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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliability is assumed to be 1 as data are migrated from NONS file

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1987

Materials and methods

Objective of study:
other: Absorption, distribution and excretion after one application to rat.
Test guideline
Qualifier:
according to guideline
Guideline:
other: 88/302/EEC Part B
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
401-540-3
EC Name:
-
Cas Number:
84632-65-5
Molecular formula:
C18H10Cl2N2O2
IUPAC Name:
3,6-bis(4-chlorophenyl)-1H,2H,4H,5H-pyrrolo[3,4-c]pyrrole-1,4-dione
Details on test material:
- Name of test material (as cited in study report): none specified, but the substance was Pigment Red 254 (EC 401-540-3; CAS 84632-65-5)
- Substance type: pigment
- Physical state: solid
- Analytical purity: -
- Other: -
Radiolabelling:
yes
Remarks:
The labelling was achieved by C-14 in both carbons which belong to both pyrrol-rings.

Test animals

Species:
rat
Sex:
male

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
suspension in 0.5 % CMC in 0.9 % NaCI
Duration and frequency of treatment / exposure:
7 d
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg and 1000 mg/kg
No. of animals per sex per dose / concentration:
5 males per dose
Control animals:
no

Results and discussion

Main ADME results
Type:
absorption
Results:
not bioavailable

Any other information on results incl. tables

The animals were killed 168 h p.a.. During the 168 h 0.3 resp. 0.6% of the applied radioactivity was found in the urine; 0.3 rsp. 0.4% were just detected after 24 h in the urine. These small amounts are interpreted as technic-related faecalic impurities.

The part which was incorporated in the faeces were in average 119.7 % (low dose group) rsp. 96.0%. The corresponding fraction after 24 h was 101.4% rsp. 79.7 %.

In both dosage groups only neglictible amounts of the radioactive substance were detected in the organs and the tissue, in the intestinal tract, in the blood and in the carcasse. The maximal concentration in the blood was 0.139 Ag/g (low dosage group) rsp. 1.152 Ag/g and in the plasma 0.140 rsp. 1.048 ag/g. The maxima were reached 1 to 2 h after application. As the concentration is closed to the

detection limit the kinetics of the elimination and the area under the curve could not be calculated.

From the study can be stated that the notified substance is not bioavailable when it is applied once orally under the conditions mentioned above.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
In GLP-study according to guideline 88/302/EEC Part B the absorption, distribution and excretion of radiolabelled PR 254 after single application to rat was investigated. PR 254 was not bioavailable.
Executive summary:

In GLP-study according to guideline 88/302/EEC Part B the absorption, distribution and excretion of radiolabelled PR 254 was investigated. 100 mg/kg bodyweight and 1000 mg/kg bodyweight were applied once to groups of five male rats.

The animals were killed 168 h p.a.. During the 168 h 0.3 resp. 0.6% of the applied radioactivity was found in the urine; 0.3 rsp. 0.4% were just detected after 24 h in the urine. These small amounts are interpreted as technic-related faecalic impurities.

The part which was incorporated in the faeces were in average 119.7 % (low dose group) rsp. 96.0%. The corresponding fraction after 24 h was 101.4% rsp. 79.7 %.

In both dosage groups only neglictible amounts of the radioactive substance were detected in the organs and the tissue, in the intestinal tract, in the blood and in the carcasse. The maximal concentration in the blood was 0.139 Ag/g (low dosage group) rsp. 1.152 Ag/g and in the plasma 0.140 rsp. 1.048 ag/g. The maxima were reached 1 to 2 h after application. As the concentration is closed to the

detection limit the kinetics of the elimination and the area under the curve could not be calculated.

From the study can be stated that PR 254 is not bioavailable when it is applied once orally under the conditions mentioned above.