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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.
Adequacy of study:
key study
Study period:
The assessment was conducted in May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requ irements of Annex VIII (8.8).
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
n accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c: Endpoint specific guidance (ECHA, November 2014)
GLP compliance:
no
Remarks:
No relevant for assessment
Radiolabelling:
no
Metabolites identified:
not measured

TOXICOKINETIC BEHAVIOUR

1132 intermediate is a off white colored powder with physico-chemical properties which imply the risk of particle inhalation of 1132 to be minimal based on the low vapour pressure. . 1132 was identified not to be a irritiant ; the in vitro genotoxicity panel indicates that there are no concerns for genotoxicity. 1132 can be considered to be a skin Sensitiser absed on the available animal study.

The results from a single dermal dose toxicity study, indicate only limited absorption might occur via the dermis. Acute oral toxicity results showed the LD50 to be >2000 mg/kg body weight, however the Oral (Gavage) Repeated Dose Toxicity Study in the rat resulted no test susbtance related effects up to the highest dose tested 1000mg/kg, indicating limited gasto-intestinal absorption.

Absorption

The general physico-chemical properties of 1132 including very low water solubility would be factors that would inhibit significant absorption. The mean particle diameter was 43um with 50% of the the particle size within the inhalable range and based on the LogKow and low water solubility, a small quantity may be phagocytosed and transported to the blood via the lymphatic system

Supporting results from the Oral (Gavage) Repeated Dose Toxicity Study indicated limited absorption from the gut.

Distribution

Information relating to the distribution of 1132 is limited; however, the chemical characteristics and findings from the Oral (Gavage) Repeated Dose Toxicity Study implies systemic distribution would most likely occur via the serum following oral administration and gastric absorption. Furthermore while the properties (i.e. poor water solubility) of 1132 and high lowKow suggest a potential to accumulate in adipose tissue, none of the studies conducted showed any evidence of this.

Metabolism

There is limited evidence of test item or metabolite influenced by hepatic metabolism from the Oral (Gavage) Repeated Dose Toxicity Study, some effects were seen in alanine aminotransferase however this not dose related but may indicate low levels of metabolism

Excretion

The most plausible route of clearance for relatively low water soluble chemicals would be by transfer of test material and/or metabolites from the plasma to the bile through the hepatocytes leading to clearance

of any metabolic breakdown products primarily via the faeces. However histopathological effects were observed in the kidneys at the highest dose, indicating renal excretion of substance or metabolites.

Conclusions:
The available information suggests that absorption of substance from the gastrointestinal tract following oral ingestion is likely despite the test items physico-chemical characteristics.
These characteristics together with the low volatility of CQ also indicate absorption via inhalation or dermal exposure of test item to be unlikely. Any absorbed test material has the potential to undergo hepatic transformation and subsequent reanal clearance, however the physical characteristics of the substance also indicate that clearance can also be expected to be via the bile with subsequent excretion in the faeces.

Description of key information

The available toxicological information suggests that absorption of substance from the gastrointestinal tract following oral ingestion is unlikely despite some of the substance's physico-chemical characteristics (i.e. estimated Logkow and molecular weight).

These characteristics together with the low volatility of 1132 also indicate absorption via inhalation or dermal exposure of test item to be unlikely. Any absorbed test material has the potential to undergo hepatic transformation and subsequent renal clearance, however the physical characteristics of the substance also indicate that clearance can also be expected to be via the bile with subsequent excretion in the faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information