Registration Dossier

Administrative data

Description of key information

No in vivo, in vitro or in chemico studies for skin sensitisation or respiratory sensitisation are available for tetrachlorophthalic anhydride (CAS 117-08-8). However occupational asthma caused by tetrachlorophthalic anhydride was reported in several surveys (see IUCLID section 7.10.4)

According to REACH - Regulation (EC) No 1907/2006 Annex XI 1.3 testing does not appear scientifically necessary if results obtained from valid qualitative or quantitative structure-activity relationship  models ((Q)SAR) may indicate the presence or absence of a certain dangerous property. According to VEGA (www.vegahub.eu/) tetrachlorophthalic anhydride (CAS 117-08-8) is predicted as sensitizer.  

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation, other
Remarks:
QSAR
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
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: VEGA

2. MODEL (incl. version number): Skin Sensitization model (CAESAR) 2.1.6

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: O=C1OC(=O)c2c1c(c(c(c2Cl)Cl)Cl)Cl

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Skin Sensitization model (CAESAR) 2.1.6

5. APPLICABILITY DOMAIN
see attached report

6. ADEQUACY OF THE RESULT
The model provides a qualitative prediction of skin sensitisation on mouse (local lymph node assay model). It is implemented inside the VEGA online platform, accessible at:http://www.vega-qsar.eu/
The model consists in an Adaptive Fuzzy Partition (AFP) based on 8 descriptors. The AFP produces as output two values O(positive) and O(negative) that represent the belonging degree respectively
to the sensitiser and non-sensitise classes and the reliability of the result. An adequate and reliable documentation of the applied method is provided.
Principles of method if other than guideline:
VEGA Skin Sensitization model (CAESAR) 2.1.6

Remarks on result:
positive indication of skin sensitisation
Remarks:
QSAR Prediction
Interpretation of results:
other:
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No in vivo, in vitro or in chemico studies are available for tetrachlorophthalic anhydride (CAS 117-08-8).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No in vivo, in vitro or in chemico studies are available for tetrachlorophthalic anhydride (CAS 117-08-8).

In a study with phthalic anhydride (CAS 85-44-9) Guinea pigs were exposed through inhalation to phthalic anhydride dust at up to 5.0 mg/m³. Inhalation challenge with aerosolized phthalic anhydride-guinea pig serum albumin (PA-GPSA) conjugates elicited immediate onset respiratory reactions in animals exposed to all 3 levels of dust. Inhalation challenge of a subgroup of animals with phthalic anhydride dust did not elicit an immediate response, as measured in respiratory frequency and plethysmograph pressure. Serologic studies showed that these animals had allergic IgG1a antibody to PA-GPSA. There was a dose-dependand increase in specific IgG antibody activity as measured by ELISA. Animals exposed to and challenged with 5.0 mg/m³ phthalic anhydride dust had significant numbers of hemorrhagic foci.


Migrated from Short description of key information:
No studies are available for tetrachlorophthalic anhydride - a read-across from supporting substance (structural analogue or surrogate) with pthalic anhydride was conducted. Due to the structural and chemical similarity the same mode of action for sensitisation is expected.

Justification for classification or non-classification

The harmonised classification is adopted for tetrachlorophthalic anhydride: GHS: Resp. Sens.1, H334; skin Sens.1, H317.