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Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The complete read across justification is detailed in section 13. Test substance is an isomer of the substance under registration; structural difference is not expected to significantly impact toxicokinetic and metabolic pattern. Source study has reliability 2: only limited information available from a migrated NONS file, as per Article 25(3) request.

Data source

Reference
Reference Type:
other: information from migrated NONS file, as per Article 25(3) request, permission to refer granted by ECHA
Title:
Unnamed
Year:
1985

Materials and methods

Objective of study:
other: assessment of toxicokinetic behaviour
Principles of method if other than guideline:
Assessment of toxicokinetic behaviour.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Similar Substance 01
IUPAC Name:
Similar Substance 01
Test material form:
solid

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The notified substance, a blue-violet powder, has a molecular weight that does not preclude absorption. Given the high water solubility of test substance, it is expected that some may be absorbed across the respiratory tract. It is unlikely that it will accumulate in the lungs.

Water solubility (~50 g/l) and log Pow (~ -3) are suggestive of a potential for intestinal absorption, while molecular mass (~939.6 g/mol) is in a range where molecular size may become a factor limiting intestinal absorption.
An acute oral toxicity study indicated similar conclusions and there was evidence (including blue tinting of the extremities and organs and signs of systemic toxicity) that either the substance and/or its degradants/components were absorbed via the gastrointestinal tract to some extent.

There is no evidence of absorption through the skin and log Pow suggest limited uptake.
Details on distribution in tissues:
A low log Pow value (ca. -3) suggests that bioaccumulation in fat or tissue is unlikely; moreover, high water solubility (ca. 50 g/l) suggests limited potential for bioaccumulation.
However, test substance appears to be widely distributed following oral exposure as blue discoloured organs were observed at necropsy in the acute oral toxicity study. Negative results in guinea pig skin sensitisation test indicate that protein binding in the blood does not occur.
Details on excretion:
Elimination via the lungs is not expected as the substance is non-volatile. Physicochemical properties of the substance suggest that most of the ingested substance would be eliminated in faeces; moreover the presence of blue viscous contents in intestines at necropsy in the acute oral toxicity study suggests that at least some of test substance may be excreted unchanged via this route.

Any other information on results incl. tables

No conclusions regarding metabolism of test substance could be drawn from the bacterial mutation assay as this test gave negative results in the presence and absence of S9. Based on results of in vivo mouse micronucleus assay, it is concluded that DNA-reactive metabolites most probably will not be generated in mammals in the course of (hepatic) biotransformation.

Applicant's summary and conclusion

Conclusions:
Low bioaccumulation potential based on study results.
Executive summary:

Method

Assessment of toxicokinetic behaviour. Information derived from migrated NONS file, as per Article 25(3) request; permission to refer granted by ECHA.

 

Observations and results

Absorption

The notified substance, a blue-violet powder, has a molecular weight that does not preclude absorption. Given the high water solubility of test substance, it is expected that some may be absorbed across the respiratory tract. It is unlikely that it will accumulate in the lungs. Water solubility (ca. 50 g/l) and log Pow (ca. -3) are suggestive of a potential for intestinal absorption, while the molecular mass (939.6 g/mol) is in a range where molecular size may become a factor limiting intestinal absorption. In the acute oral toxicity study there was evidence (including blue tinting of the extremities and organs and signs of systemic toxicity) that either the substance and/or its degradants/components were absorbed via the gastrointestinal tract to some extent. There is no evidence of absorption through the skin and low log Pow suggests limited uptake.

Distribution

Low log Pow value along with high water solubility suggests that bioaccumulation in fat or tissue is unlikely. However, test substance would appear to be widely distributed folowing oral exposure as blue discoloured organs were observed at necropsy in the acute oral toxicity study. Negative results in guinea pig skin sensitisation test indicate that protein binding in the blood is not likely.

Metabolism

No conclusions regarding metabolism of test substance could be drawn from the bacterial mutation assay as this test gave negative results in the presence and absence of S9. Based on results of an in vivo mouse micronucleus assay, it is concluded that DNA-reactive metabolites most probably will not be generated in mammals in the course of (hepatic) biotransformation.

Excretion

Elimination via the lungs would not be expected as substance is non-volatile. Physicochemical properties of the notified substance suggest that most of the ingested substance would be eliminated in the faeces; moreover the presence of blue viscous contents in the intestines at necropsy in the acute oral toxicity study suggests that at least some of the test substance is excreted unchanged via this route.