Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
other: Expert statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The expert statement has been based on a series of physicochemical and toxicology studies performed with S 900 according to technical guidelines and in compliance with GLP in internationally recognized contract research organizations.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Conclusions:
Toxicokinetic Assessment
No specific study has been performed on the absorption/distribution/metabolism/excretion (ADME) of Sakuralube S-900.However, data are currently available from in vivo toxicity studies performed with this substance.
Sakuralube S-900 is an additive for lubricants, it is a dark brown paste/viscous liquid,with a high molecular weight 920-1200 Da. and a Log P value of >4.64. It has a low water solubility (<1.09x10-4g/L).These physicochemical properties suggest that Sakuralube S-900 will not be readily absorbed across biological membranes. It is expected to have a low bioavailability but have the potential to bioaccumulate.Sakuralube S-900 is not volatile (2.0x10-20Pa at 25°C) and has a high boiling point (the test material decomposes at 515 ±0.5K at 101.325kPa without boiling but the estimated boiling point =633K (360°C), based on vapour pressure data and chemical structure) therefore the inhalation route will not be a route of exposure. 
 
Absorption
 
Oral route
During acute oral studies in rats all behavioural, clinical and physiological responses after administration were considered normal. The oral LD50 for Sakuralube S-900 was >2000 mg/kg body weight in rats. Without pharmacokinetic data it is difficult to say if absorption occurred in these studies.
Dermal route
It is generally accepted that compounds with a partition coefficient in the range of 1 to 4 (optimally between 1 and 2) and a molecular weight of less than 500 may be absorbed, at least in part, via the dermal route. The partition coefficient of Sakuralube S-900 is log Pow >4.64 and the molecular weight is 920-1200 Da.; accordingly, it is not considered likely that this material will cross the skin barrier. Although there were some signs of dermal irritation noted these were resolved 2-7 days after dosing. There was no sign of toxicity or ill health in any rabbit during the observation period.
 
 
Inhalation route
There are no toxicokinetics or inhalation toxicity studies available with Sakuralube S-900.
 
Distribution
The findings from the oral 28-day repeat dose and reproductive/development screening tests did not provide evidence that Sakuralube S-900 was distributed systemically following oral administration. It was concluded that oral administration of Sakuralube S-900 to Sprague-Dawley CrI:CD®BR rats for 28-days at doses of 15, 150 and 1000 mg/kg/day (repeat dose test) or 100,300 and 1000 mg/kg/day (reproductive /development screening test) was well tolerated with no toxicologically significant adverse systemic effects. It was also concluded that there was no effect of treatment on reproductive performance, including mating performance, fertility and offspring survival and development up to Day 7 of age.

Metabolism
No data are available on metabolism in the existing toxicity studies. As no effects were seen in the repeat dose studies it cannot be stated with certainty that absorption of Sakuralube S-900 occurred.
 
Excretion
No data are available on excretion in the existing toxicity studies.
 
Conclusion
 
From the data available so far there is no evidence that the test substance is absorbed via the gastrointestinal tract following oral administration or via the skin following dermal administration.