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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral, other
Remarks:
subchronic and chronic
Type of information:
experimental study
Remarks:
Review and evaluation of experimental data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer-reviewed data, evaluation of current databases for deriving permissible exposure levels

Data source

Referenceopen allclose all

Reference Type:
other: Expertise, assessment report
Title:
Unnamed
Year:
2001
Report date:
2001
Reference Type:
publication
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
RIVM project 711701 "Risk in relation to Soil Quality", RIVM Bilthoven/NL; the project has the aim to derive Maximum Permissible Risk levels (MPR) for the oral route and in isolated cases for inhalation based on available data. The evaluation comprises besides others chemical classes PAH including phenanthrene. The MPR(human) is defined as the amount of a substance (usually a chemical substance) that any human individual can be exposed to daily during lifetime without significant health risk..... For genotoxic carcinogens the MPR has been defined as the excess lifetime cancer risk of 1 in 10000 (1:10E4) (RIVM 2001 (Ref. 1), Chap. 2, p. 9). For substances causing threshold effects, MPRs are expressed as Tolerable Daily Intake (TDI) or Tolerable Concentration in Air (TCA) [see Results]. For background information on MPR see Janssen and Speijers 1997 (Ref. 2).
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Phenanthrene
EC Number:
201-581-5
EC Name:
Phenanthrene
Cas Number:
85-01-8
Molecular formula:
C14H10
IUPAC Name:
phenanthrene
Test material form:
solid
Remarks:
as neat substance
Specific details on test material used for the study:
- Name of test material (as cited in study report): phenanthrene; generic substance as evaluated in the report Ref. 1.

Test animals

Species:
other: mouse and rat
Strain:
other: various
Sex:
male/female
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
other: oral and inhalation
Vehicle:
not specified
Details on oral exposure:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
not applicable
Frequency of treatment:
not applicable
No. of animals per sex per dose:
not applicable
Details on study design:
not applicable
Positive control:
not applicable

Examinations

Observations and examinations performed and frequency:
not applicable
Sacrifice and pathology:
not applicable
Other examinations:
Evaluation of databases (see "Any other information..")

Results and discussion

Results of examinations

Details on results:
not applicable

Effect levels

open allclose all
Key result
Dose descriptor:
other: TDI (Tolerable Daily Intake)
Effect level:
0.04 other: mg/kg bw/day (lifelong for any human)
Based on:
other: evaluation of toxicity database of petroleum products
Sex:
male/female
Basis for effect level:
other: non-neoplastic effects, derived as mean/representative for the aromatic >EC9 to EC 21 fraction of TPH (total petroleum hydrocarbons)
Remarks on result:
other: amount of a substance that any human individual can be exposed to daily during lifetime without significant health risk
Key result
Dose descriptor:
other: TCA (Tolerable Concentration in Air)
Effect level:
0.14 other: mg/m³ (lifelong for any human)
Based on:
other: evaluation of toxicity database of petroleum products
Sex:
male/female
Basis for effect level:
other: non-neoplastic effects; value is derived from the oral TDI above, assuming an absorption rate of 100 % in either case: TCA = (TDI x 70 kg/bw) / (20 m³/d)
Remarks on result:
other: concentration of a substance in air that any human individual can be exposed to daily during lifetime without significant health risk
Key result
Dose descriptor:
NOAEL
Remarks:
for aromatic >EC9 to EC 21 fraction from TPH
Effect level:
120 other: mg/kg bw/day, mean for the TPH fraction
Based on:
other: evaluation of toxicity database of petroleum products
Sex:
male/female
Basis for effect level:
other: non-neoplastic effects, derived from TDI value by application of the correction factor (3000) used for RfD derivation (mean/representative for the aromatic >EC9 to EC 21 fraction of TPH)

Target system / organ toxicity

Key result
Critical effects observed:
not specified

Any other information on results incl. tables

For methodology see above under ‘Any other information on materials and methods incl. tables’.

In the aromatic >EC9 to EC16 fraction, relevant for phenanthrene, 77 compounds have been identified: RfDs have been developed for 8 of these (all with ECs > 9), ranging from 0.03 to 0.3 mg/kg bw/day. There are also data available on a mixture within this range: naphthalene/methylnaphthalenes: for this mixture, a RfD of 0.03 mg/kg bw/day was developed. After reviewing the information, a fraction-specific RfD of 0.04 mg/kg bw/day was considered to be appropriate (based on the 8 individual RfDs, 4 of which were 0.04 mg/kg bw/day and considering the range of the remaining RfDs). The constituent pyrene is characteristic for the >EC16 to EC21 fraction. For this substance, a RfD of 0.03 mg/kg bw/day is available. As the RfD values are very similar, the fractions considered can be combined to an >EC9 to EC21 fraction. Taking into account the combined evidence, a fraction specific RfD of 0.04 mg/kg bw/day can be adopted for the combined fraction. This fraction specific RfD value is adopted for phenanthrene as constituent contained in this fraction.

For the RfD estimation of substances present in the fraction, uncertainty factors of 3000 have be used reflecting 10 each for intra- and interspecies variability, 10 for the use of sub-chronic studies for chronic RfD derivation, and an additional 3 for quality rating of the database. Thus, the RfD estimates can be considered to be quite conservative. RfDs and the experimental database for different PAH can be extracted from the US EPA IRIS data system (URL: https://cfpub.epa.gov/ncea/iris/search/index.cfm).

The fraction-specific RfD developed using the TPHCWG approach has been uses by RIVM as Maximum Permissible Risk (MPR) level. For threshold effects, the MPR is expressed as Tolerable Daily Intake (TDI, oral route).

Reliable RfCs for inhalation have not been identified. Therefore, oral TDI values are converted to tolerable concentrations in air (TCD values) covering inhalation exposure. TCA values can be derived from TDI values taking into account the body weight, the daily respiratory volume, and different absorption rates for oral and inhalation exposure using the following equation: TCF = (TDI x 70 kg x 100) / (20 m³ x 75). But assuming equal absorption rates for either route (more conservative approach), the equation reduces to TCA = TDI x 70 kg / 20 m³.

Applicant's summary and conclusion

Conclusions:
For phenanthrene a TDI value of 40 µg/kg bw/day was established by evaluation of the oral repeated dose toxicity of an aromatic fraction of Total Petroleum Hydrocarbons (TPH). This fraction (ES>9 to 21) includes PAH from naphthalene to pyrene. A group TDI considered valid for PAH components in this mixture was developed by comparison of individual components of the mixture and selecting a most appropriate value for the total mixture.
The value derived is adopted for phenanthrene.