Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: Assessment of toxicokinetic bahaviour
Adequacy of study:
key study
Study period:
The assessment was conducted in September 2016.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of relevant results.
Justification for type of information:
.
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (RECH), a paper-based toxcokinetic assessment has been conducted for the substance. Summaries of studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH.The assessment of the likely toxic behaviour of the substance was provided to the extent that can be derived from the relevant available information at the time of the assessment. The assessment is based on the Guidance on information requirement and chemical safety assessemnt Chapter R.7.c: Endpoint specific guidance (ECHA, November 2012).
GLP compliance:
no
Radiolabelling:
no
Species:
other: Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
Details on test animals and environmental conditions:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
Route of administration:
other: Not applicable
Vehicle:
unchanged (no vehicle)
Details on exposure:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
Duration and frequency of treatment / exposure:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
Remarks:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
No. of animals per sex per dose:
Not applicable, a paper-based toxicokinetic assessment has been conducted for the substance at the current tonnage level.
Control animals:
other:
Details on absorption:
The available data indicated that the test item would quickly hydrolyse. The results from both the single and repeat dose oral gavage toxicity studies confirmed test item systemic toxicity and in the latter study that bioavailability in all probability would be via the gastro-intestinal tract; subsequently entering the circulatory system via the blood. Clinical findings from these studies also supported the existing evidence that the test item had irritative properties.
Details on distribution in tissues:
Systemic distribution was evident from the single and repeat dose toxicity studies with macroscopic and histopathological changes recorded in the latter study.
Details on excretion:
There was no evidence to verify the route of excretion however there was confirmation of hepatic metabolism and as the consequence of xenobiotic metabolism is to render the product more water soluble; it is reasonable to conclude absorption of the test substance would primarily take place in the gastrointestinal tract following oral ingestion and once absorbed in all likelihood be distributed in the liver with excretion of hepatic metabolites in the urine. Any remaining unabsorbed test item would be excreted via the faeces.
Metabolites identified:
no
Details on metabolites:
MetabolismThe results of the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test provided evidence of centrilobular hepatocellular hypertrophy, an adaptive response of the liver following exposure to xenobiotics.
Conclusions:
The studies conducted for the test substance provided evidence that following oral ingestion the test item would be bioavailable with absorption occurring in the gastrointestinal tract, distribution in the serum leading to test item or metabolite influenced hepatic metabolism. Excretion of the test substance and/or its metabolites would be predominantly via the urine and faeces.
Executive summary:

The absorption, distribution, metabolism and excretion of the test item have been predicted based on the following information:

The available data indicated the substance would be bioavailable via absorption through the gastrointestinal tract, subsequently entering the circulatory system via the blood.

Systemic distribution was evident in both the single and repeat dose toxicity studies with macroscopic and histopathological changes resulting from exposure to the test item recorded in the latter study.

The results from the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test provided evidence of test item or metabolite influenced hepatic metabolism; characterised by centrilobular hepatocellular hypertrophy an adaptive response of the liver following exposure to xenobiotics.

There was no evidence to indicate the route of excretion however in all probability this would be via the urine with any remaining unabsorbed test item excreted in the faeces.

The studies conducted for the test item provided evidence that following oral ingestion the test item would be bioavailable with absorption occurring in the gastrointestinal tract, distribution in the serum leading to test item or metabolite influenced hepatic metabolism. Excretion of the test substance and/or its metabolites would be predominantly via the urine and faeces.

Description of key information

The absorption, distribution, metabolism and excretion of the substance have been predicted based on the following information: The available data indicated the substance would be bioavailable via absorption through the gastrointestinal tract, subsequently entering the circulatory system via the blood. Systemic distribution was evident in both the single and repeat dose toxicity studies with macroscopic and histopathological changes resulting from exposure to the test item recorded in the latter study. The results from the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test provided evidence of test item or metabolite influenced hepatic metabolism; characterised by centrilobular hepatocellular hypertrophy an adaptive response of the liver following exposure to xenobiotics. There was no evidence to indicate the route of excretion however in all probability this would be via the urine with any remaining unabsorbed test item excreted in the faeces. The studies conducted for the substance provided evidence that following oral ingestion the test item would be bioavailable with absorption occurring in the gastrointestinal tract, distribution in the serum leading to test item or metabolite influenced hepatic metabolism. Excretion of the test substance and/or its metabolites would be predominantly via the urine and faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information