Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A single dermal dose of 200 uL test substance was given to 5 male and 5 female rats. Samples of urine and feces were taken at pre-dose 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for 1 animal of each sex at 4, 8, 24, and 96 hrs after dosing. Cold traps were used to collect any test substance that volatilized.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
2-phenyldodecane
IUPAC Name:
2-phenyldodecane
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: Crl: CD(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Ltd.
- Age at study initiation: 8 weeks of age
- Weight at study initiation: males 237-272 g, females 190-212 g
- Housing: individual all-glass cages suitable for collecting urine and feces, identified with ear notching
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No. 1, Expanded, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: October 20, 1992 To: February 5, 1993

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
ethanol
Duration of exposure:
Single dermal application
Doses:
200 ul test substance per animal
No. of animals per group:
5 of each sex per dose
Control animals:
no
Details on study design:
- Tissues and body fluids sampled: Urine and faeces were collected using suitable vessels surrounded by solid CO2. Cage washings and cage debris were also collected. Whole-body autoradiography was done for 1 animal of each sex at 4, 8, 24, and 96 hrs after dosing. A back-wash was done prior to necropsy. Sections obtained include the exorbital lachrymal gland or ovaries, intra-orbital lachrymal gland, Harderian gland, adrenal gland, thyroid, and brain and spinal cord. Expired air was collected in cold traps. The cold traps were changed pre-dose, 4, 8, and 24 hrs post-dose. Collection ended at 48 hrs.
- Time and frequency of sampling: Urine and feces: pre-dose, 4, 8, 24, 72, and 96 hrs post-dose
- Method type(s) for identification: Liquid scintillation counting and TLC, urine and feces were pooled by time point and sex
- Limits of detection and quantification: for LSC the limit of detection was twice the background disintegration rate obtained from the measurement of the pre-dose samples.

Results and discussion

Signs and symptoms of toxicity:
no effects
Remarks:
No clinical signs were observed during the study.
Dermal irritation:
no effects
Remarks:
No clinical signs were observed during the study.
Total recovery:
Excretion was primarily through the urine, though there was some excretion through the feces. 10.58% of the test substance was excreted in males, and 7.95% in females. 7.668% was excreted through the urine in males, and 6.129% by females. The excretion rate in urine was greatest between 24 and 48 hrs post-dose. 2.004% was excreted through the feces in males, and 0.889% in females. No radioactivity was detected in the cold traps. Most of the radioactivity was recovered in the back wash, and the remainder at the dose site.
Percutaneous absorption
Dose:
2 mg
Parameter:
percentage
Absorption:
8 - <= 10 %
Remarks on result:
other: 4-96 hr
Remarks:
A minimum of 10% (male) and 8% (female) of the dose was absorbed. The majority of the test substance remained on the skin through the end of the study.

Any other information on results incl. tables

No clinical signs were observed during the experiment.

Applicant's summary and conclusion

Conclusions:
The test substance was poorly absorbed through the skin with only 8-10% being absorbed. The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid and mostly complete, and it was eliminated mostly through the urine.
Executive summary:

In cases where no data were available on the target substance, Benzene, C15 -16 -alkyl derivs., data were read across from a structurally related material (the test substance).

A single dermal dose of 200 uL test substance was given to 5 male and 5 female rats. Samples of urine and feces were taken at pre-dose 4, 8, 24, 72, and 96 hrs post-dose. Whole body autoradiography was done for 1 animal of each sex at 4, 8, 24, and 96 hrs after dosing. Cold traps were used to collect any test substance that volatilized. No clinical signs were observed during the study. The test substance was poorly absorbed through the skin, with only 8 -10% being absorbed. The test substance was rapidly eliminated from the majority of tissues, though some remained in fatty tissues. Metabolism of the test substance was rapid, and it was eliminated mostly through the urine.