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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because though it did not follow OECD guidelines, it is a well conducted and well reported study.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not specified
Remarks:
Data regarding GLP adherence is not provided in the study report
Principles of method if other than guideline:
Though a specific guideline is not followed, the study is well conducted and well reported.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): RAE E, RAE C, RAE D
- Substance type: Residual Aromatic Extract
- Physical state: Liquid
Radiolabelling:
yes
Remarks:
BaP; 0.1%, w/w

Test animals

Species:
mouse
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
6 hours
Doses:
No data
Control animals:
no
Remarks:
No data
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: 0.5 mL of 5% solution of cyclohexane on a Sep-Pak silica and a Sep-Pak alumina cartridge

TEST SITE
- Preparation of test site: Shaving prior to application
- Area of exposure: Dorsal region
- Type of cover / wrap if used: Aluminum foil

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes: aluminum foil used as an occulusive covering

SAMPLE COLLECTION
- Collection of blood: Yes, using cardiac puncture
- Collection of urine and faeces: No
- Collection of expired air: No
- Terminal procedure: Anaesthesia
- Analysis of organs: No
-DNA extraction: Yes, from proteinase K digests of skin using automated DNA extraction

ANALYSIS
- Method type(s) for identification: HPLC-UV, Liquid scintillation counting

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
no effects
Total recovery:
No data
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

Table 2: Amounts of adduct formation in DNA and blood  

 

Oils

Blood, pmol adduct/ 25µL blood

DNA, pmol adduct/ mg DNA

Average

SD

Average

SD

RAE E

-

-

-

-

RAE C

0.73

0.22

0.92

0.22

RAE D

0.75

0.26

0.78

0.17

Applicant's summary and conclusion

Conclusions:
Both low and high CPI values were calculated for RAE's and higher values are consistent with previous findings which indicate that some RAE's may be carcinogenic in rodent skin painting tests. The authors conclude that this is primarlily caused by high (3-6) ring PAC contents.
Executive summary:

In a toxicokinetic study examining dermal absorption, groups of mice were exposed to residual aromatic extracts (C, D, and E) for 6 hours. Test substance was applied to the dorsal area and the treated area was covered with aluminum foil, which created occlusion and prevented oral ingestion. While under anesthesia, blood samples were removed by cardiac puncture and radioactivity measurement s were made followed by liquid scintillation counting. After terminal anesthesia, the test area of the skin was removed and extracted with solvent so that DNA could be isolated from proteinase K digests of skin. Purity was assayed using absorbance ratios of 260:280 and 230:260 nm.

 

An inverse relationship between viscosity and levels of DNA adducts were observed. The DNA adduct level in skin decreased by a factor of 3, over an increase in viscosity of 4 orders of magnitude. The relationship was not linear but rather a composite of 2 linear relationships. Aromaticity changed by a significant factor in RAEs. There is a significant amount of variation in the BI for RAEs. In this study, the CPIs for RAEs are high and consistent with the findings that some RAEs may be carcinogenic in rodent skin painting tests as a result of a high level of high (3-6) ring PAC contents.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions. The study does not mention following a specific guideline or GLP, but is well conducted and well reported.