Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Expert assessment

Type of information:

other: Expert assessment

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Expert assessment

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

EC Number:

274-397-6

EC Name:

Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Cas Number:

70209-99-3

Molecular formula:

C23H16BrN3O9S2.2Na

IUPAC Name:

disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

None

Specific details on test material used for the study:

Name: FAT 92349/B

Results and discussion

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR

The substance composed, as listed in Section 3 is a blue solid with a molecular weight of 666.39 g/mol and high water solubility (57.8 g/L) plus high melting and auto-ignition points together with a low log octanol/water partition coefficient value (Log10 Pow -3.33). These physico-chemical properties together with the particle size fractions indicate the risk of inhalation of FAT 92349/B to be minimal. A chemically related structure to FAT 92349/B was shown to be mutagenic in a bacterial assay with or without S9 mixture activation but non-clastogenic in an in vivo micronucleus assay. The results from a repeated dose reproductive screening study using a similar chemical structure to FAT 92349/B was shown to have no observed adverse effect on systemic toxicity or effects on reproductive performance/offspring development up to a dose level of 1000 mg/kg bw/day.

Absorption

FAT 92349/B was indicated to be highly water soluble and would therefore be bioavailable through absorption via the gastrointestinal tract subsequently entering the circulatory system in the blood. This premise was supported in the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction /Developmental Toxicity Screening Test in the Rat (OECD 422) in which evidence of blue colouration (presumably from the test item and or its metabolites) was observed externally on the skin and fur and in internal tissues (kidneys, thymus, female reproductive tract and alimentary canal). However, in consideration of the hydrophilic nature and molecular weight of FAT 21036/G passage across biological membranes is likely to be limited.

Distribution

Due to the high water solubility of FAT 92349/B systemic distribution is considered most likely to occur via the serum. This opinion was further supported by the data derived from the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction /Developmental Toxicity Screening Test in the Rat (OECD 422) in which test item or metabolite staining of external and internal organs was observed together with blue stained faeces and bedding. There was no supporting evidence to indicate test item deposition in body fat.

Metabolism

A closely related chemical structure to FAT 92349/B exerted a clear mutagenic action. This effect was less pronounced when metabolic activation mixture (S9) was added. However, this isolated result may not necessarily reflect human metabolism and there was no evidence from the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction /Developmental Toxicity Screening Test in the Rat (OECD 422) to indicate test item or metabolite influenced hepatic metabolism.

Excretion

Based on the available evidence including blue stained faeces and bedding observed in the Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction /Developmental Toxicity Screening Test in the Rat (OECD 422) together with the high water solubility of FAT 92349/B; biliary excretion is unlikely and the primary route of clearance would be via the urine with any remaining test item not absorbed being excreted in the faeces.

CONCLUSION

From the information provided it has been concluded the risk of systemic toxicity from FAT 92349/B would be minimal.

Applicant's summary and conclusion

Conclusions:

From the information provided it has been concluded the risk of systemic toxicity from FAT 92349/B would be minimal.

Executive summary:

The absorption, distribution, metabolism and excretion of FAT 92349/B has been predicted based on the physico-chemical properties and supporting toxicological information provided for FAT 92349/B. FAT 92349/B is a highly water soluble reactive dye and on this basis it is reasonable to conclude that absorption following oral (gavage) administration would be via the gastro-intestinal tract with subsequent systemic distribution expedited in serum. Furthermore, as characteristically reactive dyes are designed to bind with the majority of chemical groups and substrates there is also the possibility some absorption could occur through damaged skin facilitating test item systemic distribution through binding to carrier proteins in the circulatory system. The physico-chemical properties in particular particle size would indicate the risk of inhalation of the test item to be minimal and the supporting toxicological information suggests that were any to occur, no elevated toxicity would be anticipated. There was no evidence to indicate how FAT 92349/B or any of its intermediate products are metabolised however the hydrophilic nature and molecular weight of FAT 92349/B and or its metabolites would suggest passage across biological membranes would be limited. Furthermore, the histopathological evidence derived from an Oral (Gavage) Combined Repeat Dose Toxicity Study with Reproduction/Developmental Toxicity Screening Test in the Rat (OECD 422) using a similar test material to FAT 92349/B provided no evidence of test item or metabolite influenced hepatic metabolism. In consideration of the chemical attributes of FAT 92349/B and supporting toxicological evidence the route of clearance is considered to be via the urine with any remaining test item not absorbed excreted in the faeces. Based on review of the available information it has been concluded that the risk of systemic toxicity from FAT 92349/B would be minimal.