4,4'-methylenebis[2-chloroaniline]

Basic toxicokinetics

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

Test material information

Constituent 1

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 or test system 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 / concentration:

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.