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Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert assessment
Study period:
2017
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Objective of study:
toxicokinetics
Qualifier:
no guideline followed
Principles of method if other than guideline:
An expert assessment was performed by a qualified toxicologist.
GLP compliance:
no
Specific details on test material used for the study:
None

TOXICOKINETIC BEHAVIOUR

The substance composed, as listed in Section 3 is a blue solid with a molecular weight of ~362 g/mol and

to have low water solubility and high melting and auto-ignition points. The supporting physicochemical

properties together with the inhalable particle size fraction of ~2% at <100 μm indicate low

volatility which together with supporting toxicological results indicate the risk of particle inhalation to be

minimal. Genotoxicity assays all proved negative (non-mutagenic) and a single dose toxicity study

established the oral LD50 to be >1000 mg/kg body weight. Derivatives of FAT 36002/G TE were shown

to be mildly irritative to the skin and eyes and in all likelihood to cause skin sensitization. A rodent

repeated dose oral (gavage) combined toxicity and reproduction/developmental toxicity screening

(OECD 422) study conducted on a closely related chemical provided evidence of absorption,

distribution, metabolism and excretion.

Absorption

The low water solubility and high octanol/water partition coefficient would inhibit passage across

biological membranes. However, generalized blue staining of both external and internally body surfaces

and organs together with evidence of staining in the faeces and bedding that were identified in the OECD

422 study would indicate some passive absorption would occur through the gastro-intestinal tract

following oral ingestion before entering the circulatory system via the blood. Further information

indicated the test material may be a skin sensitizer implying injury to the skin barrier could increase the

chances of test item penetration with subsequent binding to carrier proteins in the circulatory system.

Distribution

The physico-chemical properties suggest the possibility that some accumulation in adipose tissue could

occur. However, the results from the OECD 422 study provided sufficient evidence to establish the most

probable route of absorption and systemic distribution to take place along the gastrointestinal tract and

serum.

Metabolism

The results of the repeated dose oral (gavage) combined toxicity and reproduction/developmental toxicity

screening (OECD 422) study did not show any evidence of test material influenced hepatic metabolism.

The results of the genotoxicity assays also proved negative. Furthermore, while the physico-chemical

properties might suggest the test material to be lipophilic the supporting evidence strongly suggest that

metabolism to a more hydrophilic product to actuate excretion would take place.

Excretion

The most plausible route of clearance for low water soluble materials such as FAT 36002/G TE would be

by transfer of test material and/or metabolites from the plasma to the bile through the hepatocytes and

then by way of a process known as enterohepatic cycling the final clearance of any metabolic breakdown

products would primarily be via the faeces. To further support this viewpoint, dark blue stained faeces

were identified from animals of all test groups in the OECD 422 study.

CONCLUSION

The available information suggests that absorption of FAT 36002/G TE will primarily take place in the

gastrointestinal tract following oral ingestion. Some absorption may also take place via the skin. Once

absorbed, the substance would primarily be distributed in the serum with excretion primarily being via

the faeces.

Conclusions:
The available information suggests that absorption of FAT 36002/G TE will primarily take place in the
gastrointestinal tract following oral ingestion. Some absorption may also take place via the skin. Once
absorbed, the substance would primarily be distributed in the serum with excretion primarily being via
the faeces.
Executive summary:

The absorption, distribution, metabolism and excretion of FAT 36002/G TE has been predicted based on

the physico-chemical properties and supporting toxicological information provided for FAT 36002/G TE.

FAT 36002/G TE would in all probability be absorbed via the gastrointestinal tract subsequently entering

the circulatory system in the blood. It is also possible some absorption could take place through the skin.

However, the risk of uptake via the inhalation route was considered to be low as the test material was not

volatile and the available supporting toxicological information would suggest no elevation in systemic

toxicity would be expected.

The available evidence including single dose and repeated dose oral (gavage) combined toxicity study

with reproduction /developmental toxicity screening test in the rat indicated the test item and/or its

predicted metabolites to have only low toxic potential when absorbed or distributed through the gastrointestinal

tract and serum.

Excretion of FAT 36002/G TE and any of its predicted metabolites is expected to be primarily from the

faeces.

Description of key information

The absorption, distribution, metabolism and excretion of FAT 36002/G TE has been predicted based on

the physico-chemical properties and supporting toxicological information provided for FAT 36002/G TE.

FAT 36002/G TE would in all probability be absorbed via the gastrointestinal tract subsequently entering

the circulatory system in the blood. It is also possible some absorption could take place through the skin.

However, the risk of uptake via the inhalation route was considered to be low as the test material was not

volatile and the available supporting toxicological information would suggest no elevation in systemic

toxicity would be expected.

The available evidence including single dose and repeated dose oral (gavage) combined toxicity study

with reproduction /developmental toxicity screening test in the rat indicated the test item and/or its

predicted metabolites to have only low toxic potential when absorbed or distributed through the gastrointestinal

tract and serum.

Excretion of FAT 36002/G TE and any of its predicted metabolites is expected to be primarily from the

faeces.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information