Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
Assessment of toxicokinetic behaviour
Type of information:
other: Assessment of toxicokinetic behaviour
Adequacy of study:
key study
Reliability:
other: Assessment of toxicokinetic behaviour
Rationale for reliability incl. deficiencies:
other: other: Assessment of toxicokinetic behaviour

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1992
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Objective of study:
other: Assessment of toxicokinetic behaviour
Principles of method if other than guideline:
Assessment of toxicokinetic behaviour
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Assessment of toxicokinetic behaviour

Results and discussion

Preliminary studies:
There are no study data available for the toxicokinetic of the test substance Vulcuren VP KA 9188.
The test substance Vulcuren VP KA 9188 has a solid state under normal condition. The calculated vapor pressure is about 3.9E-18 Pa (20°C) and thus an exposure to the inhalation route could be practically excluded.
The physical and chemical properties (like water solubility < 0.05 mg/l at 25°C, log Pow: 10.4 at 20°C) as well as the molecule size (mol weight: 693.12) let to the conclusion that the oral and dermal resorption rate is low.
This assumption is in line by the available data from acute oral and acute dermal studies (Hüls AG 1992a, Hüls AG 1992b). After a single oral or dermal application of the test substance (2000 mg/kg bw) to male or female rats only transient and weak clinical symptoms and no mortality were seen. On the other hand, no mortality was observed in the in vivo micronucleus assay with male rats, which were treated ip. with up to 4000 mg/kg test substance (twice, 24 h interval) (Bayer 2000c). The bypass of the absorption barrier of the gastrointestinal tract or the skin and thus a presumably higher systemic availability from the test substance, no mortality was seen. This could be evidence that the test substance has a very low intrinsic toxic potential.
In a subacute toxicity study with Wistar rats (Bayer AG 2000f), which were treated per gavage with 0, 40, 200 and 1000 mg/kg bw and day, no substance-related toxicity was observed. Thus, even with a log Pow of 10.4 there is no evidence of appreciable cumulative potential of the test substance. Based on data from the clinical chemistry, gross pathology and histopathology, as well as the evaluation of the excrements, no conclusion of the main elimination ways could be drawn.
The results from the in vitro chromosome aberration assay (Bayer 2000b) showed an increase in cytotoxicity in presence of metabolic activation (S9-mix). Thus, it could be concluded, that the test substance Vulcuren VP KA 9188 could be metabolized by microsome enzymes of the rat liver; whereas the metabolite is more reactive than Vulcuren VP KA 9188. The weak positive effect in the in vitro chromosome aberration assay indicated the induction of DNA-reactive metabolites. However the negative results in the in vivo micronucleus assay (Bayer AG 2000e) and in vivo comet assay (Lanxess GmbH 2005) indicated that in mammalians no appreciable amounts of these DNA-reactive metabolites are generated.

Any other information on results incl. tables

Assessment of toxicokinetic behaviour

Applicant's summary and conclusion

Executive summary:

There are no study data available for the toxicokinetic of the test substance Vulcuren VP KA 9188.

The test substance Vulcuren VP KA 9188 has a solid state under normal condition. The calculated vapor pressure is about 3.9E-18 Pa (20°C) and thus an exposure to the inhalation route could be practically excluded.

The physical and chemical properties (like water solubility < 0.05 mg/l at 25°C, log Pow: 10.4 at 20°C) as well as the molecule size (mol weight: 693.12) let to the conclusion that the oral and dermal resorption rate is low.

This assumption is in line by the available data from acute oral and acute dermal studies (Hüls AG 1992a, Hüls AG 1992b). After a single oral or dermal application of the test substance (2000 mg/kg bw) to male or female rats only transient and weak clinical symptoms and no mortality were seen. On the other hand, no mortality was observed in the in vivo micronucleus assay with male rats, which were treated ip. with up to 4000 mg/kg test substance (twice, 24 h interval) (Bayer 2000c). The bypass of the absorption barrier of the gastrointestinal tract or the skin and thus a presumably higher systemic availability from the test substance, no mortality was seen. This could be evidence that the test substance has a very low intrinsic toxic potential.

In a subacute toxicity study with Wistar rats (Bayer AG 2000f), which were treated per gavage with 0, 40, 200 and 1000 mg/kg bw and day, no substance-related toxicity was observed. Thus, even with a log Pow of 10.4 there is no evidence of appreciable cumulative potential of the test substance. Based on data from the clinical chemistry, gross pathology and histopathology, as well as the evaluation of the excrements, no conclusion of the main elimination ways could be drawn.

The results from the in vitro chromosome aberration assay (Bayer 2000b) showed an increase in cytotoxicity in presence of metabolic activation (S9-mix). Thus, it could be concluded, that the test substance Vulcuren VP KA 9188 could be metabolized by microsome enzymes of the rat liver; whereas the metabolite is more reactive than Vulcuren VP KA 9188. The weak positive effect in the in vitro chromosome aberration assay indicated the induction of DNA-reactive metabolites. However the negative results in the in vivo micronucleus assay (Bayer AG 2000e) and in vivo comet assay (Lanxess GmbH 2005) indicated that in mammalians no appreciable amounts of these DNA-reactive metabolites are generated.