Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.

REACH

p-phenylene diisocyanate

EC number: 203-207-6 | CAS number: 104-49-4

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:: skin sensitisation: in chemico
Type of information:: (Q)SAR
Adequacy of study:: weight of evidence
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:: 1. SOFTWARE
QSAR Toolbox 4.0
2. MODEL (incl. version number)
Protein binding alerts for skin sensitization by OASIS v1.4
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C=Nc1ccc(cc1)N=C=O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: Skin Sensitization
- Defined domain of applicability:
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 6 values, 6 of them (100%) equal to predicted value Prediction confidence is measured by the p-value: 0.0313

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: log Kow (calculated)
- Similarity with analogues in the training set: The prediction is based on 6 values, 6 of them (100%) equal to predicted value
Prediction confidence is measured by the p-value: 0.0313
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
The substance is in the Annex III Inventory as a suspected skin senzitizer, the QSAR prediction confirms the skin senzitising and therefore in order to avoid unnecessary testing the substance will be classified as a Skin Senz. Cat 1.
Qualifier:: no guideline required
Principles of method if other than guideline:: - Software tool(s) used including version: QSAR Toolbox 4.0
Database version: 4.0//3.4
- Model(s) used: Protein binding alerts for skin sensitization by OASIS v1.4
- Model description: see field 'Justification for non-standard information'
- Justification of QSAR prediction: see field 'Justification for type of information'
Details on the study design:: Skin sensitisation (In chemico test system) - Details on study design:
QSAR Toolbox prediction for single chemical
Date: 17 Jan 2018
Author(s):
C ontact details:
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 1 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Target information
Structural information
SMILES:
O=C=Nc1ccc(cc1)N=C=O
Structure
Numerical identifiers
EC#: N/A
CAS#: 104-49-4
Other: N/A
Chemical names
Isocyanic acid, p-ph
enylene ester
1,4-diisocyanatobenz
ene
Benzene, 1,4-diisocy
anato-
Prediction summary
Predicted endpoint: EC3, S M W N; No effect specified; No species specified; No duration specified;
No guideline specified
Predicted value: Positive
Unit/scale: Skin sensitisation II (ECETOC)
Data gap filling method: Read-across analysis, executed via AW "Skin sensitization"
Summary: manually editable field
Not provided by the user
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 2 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Prediction details (I)
Predicted value: Positive
Predicted endpoint (OECD Principle 1 - Defined endpoint): Human Health Hazards -> Sensitisation ->
EC3 S M W N -> in Vivo -> Skin
Prediction plot:
Calculation approach (OECD principle 2 - Unambiguous algorithm): takes the highest mode value
from the nearest 6 neighbours
Active descriptor: log Kow (calculated)
Data usage: Maximal value*
*When multiple values are available for the same chemical, their maximal value is taken in prediction
calculations
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 3 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Prediction details (II)
Uncertainty of the prediction (OECD principle 4 - Uncertainty of the prediction):
The prediction is based on 6 values, 6 of them (100%) equal to predicted value
Prediction confidence is measured by the p-value: 0.0313
Mechanistic interpretation: manually editable field
Not provided by the user
Adequacy of the prediction: manually editable field
Not provided by the user
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 4 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Target profiles
(OECD principle 5 - Chemical and biological mechanisms)
Profiles used for grouping/subcategorization
Protein binding alerts for skin sensitization by OASIS
v1.4 (primary grouping)
Acylation;
Acylation >> (Thio)carbamoylation of
protein nucleophiles;
Acylation >> (Thio)carbamoylation of
protein nucleophiles >> Isocyanates,
Isothiocyanates
Substance type (subcategorization) Discrete chemical;
Unspecified (predefined)
Protein binding alerts for skin sensitization by OASIS
v1.4 (subcategorization)
Acylation;
Acylation >> (Thio)carbamoylation of
protein nucleophiles;
Acylation >> (Thio)carbamoylation of
protein nucleophiles >> Isocyanates,
Isothiocyanates
log Kow (calculated): 3.19
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 5 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Analogue(s) selection
(OECD principle 3 - Applicability domain)
Database(s) used:
- Skin sensitization ECETOC
- Skin Sensitization
Category boundaries (applicability domain):
- Active descriptor(s) range:
- log Kow: from 2.59 to 5.22 target chemical is in domain
- Response range:
- EC3 S M W N: from Positive to Positive
Profilers:
- Protein binding alerts for skin sensitization by
OASIS v1.4 (primary grouping)
target chemical is in domain
- Substance type (subcategorization) target chemical is in domain
- Protein binding alerts for skin sensitization by
OASIS v1.4 (subcategorization)
target chemical is in domain
Additional data pruning:
none
Manually eliminated data points:
none
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 6 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Data for analogues
Data for analogues are reported in a separate Excel file.
Prediction of EC3, S M W N for 1,4-diisocyanatobenzene 7 / 7
QSAR Toolbox 4.0
Database version: 4.0//3.4
TPRF v4.0
Appendix: Grouping / subcategorization
Protein binding alerts for skin sensitization by OASIS v1.4 (primary grouping)
Description: Target:
Acylation >> (Thio)carbamoylation of protein
nucleophiles >> Isocyanates, Isothiocyanates
(Protein binding alerts for skin sensitization by
OASIS v1.4)
Acylation
Acylation >> (Thio)carbamoylation of
protein nucleophiles
Acylation >> (Thio)carbamoylation of
protein nucleophiles >> Isocyanates,
Isothiocyanates
Substance type (subcategorization)
Description: Target:
Differ from target by: At least one category Discrete chemical
Removed categories: Unspecified (predefined)
Protein binding alerts for skin sensitization by OASIS v1.4 (subcategorization)
Description: Target:
Differ from target by: At least one category Acylation
Removed categories: Acylation >> (Thio)carbamoylation of
protein nucleophiles
Acylation >> (Thio)carbamoylation of
protein nucleophiles >> Isocyanates,
Isothiocyanates
: Key result
Run / experiment:: other: QSAR prediction
Parameter:: other: QSAR
Vehicle controls validity:: not applicable
Negative controls validity:: not applicable
Positive controls validity:: not applicable
Remarks on result:: positive indication of skin sensitisation
Interpretation of results:: Category 1 (skin sensitising) based on GHS criteria
Conclusions:: The substance is in the Annex III Inventory as a suspected skin senzitizer, the QSAR prediction confirms the skin senzitising and therefore in order to avoid unnecessary testing the substance will be classified as a Skin Senz. Cat 1.
Executive summary:: The substance is in the Annex III Inventory as a suspected skin senzitizer, the QSAR prediction confirms the skin senzitising and therefore in order to avoid unnecessary testing the substance will be classified as a Skin Senz. Cat 1.

Endpoint conclusion

Endpoint conclusion:: adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:: adverse effect observed (sensitising)

Justification for classification or non-classification

The substance has to be classified for Skin Sens. 1 and Resp. Sens. 1 according to CLP Regulation 1272/2008.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.