p-isopropylphenyl isocyanate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Independent evaluation by Pauluhn 2015.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1987

Reference 2

Reference Type:

other: Independent Evaluation of this study

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

no guideline followed

GLP compliance:

not specified

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

p-isopropylphenyl isocyanate

EC Number:

250-439-9

EC Name:

p-isopropylphenyl isocyanate

Cas Number:

31027-31-3

Molecular formula:

C10H11NO

IUPAC Name:

1-isocyanato-4-(propan-2-yl)benzene

Details on test material:

no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

0.001 up to 2.407 mg/l air

No. of animals per sex per dose:

5

Control animals:

not specified

Results and discussion

Mortality:

7/10 animals died 45 minutes to 31 days after exposition in the lowest dose group
10/10 animals died in all higher dose groups

Clinical signs:

other: irregular breathing, breath sounds, elevated breathing frequence, salivation, nose effluent, closed eye lids, staggered gait, ruffled coat, drowsiness, convulsion, cyanosis, sneezing

Body weight:

all exponated animals showed clearly decrease of body weight

Gross pathology:

red dark to black colored lungs, increased and inflated lungs. red colored liver and adrenal gland, intestines were balloned and filled with with reddish-brown liquid, in which haemoglobin was detected. macroscopic changes were also seen in animals killed at termination of experiment

Any other information on results incl. tables

Dose depending 7/10 animals died between 45 minutes and 31 days in the lowest tested dosage of 0.001 mg/l air and 10/10 animals in the higher dose groups until the highest tested concentration of 2.407 mg/l air. Signs of intoxication were irregular and noisy breathing, elevated respiration, salivation, nose effluent, incoordination, ruffle fur, drowsiness, cyanosis and sneezing

Applicant's summary and conclusion

Executive summary:

The study is invalid based on an expert evaluation (Pauluhn 2015). The following summary on the study is drawn:

"Phenyl isocyanate was examined using a directed-flow nose-only mode of exposure (rebreathing of atmosphere not possible, i.e., reactions of isocyanate vapor with the humidity from exhaled air cannot occur). Chamber atmospheres were generated by evaporation from small, temperature controlled gas bubblers through which dry nitrogen was metered using a precision gas-metering pump. This atmosphere was diluted to attain a stable air flow rate of 20 L/min (1 L/exposure port) with a positive balance of airflows, i.e., at least 10% of the airflow was allowed to escape from the chamber via apertures and animal exposure restrainers. Hence, dilution of atmospheres at the exposure zone is excluded under such arrangement of air flows. Time-weighted average concentrations were continually measured using a Total Hydrocarbon Analyzer to verify the temporal stability of test atmospheres. Nominal undiluted concentrations were calculated by the weight-loss of gas bubblers and the total nitrogen flow through the bubbler. Under the conditions of this study the vapor saturation concentration was calculated to be 13971±2275 mg/m3. This measured concentration was essentially similar to the thermodynamically calculated concentration of 13000 mg/m3. The nominal chamber concentrations considered the respective dilution to attain the targeted concentration. Actual concentrations utilized the nitro-reagent in situ derivatization principle which scavenges reactive isocyanates groups yielding a stable urea-analyte of the respective isocyanate at a yield of about 50% following its quantification by HPLC. Adjustment to 100% yield was not considered. Due to the similarity of thermodynamically calculated and empirically measured nominal concentrations, the ‘true actual concentration’ may have been underestimated by 50%."