2-(2H-benzotriazol-2-yl)-p-cresol

Basic toxicokinetics

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

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

Test material information

Constituent 1

Reference substance name:

2-(2H-benzotriazol-2-yl)-p-cresol

EC Number:

219-470-5

EC Name:

2-(2H-benzotriazol-2-yl)-p-cresol

Cas Number:

2440-22-4

Molecular formula:

C13H11N3O

IUPAC Name:

2-(2H-1,2,3-benzotriazol-2-yl)-4-methylphenol

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 or test system 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 / concentration:

4 males

Control animals:

no

Positive control reference chemical:

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