60% survival, and on all animals including those that dies or were killed moribund before the end of the studies in the higher dose groups. Target tissues ID'd, and examined in all animals from the lower dose groups until a no effect level was determined. all gross lesions also examined histologically. In rats, the target organ was the kidney and was evaluated in all males and females in all dose groups. No target organs were ID'd in mice.

Clinical pathology performed in rats i nteh 0, 94, 375 and 1500 mg/kg groups on days 6, 20, and at the end of the study. Hematology performed in all animals at end of study. blood collected via retroorbital sinus after CO2 anesthesia.

Sperm morphology in male rats from the 0, 94, 375 and 750 mg/kg groups. Vaginal cytology performed on female rats from the 0, 94, 375 and 1500 mg/kg groups. Similar exams on mice in hte 0, 94, 375 and 1500 mg/kgg. Methods were those of Morrissey et al. 1988.




Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
5 M rats, 1500 mg/kg, died during wks 5-8 due to toxicity. 2 F rats, 1 each @ 750 and 1500 mg/kg died during wks 6 - 10 due to xicity.
Mortality:
mortality observed, treatment-related
Description (incidence):
5 M rats, 1500 mg/kg, died during wks 5-8 due to toxicity. 2 F rats, 1 each @ 750 and 1500 mg/kg died during wks 6 - 10 due to xicity.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean final body weights and weight gains of male rats in the 375, 750 and 1500 mg/kg groups and F rats in all dose groups were less than those of controls
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Decreased in rats of all groups.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Absolute and relative kidney weights increased in dose-dependednt manner in female rats. In males increased relative kidney weights from 187 mg/kg and above.
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
In male rats, renal tubule degnerative changes characterized by tubule epitheial necrosis at the higher dose levels and tubule dilation at lower dose levels. Necrosis of the tubule epithelium was seen in the nmajority ofmale and female rats in the 1500 m
Details on results:
Sperm morphology and vaginal cytology evaluations in rats revealed no changes between control and treated animals.

Effect levels

Dose descriptor:
LOAEL
Effect level:
94 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Clear evidence of renal toxicity.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Clear evidence of renal toxicity in rats was observed following administration of tetrachlorophthalic anhydride in corn oil by gavage for 13 weeks. The no-observed-adverse-effect level for histopathological lesions in this tissue was not achieved with doses as low as 94 mg/kg/d.
Executive summary:

Clear evidence of renal toxicity in rats was observed following administration of tetrachlorophthalic anhydride in corn oil by gavage for 13 weeks. The no-observed-adverse-effect level for histopathological lesions in this tissue was not achieved with doses as low as 94 mg/kg/d.