Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well performed research study, no guideline study, no GLP

Data source

Reference
Reference Type:
publication
Title:
Investigations on the disposition of oral doses of some water-insoluble pigments
Author:
El Dareer SM,Tillery KF & Hill DL
Year:
1984
Bibliographic source:
Bull. Environ. Contam. Toxicol. 32: 171-174
Report Date:
1984

Materials and methods

Objective of study:
other: Absorption, distribution and excretion
Principles of method if other than guideline:
investigation of absorption, distribution and excretion after a single oral application
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): C.I. Pigment Yellow 74 (Yellow #74)
- Analytical purity: 89.1%
- Impurities (identity and concentrations): no data


Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 146-180 g
- Fasting period before study: no data
- Housing: no data
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
single exposure, investigation after 1, 4, 24 and 48 hours after dosing
Doses / concentrations
Remarks:
Doses / Concentrations:
12.6 mg/kg
No. of animals per sex per dose:
3 animals per time point
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, stomach contents, intestinal contents and "various tissues"
- Time and frequency of sampling: 1, 4, 24, 48 h after dosing

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The study did not find evidence of systemic absorption on Pigment Yellow 74. Small quantities of componds present in samples of tissues that were in direct contact with the substance were be attributed to mechanical adherance to the tissues rather than to absorption.
Details on distribution in tissues:
1 and 4 hours after dosing most of the administered material was present in the gut contents and none was in the faeces. 24 and 48 after dosing, most substance was in the faeces (up to 86%). Detectable amounts (>3%) were only in those tissues directly in contact with the compound. No compound was found in samples of plasma, whole blood, liver, kidney, or lungs, even after administration of doses ten times larger (data not shown).
Details on excretion:
After 48 hours, about 86% of the administered dose was excreted via the feces.

Any other information on results incl. tables

Disposition of PY 74 (values in table given represent the mean % of dose for three rats (SD in brackets)):

          Disposition
 Time after dosing (h)  Gut contents  Faeces* Tissues collected   Total
 1  111 (2) < 0.1   2.6 (0.4)  114 (2)
 4  103 (1) < 0.1  2.1 (0.3)  105 (1)**
 24  25.5 (16.1) 70.4 (11.5)  0.1 (0.8)  95.9 (7.1)
 48  2.1 (1.4) 85.9 (22.3)  not measured  88.2 (21.7)

* the amounts present in urine samples were included in the values for faeces, because the authors concluded that the small amounts in urine were probably due to contamination of urine by faeces

** only values for two rats in this group

Results were described by the authors as follows:

One and four hours after dosing most of the administered material was present in the gut contents and none was in the faeces. Twenty four and 48 after dosing, most substance was in the faeces. Detectable amounts were only in those tissues directly in contact with the compound. No compound was found in samples of plasma, whole blood, liver, kidney, or lungs, even after administration of doses ten times larger (data not shown).

The authors concluded that the small quantities of componds present in samples of tissues that were in direct contact with the substance can be attributed to mechanical adherance to the tissues rather than to absorption.

Recoveries of the pigment was nearly complete.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: The study did not find evidence of systemic absorption on Pigment Yellow 74.
The study did not find evidence of systemic absorption on Pigment Yellow 74.
Executive summary:

Male Fischer 344 rats received 12.6 or 126 mg/kg Pigment Yellow 74 by gavage. Twenty four and 48 hours after dosing most part of the substance was detected in the faeces (up to 86%). Only minor amounts (< 3%) were detected in tissues all of which were in direct contact with the substance, so that it can be attributed to mechanical adherance to the tissues rather than to absorption.