Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

No quantitative data is available for oral, inhalation or dermal absorption.  Given the physical chemical properties, absorption is expected to be practically zero via all routes.  However in the absence of quantitative data  ECHA defaults are assumed, not as a reflection of the actual absorption, but rather to reflect potential ratios of absorption between the routes that are important when making route to route extrapolations in deriving DNELs:
Oral absorption is taken as 50%, dermal absorbtion as 10% and dermal absorbtion as 50%.
For material that is absorbed, extensive metabolism and distribution is not expected. Excretion is likely to be mainly via the bile.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

Introduction

The physico-chemical properties and the results of repeat dose toxicity studies with animals for Y-1189 (CAS 214559-61-2, a sulphonated azo dye) have been used to estimate a toxicokinetic profile. 

 

 

Physicochemical properties

The substance is an orange granular solid and has the molecular formula C26H24N6O13S6Na4 with a molecular weight of 912.85 g/mol. It is very water soluble (>1000 g/L at 20°C) with a log Pow value of < -4 at 20°C. It possesses sulphate groups, an azide bond and a triazine. It is not readily biodegradeable. 

 

Absorption

 

No quantitative data is available for oral, inhalation or dermal absorption. Given the physical chemical properties, absorption is expected to be practically zero via all routes. However in the absence of quantitative data ECHA defaults are assumed, not as a reflection of the actual absorption, but rather to reflect potential ratios of absorption between the routes that are important when making route to route extrapolations in deriving DNELs.

 

Oral absorption

Given the very large molecular weight (approaching 1000) and the extremely low Kow, oral absorption is expected to be very low. This is supported by absence of adverse effects in the repeat dose toxicity studies, for which the NOAELs were set at the highest doses tested These NOAELs were 1000 mg/kg bw/day for parental, reproductive and developmental effects in the OECD 421 study (Petus – Árpásy, 2014; summarised at 7.8.1 and 7.8.2 (Dossier) / 5.9.1 (CSR)) and 600 mg/kg bw/day in an OECD 407 study (Lortie, 2002; Summarised at 7.5.1 (Dossier) / 5.6.1 (CSR)). In the absence of any quantitative information however 50% oral absorption is assumed.

Dermal absorption

No dermal absorption data is available for Y-1189. Given the very large molecular weight (approaching 1000) and the extremely low Kow, dermall absorption is expected to be practically zero. However in the absence of quantitative information and, on the basis of a molecular weight > 500 and a Kow >4, dermal absorption is taken as 10% (ECHA Guidance R.7)

Inhalation absorption

No data is available and inhalation absorption is assumed to be 100%

 

Distribution

No absorption is expected, but based on the high water solubility and low Kow, any material that was absorbed would not be expected to be distributed to fatty tissues. Highest concentrations might be expected in organs of excretion, particularly the liver where excretion of materials with a MW of >300 tends to happen via the bile. Given the low Kow and high water solubility no potential for bioaccumulation is anticipated.

 

Metabolism

 

No absorption is expected, but if some material were absorbed, because it is not readily biodegradeable, this might suggest that metabolism will not be extensive. Overall however, the potential for mammalian metabolism is not known.

 

Elimination

No absorption is expected, but materials with a MW of >300 tend to be excreted via the bile.

 

Conclusion

No quantitative data is available for oral, inhalation or dermal absorption. Given the physical chemical properties, absorption is expected to be practically zero via all routes. However in the absence of quantitative data ECHA defaults are assumed, not as a reflection of the actual absorption, but rather to reflect potential ratios of absorption between the routes that are important when making route to route extrapolations in deriving DNELs:

Oral absorbtion is taken as 100%, dermal absorbtion as 50% and dermal absorbtion as 10%.

 

For material that is absorbed, extensive metabolism and distribution is not expected. Excretion is likely to be via the bile.