Extracts (petroleum), heavy paraffinic distillates, solvent-deasphalted

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: This study is classified as not assignable.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Examined bioavailability in pregnant rats with three doses of 1000 mg/kg of radiolabelled test material dermally administered on gestation days 10, 11, and 12. Maternal tissues, blood, placentas, uteri, embryos, and yolk sacs were collected and analyzed for radioactivity on gestation day 13 following sacrifice. Urine, faeces, and cage wash was collected every 24 hours and also analyzed for radioactivity.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

318 isthmus furfural extract (CAS # 64742-04-7)

IUPAC Name:

318 isthmus furfural extract (CAS # 64742-04-7)

Details on test material:

Treated distillate aromatic extracts (TDAEs) are a further processing of distillate aromatic extracts (DAEs) in an attempt to reduce the amount of 3-7 ring PAC that is present. Since the treatment is mostly a selective reduction of PACs, the data from DAEs can serve as read across where treatment was insufficient and a significant amount of PACs still remain (≥ 3 wt% DMSO extractables as measured by IP-346). 

- Name of test material (as cited in study report): 318 isthmus furfural extract
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: vacuum distillate treated with furfural solvent; treated distillate aromatic extract; CRU # 86187
- Physical state: liquid
- Analytical purity: not reported
- Impurities (identity and concentrations): not reported
- Composition of test material, percentage of components: not reported
- Isomers composition: not reported
- Purity test date: not reported
- Lot/batch No.: not reported
- Expiration date of the lot/batch: 1991-04-30
- Radiochemical purity (if radiolabelling): N/A
- Specific activity (if radiolabelling): N/A
- Locations of the label (if radiolabelling): N/A
- Expiration date of radiochemical substance (if radiolabelling): N/A
- Stability under test conditions: not reported
- Storage condition of test material: not reported
- Other:

Radiolabelling:

yes

Remarks:

14C-carbazole and 3H-benzo(a)pyrene

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 9 weeks old
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: housed in individual metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: from 1988-08-30 to 1988-09-12


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22 °C
- Humidity (%): 40 to 60%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark


IN-LIFE DATES: not reported

Administration / exposure

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: not reported
- % coverage: not reported
- Type of wrap if used: protective device; not reported
- Time intervals for shavings or clippings: not reported


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: not reported


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1000 mg/kg bw
- concentration (if solution): undiluted


VEHICLE
- Justification for use and choice of vehicle (if other than water): not reported
- Amount(s) applied (volume or weight with unit): not reported
- Concentration (if solution): not reported
- Lot/batch no. (if required): not reported
- Purity: not reported


USE OF RESTRAINERS FOR PREVENTING INGESTION: yes; Elizabethan-style collar

Duration and frequency of treatment / exposure:

Test material was applied dermally on gestation days 10, 11, and 12.

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg bw

No. of animals per sex per dose / concentration:

three females

Control animals:

other: yes, but not for bioavailability group (9)

Positive control reference chemical:

not reported

Details on study design:

- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): N/A

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): blood, thymus, liver, small intestine, large intestine, kidneys, stomach, and ovaries. Placenta, embryos, amniotic fluid, and yolk sacs were pooled for each dam. Urine and faeces were also collected.
- Time and frequency of sampling: Tissues were collected upon sacrifice on gestation day 13. Urine and faeces were collected every 24 hours until sacrifice.
- Other: body weight was measured on gestation days 0,3,6, and 10.


METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): N/A
- Time and frequency of sampling: N/A
- From how many animals: N/A
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC): N/A
- Limits of detection and quantification: N/A
- Other:


TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable):

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Dermal absorption of 14C-carbazole occurred more extensively than did 3H-benzo9a)pyrene over a 72 hour period. About 19.9% of the total applied 14C-radioactive dose was dermally absorbed. About 4.1% of the total applied 3H-benzo(a)pyrene dose was systemically absorbed.

Details on distribution in tissues:

Of the total absorbed dose of 14-C-carbazole 2.1% was found in the maternal tissues and less than 0.01% was detected in the embryo. 0.75% of the radioactive dose was found in the maternal blood, 0.58% in the large intestine, 0.10% in small intestine, 0.21% in liver. The amount of 3H-BaP found in maternal tissues and embryo at the end of 72 hours was 1.8% and less than 0.01%, respectively, of the total administered dose. 0.54% of the radioactive dose was found in the large intestine, 0.08% in the small intestine, 0.12% in the liver, and 0.13% in the maternal blood.

Details on excretion:

17.7% of 14C-carbazole was excreted in the urine and faeces over 72 hours. 2.3% of 3Hbenzo(a)pyrene was excreted in the urine and faeces over 72 hours.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
Less than 0.01% of the 14C-carbazole or 3H-benzo(a)pyrene in the radioactive dose of 318 isthmus furfural extract was detected in the embryos. Neither 14C-carbazole nor 3H-benzo(a)pyrene were found to selectively accumulate in the embryo. These findings indicate that the placenta serves as an effective barrier against the transport of carbozole and benzo(a)pyrene to the embryo.

Executive summary:

Justification for Read Across

Treated distillate aromatic extracts (TDAEs) are a further processing of distillate aromatic extracts (DAEs) in an attempt to reduce the amount of 3-7 ring PAC that is present. Since the treatment is mostly a selective reduction of PACs, the data from DAEs can serve as read across where treatment was insufficient and a significant amount of PACs still remain (≥ 3 wt% DMSO extractables as measured by IP-346). Where treatment was sufficient to reduce the 3-7 ring PACs (<3 wt% DMSO extractables as measured by IP-346), the material is most similar to a lubricating base oil and it is this data that should be used for read across. 

 

In a bioavailability toxicokinetics study in pregnant rats, three doses of 1000 mg/kg of radiolabelled 318 isthmus furfural extract was dermally administered on gestation days 10, 11, and 12. Maternal tissues, blood, placentas, uteri, embryos, and yolk sacs were collected and analyzed for radioactivity on gestation day 13 following sacrifice. Urine, faeces, and cage wash was collected every 24 hours and also analyzed for radioactivity.

Dermal absorption of 14C-carbazole occurred more extensively than did 3H-benzo9a)pyrene over a 72 hour period. About 19.9% and 4.1% of the total applied of 14C-carbazole and 3H-benzo(a)pyrene, respectively, was dermally absorbed. Of the total absorbed dose of 14-C-carbazole, 2.1% was found in the maternal tissues and less than 0.01% was detected in the embryo. Of the total absorbed dose of 3H-benzo(a)pyrene 1.8% was detected in the maternal tissue and less than 0.01% was found in the embryo. 17.7% of 14C-carbazole was excreted in the urine and faeces over 72 hours. 2.3% of 3Hbenzo(a)pyrene was excreted in the urine and faeces over 72 hours.

Based on the bioavailability results, the neither of the radiolabelled components of 318 isthmus furfural extract were found to selectively accumulate in the embryo.

This study received a Klimisch score of 4 and cannot be assigned a classification.