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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:
1952
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study, meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1952

Materials and methods

Objective of study:
absorption
metabolism
Test guideline
Guideline:
other: follows basic principles of pharmacokinetics studies
Principles of method if other than guideline:
In this study We have attempted to draw up balance sheets for these compounds and to isolate their principal metabolites. Minor metabolites can be regarded as derivatives of o-aminophenol (I), which might be formed from them on hydrolysis.
These compounds may, therefore, be considered as having potential centres for conjugation (see Bray, Ryman & Thorpe, 1948; Thorpe, 1950). Williams (1938, 1943) and Smith & Williams (1949) found that the rabbit excretes the aminophenols mainly as
0-conjugates, i.e. ethereal sulphates and glucuronides. The only other compound of this group which appears to have been investigated previously is were detected by means of paper chromatography.
The results obtained show the influence of substituents
upon the stability of the oxazole ring.
Metabolism of o-, m- and p-aminophenols
Quantitative. The results of determinations on
urines excreted by rabbits which had received o-,
m-, or p-aminophenol are summarized in Table 2.
From these values the amounts of the different
metabolites excreted have been calculated
Amounts of mnetabolites excreted by rabbits after administration of aminophenols
The presence of aminophenot and acetamidophenol
in ether extracts of the urines was detected
by two-dimensional paper chromatograms using
solvent mixture A followed by solvent mixture B
(Table 1). Approximate estimations of the amounts
present were made from one-dimensional chromatograms
using solvent mixtures A (o- and p-aminophenol),
B (m-acetamidophenol) and C (o- and pacetamidophenol).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
The aminophenols were purchased (British Drug Houses Ltd. and Light and Co.).
Radiolabelling:
no

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 -3 kg

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
1 g/animal
No. of animals per sex per dose:
no data
Control animals:
not specified
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: no data
- From how many animals: no data
- Method type(s) for identification: Chromatography

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Unchanged =2%
Acetaminophenol=25%
Aminophenyl sulfate=8%
Acetamindophenyl sulfate=4%
Aminophenyl glucuronide =45%
Acetamidophenyl glucuronide =16%

Applicant's summary and conclusion

Executive summary:

The metabolism p-aminophenol, in the rabbit was studied. P-aminophenol were excreted 2 %; they were excreted conjugated with acetic acid 45 %, with sulphuric acid 12% and with glucuronic acid 61 % of the dose respectively.