4,11-diamino-2-(3-methoxypropyl)-1H-naphth[2,3-f]isoindol-1,3,5,10(2H)-tetrone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

calculation (if not (Q)SAR)

Remarks:

estimated by calculation

Adequacy of study:

key study

Study period:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: expert statement

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

None

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,11-diamino-2-(3-methoxypropyl)-1H-naphth[2,3-f]isoindol-1,3,5,10(2H)-tetrone

EC Number:

235-402-7

EC Name:

4,11-diamino-2-(3-methoxypropyl)-1H-naphth[2,3-f]isoindol-1,3,5,10(2H)-tetrone

Cas Number:

12217-80-0

Molecular formula:

C20H17N3O5

IUPAC Name:

4,11-diamino-2-(3-methoxypropyl)-1H-naphtho[2,3-f]isoindole-1,3,5,10(2H)-tetrone

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

None

Radiolabelling:

no

Test animals

Species:

other: None

Strain:

other: None

Sex:

not specified

Details on test animals or test system and environmental conditions:

None

Administration / exposure

Route of administration:

other: None

Vehicle:

other: None

Details on exposure:

None

Duration and frequency of treatment / exposure:

NOne

Doses / concentrations

Remarks:

Doses / Concentrations:
None

No. of animals per sex per dose / concentration:

None

Control animals:

not specified

Positive control reference chemical:

None

Details on study design:

None

Details on dosing and sampling:

None

Statistics:

None

Results and discussion

Preliminary studies:

None

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Findings from the oral gavage combined repeated dose toxicity, reproductive and developmental toxicity screening study included instances of test material (blue) staining of tissues, blood plasma, adipose tissue and urinary bladder contents indicating test item bioavailability and that in all probability the gastrointestinal tract provides the primary route of absorption; subsequently entering the circulatory system via the blood. However, there was no evidence of any systemic toxicity from the single dose oral toxicity or any significant systemic toxicity from the repeat dose study indicating the test item has minimal toxic
potential.

Details on distribution in tissues:

Results from the combined repeated dose toxicity, reproductive and developmental toxicity screening study included (blue) stained adipose tissue. While this suggests in all likelihood that systemic distribution will be via the serum following oral administration and gastric absorption; the limited water solubility and low log POW value of the test item may also have contributed to the presence of blue staining of adipose tissue with enterohepatic cycling and biliary clearance an added possibility, albeit there was no direct evidence to support this hypothesis.

Details on excretion:

The results (blue soiled bedding) from the combined repeated dose toxicity, reproductive and developmental toxicity screening study suggest the primary route of clearance to be via urinary excretion. However, with lower water soluble products (FAT 36152/M TE; <2.5 μg/L) biliary excretion can also be a route of clearance with any remaining test item not absorbed being excreted via the faeces.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

The results of the repeated dose reproductive screening study did not provide any conclusive evidence to suggest either test item or metabolite influenced hepatic metabolism.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The available information suggests that absorption of the test substance will primarily take place in the gastrointestinal tract following oral ingestion. Once absorbed, in all likelihood the substance would be distributed in the serum and excreted via the urine and faeces albeit biliary excretion may be a secondary
(minor) route of excretion.

Executive summary:

The absorption, distribution, metabolism and excretion of FAT 36152/M TE have been predicted based on the following information: FAT 36152/M TE absorption was indicated via the gastro-intestinal tract following oral gavage administration.

FAT 36152/M TE no absorption was indicated via the skin or ocular routes of exposure.

FAT 36152/M TE no uptake via inhalation is anticipated on the basis of the low vapour pressure value and low inhalable particle size which indicated almost all inhaled particles would be cleared in the oral/nasal region and subsequently swallowed with the mucus.

FAT 36152/M TE based on the available evidence including single oral dose and repeated oral dose reproductive screening studies that the test item and/or its predicted metabolites to have limited toxic potential when absorbed through the gastro-intestinal tract.

Excretion of FAT 36152/M TE and any of its predicted metabolites is expected to be from urine and faeces.