Benzophenone-3,3':4,4'-tetracarboxylic dianhydride

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: experimental result, precedes establishment of guideline and GLP. Documentation is limited.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1966

Report date:

1977

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Study precedes establishment of guideline protocols and GLP. Guinea pigs are exposed (full body) to dust of BTDA for 6 hours/day, 5 days per week for 14 days. Animals are euthanized and organs are examined. Specific attention is paid to the immune response in lung and lymph tissue.

GLP compliance:

no

Remarks:

preceeds establishment of GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzophenone-3,3':4,4'-tetracarboxylic dianhydride

EC Number:

219-348-1

EC Name:

Benzophenone-3,3':4,4'-tetracarboxylic dianhydride

Cas Number:

2421-28-5

Molecular formula:

C17H6O7

IUPAC Name:

5-(1,3-dioxo-1,3-dihydro-2-benzofuran-5-carbonyl)-1,3-dihydro-2-benzofuran-1,3-dione

Test material form:

solid: crystalline

Test animals

Species:

guinea pig

Strain:

other: English short-hair

Sex:

not specified

Details on test animals or test system and environmental conditions:

200-300 g body weight.
1530 liter exposure chamber, full body exposure.
The animals were group-housed in metal cages suspended above the droppings. Food and water were available ad libitum.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

not specified

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

Exposure occurred in a 1530 liter stainless steel inhalation chamber. The total air flow through the system was 50 liters per minute.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No attempt was made to determine the actual chamber concentration during the exposure. The mean theoretical concentration was calculated from the air flow and net loss of material.

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

daily for 5 days/week, for two continuous weeks.

Doses / concentrations

Dose / conc.:

136 mg/m³ air (nominal)

Remarks:

Theoretical, as calculated. Ranges up to 251 mg/m3

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

During the 6 hour exposure period, all animals were continuously observed for mortality and toxic effects. Following exposures, the animals were observed daily for possible latent effects. After sacrifice, the animals underwent a necropsy.

Examinations

Observations and examinations performed and frequency:

clinical signs, signs of toxicity, death

Sacrifice and pathology:

necropsy

Statistics:

Theoretical doses were calculated from air flow and net loss of material.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

2 of 10 animals showed marked dyspnea and cyanosis, and later died; survivors displayed sneezing and muscle spasms.

Mortality:

mortality observed, treatment-related

Description (incidence):

2 of 10 animals showed marked dyspnea and cyanosis, and later died; survivors displayed sneezing and muscle spasms.

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Marked to severe but reversible granulomatous pneumonia and hyperplasia of mediastinal lymph nodes. Also moderate diffuse granulomatous mediastinitis.

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not examined

Details on results:

Survivors displayed sneezing, muscle spasms and slight dyspnea. Two of ten animals showed marked dyspnea and cyanosis and later died. Animals showed marked to severe but reversible granulomatous pneumonia and hyperplasia of mediastinal lymph nodes. Moderate diffuse granulomatous mediastinitis was also observed.

Effect levels

Key result

Dose descriptor:

LOAEC

Effect level:

136 mg/m³ air (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Death and toxicity observed. Doses ranged from 136 to 251 mg/m3.

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

136 mg/L air (nominal)

System:

other: granulomatous pneumonia and hyperplasia of mediastinal lymph nodes

Organ:

lungs

lymph node

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

Guinea pigs were exposed by inhalation (whole body) to the dust of 1,3-Isobenzofurandione, 5,5'-carbonylbis- (BTDA), 6 hours per day, five days per week (whole body) for two continuous weeks. Two of twenty animals died, and severe but reversible granulomatous pneumonia, moderate diffuse granulomatous mediastinitis and hyperplasia of lymph nodes was found on necropsy. No NOAEL could be determined, but is presumed lower than 136 mg/m3, (LOAEC), under conditions of this study.