2-{[4-({4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulfo-1-naphthyl}diazenyl)-(6 or 7)-sulfo-1-naphthyl]diazenyl}benzene-1,4-disulfonic acid, lithium sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

other: Expert assessment

Adequacy of study:

key study

Study period:

2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Expert assessment

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

An expert assessment was performed.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 1,4-Benzenedisulfonic acid, 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulfo-1-naphthalenyl]azo]sulfo-1-naphthalenyl]azo]-, tetrasodium salt and lithium chloride

Molecular formula:

Not applicable; this UVCB substance contains: C29H16ClN9O12S4.xLi.yNa, (x + y) = 4; 0 < (x,y) < 4 with 873.9 < MW < 938.1 g/mol (UVCB substance), and traces of NaCl.

IUPAC Name:

Reaction products of 1,4-Benzenedisulfonic acid, 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulfo-1-naphthalenyl]azo]sulfo-1-naphthalenyl]azo]-, tetrasodium salt and lithium chloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Applicant's summary and conclusion

Conclusions:

The available information suggests that absorption of FAT 40032/G TE would primarily take place in the gastrointestinal tract following oral ingestion with some absorption potentially also capable of taking place via damaged skin albeit uptake via intact skin is considered unlikely to occur. Once absorbed, the substance would primarily be distributed in the serum with excretion via the urine and faeces.

Executive summary:

The absorption, distribution, metabolism and excretion of FAT 40032/G TE have been predicted primarily using information derived from closely related chemical structures to FAT 40032/G TE. The derivatives of FAT 40032/G TE are highly water soluble which suggests absorption of FAT 40032/G TE would occur in the gastro-intestinal tract following oral gavage administration subsequently entering the circulatory system via the blood stream. The physico-chemical properties of the test substance indicate the risk of uptake from inhalation of volatile material to be unlikely. However, derivatives of FAT 40032/G TE were shown to elicit irritation to the skin and eyes and to cause skin sensitization hence limited absorption may also occur via damaged skin which suggests FAT 40032/G may have the capacity to bind to carrier proteins. Single and repeated dose toxicological studies conducted on derivatives of FAT 40032/G TE indicated low general systemic toxicity. However, selective toxicity namely for parental reproductive toxicity (NOAEL: 300 mg/kg bw/day) and offspring developmental toxicity (NOAEL 100 mg/kg bw/day) were identified in the reproductive and developmental rodent screening study conducted with a derivative of FAT 40032/G TE. The data derived from the repeated dose toxicity and reproductive screening studies also identified test item or metabolite staining of the urine, faeces and internal organs. Such findings would corroborate that systemic distribution of FAT 40032/G TE would be via the serum. However, the low log octanol/water partition coefficient and water solubility indicate FAT 40032/G TE to be largely hydrophilic and hence unlikely to accumulate in body fat.

There was no evidence to indicate test item influenced hepatic metabolism and available results also verified that FAT 40032/G TE is unlikely to be mutagenic. Based on the available facts excretion of FAT 40032/G TE and any of its predicted metabolites is expected to be from the urine and faeces with the latter from non-absorbed test material. To conclude, the results from the studies conducted provide evidence that absorption of FAT 40032/G TE would primarily take place in the gastrointestinal tract following oral ingestion. Once absorbed, FAT 40032/G TE would in all probability be distributed in the serum. Some absorption may also potentially occur through the skin barrier although low fat solubility would suggest that significant binding to body fat is unlikely. There was no evidence to indicate test item or metabolite influenced hepatic metabolism and excretion of the test substance and/or its metabolites would predominantly be via the urine and faeces.