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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study report, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
other company data
Title:
Unnamed
Year:
1988
Report date:
1988
Reference Type:
other company data
Title:
Unnamed
Year:
1989

Materials and methods

Principles of method if other than guideline:
Triethanolamine uniformly radiolabeled with 14C was administered to C3H/HeJ mice intravenously or dermally to study the skin penetration of the test substance in vitro.
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
triethanolamine
IUPAC Name:
triethanolamine
Constituent 2
Chemical structure
Reference substance name:
2,2',2''-nitrilotriethanol
EC Number:
203-049-8
EC Name:
2,2',2''-nitrilotriethanol
Cas Number:
102-71-6
Molecular formula:
C6H15NO3
IUPAC Name:
2,2',2''-nitrilotriethanol
Details on test material:
- Name of test material (as cited in study report): triethanolamine
- Analytical purity: 99.6 %
- Lot/batch No.: 7H-5317
- Radiochemical purity (if radiolabelling): 97-98 % (98.6 % by liquid chromatography reanalysis)
- Specific activity (if radiolabelling): 34.7 mCi/mmol
- Supplier: Amersham Cororation, Arlington Heights, IL, USA (labelled TEA)
- Supplier: Texaco Chemical Company, Austin, Texas, USA (unlabelled TEA)
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, NY)
- Weight at study initiation: 231 to 247 g
- Fasting period before study: none
- Housing: glass Roth-style metabolism cages
- Individual metabolism cages: yes
- Diet: Purina® Certified Rodent chow #5002 ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40-60
- Air changes (per hr): ca. 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
48 hours
Doses:
1000 mg/kg bw
No. of animals per group:
3
Control animals:
no
Details on study design:
About 48 hours prior to dosing, indwelling cannulas were surgically implanted into the jugular vein of the rats while they were under methoxyflurane anesthesia using a modification of the method described by Harms and Ojeda, 1974. Approximately, 16 hours prior to dosing, die animals were anesthetized with methoxyflurane and the skin on the back of the rats was shaved using Ivory® soap and a straight razor. The skin was dried and a glass ring (as previously described) was attached to the skin using cyanoacrylate. At the time of dosing, die animals were anesthetized with methoxyflurane and a dosing volume targeted at 200 µl of "neat" 14C-TEA was applied within the ring. The ring was then covered with a round glass cover slip attached with cyanoacrylate to restrict the animals access to the dose site while grooming and to aid in containing this large volume of dose at one site. The dosing volume applied dermally was 96.8 ± 0.3 % (mean ± S.D.) of the target dosing volume. The average amount of radioactivity applied was 4.42 µCi/rat.
Immediately following dosing the animals were placed in glass Roth cages for the separation of urine and feces. Urine and feces were collected at 6, 12, 24 and 48 hours post-dosing. Blood samples (= 0.2 ml) were taken via the indwelling jugular cannulas at 0.5, 1, 2, 4, 6, 12, 24 and 36 hours post-dosing. An additional blood sample was drawn from one animal at 31 hours post-dosing. At 48 hours post-dosing the animals were anesthetized with methoxyflurane and sacrificed by exsanguination via cardiac puncture. Following sacrifice, the skin from the dose site was excised, the remaining skin removed, the liver and kidneys excised, and each Roth cage was washed with a solution of acetone and water. The glass rings used to restrict access to the dosed site were removed from the skin and washed with water to recover any residual radioactivity on thie rings. Radioactivity in excreta, cage wash solution, ring wash solution, liver, kidneys, skin and remaining carcass were determined.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
Upon dermal application, the dermal absorption of triethanolamine was less extensive and much slower than in mice. Absorption values have not been provided.
Total recovery:
The urinary interval excretion data show that the percentage of the administered dose found in the urine per collection interval (0-6, 6-12, 12-24 and 24-48 hrs) was 3% or less.
The level of radioactivity was non-detectable (2x background) in the blood samples taken at 0.5, 1, 2, 4 and 6 hrs post-dosing
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

As long as the glass ring and coverslip attached to the skin to restrict the animals access to the dosed was intact, the results are as indicated above. Once the integrity of the glass ring or coverslip failed, the dose was leaked to other areas of the skin and ingestion of the dose incidental to grooming could occur. Indeed, the percentage radioactivity found in the urine increased markedly in each as soon as the device for restricting access to the dosed site failed. In the blood, radioactivity was only detectable at sampling times which were after the integrity of the glass ring restricting access to the dosed site had failed. This suggests that most of the blood radioactivity found may have been a result of ingestion incidental to grooming after access to the test material on the skin was obtained. Data were not sufficient to construct a meaningful blood concentration-time profile.

Applicant's summary and conclusion