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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The data concern a literature study; GLP conditions or Guidelines for testing are not mentioned, but the study is well performed and documented.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Objective of study:
other: absorption plus excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Radiolabeled MOCA was administered orally or dermally to rats. MOCA was measured in urine, faeces, skin, total carcasses at several intervals (up to 120 hr.).
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: pale-yelow, pelleted powder
- Physical state: solid
- Analytical purity: probably 92.36% as detected by UV detection
- Impurities (identity and concentrations): one other peak of 7.56%
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding
- Weight at study initiation: 151-175 g
- Fasting period before study: 18 hr.
- Housing: stainless steel metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
Not mentioned.

Administration / exposure

Route of administration:
other: oral gavage and skin application
Vehicle:
other: PEG and aceton
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
62.5 mg MBOCA in 10 ml PEG plus 2.5 ml *MBOCA


TEST SITE
- Area of exposure: 6x6 cm
- Type of wrap if used: gauze pad + adhesive tape
Duration and frequency of treatment / exposure:
Oral gavage: single dose; follow-up up to 120 hr.
Skin application: single dose; follow-up up to 72 hr.
Doses / concentrations
Remarks:
Doses / Concentrations:
Oral: ca. 11 µg MOCA
Skin: 50µgl of 2.5 mg MOCA
No. of animals per sex per dose:
6 to 8

Results and discussion

Main ADME results
Type:
other: absorption + excretion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
In two indepent experiments studying oral gavage in rats, 14.5% *MOCA was excreted in urine in the first 24 hours, although ony ca. 1% is excreted as parent MOCA. By far the largest percentage of *MOCA was excreted in the faeces (ca. 53.5% in the first 24 hours). By 96 hours the rate of exretion in both urine and faeces had been reduced below 1%.

In the skin experiments, the rate of excretion of *MOCA was fairly constant during a 3-day period.

Metabolite characterisation studies

Metabolites identified:
not specified

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: upon oral administration in rats ca. 13.7% of *MOCA was retained in tissue and ca. 5-13% upon dermal administration
Upon oral administration of *MOCA to rats, ca. 68% is excreted via urine and faeces during the first 24 hours, excretion fells down rapidly during the third day. Within 72 hours ca. 16.5% of the administered compound is excreted in urine, but only 0.25% as parent MOCA. Circa 13% of *MOCA is retained in the tissues after 72 hours. Upon dermal administration of *MOCA to rats, ca. 2.5% is excreted via urine and faeces during the first 72 hours, wherease only very small amounts are excreted as parent MOCA.
Overall, urinary analysis for MOCA may not be a suitable indicator of the extent of recent exposure.