Disodium 4-[4-[[5-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]-2,5-dichlorobenzenesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

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

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 4-[4-[[5-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]-2,5-dichlorobenzenesulphonate

EC Number:

274-499-0

EC Name:

Disodium 4-[4-[[5-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]-2,5-dichlorobenzenesulphonate

Cas Number:

70247-70-0

Molecular formula:

C19H14BrCl2N5O8S2.2Na

IUPAC Name:

disodium 4-[4-({5-[(2-bromoacryloyl)amino]-2-sulfonatophenyl}diazenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-2,5-dichlorobenzenesulfonate

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The test item was considered to be bioavailable based on being highly water soluble this assertion is further supported by results from the repeated dose reproductive screening study of yellow staining from the test item in various parts of the body together with yellow stained bedding and/or faeces. These findings indicate that the gastro-intestinal tract provides the primary route of absorption, following oral administration subsequently entering the circulatory system via the blood. The test item was also shown to be a skin sensitizer; therefore, damage to the skin surface may permit increased test item penetration. However, the lack of evidence of any form of irritation from the topical dermal and ocular irritation studies together with absence of any convincing evidence of systemic toxicity from the single dose oral toxicity (LD50 >5000 mg/kg) and repeated dose reproductive screening studies substantiate that the test item has minimal toxic potential whether absorbed through the dermis, ocular or gastro-intestinal routes.

Details on distribution in tissues:

Due to the high water solubility systemic distribution in all likelihood will be via the serum. The positive response in the skin sensitisation study is a common response to reactive dyes which tend to bind to proteins in the circulatory system further facilitating systemic distribution. The staining of tissues in the repeated dose study further confirmed the primary route of systemic distribution, however, the test item being highly water solubility and subsequent low log POW value( -3.3) would suggest it is unlikely to accumulate in body fat.

Details on excretion:

The results of the repeated dose reproductive screening study indicate the route of excretion to be via urinary excretion with any remaining unabsorbed test item excreted in the faeces following ingestion.

Metabolite characterisation studies

Details on metabolites:

The results of the repeated dose reproductive screening study did not provide any evidence to indicate either test item/metabolite influenced hepatic metabolism. The high water solubility of the parent test material; suggests that metabolism would not be required to facilitate renal excretion.

Any other information on results incl. tables

The substance is a dark yellow solid and the molecular weight is 699.25 g/mol. The predicted negative explosive properties shows that the substance is non volatile therefore inhalation is unlikely to be a significant route of exposure. The substance has a low log octanol/water partition coefficient value (Log10 Pow -3.3) and high water solubility (100g/L at 23°C). The available repeated dose reproductive screening study showed evidence of absorption, metabolism and excretion. The test item is not a skin or eye irritant but was shown to be sensitising to the guinea pig skin with the possibility of also causing respiratory sensitisation. The acute oral toxicity study (LD50 >5000 mg/kg bw) and available reproductive and developmental study showed no convincing evidence of systemic toxicity and no maternal or developmental toxicity up to dose a dose level of 1000 mg/kg/day.

Applicant's summary and conclusion

Conclusions:

The available information suggests that absorption of the test substance will primarily take place in the gastrointestinal tract following oral ingestion. Some absorption may also take place via damaged skin. Once absorbed, the substance would be distributed in the serum and excretion via the urine and faeces. No bioaccumulation potential based on study results.

Executive summary:

The absorption, distribution, metabolism and excretion of FAT 40061/F TE have been predicted based on the following information:

Absorption was indicated via the gastro-intestinal tract following oral gavage administration. No absorption was indicated via intact skin or ocular routes of exposure. However, available data confirmed the test item was a sensitizer to Guinea pig skin and also indicated to potentially cause respiratory sensitisation. No uptake via inhalation is anticipated on the basis that the inhalable fraction was shown from the Particle size test to be ~99 % at <100 μm indicating almost all inhaled particles will be cleared in the oral/nasal region and subsequently swallowed with the mucus. 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 whether absorbed through the skin or gastro-intestinal tract. Excretion of FAT 40061/F TE and any of its predicted metabolites is expected to be from urine and faeces.