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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No details provided in report
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)
GLP compliance:

Test material

Constituent 1
Reference substance name:
diallyl phthalate
diallyl phthalate
Test material form:
Details on test material:
The test material is described as a light, straw coloured liquid and is said to have been labeled: "FMC Corp., Chemical and Development Center, Box 8, Princeton, N.J., 08540, 179-313, E104-2, For experimental use only." The test substance was received on March 11, 1980.

Test animals

Details on test animals or test system and environmental conditions:
Supplier: Charles River Breeding Laboratories, Wilmington, Massachusetts
Received: March 25, 1980
Pre-exposure body weights: 256-288 g (males); 227-247 g (females)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
(Dry air, flow rate 15 L per minute)
Details on inhalation exposure:
- The test material was placed in a 500 ml graduated cylinder connected to an FMI fluid metering pump (Model ARPG 201 with a 1/3 inch piston set to deliver at 60%. The test material was fed directly into a Round Spray Atomizing Nozzle mounted inside the 100 liter plexiglass chamber housing the test animals. Dry air, at a flow rate of 15 liters per minute, was passed through the atomizer to generate the aerosol. The exlosure lasted for four hours.
- The air temperature and humidity were monitored continuosly using a wet bulb/dry bulb hygrometer, during the exposure and readings were recorded hourly.
- The nominal exposure concentration was 67.2 mg/L
- The mean airborne concentration was 4.47 mg/L which represents 7% of the nominal exposure concentration
- The average aerodynamic mass median diameter of the aerosol particles was 2.51µm, with a geometric standard deviation range of 2.39 to 3.60 (See Table 2 of the attached report)
- The mean temperature in the chamber during the test material exposure was 69°F and the mean relative humidity was 85%
Analytical verification of test atmosphere concentrations:
Gas Chromatography-analysis of samples on charcoal tubes taken hourly during exposure
Duration of exposure:
4 h
- The nominal exposure concentration was 67.2 mg/L
- The mean airborne concentration was 4.47 mg/L which represents 7% of the nominal exposure concentration
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration:
- Frequency of observations and weighing: Air temperature and humidity were monitored continuosly during the exposure and readings were recorded hourly. Samples of the chamber atmosphere were taken at approximately 1, 2, 3 and 4 hours into the exposure. Particle size distribution samples were taken at approximately 30 minute intervals during the exposure.
- Necropsy of survivors performed: yes (Gross necropsy examinations were performed as soon as posstble after death on all animals dying spontaneously)
- Other examinations performed: clinical signs, body weight and histopathology (tissues for histopathological examination: lungs, liver, kidneys and any gross lesions)

No details provided in report

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
4.47 mg/L air
Exp. duration:
4 h
On day 1, 4 out of 5 males died and all females died. The remaining male died the following day.
Clinical signs:
other: Reddening of nasal tissues (mucosal surfaces, nasal turbinates), lung lobes and liver in all animals. Further observations were vascularized and friable brain, reddening of brain tissue, kidney medulla and/or the glandular surface of stomach.
Body weight:
Only the male rat, which died on day 2 was weighed and its body weight had decreased from 270 to 235 g.
Gross pathology:
No data presented.

Any other information on results incl. tables

- During the exposure period, all visible animals exhibited closed eyes, reduced activity, labored breathing, and wet and matted fur. Some lacrimation and salivation were observed and one female exhibited chromodacryorrhea. Observations of abnormal signs commenced at the 15-minute interval of exposure and disappeared by exposure termination or during the four-hour post-exposure periodexcept laboured breathing, which persisted until death.

- During the post-exposure period mucoid nasal discharge, laboured breathing with occasional gasping, wet and matted fur, purple skin coloration, flushed skin, stained fur around the eyes, nose and/or mouth, dilated pupils, loss of pupillary reflexes, and rough, dry and/or dull corneal surfaces were most frequently observed. Lacrimation, salivation, shallow breathing, dry rales, uncoordinated movement, general poor condition, lack of grip, prostration, yellow stained ano-genital fur, brown stained ano-genital fur miosis, and corneal opacity were observed less frequently. A complete list of exposure and post-exposure observations is presented in Table 3 (although not attached in the reprot).

- By the 480 -minute interval, one of ten rats died. By the morning of Day 1 eight more animals had died, and the surviving animal died after observation on Day 1. Observations for this animal on Day 1 include reduced activity yellow stained ano-genital fur, general poor condition, laboured breathing, damp and matted fur, cool body, purple skin coloration, and lack of grip and support on all limbs.

- Necropsy examination revealed lung and nasal turbinate discoloration in four males and all females which were considered related to exposure. Other abnormal necropsy findings were obscured by post-mortem changes.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
- Exposure to the test material produced immediate signs of irritation and 100% mortality by Day 1. Necropsy examination revealed discoloration of the nasal turbinates and lungs.
- A group of Sprage-Dawley rats was exposed to an aerosol of compound ''D'' for four hours at a nominal concentration of 67.2 mg/l. Direct chamber measurements indicated a mean airborne concentration of the test material - 4.47 mg/l with an average aerodynamic mas median diameter of 2.51µm.
- Exposure to the test material produced immediate signs of irritation and 100% mortality by Day 1. Necropsy examination revealed discoloration of the nasal turbinates and lungs.