Tetrachlorophthalic anhydride

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1993

Reference 2

Reference Type:

publication

Title:

Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats

Author:

Travlos GS, Morris RW, Elwell MR, Duke A, Rosenblum S, Thompson MB

Year:

1996

Bibliographic source:

Toxicology 107, 17-29

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Groups of 10 rats of each sex received TCPA (tetrachlorophthalic anhydride) in corn oil vehicle by oral gavage (5 days/week) at doses of 0, 94, 187, 375, 750, and 1500 mg/kg. All animals were observed twice daily for morbidity and mortality and detailed clinical signs. Food consumption was recorded weekly and individual body weights were recorded at study initiation and then weekly thereafter until study term. The examinations performed included reproductive system, clinical pathology, and histopathologic evaluations.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachlorophthalic anhydride

EC Number:

204-171-4

EC Name:

Tetrachlorophthalic anhydride

Cas Number:

117-08-8

Molecular formula:

C8Cl4O3

IUPAC Name:

tetrachloro-1,3-dihydro-2-benzofuran-1,3-dione

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

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

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 94, 187, 375, 750 or 1500 m/kg/d
Basis:
actual ingested

No. of animals per sex per dose:

Ten (10) male and 10 female F344 rats/dose

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

2

Dose descriptor:

LOAEL

Effect level:

94 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on microscopic kidney lessions in males and females

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The deaths of 5 male rats and 1 female rat in the 1500 mg/kg dose group and 1 female rat in the 750 mg/kg dose group were considered due to chemical toxicity. Mean final body weights and body weight gains were depressed in male rats in the 375, 750, and

1500 mg/kg groups and in all groups of female rats receiving TCPA. No clinical pathology changes or hematological changes were clearly associated with chemical exposure.

Relative liver weights were slightly increased in males and females at doses of 187 mg/kg and higher, although a dose relationship was not apparent. Heart weights of surviving male rats in the high-dose group were also increased. Male and female rats exhibited dosedependent increases in kidney weights and in the incidence and severity of renal tubule necrosis and/or dilation.

Applicant's summary and conclusion

Executive summary:

Groups of 10 rats of each sex received TCPA (tetrachlorophthalic anhydride) in corn oil vehicle by oral gavage (5 days/week) at doses of 0, 94, 187, 375, 750, and 1500 mg/kg. All animals were observed twice daily for morbidity and mortality and detailed clinical signs. Food consumption was recorded weekly and individual body weights were recorded at study initiation and then weekly thereafter until study term. The examinations performed included reproductive system, clinical pathology, and histopathologic evaluations.

The deaths of 5 male rats and 1 female rat in the 1500 mg/kg dose group and 1 female rat in the 750 mg/kg dose group were considered due to chemical toxicity. Mean final body weights and body weight gains were depressed in male rats in the 375, 750, and

1500 mg/kg groups and in all groups of female rats receiving TCPA. No clinical pathology changes or hematological changes were clearly associated with chemical exposure.

Relative liver weights were slightly increased in males and females at doses of 187 mg/kg and higher, although a dose relationship was not apparent. Heart weights of surviving male rats in the high-dose group were also increased. Male and female rats exhibited dosedependent increases in kidney weights and in the incidence and severity of renal tubule necrosis and/or dilation.

In summary, clear evidence of organ toxicity following administration of TCPA in corn oil by gavage for 13 weeks was limited to the kidney of rats. The no-observed-adverseeffect level for histopatholologic lesions in this tissue was not achieved with doses as low as 94 mg/kg per day.