Butyl isocyanate

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No validated and suitable experimental animal model to assess the potential for respiratory sensitization or asthma

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Principles of method if other than guideline:

Guinea pigs were exposed by head only to an aerosol of protein-isocyanate conjugate according to the following procedure: A 5-minute control during which the animals breathed house-line air A 10-minute exposure to an aerosol of protein conjugate A 5-minute recovery period on house-line air Animals were exposed once daily, five days a week. Their chamber positions were rotated every other day to eliminate possible effects of differences in aerosol distribution. Animals were exposed to protein isocyanate conjugate until a positive respiratory response occurred as determined by respiratory index. After a response the animals were challenged the following day with 1.) bovine serum albumin (BSA) alone to confirm that the animal was not responding to the carrier protein; then 2.) guinea pig albumin (GSA)-isocyanate conjugate to verify that the response was to the isocyanate hapten 3.) if no response occurred, the animal was re-exposed to the original BSA-isocyanate conjugate to determine whether it was still responsive to it. Chamber concentration of protein was determined as mg protein per liter air sampled. The degree of isocyanate protein conjugation was determined prior to testing. DATA ANALYSIS: A positive asthmatic response in guinea pigs was characterized by a marked increase in respiration rate. This was followed in some cases by respiratory "collapse"-a violent anaphylactic response caused by contraction of the bronchial smooth musculature resulting in gasping respiration. Both parameters were used to calculate the respiratory index (RI). A positive response was an increase in rate of greater than three standard deviations from the test animal´s average respiratory index of preceding exposure days. A negative respiratory index resulted if rate during or following exposure never exceeded the control rate.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl isocyanate

EC Number:

203-862-8

EC Name:

Butyl isocyanate

Cas Number:

111-36-4

Molecular formula:

C5H9NO

IUPAC Name:

1-isocyanatobutane

Details on test material:

IUCLID4 Test substance: other TS: bovine serum albumin (BSA)-butyl isocyanate

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Test system

Route of induction exposure:

inhalation

Route of challenge exposure:

inhalation

Vehicle:

other: serum albumin as carrier

Concentration:

BSA-butyl isocyanate (conjugation: 63 %; average chamber concentration: 36 µg protein/l)

No. of animals per dose:

4

Results and discussion

Results:

3/4 animals induced with BSA-butyl isocyanate (conjugation: 63 %; average chamber concentration: 36 µg protein/l) 
after 15 exposure days. The responses did not last long enough to challenge the test animals with other conjugates.
BSA-BI (bovine serum albumin-butyl isocyanate conjugate) induced only weak, transient responses to a few guinea pigs.

Applicant's summary and conclusion

Executive summary:

Method: Guinea pigs were exposed by head only to an aerosol of protein-isocyanate conjugate. 

Result: BSA-BI (bovine serum albumin-butyl isocyanate conjugate) induced only weak, transient

responses to a few guinea pigs.