Registration Dossier

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: Expert assessment
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

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of tetrasodium 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulphonato-1-naphthyl]azo]-6-sulphonato-1-naphthyl]azo]benzene-1,4-disulphonate and tetrasodium 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulphonato-1-naphthyl]azo]-7-sulphonato-1-naphthyl]azo]benzene-1,4-disulphonate
EC Number:
916-837-8
Molecular formula:
C29H16Na4ClN9O12S4
IUPAC Name:
Reaction mass of tetrasodium 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulphonato-1-naphthyl]azo]-6-sulphonato-1-naphthyl]azo]benzene-1,4-disulphonate and tetrasodium 2-[[4-[[4-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amino]-5-sulphonato-1-naphthyl]azo]-7-sulphonato-1-naphthyl]azo]benzene-1,4-disulphonate
Test material form:
solid: particulate/powder

Results and discussion

Any other information on results incl. tables

The substance composed, as listed in Section 3 is a black solid with a molecular weight of 938 g/mol.

The predicted self-ignition temperature of >500°C (indicating low volatility) and high melting point (>350 °C) would indicate the substance to be non-volatile therefore inhalation is unlikely to be a significant route of exposure. FAT 40032/G TE also has a low octanol/water partition coefficient value and high water solubility indicators that FAT 40032/G TE is hydrophilic. Data from repeated dose oral gavage toxicity and reproductive screening studies provided evidence of absorption, distribution metabolism and probable routes of excretion. Available information also indicated FAT 40032/G TE to be non-mutagenic but potentially irritant to the skin and eyes and to cause skin sensitization. Single dose oral LD50 data together with results from repeated dose toxicity studies indicated a low risk of 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 a reproductive and developmental screening study conducted with a derivative of FAT 40032/G TE.

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.