Phenyl isocyanate

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Reference 2

Reference Type:

publication

Title:

Phenyl isocyanate-induced asthma in rats following a 2-week exposure period

Author:

Pauluhn , Ruengeler W, Mohr U

Year:

1995

Bibliographic source:

Fundam Appl Toxicol 24, 217-228

Reference 3

Reference Type:

publication

Title:

Predictive testing for respiratory sensitisation

Author:

Pauluhn J

Year:

1996

Bibliographic source:

Toxicol Lett 86, 177-185

Reference 4

Reference Type:

publication

Title:

Tierexperimentelle Ansaetze zur Beschreibung der Atemwegshypersensitivitaet

Author:

Pauluhn J

Year:

1998

Bibliographic source:

Zbl Arbeitsmed 48, 453-458

Materials and methods

Principles of method if other than guideline:

Groups of 10 male and 10 female Wistar rats were exposed to 1.04, 4.10, 7.18 and 10.39 mg phenyl isocyanate/m³ for 2 weeks, 6 hours per day. The animals were observed for body weight and clinical signs through day 14 followed by chemical, biochemical and histopathological examinations which indicate a lung sensitizing potential of the test compound

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl isocyanate

EC Number:

203-137-6

EC Name:

Phenyl isocyanate

Cas Number:

103-71-9

Molecular formula:

C7H5NO

IUPAC Name:

isocyanatobenzene

Details on test material:

content: 99.9 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Test system

Route of induction exposure:

inhalation

Route of challenge exposure:

inhalation

Vehicle:

other: air

Concentration:

0.0, 0.35, 0.83, 2.79 and 10.07 mg phenyl isocyanate/m³

No. of animals per dose:

8 male rats/dose

Results and discussion

Results:

All examined parameters of the 1.04 mg/m³ exposure group were unaffected. Little changes of the parameters ( lung function test, goblet cell hyperplasia) were found in the 4.1 mg/m³ exposure group at the end of the post-exposure period. In the groups exposed to 7.2 mg/m³ and 10.4 mg/m³ a progredient decrease of body weight, and an increase of hypothermia, mortality and clinical symptoms caused by the irritant potential of phenyl isocyanate to the respiratory tract. The following toxicological relevant changes were found. An increase of lung weight, and a decrease of spleen, thymus, liver and kidneys and an increase of blood parameters of the lung. In the bronchial lavage the biochemical and cytological correlates of a bronchioaveleolitis were determinable (increase of alkaline phosphatase, LDH, protein concentration, leucotriene). An obstructive alteration of the lung and a respiratory hyper reactivity was found. Within the post-exposure period the changes were not or only partly reversible.

Any other information on results incl. tables

On the basis of these examinations a respiratory sensitization potential of phenyl isocyanate was found.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (respiratory sensitising) based on GHS criteria

Conclusions:

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Resp. Sens. 1 is justified.

Executive summary:

Groups of 10 male and 10 female Wistar rats were exposed to 1.04, 4.10, 7.18 and 10.39 mg phenyl isocyanate/m³ for 2 weeks, 6 hours per day. The animals were observed for body weight and clinical signs through day 14 followed by chemical, biochemical and histopathological examinations which indicate a lung sensitizing potential of the test compound.

All examined parameters of the 1.04 mg/m³ exposure group were unaffected. Little changes of the parameters ( lung function test, goblet cell hyperplasia) were found in the 4.1 mg/m³ exposure group at the end of the post-exposure period. In the groups exposed to 7.2 mg/m³ and 10.4 mg/m³ a progredient decrease of body weight, and an increase of hypthermia, mortality and clinical symptoms caused by the irritant potential of phenyl isocyanate to the respiratory tract. The following toxicological relevant changes were found. An increase of lung weight, and a decrease of spleen, thymus, liver and kidneys and an increase of blood parameters of the lung. In the bronchial lavage the biochemical and cytological correlates of a bronchioaveleolitis were determinable (increase of alkaline phosphatase, LDH, protein concentration, leucotriene). An obstructive alteration of the lung and a respiratory hyper reactivity was found. Within the post-exposure period the changes were not or only partly reversible.

On the basis of these examinations a respiratory sensitization potential of phenyl isocyanate was found.

NOAEL = 1.04 mg phenyl isocyanate/m³ air