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.
EC number: 215-035-9 | CAS number: 1271-19-8
There were no early decedents during the Main study.
At the macroscopic examination, a hard mass, which was adherent to the overlying skin, was seen under the right leg of 5/10 treated animals (Group 2 animal Nos. C8071, C8072, C8074, C8075 and C8076).
Treatment Related Findings
Changes related to treatment with dichlorobis(η-cyclopentadienyl)titanium were seen in the skin of the inter-scapular area, the site of intradermal injection and subsequent topical application.
Dermal injection site
Minimal or slight crystalline foreign body granuloma(ta) with associated mineralization and pigmented macrophages were seen in the dermis and/or subcutis of 3/10 treated animals.
Summary of treatment related findings at the dermal injection site for animals killed at at Scheduled Termination
Granuloma, crystalline foreign material, with associated mineralization and pigmented macrophages, dermal/subcutaneous
Number of tissues examined
At the inter-scapular area used as the site for intra-dermal injection (1stinduction) and subsequent topical application (2ndinduction), a consistent finding in the skin of all control and treated animals was a slight to marked macrophage infiltrate in the dermis and subcutis. This infiltrate was considered to be an expected response to the injection of Freund’s Complete Adjuvant, a macrophage–attractant, at two of the three pairs of intra-dermal injection sites during the 1stinduction procedure. Combinations of other findings were seen in the epidermis (scabs, ulceration, erosion and hyperplasia), dermis/subcutis (abscessation, inflammatory cell infiltrate and hair shaft/keratin microgranuloma(ta)) and panniculus muscle (myofibre atrophy/degeneration/necrosis), at similar or lower relative incidences in treated animals (Group 2) compared with controls (Group 1). These changes were considered related to the combination of the intra-dermal and topical application procedures, the application of sodium lauryl sulphate (a local irritant) and the vehicles (i.e. olive oil and liquid paraffin) and/or solvent used.
Non-protocol skin (under right forelimb)
It should be noted that only subcutaneous tissue from this untreated site was presented for examination for 4/5 treated animals and that full thickness skin (epidermis, dermis and subcutis) was only present for animal No. C8075. For one animal, (No. C8072), a lymph node, probably the right axillary, was present in the tissue examined and was of normal appearance.
Moderate or marked macrophage infiltration was seen in the subcutis of all five treated animals, which accounted for the macroscopic masses under the right forelimb of each of these animals. For animal No. C8071, a minimal amount of crystalline foreign material, which was similar in appearance to the crystalline material seen in the inter-scapular skin of this animal, with associated inflammatory cell infiltrate was seen in the subcutis. Although no masses were reported in negative control animals (Group 1) in the skin under either forelimb, it was considered that the presence of the macrophage infiltrate at this non-protocol site, and thecrystalline foreign material for animal No. C8071,may have represented the effect of residual adjuvant (Freund’s Complete Adjuvant) and test item material respectively, that had possibly migrated ventrally from the scapular area due to a combination of the movement of the animal during the main study and gravity. Combinations of other findings were seen in the subcutis (abscessation, granuloma(ta) and inflammatory cell infiltrate) and panniculus muscle (myofibre atrophy/degeneration/necrosis). Therefore, in general, the findings seen in the skin caudal to the right forelimb were similar in severity and relative incidence to the findings seen at the inter-scapular skin of control and/or treated animals.
Summary of procedure-related findings in the non-protocol skin for animals killed at Scheduled Termination
Infiltrate, macrophage, subcutaneous
Crystalline foreign material, with associated inflammatory cell infiltrate, subcutaneous
Infiltrate, inflammatory cell, subcutaneous
Atrophy/degeneration/necrosis, myofibre, panniculus muscle
Histopathology – Group distribution of findings
Histopathology - group distribution of findings
Request ID: 5169436
Number of animals affected
Tissue/Organ and Findings
No. of animals
Infiltrate, Inflammatory Cell, Dermal/Subcutaneous
Atrophy/Degeneration/Necrosis, Myofiber, Panniculus Muscle
Infiltrate, Macrophage, Dermal/Subcutaneous
Microgranuloma(ta), Hair Shaft/Keratin
Granuloma(ta), Crystalline Foreign Material, with Associated Mineralization and Pigmented Macrophages, Dermal/Subcutaneous
Crystalline Foreign Material, with Associated Inflammatory Cell Infiltrate, Subcutaneous
Infiltrate, Macrophage, Subcutaneous
Infiltrate, Inflammatory Cell, Subcutaneous
The objective of this study was to perform a histopathological assessment on fixed guinea pig tissues (identified as SMK-PH-16-0617) provided byPhycher Bio Développement,to investigate macroscopic tissue abnormalities seen following a sensitisation study performed under Envigo project number SS90QG.
All dose administration and animal identification performed atPhycher Bio Développementwas as follows:
Female Dunkin-Hartley guinea pigs received two induction administrations followed by a challenge administration of the test material (treated) or sham inductions followed by a test material challenge administration (control)
Group1 (Control): C8056, C8066, C8067, C8068 and C8069
Group 2 (Treated): C8070, C8071, C8072, C8073, C8074, C8075, C8076, C8077, C8078 and C8079
Histological processing of the tissues provided was conducted at the Eye Test Facility with pathological evaluation performed at the Huntingdon Test Facility of Envigo CRS Limited respectively.
Minimal or slight crystalline foreign body granuloma(ta) with associated mineralization and pigmented macrophages were seen at the dermal injection site in the dermis and/or subcutis of 3/10 treated animals.
Following the main study period, a test item (dichlorobis(η-cyclopentadienyl)titanium) related finding was seen in the dermis and subcutis of the skin of the inter-scapular area (crystalline foreign body granuloma(ta) with associated mineralization and pigmented macrophages).
The macroscopic masses in the untreated skin caudal to the right forelimb of 5/10 treated (Group 2) animals were accounted for bymacrophage infiltration in the subcutis, a change that was also seen in the treated inter-scapular skin of all control and treated animals.
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again