Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Assessment made using data derived from guideline studies

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The toxicokinetic assessment is prepared by evaluating the available physical properties and toxicological properties.
GLP compliance:
no
Remarks:
Assessment

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Everdirect SH12
- Substance type: Powder
- Composition of test material, percentage of components: 69.96 %
- Lot/batch No.: 3506
- Storage condition of test material: Ambient
Radiolabelling:
no

Results and discussion

Preliminary studies:
Genetic toxicological information:
Bacterial reverse mutation test: Negative; 5 mg/plate was the highest concentration (according to the SuperLab Final Report M62-151100084).
In vitro mammalian chromosomal aberration test: Negative; 2.0 mg/mL was the highest concentration treated with or without S9 Mix (according to the SuperLab Final Report (M62-151100085).
In vitro mammalian cell gene mutation test: Negative; 2.0 mg/mL was the highest concentration treated with or without S9 Mix (according to the SuperLab Final Report M62-151100091).

General toxicological information:
Subacute oral toxicity: NOAEL > 1,000 mg/kg B.W. (according to the SuperLab Final Report M62-151100083).
Acute dermal toxicity: LD50 > 2,000 mg/kg B.W. (according to the SuperLab Final Report M62-151100081).
Skin sensitization: Negative (test concentration: 6%) (according to the SuperLab Final Report M62-151100082).

Ecological toxicological information:
Adsorption coefficient test: sludge Koc < 28.84; soil Koc = 61.24 (according to the SuperLab Final Report M62-151100089).
Activated sludge respiration inhibition test: EC50 > 1,000 mg/L (according to the SuperLab Final Report M62-151100088).
Alga growth inhibition test: ErC50 = 2.81 mg/L; EyC50 = 0.76 mg/L (according to the SuperLab Final Report M62-151100086)
Daphnia sp., Acute immobilisation test: EC50 = 3.34 mg/L (according to the SuperLab Final Report M62-151100087).
Ready biodegradability: It was not the readily biodegradable article (according to the SuperLab Final Report M62-151100090).
Main ADME resultsopen allclose all
Type:
absorption
Results:
No evidence of oral or dermal absorption. Discoloured faeces observed after dosing of the coloured material.
Type:
distribution
Results:
In the absence of apparent absorption, distribution was not seen
Type:
metabolism
Results:
There is no evidence of metabolic activity
Type:
excretion
Results:
In the absence of apparent absorption, no excretion was seen. Discoloured faeces observed after dosing of the coloured material.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
with the repeat oral study and reproduction toxicity screening tests conclude that there was no adverse effect at the top dose of 1000 mg/kg/day.

However, had absorption taken place, the intense colour of the test material could be expected to have provided visual observations to confirm absorption. There was no red discolouration of organs and this suggests that there is no significant absorption.

Red/purple faeces were observed through the test period for the repeated dose toxicity studies suggesting that a significant proportion of the substance passes through without absorption. The intestines were not observed to be red, but otherwise non-affected by the test material in the oral reproduction toxicity study.

There is no evidence of dermal absorption and from the high molecular weight and lack of surface active properties, it is likely to have a low rate of dermal absorption. Guidance suggests that a default of 10% can be used in such cases.

Discolouration of skin and fur was seen in many animals in the reproductive toxicity screening test, but this was considered to grooming activities where faeces and saliva are discoloured.

Details on distribution in tissues:
Discolouration of organs was not noted and no other adverse effects reported. In the absence of toxicological findings, no target organ has been identified.

The substance is water soluble and distribution would be expected had there been absorption.
Details on excretion:
The kidneys and urine were not discoloured, suggesting no excretion of absorbed material in the urine. However, the intense dark red of the faeces suggests that a significant proportion is excreted unchanged following oral exposure.

In the oral reproduction toxicity screening test, red faeces were seen shortly after administration representing normal passage through the GI tract.

Any other information on results incl. tables

Estimated dermal adsorption factor 10%

Low bioaccumulation potential

Applicant's summary and conclusion

Conclusions:
Interpretation of results: low bioaccumulation potential based on study results
Executive summary:

The intense colour of the test material means it is potentially possible to identify absorption, distribution and excretion. In the absence of specific toxicokinetic data from animal testing it is not possible to make firm conclusions concerning metabolism, but the limited biodegradation will indicate that some limited metabolism is likely.   

 

There is no indication of accumulation.  

 

It is not considered appropriate to perform further animal studies on this substance.