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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: special investigation

Data source

Reference
Reference Type:
publication
Title:
CYP oxidative metabolism contributes to the potency of phenylisocyanate
Author:
Chadda GP, Lange RW, Korzekwa K, Romkes M, Day BW, Karol MH
Year:
1998
Bibliographic source:
The Toxicologist

Materials and methods

Principles of method if other than guideline:
Cell-mediated immunity (CMI) responses were examined in Balb/c mice after sensistisation.
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
repeated dose toxicity: inhalation

Test material

Constituent 1
Chemical structure
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

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
not specified

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
not specified
Duration of treatment / exposure:
see examinations
Frequency of treatment:
see examinations
Post exposure period:
see examinations
No. of animals per sex per dose:
no data

Results and discussion

Details on results:
Antibody titers, measured by ELIDS were reduced > 50% in ABT pretreated animals. ABT administered alone had no effect on either CMI or HI. These results suggest that oxidative metabolism of aromatic isocyanates, creating a bifunctional hapten, enhances the sensitisation potency of these chemicals

Any other information on results incl. tables

Antibody titers, measured by ELIDS were reduced > 50% in ABT pretreated animals. ABT administered alone had no effect on either CMI or HI. These results suggest that oxidative metabolism of aromatic isocyanates, creating a bifunctional hapten, enhances the sensitisation potency of these chemicals

Applicant's summary and conclusion

Executive summary:

Balb/c mice were sensitised by subcutaneous injection of 30 µmol PI (day 0) inthe presence and absence of molar equivalents of the CYP suicide inhi9bitor 1 -aminobenzothiazole (ABT). ABT was administered at 0.25 and 2 hr prior to sensitisation. Cell-mediated immunity (CMI) responses were elicited by challenge at the dorsal sufrace of the ear (day 4) with 0.67 µmoles PI. ear thickness measurements were obtained 48 hr later (day 6). CMI was significantly reduced (> 20%) by ABT pretreatemnt. Effects on humoral immunity (HI) were assessed in a separate group of animals where PI sensitisation was performed with or without ABT pretreatment. After 14 days, sera were obtained for evaluation of PI-specific IgG.

Antibody titers, measured by ELIDS were reduced > 50% in ABT pretreated animals. ABT administered alone had no effect. on either CMI or HI. These results suggest that oxidative metabolism of aromatic isocyanates, creating a bifunctional hapten, enhances the sensitisation potency of these chemicals.