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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1962
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: public available literature, non GLP, non Guideline
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1962

Materials and methods

Objective of study:
absorption
excretion
metabolism
Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
not indicated

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
body weight: about 100 g
Rats were fed with normal diet during the test period

Administration / exposure

Route of administration:
dermal
Vehicle:
ethanol
Details on exposure:
The test item was diluted in 50% ethanol (22.8 mg in 0.2 ml). 0.2 ml were dermally applied to the shaved neck of male rats. Control animals received 0.2 ml of 50% ethanol.
Duration and frequency of treatment / exposure:
one treatment only
Doses / concentrations
Remarks:
Doses / Concentrations:
22.8 mg in 0.2 ml 50% ethanol
No. of animals per sex per dose:
9 males in exposure group
4 males in control group
Control animals:
yes, concurrent vehicle
Positive control:
no
Details on study design:
After dermal application, the urine of the animals was collected periodically during 5 days. The metabolite of the test item was measured in a bioassay.
Details on dosing and sampling:
The first measurement was done 18 after exposure. The next measurements were done every 24 h. The quantitative measurement of metabolite was done periodically in the urine samples. The samples were diluted with 100 mL water and the metabolite was detected using a microbiological assay.
Statistics:
mean and standard deviation

Results and discussion

Preliminary studies:
no preliminary results

Toxicokinetic / pharmacokinetic studies

Details on absorption:
At least 36 % of the dermally applied dose of the test item were bioavailable (excretion via the urine as metabolite).
Details on distribution in tissues:
Not measured.
Details on excretion:
At least 36 % of the dermally applied dose of the test item were found in the urine as metabolite.
Toxicokinetic parameters
Test no.:
#1
Toxicokinetic parameters:
AUC:

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The metabolite is formed from the test item. The same metabolite is formed after dermal application of structur analog.

Any other information on results incl. tables

It has been shown that following topical administration of the test item to rats, there is a rise in the urinary metabolite concentration (as measured by bioassay) with an AUC of approximately 70% of that for the same dose of topically applied structur analog. The Tmax of metabolite in urine following topical administration of the test item was delayed in comparison to topically applied structur analog. These data suggest that there is dermal penetration of the test item with associated extensive formation of metabolite.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
It has been shown that following topical administration of the test item to rats, there is a rise in the urinary main metabolite concentration (as measured by bioassay) with an AUC of approximately 70% of that for the same dose of topically applied test item analog. The Tmax of main metabolite in urine following topical administration of the test item was delayed in comparison to topically applied test item structure analog. These data suggest that there is dermal penetration of the test item with associated extensive formation of metabolite. These data support the test item as well as test item strucutre analog being vitamin B5 provitamins.
Executive summary:

In a absorption/excretion/metabolism study the test item was administered to 9 male Wistar rates dermally in a single dose of 22.8 mg in 0.2 ml 50% ethanol.

It has been shown that following topical administration of the test item to rats, there is a rise in the urinary main metabolite concentration (as measured by bioassay) with an AUC of approximately 70% of that for the same dose of topically applied test item structure analog. The Tmax of metabolite in urine following topical administration of the test item was delayed in comparison to topically applied test item structure analog. These data suggest that there is dermal penetration of the test item with associated extensive formation of metabolite. These data support the test item as well as test item structure analog being vitamin B5 provitamins.

At least 36 % of the dermally applied dose of the test item were bioavailable (excretion via the urine as metabolite).

This study in the rat is classified acceptable.