Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2010
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
No direct studies were performed in order to check ADME profile of the substance. The assessment of the absorption, distribution, metabolism and excretion of the substance is derived from the available experimental studies.
GLP compliance:
no

Test material

Specific details on test material used for the study:
Test name of the substance: Fatty acids, C10-20 neo, reaction product with diethylenetriamine
Previuos names of the test material: Naphthenic acids, reaction products with diethylenetriamine; MK195KSF
Physical State at RT: hazy solid
Colour: orange/brown
Volatile: no
Active Components (%): 100

Results and discussion

Applicant's summary and conclusion

Executive summary:

Absorption, Distribution, Metabolism and Excretion of the substance has been assessed on the basis of the available experimental studies results.

Toxicity                            

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

In the 28 -day toxicity combined with reproductive endpoint study in rats, the repeated administration by oral route showed some adverse systemic effects. NOAEL was considered to be lower than 100 mg/kg/day for males and females.

The presence of general effects does lead to conclude that the test item is adsorbed and distributed systemically.

For reproductive end-points the effects were seen at 750 mg/kg/day. NOAEL for reproduction is therefore set at 300 mg/kg/day.

No information are available concerning excretion rates.          

                

Mutagenicity

The test substance was not mutagenic in the bacterial mutation assay and in the "in vitro" chromosome aberration study using CHO V79 cells, with and without metabolic activation system as well as in the mouse lymphoma test (MLA). These studies also demonstrated that no difference of behaviour has been showed after metabolic activation of the substance with S9 mix. Toxicity is therefore not induced or enhanced by the metabolism of the substance.                              

 

Assessment                                                 

The effects seen do suggest a possible absorption by GI tract at given doses.

The bioaccumulation evaluation suggests that the test substance will not bioaccumulate in aquatic organisms and no secondary poisoning through the food chain may be realistic.    

No skin absorption was observed when applied during the acute dermal toxicity study as no systemic effect were observed.

In the 28 -day toxicity combined with reproductive endpoint study in rats, the repeated administration by oral route showed some adverse systemic effects: th test substance is therefore considered to be absorbed systemically and hence could show toxic potential.

 

Conclusion                                                 

The results of the toxicity studies by gavage showed that the test substance was absorbed and distributed systemically; absorption leads to some toxic effect.

Excretion in urine is deemed to be realistic as the substance is absorbed systematically.