Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: estimated
Reliability:
1 (reliable without restriction)
Data waiving:
exposure considerations
Justification for data waiving:
other:

Data source

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion

Conclusions:
The results of the toxicity study conducted with the test substance by gavage showed that it was absorbed and distributed systemically while when administered by dermal route, lack of absorption did not lead to any toxic effect. Excretion in urine is deemed to be realistic when absorbed.                         
Executive summary:

The present assessment of the absorption, distribution, metabolism and excretion of UVASORB HEB is derived from data produced for the notification submitted as for EEC 92/32 as well as the OECD 421 combined study performed as for the Annex VIII of the REACH regulation.

 

Toxicity

Acute oral toxicity in rats: in the limit test at a fixed dose of 2000 mg/kg no significant treatment related effects were seen. In such study LD50 was higher than 2000 mg/kg.                                                

The repeated administration in the 13-week toxicity study in rodent by oral (into the diet) did not showed any effects. NOAEL is considered to be 831 mg/kg/day for males and 963 mg/kg/day for females.                                           

The lack of general effects and of the target organ toxicity does not lead to concluded that the test item is adsorbed and distributed systemically.

A combined OECD 421 Reproduction/Developmental Toxicity Screening Test by gavage showed some effects related to treatment at the high dose applied (1000 mg/kg/day). NOAEL was recorded at 500 mg/kg/day for toxicity. It is therefore clear that the substance was absorbed via gastro-enteric mucosa and distributed systematically. No effect were seen on mating activity (fertility) and on F1 animals.

No information are available concerning excretion rates.          

Skin and eye irritation did not show any local or systemic toxicity; in the eye irritation study the animals treated showed slight redness fully reversible within 48 hours post instillation. In the skin sensitisation study the test item did not show any degree of allergenicity.                      

 

Mutagenicity

The test substance was not mutagenic in the bacterial mutation assay and in the "in vitro" chromosome aberration study using CHO, with and without metabolic activation system as well as in the mouse lymphoma test. These studies also demonstrated that no difference of behaviour has been showed after metabolic activation of the substance with S9mix. Toxicity is therefore not induced or enhanced by the metabolism of the substance.       

Assessment

The effects seen suggest a possible absorption by GI tract ; the log Pow value suggests that the test substance probably will not bioaccumulate in aquatic organisms and that no secondary poisoning through the food chain may be realistic.    

The acute and repeated dermal toxicity study in rats were not carried out on the basis of the very low absorption rate (less than 0.1%) seen in the “in vitro” percutaneous absorption study using human skin. In such study UVASORB HEB has been showed to have a percentage of absorption lower than 0.1 % when applied with oil-in water emulsion or isopropyl myristate after 24 hours. No skin absorption was observed when applied as a powder. The test substance is not absorbed systemically and hence could not show toxic potential.

Skin sensitisation study did not show a sensitisation potential.

 

Conclusion

The results of the toxicity study conducted with the test substance by gavage showed that it was absorbed and distributed systemically while when administered by dermal route, lack of absorption did not lead to any toxic effect.

Excretion in urine is deemed to be realistic when absorbed.