Safrole: Carcinogenic Potency Database

Safrole (CAS 94-59-7)
SMILES, InChI and Structure are below.
Rats and Mice: Cancer Test Summary

Rat Target Sites		Mouse Target Sites		TD₅₀ (mg/kg/day)
Male	Female	Male	Female	Rat	Mouse
liv	liv(B)	liv	liv	441^m	51.3^m,P,v

Key to the Table Above

Positivity: For each chemical with a positive (carcinogenic) experiment in the Carcinogenic Potency Database (CPDB), results are included on carcinogenic potency (TD₅₀) in each species and target sites in males and females. Positivity is determined by an author’s opinion in a published paper. If all experimental results in the CDPB are negative in a sex-species group, “no positive” appears. If the CPDB has no experiments in the sex-species group, “no test” appears. The summary presents the strongest evidence of carcinogenicity in each group. If there are both positive and negative experiments in a sex-species, the negative results are ignored in this Summary Table.

Target Site Codes: liv = liver. (B) = experimental results were reported only for both sexes together. Target sites are listed if any author of published experimental results concluded that tumors were induced in that organ by the test agent. If there is more than one positive experiment in a sex-species, target sites listed may be from more than one experiment, e.g. if liver and lung are both listed, then liver may have been a target in one experiment and lung in another.

TD₅₀: Our standardized measure of carcinogenic potency, TD₅₀, is the daily dose rate in mg/kg body weight/day to induce tumors in half of test animals that would have remained tumor-free at zero dose. Whenever there is more than one positive experiment in a species, the reported TD₅₀ value is a Harmonic Mean calculated using the TD₅₀ value from the most potent target site in each positive experiment.

Superscripts: m = There is more than one positive experiment in the species, and TD₅₀ values from each positive experiment are used in the calculation of the reported Harmonic mean of TD₅₀. P = 100% of dosed animals had tumors at a target site in an experiment in this species. v = Variation is greater than ten-fold among statistically significant (two-tailed p<0.1) TD₅₀ values from different positive experiments.

The Carcinogenic Potency Database (CPDB) is a unique and widely used international resource of the results of 6540 chronic, long-term animal cancer tests on 1547 chemicals. The CPDB provides easy access to the bioassay literature, with qualitative and quantitative analyses of both positive and negative experiments that have been published over the past 50 years in the general literature through 2001 and by the National Cancer Institute/National Toxicology Program through 2004. The CPDB standardizes the diverse literature of cancer bioassays that vary widely in protocol, histopathological examination and nomenclature, and in the published author’s choices of what information to provide in their papers. Results are reported in the CPDB for tests in rats, mice, hamsters, dogs, and nonhuman primates.

For each experiment, information is included on species, strain, and sex of test animal; features of experimental protocol such as route of administration, duration of dosing, dose level(s) in mg/kg body weight/day, and duration of experiment; experimental results are provided on target organ, tumor type, and tumor incidence; carcinogenic potency (TD₅₀) and its statistical significance; shape of the dose-response, author’s opinion as to carcinogenicity, and literature citation.

Only tests with dosing for at least ¼ the standard lifespan of the species and experiment length at least ½ the lifespan are included in the CPDB. Only routes of administration with whole body exposure are included. Doses are standardized, average dose rates in mg/kg/day. A description of methods used in the CPDB to standardize the diverse literature of animal cancer tests is presented for: 1) Criteria for inclusion of experiments 2) Standardization of average daily dose levels and 3) TD₅₀ estimation for a standard lifespan. See Methods for other details.

TD₅₀ provides a standardized quantitative measure that can be used for comparisons and analyses of many issues in carcinogenesis. The range of TD₅₀ values across chemicals that are rodent carcinogens is more than 100 million-fold. More than half the chemicals tested are positive in at least one experiment.

A plot of all results on each experiment in the CPDB for this chemical is presented below. These results are the source information for the Cancer Test Summary table above.

Safrole: All Experiments and Citations in CPDB

The definition of each code in the plot below will appear in a pop-up window when the field name in the header line is clicked, e.g., Strain, Site, Path. Each numbered line starts a new experiment and reports protocol information in black. Average daily dose-rates per kg body weight per day are in green. Remaining lines report experimental results in blue.

Abbreviations of fields in header line: # = the line number in the plot of all CPDB chemicals; Xpo = duration of dosing; Xpt = duration of experiment; Site = tissue; Path = tumor type; DR = dose-response; AuOp = author’s opinion about carcinogenicity; LoConf, UpConf = confidence limits (99%) on TD₅₀; Inc = tumor incidence for each dose group.

See Guide to reading the plot for details on each field, using an example of one experiment.

See Help to improve readability, or to fit the plot onto the screen or a printed page.



Chemical (Synonym) CAS
# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
Site Path Notes   TD50  DR Pval    AuOp LoConf UpConf   Cntrl   1 Inc  2 Inc   3 Inc                                                        Brkly Code



SAFROLE   94-59-7
5596 M f b6a orl 81w81 267                           0    156.mg                                                Innes;ntis,1968/1969
 liv hpt evx    23.5mg   P<.0005 +  9.22mg 60.3mg   1/15   16/17
 lun ade evx    no dre   P=1.       332.mg n.s.s.   2/15    0/17
 tba mix evx    24.2mg   P<.0005    9.32mg 66.2mg   2/15   16/17
5597 M m b6a orl 81w81 267                           0    146.mg
 liv hpt evx    312.mg   P<.04      94.1mg n.s.s.   0/18    3/17
 lun mix evx    no dre   P=1.       310.mg n.s.s.   3/18    0/17
 tba mix evx    5.12gm   P<1.       120.mg n.s.s.   3/18    3/17
5598 M f b6c orl 81w81 267                           0    156.mg
 liv hpt evx    noTD50   P<.0005 +  n.s.s. 38.8mg   0/17   16/16
 lun mix evx    no dre   P=1.       313.mg n.s.s.   0/17    0/16
 tba mix evx    noTD50   P<.0005    n.s.s. 40.5mg   1/17   16/16
5599 M f b6c gav 90w90 1039                          0    34.3mg                               Vesselinovitch;canr,39,4378-4380;1979
 liv mix e      27.0mg   P<.0005 +  16.2mg 49.9mg   0/98   22/46
 liv hpc e      33.0mg   P<.0005 +  19.1mg 64.0mg   0/98   19/46
 lun tum e      no dre   P=1.       243.mg n.s.s.   0/98    0/46
5600 M m b6c orl 81w81 267                           0    146.mg                                                Innes;ntis,1968/1969
 liv hpt evx    61.7mg   P<.0005 +  28.6mg 202.mg   1/17   11/17
 lun ade evx    no dre   P=1.       310.mg n.s.s.   1/17    0/17
 tba mix evx    119.mg   P<.2       35.3mg n.s.s.   7/17   11/17
5601 M m b6c gav 90w90 1039                          0    34.3mg                               Vesselinovitch;canr,39,4378-4380;1979
 liv mix e      178.mg   P<.07   -  50.7mg n.s.s.   3/100   4/33
 liv hpc e      281.mg   P<.02   -  69.2mg n.s.s.   0/100   2/33
 lun mix e      no dre   P=1.       185.mg n.s.s.   3/100   0/35
5602 M m bal eat 52w52 1474m                         0    480.mg                                         Lipsky;jnci,67,365-371;1981
 liv hpa ek     68.3mg   P<.0005 +  27.1mg 234.mg   0/10    7/10
 liv hpc ek     368.mg   P<.09   +  90.1mg n.s.s.   0/10    2/10
 lun tum ek     no dre   P=1.       247.mg n.s.s.   0/10    0/10
5603 M m bal eat 52w75 1474n                         0    333.mg
 liv hpa ek     noTD50   P<.009  +  n.s.s. 164.mg   0/5     5/5
 liv hpc ek     129.mg   P<.02   +  36.1mg n.s.s.   0/5     3/5
 lun tum ek     no dre   P=1.       178.mg n.s.s.   0/5     0/5
5604 M f cd1 eat 51w73 1035a                         0    439.mg                                     Wislocki;canr,37,1883-1891;1977
 liv hpc ev     125.mg   P<.0005 +  74.9mg 225.mg   0/53   25/36
 lun tum ev     no dre   P=1.       2.23gm n.s.s.   0/55    0/50
5605 M f cd1 eat 52w69 1581                          0    125.mg  241.mg                               Boberg;canr,43,5163-5173;1983
 liv hpt ev     59.7mg * P<.0005 +  39.3mg 95.8mg   0/32   13/28   24/34
 lun tum ev     3.50gm * P<1.       571.mg n.s.s.   0/32    1/28    0/34
5606 M f cd1 eat 50w78 1582m                         0    176.mg                                       Miller;canr,43,1124-1134;1983
 liv hpt v      56.4mg   P<.0005 +  32.3mg 108.mg   0/30   21/30
 lun ade v      no dre   P=1.       370.mg n.s.s.   1/30    1/30
5607 M f cd1 eat 51w86 1582n                         0    80.7mg  161.mg
 liv hpt v      41.5mg * P<.0005 +  30.2mg 58.5mg   0/50   34/50   39/50
 --- ang v      213.mg * P<.0005    130.mg 389.mg   0/50    7/50   16/50
 lun ade v      no dre   P=1.       1.09gm n.s.s.   2/50    2/50    0/50
5608 M m cd1 eat 51w73 1035a                         0    405.mg                                     Wislocki;canr,37,1883-1891;1977
 liv car ev     249.mg   P<.0005 +  123.mg 612.mg   0/44   11/26
 lun tum ev     no dre   P=1.       1.07gm n.s.s.   0/44    0/26
5609 M m cd1 eat 56w69 1042a                         0    390.mg  488.mg                               Borchert;canr,33,590-600;1973
 liv hpc        731.mg * P<.03      335.mg n.s.s.   4/50   11/40    8/40
 lun ade        no dre   P=1.       786.mg n.s.s.   1/50    0/40    0/40
5610 M m cd1 eat 56w69 1042b                         0    390.mg
 liv car        3.71gm   P<.7       417.mg n.s.s.   3/35    4/35
 tba mix        3.71gm   P<.7       417.mg n.s.s.   3/35    4/35
5611 R m cdr eat 73w95 1035a                         0    68.0mg                                     Wislocki;canr,37,1883-1891;1977
 liv hpc e      no dre   P=1.    -  210.mg n.s.s.   0/18    0/18
5612 R m cdr eat 95w95 1035b                         0    200.mg
 liv hpc e      627.mg   P<.05   +  189.mg n.s.s.   0/15    3/18
5613 R m cdr eat 43w69 1042a                         0    125.mg                                       Borchert;canr,33,590-600;1973
 liv tum        no dre   P=1.       136.mg n.s.s.   0/12    0/12
 tba tum        no dre   P=1.       136.mg n.s.s.   0/12    0/12
5614 R m cdr eat 47w69 1042b                         0    82.5mg  138.mg
 liv mix        576.mg * P<.2       142.mg n.s.s.   0/18    0/18    2/18
 tba mix        1.32gm * P<.7       157.mg n.s.s.   1/18    0/18    2/18
5615 R m cdr eat 36w52 1042c                         0    142.mg
 liv car        425.mg   P<.3    +  69.1mg n.s.s.   0/18    1/18
 tba mix        425.mg   P<.3       69.1mg n.s.s.   0/18    1/18
5616 R b osm eat 24m24 268                           0    4.50mg  22.5mg  45.0mg  225.mg                   Long;arpa,75,595-604;1963
 liv hpa s      250.mg Z P<.004     113.mg 1.90gm   1/50    1/50    2/50    8/50   (6/50)
 liv mix s      340.mg * P<.0005 +  199.mg 736.mg   3/50    1/50    3/50    8/50   19/50
 liv mal s      624.mg * P<.0005 +  331.mg 1.53gm   2/50    0/50    2/50    0/50   14/50
 liv hpc s      921.mg * P<.0005    433.mg 3.23gm   2/50    0/50    2/50    0/50   10/50
 liv mhc s      1.96gm * P<.0005    743.mg 8.16gm   0/50    0/50    0/50    0/50    5/50
5617 R f osm eat 24m24 268                           0    5.00mg  25.0mg  50.0mg  250.mg
 liv tum s      231.mg * P<.0005    133.mg 457.mg   0/25    0/25    1/25    6/25   12/25
5618 R m osm eat 24m24 268                           0    4.00mg  20.0mg  40.0mg  200.mg
 liv tum s      593.mg * P<.02      221.mg n.s.s.   3/25    1/25    2/25    2/25    7/25

Mutagenicity in Salmonella: negative
SMILES Code for Safrole: C=CCC1=CC=C2C(=C1)OCO2
InChI Code for Safrole: InChI=1/C10H10O2/c1-2-3-8-4-5-9-10(6-8)12-7-11-9/h2,4-6H,1,3,7H2
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database

Chemical Structure for Safrole:

Source for structure: National Library of Medicine ChemIDPlus

See full CPDB Summary Table on 1547 chemicals. See Full CPDB for all results on 6540 experiments of 1547 chemicals.

A complete list of CPDB chemicals, which is searchable by name or by CAS number, is available here.

For a compendium of CPDB results organized by target organ, which lists all chemicals in each species that induced tumors in each of 35 organs, see Summary Table by Target Organ.

The CPDB is available in several formats that permit printing and downloading into spreadsheets and statistical databases.

A plot of the CPDB presents results of 1547 experiments on 6540 chemicals in an easily readable format that has been used in publications of the CPDB.
A Screen version plot for use on a single computer screen, with the same data.
Excel version of the same data.
Tab-separated versions of the same data, which can be easily read into databases.

A Supplementary Dataset gives details on dosing and survival for each experiment.

Relatively precise estimates of the lower confidence limit on the TD₁₀ (LTD₁₀) are readily calculated from the TD₅₀ and its lower confidence limit, which are reported in the CPDB. For researchers and regulatory agencies interested in LTD₁₀ values, we provide them in an Excel spreadsheet.

PDF versions of our publications of analyses using the CPDB are available, organized by year and by research topic.

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Last updated: October 3, 2007