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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004
Reference Type:
secondary source
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of four female mice received a single dermal dose of 79 or 1120 mg/kg bw. Expired radioactivity was trapped and quantitated and urine and feces were collected from all B6C3F1 mice dosed via skin painting up to 72 hours after dosing.The skin site of application from all mice was examined.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
acetone
Duration of exposure:
72 hrs
Doses:
79 or 1120 mg/kg bw
No. of animals per group:
4
Control animals:
no
Details on study design:
Dermal doses were formulated in acetone and contained 65 μCi radiolabel for rats and 12 to 15 μCi for mice with an appropriate amount of nonradiolabeled triethanolamine in a volume of approximately 190 μL per dose. A dose area of 12 cm2 for rats and 1.44 cm2 for mice was located on each animal’s back. Approximately 24 hours prior to dosing, rats were anesthetized with 7:1 ketamine:xylazine (60 mg/kg) by intramuscular injection and mice with sodium pentobarbitol (60 mg/kg) by intraperitoneal injection. Fur at the dose area was clipped with a No. 40 blade (Oster Professional Products). The clipped area on each animal was wiped with a gauze soaked with acetone, dried, and then examined for abrasions. Any animal with abrasions in the clipped area was excluded from the study. The dose area was outlined on the animal’s back with a permanent marker, and the animal was placed in a metabolism cage.

The doses for mice were administered over the dose area using a 100 or 250 μL syringe equipped with a Teflon®-tipped plunger and a gavage needle. A metal tissue capsule was glued in place over the dose area using Duro Quick Gel™ Super Glue.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
79 mg/kg bw group
Blood: 0.00590%
Dose site: 1.35%
Faeces: 7.80%
Urine: 48.2%
Total: 57.3%
14.6% remained unabsorbed (dosing appliance, skin gauze, skin wash)

1120 mg/kg bw group
Blood: 0.00627%
Dose site: 0.576%
Faeces: 13.0%
Urine: 67.7%
Total: 81.3%
6.75% remained unabsorbed (dosing appliance, skin gauze, skin wash)
Total recovery:
60% to 80% of dermally applied 79 and 1120 mg/kg triethanolamine was absorbed by female mice within 72 hours.

Any other information on results incl. tables

On the basis of mass of triethanolamine per area of skin, the lowest dermal dose levels for rats and mice were equal at 1.09 mg/cm2. The skin of mice is thinner than that of rats, and this difference may explain the higher percentage of dose absorbed by mice. The highest dermal doses were 4 and 15 mg/cm2 for rats and mice, respectively. Triethanolamine enhances its own absorption, and the pronounced difference between the species was not unexpected. The percent of dose absorbed in each species increased with increasing dose, but in rats, the increase was not statistically significant. Both species rapidly excreted the absorbed dose, primarily in urine. In rats, less than 1% of the dose was present in the tissue samples (except the dose site) 72 hours after treatment; the heart, kidney, liver, lung, and spleen contained elevated concentrations of radiolabel relative to blood.

Applicant's summary and conclusion