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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study design appears to follow OECD Guideline 417 (1984). Study pre-dates GLP requirements.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Objective of study:
distribution
excretion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
- only 1 dose level used instead of at least 2.
GLP compliance:
no
Remarks:
Study pre-dates GLP.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Tinuvin P [2(2'-hydroxy-5'-methylphenyl)-benzotriazole]

- Radiochemical purity (if radiolabelling): > 99%
- Specific activity (if radiolabelling): 5.07 µCi/mg
The radioactive label is located in the benzotriazole core and at the methyl group
Specific details on test material used for the study:
- Name of test material (as cited in study report): Tinuvin P [2(2'-hydroxy-5'-methylphenyl)-benzotriazole]

- Radiochemical purity (if radiolabelling): > 99%
- Specific activity (if radiolabelling): 5.07 µCi/mg
The radioactive label is located in the benzotriazole core and at the methyl group
Radiolabelling:
yes
Remarks:
Radiolabelled substance was diluted with non-radiolabelled test substance

Test animals

Species:
rat
Strain:
other: Tif:RAIF (SPF)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sisseln animal farm
- Age at study initiation: Not reported
- Weight at study initiation: 200 g
- Fasting period before study: overnight
- Housing: in metabolism cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported


IN-LIFE DATES: From: Not reported To: Not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on exposure:
TEST MATERIAL
- Amount applied: 0.5 mL.
Duration and frequency of treatment / exposure:
Single dose.
Doses / concentrations
Dose / conc.:
10 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
4 males
Control animals:
no
Positive control:
None.
Details on study design:
- Dose selection rationale: None.
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Urine, faeces, organs, & tissues.
- Time and frequency of sampling: Urine and faeces = collected in 24 hour periods until 168 hours after dosage. Organs and tissues = 168 hours.

Investigated for distribution were blood, plasma, heart, aorta, lung, brain, nerve, eye, adrenals, thyroid gland, Thymus, Salivary gland, testes, spleen,, bone marrov, muscle, skin, fat (white), fat (brown), pancreas, liver, kidneys, stomach, small intestine
Statistics:
Not reported.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
168 hours after dosage the residual radioactivity measured in most organs and tissues were below 0.02 µg/g. Levels significant above this value were detected only in kidney, aorta, and liver (0.10-0.22 µg/g).
Details on excretion:
Within the first 48 hours after administration about 91% of the dose was eliminated from the body. The peak of elimination with 56% of the applied dose occurred in the urine between 6 and 24h. Between 0 and 6h, only 9% of the dose was found in the urine. After 168 hours 94% of the dose was recovered, 69% in the urine and 25% in the faeces. The results indicate that the substance is well absorbed from the gastro-intestinal tract and rapidly and almost completely eliminated via feces and urine.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
No bioaccumulation potential based on study results