Isophthaloyl dichloride

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

DuPont assigned Klimisch score. Air concentrations could not be characterized.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1962

Report date:

1962

Materials and methods

Principles of method if other than guideline:

Four male albino rats (CR-CD), weighing initially about 275 grams, were exposed in a glass chamber of 8 litre capacity, 4 hours daily, 5 days a week, for a maximum of 10 exposures/per temperature series. In the room temperature (25 ºC) series, dry air was passed at a flow rate of 2 L/min through the test substance that was packed in a Drierite tube and into the chamber. In two additional series (60 ºC and 150 ºC), the test substance was placed in a 1 litre three-necked flask which was heated by means of an electric heating mantle controlled to the desired temperature by a Brown Electronik controller-recorder and dry air was passed over the sample at a flow rate of 2 L/min and into the glass chamber containing four rats.
A fresh sample of test substance was used each day of exposure.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isophthaloyl dichloride

EC Number:

202-774-7

EC Name:

Isophthaloyl dichloride

Cas Number:

99-63-8

Molecular formula:

C8H4Cl2O2

IUPAC Name:

benzene-1,3-dicarbonyl dichloride

Details on test material:

- Analytical purity: >99% Isophthaloyl Chloride

Test animals

Species:

rat

Strain:

other: CR-CD, albino

Sex:

male

Details on test animals or test system and environmental conditions:

- Weight at study initiation: about 275 grams.
- Rats were albino.

Administration / exposure

Route of administration:

other: vapour and dust

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus, source and rate of air: In the experiment at room temperature (25 ºC) the test substance was packed in a small Drierite tube and dry air at a flow rate of 2 L/min was passed through it and into the chamber containing four rats. In the experiments with test substance heated above room temperature, the sample was placed in a 1 liter three-necked flask which was heated by means of an electric heating mantle controlled to the desired temperature by a Brown Electronik controller-recorder and dry air was passed over the sample at a flow rate of 2 L/min and into the glass chamber containing four rats.
At higher temperatures some of the test substance recondensed on the walls of the chamber and the tubing leading to it. Thus, calculations of the inhaled concentrations were not possible.

- Test material concentrations
25 ºC: 20 gm sample - some deposits of the test substance were observed on the walls of the chamber.
60 ºC: 20 gm sample - some deposits of the test substance were observed on the walls of the chamber.
150 ºC: 20 gm sample - some deposits of the test substance were observed on the walls of the chamber.

-Exposure chamber volume: 8L

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Concentrations could not be characterized

Duration of treatment / exposure:

4 hours

Frequency of treatment:

5 days/week for 2 weeks. (Ten 4-hr exposures)

Doses / concentrations

Remarks:

Concentrations could not be characterized

No. of animals per sex per dose:

4

Control animals:

not specified

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

25 ºC x 4 hrs x 10 exposures:
Clinical signs during exposure were minimal. For the most part, rats gained weight throughout the course of the exposures and during the 14-day observation period. 2 rats were sacrificed immediately and 2 were sacrificed after a 14 day observation period.
- 2/2 rats sacrificed immediately after the tenth exposure showed moderate pulmonary congestion. 1/2 rats sacrificed 14 days later showed pulmonary congestion. 4/4 rats had increased kidney weights over controls. On microscopic examination of the lungs, a slight amount of pulmonary
edema was noted in the rats sacrificed at the end of exposure but not in those sacrificed 14 days after exposure. There was a slight increase in
pneumonitis, catarrhal alveolitis and emphysema in all exposed animals. No significant changes were detected in brain tissue. The liver showed minimal hypotrophy of cells in the area adjacent to the portal tracts.

60 ºC x 4 hrs x 10 exposures:
Clinical signs during exposure were minimal. All rats survived, and for the most part, gained weight during exposure but at a slightly reduced rate.
Two rats were sacrificed immediately after the tenth exposure. The remaining two were held for a 14-day observation but through error were discarded. Examination of the lungs of the two rats which were sacrificed revealed slight aggravation of the usual pneumonitis as well as slight edema and emphysema. A slight degree of hypotrophy of liver cells in the region adjacent to the portal tracts was noted. The kidneys revealed slight swelling of the glomeruli and slight hypotrophy of the proximal convoluted tubules.

150 ºC x 4 hrs x 5 exposures:
Clinical signs during exposure consisted of eye irritation, deep and irregular respiration and gasping. One rat died during the fourth exposure. All rats lost weight during the exposures and the survivors were sacrificed three days after the fifth exposure. When examined grossly, all rats were emaciated and dehydrated; and many of the organs appeared hypotrophic. Microscopic evaluation revealed aggravation of the usual endemic pneumonitis, relatively pronounced emphysema, focal hemmorrhates, alveolar cell desquamation, suppurative bronchiolitis and bronchopneumonia. Impairment of the liver cells was relatively pronounced. Kidney changes were qualitatively similar to those noted at 60C, but were more pronounced. There was a variably severe hyperemia of the brain.

Effect levels

Dose descriptor:

other: NOAEL could not be established because air concentrations could not be characterized

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Ten 4-hr exposures to air passed through the material at 25 ºC or over it at 60 ºC were not fatal and produced relatively limited pathological changes which were mainly confined to the lungs, with lesser effects on the liver and kidneys. Repeated exposures to air passed over isophthaloyl chloride at 150 ºC, however, resulted in the death of one animal during the fourth exposure. Since the remaining three rats were showing pronounced irritation, illness, and weight loss, they were sacrificed 3 days after the fifth and last exposure. Pathological changes were more severe than those noted in the other exposures. The effects of the test substance are primarily those of an irritant. It is recommended that prolonged and repeated inhalation of the dust at room temperature or of the vapours and dust at elevated temperatures be avoided, and that the concentration of the test substance in the atmosphere be kept below the level of sensory irritation.

Executive summary:

The effects of the test substance are primarily those of an irritant. It is recommended that prolonged and repeated inhalation of the dust at room temperature or of the vapours and dust at elevated temperatures be avoided, and that the concentration of the test substance in the atmosphere be kept below the level of sensory irritation.