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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Description of key information

Results of a Repeated Dose Toxicity Study Oral are reported. A testing proposal for a Sub-Chronic Toxicity Study Oral is also provided.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Information from migrated NONS file, as per inquiry number 06-2120053135-66-0000, permission to refer granted by ECHA
Qualifier:
according to guideline
Guideline:
other: Annex V
GLP compliance:
yes
Limit test:
yes
Species:
rat
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 160 mg/kg bw/day
Male: 5 animals at 400 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 160 mg/kg bw/day
Female: 5 animals at 400 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Eight animals (low dose - 1 male, middle dose - 1 male, 2 female, high dose - 1 male, 3 female) were found dead or killed in extremis.
Mortality:
mortality observed, treatment-related
Description (incidence):
Eight animals (low dose - 1 male, middle dose - 1 male, 2 female, high dose - 1 male, 3 female) were found dead or killed in extremis.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gain was lowered for males (wees 1 and 2) and females (weeks 1 - 4) in the high dose group.
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Effects in organs:
No treatment related effects were seen at necropsy or on
histological examination.
Dose descriptor:
NOAEL
Effect level:
400 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
0 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Critical effects observed:
not specified
Conclusions:
Substance is not classified
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS - This testing proposal is submitted following ECHA communication number : SUB-C-2114357560-51-03/F

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Butyl(dialkyloxy(dubutoxyphosphoryloxy)titanium(trialkyloxy) titanium phosphate

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: See attached Testing Proposal for further details.
• Acute toxicity: oral
• Acute toxicity: demal
• Skin irritation: in vivo
• Eye irritation: in vivo
• Skin sensitisation: in vivo (non-LLNA)
• Short-term repeated dose toxicity: oral
• In vitro gene mutation study in bacteria
• In vitro cytogenicity / chromosome aberration study in mammalian cells
• In vitro gene mutation study in mammalian cells
• Screening for reproductive / developmental toxicity

- Available non-GLP studies: No further studies available

- Historical human data: No further data available

- (Q)SAR: There are no adequately validated (Q)SAR models to address the endpoint; see attached Testing Proposal for further details.

- In vitro methods: There are no validated and regulatory accepted in vitro methods to address this endpoint.

- Weight of evidence: There is an insufficient weight of evidence from several independent sources to address the endpoint, see attached Testing Proposal for further details.

- Grouping and read-across: There is an unacceptable level of uncertainty regarding identification and selection of structurally and/or mechanistically related source substances; see attached Testing Proposal for further details.

- Substance-tailored exposure driven testing: The registered substance is only handled in industrial or commercial installations using closed systems and/or handled only as preparations at low concentrations, a sub-chronic study should be considered; see attached Testing Proposal for further details.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
Annex IX Column 2 specific rules for adaptation for this endpoint are not applicable for the registered substance:
• the available short-term toxicity study results do not show severe toxicity effects according to the criteria for classifying the substance as R48;
• a reliable chronic toxicity study is not available;
• while the substance is subjected to solvolysis, and, in the presence of water polymeric complexes are formed, there is insufficient data on the cleavage products; and
• the substance is reactive with water forming polymeric complexes.

Annex XI general rules for adaptations of the standard testing regime are not applicable for the registered substance; specifically:
• Use of existing data:
Existing data does not address the endpoint, see attached Testing Proposal for further details;

• Weight of evidence:
There is an insufficient weight of evidence from several independent sources to address the endpoint, see attached Testing Proposal for further details;

• Qualitative or quantitative structure-activity relationship ((Q)SAR):
There are no adequately validated (Q)SAR models to address the endpoint, see attached Testing Proposal for further details;

• In vitro methods:
There are no validated and regulatory accepted in vitro methods to address this endpoint;

• Grouping of substances and read-across approach:
There is an unacceptable level of uncertainty regarding identification and selection of structurally and/or mechanistically related source substances, see attached Testing Proposal for further details;

• Testing is not technically possible:
It is technically possible to assess the registered substance for this endpoint; and

• Substance-tailored exposure-driven testing:
The registered substance is only handled in industrial or commercial installations using closed systems and/or handled only as preparations at low concentrations, a sub-chronic study should be considered, see attached Testing Proposal for further details.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
As there were difficulties associated with the administration of the registered substance during both the 28-day and the reproduction/developmental toxicity screening studies, the administration methods employed should be scrutinized to ensure the most accurate and humane method is employed during the proposed 90-day oral repeated dose study. See attached Testing Proposal for further details and special features to be included in the study design.
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Version / remarks:
See attached Testing Proposal for further details and special features to be included in the study design
Species:
rat
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
400 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification