Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
theoretical assessment
Type of information:
other: theoretical assessment
Adequacy of study:
key study
Study period:
2018-01-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method

Data source

Reference
Reference Type:
other: theoretical assessment
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Theoretical assessment based on available information
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
semi-solid (amorphous): gel
Details on test material:
Name: Ukanol FR 70
Batch no.: 4251318
Appearance: white solid
Composition: 9,10-Dihydro-9-oxa~10-[2,3-Di-(2-hydroxyethoxy) carbonylpropyl]-10-phosphaphenanthren-10-oxid; Bis(2-hydroxyethyl)-(6H-dibenz[c,e][1,2]oxaphos-phorin-6-yl-methyl)succinat-P-oxide
CAS No.: 63562-34-5
EINECS-No.: 264-313-6
Molecular formula: C21H23O8P
Molecular weight: 434 g/mo
Purity: app. 90% (HPLC)
Homogeneity: homogeneous
Radiolabelling:
not specified

Test animals

Species:
other: not applicable
Strain:
other: not applicable
Details on species / strain selection:
not applicable
Sex:
not specified
Details on test animals and environmental conditions:
not applicable

Administration / exposure

Route of administration:
other: not applicable
Vehicle:
other: not applicable
Details on exposure:
not applicable
Duration and frequency of treatment / exposure:
not applicable
Doses / concentrations
Remarks:
not applicable
No. of animals per sex per dose:
not applicable
Positive control:
not applicable
Details on study design:
not applicable
Details on dosing and sampling:
not applicable
Statistics:
not applicable

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes

Applicant's summary and conclusion

Executive summary:

1.   Substance identity:

 

Name: Oligomeric Butanedioic acid, 2-[(6-oxido-6Hdibenz[c,e][1,2]oxaphosphorin-6-yl)methyl]-, 1,4-bis(2-hydroxyethyl) ester (DOP-ITS-Glycolic ester)

 

Structure: not applicable for UVCB; The substance is an oligomeric reaction product of Butanedioic acid, 2-[(6-oxido-6Hdibenz[c,e][1,2]oxaphosphorin-6-yl)methyl]-, 1,4-bis(2-hydroxyethyl) ester

  

Molecular formula:               not applicable for UVCB

 

Molecular weight (MW):         not applicable for UVCB

 

EC-Number:                           264-313-6

 

Description:                           white solid

 

Molecular weight:                   The molecular weights of the components of the UVCB substance                                       range from 434 (monomeric) to 2268 (heptameric).

 

2.   Physico-chemical data:

 Melting point:                        38.7 to 82.9 °C

 

 

Boiling point:                         224 °C - 246 °C (decomposition)

                                              

 

Relative density:                    1.28 g/cm3(20°C)

 

Particle size distribution:      not applicable, highly viscous

Vapour pressure:                  6.26 * 10-6Pa at 20°C,

8.95 * 10-6Pa at 25°C

 

Surface tension:                    62.26 mN/m

 

Water solubility:                    slightly soluble (0.1-100 mg/L)

 

 

Partition coefficient:              log Pow: < 0.3 to 3.324

Hydrolysis:                                     pH 7: DT-50 3.627  years

pH 8: DT-50 132.459  days

 

3.   Toxikological data:

Acute oral toxicity:           LD50> 2,000 mg/kg body weight (bw)

Acute dermal toxicity:      LD50> 2,000 mg/kg bw

 

Subacute oral toxicity:     NOAEL 300 mg/kg bw

 

Skin irritation:                  not irritating

 

Eye irritation:                   not irritating

 

Skin sensitisation:            not sensitizing 

                                        

Ames test:                        negative          

 

Chromosome aberration  negative

assay(in vitro):                

 

Mammalian cell gene      negative

mutation assay (HPRT)     

(in vitro):                          

 

4.   Toxicokinetic behaviour:

Since no toxicokinetic studies are available for DOP-ITS the assessment of the toxicokinetic behavior is based on the physico-chemical properties of the substance.

 

a)    Absorption

 

Oral absorption:

 

The slightly water soluble substance DOP-ITS will dissolve in the gastrointestinal fluids to a limited degree.

Its high molecular weight, the moderate water solubility and the moderate log Pow of < 0.3 to 3.324 do not favor its absorption in the gastrointestinal tract by passive diffusion.

Since the molecular weight is above 600 Dalton the substance may not be taken up by passing through aqueous pores of the epithelial barrier. Paracellular permeability is related to the pores in the epithelial barrier. The paracellular pathway accepts molecules with molecular mass <600 Da.

Therefore, for evaluation of DOP-ITS in the chemical safety assessment, the oral absorption is set at 10 %.

The results of the toxicity studies with DOP-ITS do not provide any reason to deviate from this proposed degree of oral absorption.

 

Dermal absorption:

 

According to the criteria given in the ECHA guidance document “Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance”,November 2012 (version 1.1) 10 % dermal absorption will be considered in case MW > 500 g/Mol and log Pow <-1 and >4, otherwise 100 % dermal absorption is assumed.

 

In consequence, 10 % dermal absorption is proposed for DOP-ITS.

 

Respiratory absorption:

Deposition pattern for dusts depends on the particle sizes of the substance to be inhaled. In general, particles having an aerodynamic diameter of greater than 10 µm are deposited in the nasopharyngeal region. Particles smaller than 10 µm are capable for reaching the alveolar region of the respiratory tract.

Since DOP-ITS is a highly viscous semi-solid substance no exposure can be assumed.

 

b)   Distribution

 

After absorption DOP-ITS is expected not to distribute easily throughout the body based on its high molecular weight, the log Pow > 0 (some lipophilicity) and the low water solubility.

 

Since the log Pow is < 0.3 to 3.324, DOP-ITS can also distribute into cells to a minor extent so that the intracellular concentration may be higher than the extracellular concentration, particularly in fatty tissues.

 

Since the log Pow of DOP-ITS is < 4 the substance is not expected to accumulate within the body.

 

c)    Metabolism

 

Once absorbed, the mammalian organism may metabolize the substance DOP-ITS by hydroxylation of appropriate carbon and nitrogen atoms which may be followed by conjugation.

  

Potential metabolites of the monomeric UVCB component were simulated with the QSAR-toolbox of the OECD (Organization for Economic Co-operation and Development) available at:http://www.qsartoolbox.org/) (see above)

No further assessment of the biological relevance of the theoretically derived metabolites is possible due to lack of information.