Compound intake estimator

From Opasnet
Jump to: navigation, search



Compound intake estimator calculates intakes of compounds based on food or food supplement intake, compound concentration in food, and guidance values for the compound. In the text, we talk about plant-based food supplements (PFSs), but the tool is generic and is usable for other products as well as long as the required concentration data is made available.

Question

How to estimate intakes of chemical compounds in plant-based food supplements and compare them to guidance values in an open collaborative web system?

Answer

The compound intake estimator calculates intakes and levels of health concern of plant-based food supplements based on product-specific concentration data and usage information provided by the user. The tool works online simply with a web browser. For user instructions and some data used, see below. The tools is openly available online at http://en.opasnet.org/w/Compound_intake_estimator.

Compound intakes and risk estimates

A concern indicator is calculated for each compound separately. If the intake is smaller than the threshold of concern, the indicator is < 1 and there is no concern. The threshold of concern is acceptable daily intake (ADI), tolerable daily intake (TDI), lower confidence limit of benchmark dose (BMDL10), or threshold of toxicological concern (TTC), depending on what data is available for each compound.

Intake information

Name of plant food supplement:

Amount of supplement per day (g /d):

Fraction of essential oil in the supplement (%):

Amount of essential oil consumed directly per day (g /d):

Show intermediate results?:

Do you want to limit to some extraction techniques?:

Do you want to add own compound data?:

Additional compound information

Name(s) of additional compound(s):

Concentration(s) of the compound(s) (mg of compound /g product):

Extraction technique

Which extraction techniques to consider?:
Not known
Hydrodistillation
Solvent extraction
Steam distillation
Supercritical fluid extraction, 120 bar, 40 °C
Supercritical fluid extraction, 90 bar, 40 °C
Supercritical fluid extraction, 90 bar, 50 °C
Superheated water extraction, 100 °C
Superheated water extraction, 150 °C
Superheated water extraction, 200 °C
Solid phase

+ Show code

Compound concentrations

The following code allows to calculate the mean and median value of the concentration of each compound in the input data.

Plot values above this limit (%):

Do you want to plot all compounds?:

Do you want to plot all extraction techniques?:

Chemical compounds

If not, what compounds do you want to plot?:
1,8-Cineole
2-Carene
2-Methoxycinnamaldehyde
2-Methoxycinnamaldehye
2-Methoxycinnamaldehye cinnamalaldehyde
3-Phenylpropyl acetate
4-Terpineol
a-Copaene
a-Muurolene
a-Terpineol
Aromadendrene
Aromatic compound
Benzaldehyde
Benzaldeyhde
Benzene propanol
Benzenepropanal
Benzenepropanol acetate
Benzylbenzoate
Borneol
Cadinene
Calamenene
Camphene
Camphor
Carvacrol
Carveol isomere
Caryophyllene
Caryophyllene alcohol
Caryophyllene oxide
Caryophyllene oxyde
Chavicol
Cinamyl acetate
Cinnamaldehyde
Cinnamic acid
Cinnamyl acetate
Cinnamyl alchol
Cinnamyl alcohol
Cinnamyl alcool
Cis-P-menth-2-en-1-ol
Cis-ß-Ocimene
Coumarin
Cryptone
Cymene isomere
E-Anethole
e-Cadinene + Pioncarvone
E-Cinnamyl acetate
E-o-Methoxycinnamaldehye
Epoxy-6.7-Humulene + Mw=220
Eugenol
Eugenol acetate
Humulene epoxide II
Isoledene
Limonene
Linalool
Linaool
Methoxy eugenol
Methyl cinnamaldehyde
Methyl eugenol
Monoterpenes
N-Hexadecanoic acid
N-Octadecanoic acid
P-Cymene
P-Cymene-8-ol
Para-Methoxy cinnamic aldehyde
Phenyl cyclohexene
Phenylmethyle isovalerate
Sabiene
Sabinene
Safrole
Sesquiterpene epoxide
Sesquiterpenol Mw=220
Sesquiterpenol Mw=222
Spathulenol
ß-Bisabolene
ß-Cubebene
ß-Elemene
ß-Myrcene
ß-Phellandrene
ß-Phellandrene + 1,8-Cineole
ß-Pinene
Styrene
Terpinen-4-ol
Terpiolene
Terpiolene isomere
Tetradecanal
Trans-2-methoxycinnamaldehyde
Trans-P-menth-2-en-1-ol
Trans-Pinocarveol
Trans-Piperitol
Trans-ß-Ocimene
Z-Cinnamaldehyde
α-Cadinol
α-Calacorene
α-Copaene
α-Cubebene
α-Famesene
α-Gurjunene
α-Humulene
α-Muurolene
α-Muurolol
α-P-Dimethylstyrene
α-Phellandrene
α-Pinene
α-Selinene
α-Terpinene
α-Terpineol
α-Thujene
γ-Cadinene
γ-Terpinene
δ-Cadinene
Δ3-Carene

Extraction technique

extraction:
Hydrodistillation
Not known
Solvent extraction
Steam distillation
Supercritical fluid extraction, 120 bar, 40 °C
Supercritical fluid extraction, 90 bar, 40 °C
Supercritical fluid extraction, 90 bar, 50 °C
Superheated water extraction, 100 °C
Superheated water extraction, 150 °C
Superheated water extraction, 200 °C

+ Show code

For seeing details of what the code actually does, click Show code. The code will appear, with documentation of each part on rows starting with ###. In brief, the code reads a piece of concentration and other data from Opasnet database, selects the rows defined by the user through the interface above, and shows the data on a summary table and a few graphs.

Rationale

For successful benefit-risk assessment of plant-based food supplements (PFSs), there is a need to estimate intakes of relevant compounds in a product. The health impacts of this exposure are then estimated based on available exposure-response functions. Optimally, all health impacts can be aggregated into e.g. disability-adjusted life years (DALYs) using disability weights or similar importance weights. However, the tool presented here does not go so far. Rather, it compares the intakes of each relevant compound to a guidance value, which is thought to separate safe intakes from non-safe intakes. Non-safe does not mean that the compound is causing health problems; it merely tells about compromised safety margins that are inherently embedded in the guidance values. Small exceedances are most likely harmless, but if the intake is clearly beyond its guidance value, careful consideration of potential risk is warranted.

This web tool, Compound intake estimator, was developed in Plantlibra project to promote the use of quantitative estimates of compound intakes and health risks. The tool consists of open data about guidance values (in the Opasnet database), an open source model (running on R software) to compute intakes and risk estimates, product-specific concentration data that is only partially available, and a user interface where the user can choose modelling options and add case-specific compound concentration data as input to the model. Detailed user guide, and the data and the model are available at http://en.opasnet.org/w/Compound_intake_estimator.

Users who are skilful with R can download the whole model to their own computers and use and develop it further as they please. This requires an R package called OpasnetUtils, which is available from the CRAN repository http://www.cran.r-project.org. It is also possible to develop a new page in Opasnet for a new product and its concentration data. Those who are interested in such work should contact the tool developer Jouni Tuomisto at THL, Finland.

Guidance values

There are several possible approaches for deriving guidance values. In this approach, we use acceptable daily intake (ADI), tolerable daily intake (TDI), lower confidence limit for benchmark dose 10 (BMDL10), and threshold for toxicological concern (TTC). If there are several guidance values available for a single compound, they are used in the preference order mentioned here.

Acceptable daily intake (ADI)
An estimate of the amount of a chemical or toxin that a person can ingest daily over a human’s lifetime without appreciable health risk, divided by an average person’s lifespan. The concept of the ADI was developed by the WHO and FAO for chemicals such as additives to foods, pesticide residues and veterinary drugs in foods; ADIs are derived from lab toxicity data and from human experiences of such chemicals when available, and incorporate a safety factor; the ADI is an estimate of the amount of a substance in food that can be ingested over a lifetime by humans without significant risk to health.[1]
Tolerable daily intake (TDI)
Refers to the daily amount of a chemical that has been assessed safe for human being on long-term basis (usually whole lifetime). Originally acceptable daily intake (ADI) was introduced in 1961 to define the daily intake of a food additive which, during the entire lifetime, appears to be without appreciable risk. For contaminants and other foreign chemicals not used intentionally, the term TDI is often preferred.[2]
Lower confidence limit for benchmark dose 10 (BMDL10)
For the dose-response function of a health impact, it is possible to estimate the dose that causes on average 10 % response compared with the highest achievable response. This is called the benchmark dose (BMD10). BMDL10 is the lower confidence limit of BMD10, typically the 2.5th percentile of the probability distribution of the BMD10 estimate.[3]
Threshold for toxicological concern (TTC)
According to the TTC concept, a "safe" level of exposure can be identified for many chemicals based on their chemical structure and the known toxicity of chemicals that share similar structural characteristics. The TTC approach is exclusively designed as a substitute for substance-specific information in situations where there is limited or no information on the toxicity of the compound and information on exposure indicates that human exposure is very low.[4]

If a compound in a PFS does not have any information on these guidance values, it is ignored in this analysis. The same happens to compounds that exist in the product but do not have any concentration information.

Intake and guidance value calculations

The total intake of essential oil is calculated like this:

intakeoil = amountsuppl * fractionoil + amountoil

where

  • intake is the total intake of essential oil (or another product part with the compounds of interest)
  • amountsuppl is the intake of food supplement
  • fractionoil is the fraction of essential oil in the food supplement
  • amountoil is the intake of the essential oil consumed directly, i.e. in addition to what is in the food supplement.

The intakes of individual compounds are calculated like this:

intakecomp (mg /kg /d) = intakeoil (g /d) * conccomp (mg /g) / 60 (kg)

where

  • intakecomp are the intakes of each compound
  • intakeoil is the total intake of essential oil (or another product part with the compounds of interest)
  • conccomp are the concentrations of each compound in the essential oil.
  • 60 kg is the assumed body weight of the person

The concern indicator is calculated like this:

concern indicatorcomp,i = intakecomp (mg /kg /d) / guidance valuecomp,i (mg /kg /d) * safety factori

where

  • concern indicatorcomp,i are the preferred indicators for each compound,
  • guidance valuecomp are the guidance values for each compound,
  • safety factori are the safety factors used for each indicator (10000 for BMDL10, 1 for others, which already include a safety factor)

The concern indicator is calculated for each compound separately. If the intake is smaller than the guidance value, the indicator is < 1 and there is no concern. Only one guidance value indicator i is used for each compound, the preference order (when there are several guidance values for a compound) is explained in the previous section.

For BMDL10, the typical approach is to divide BMDL10 by the intake and interpret values > 10000 as safe. However, it would be confusing for the user to treat one guidance value differently than others. Therefore, this tool applies the same equation to all guidance values and uses 10000 as the default safety factor for BMDL10. For all other guidance values, the default safety factor is 1, because they already have embedded safety factors for interspecies and intraspecies variation.

User interface

You can fill in the following information:

  • Name of plant food supplement (PFS) product. If this is given, it is shown on the graphs and outputs as title.
  • Fraction of essential oil in the supplement. How much (as a percentage) does the total product contain the essential oil?
  • Amount of supplement per day. How much is the supplement (the total product) consumed per day (given as grams of product per day)?
  • The compound concentration data is taken from a table in the Opasnet database. However, if you know that the product contains something that is not listed in the table, you may add the information here.
    • Name of additional compound. The name is used to combine the concentration data with toxicological data. So, the name should be found in one of these two tables on this page: Cramer classes of compounds, or Guidance values. If the name is not found, the new piece of information is ignored.
    • Concentration of the additional compound in the supplement. This is given as mg of compound per g of PFS product.
    • Technical note: You should enter the name of a single compound between quotation marks, e.g. 'Estragol'. If you add several compounds, you should use vector formatting for R, e.g. c('Estragole', 'Fenchone'). The concentration value can be without quotation marks unless it is a distribution or a vector. Acceptable entries for concentrations are e.g.: 2.1; '21.4-24.5'; and c('2.1', '21.4-24.5').
  • Show intermediate results? If Yes is selected, you will get two tables of a) concentration and b) intake estimates with all compounds in the product. Otherwise, only a default output is shown (see below).
  • Which extraction techniques to consider? Different extraction methods may result in different concentration estimates even from the same product. Some of the toxicological information is given having a particular extraction method in mind, and it is not always possible to use toxicological information with any concentration information. Therefore, if you know that some extraction methods should not be used to estimate toxicology, you can unselect them from the list. The default is to use all data, but you can select Yes, let me choose to the extraction techniques, and then select from the list that appears.
  • The default outcome shows a table and a graph where the level of concern is shown for each compound. However, because there are dozens of compounds in any product, the graph shows only those that have the level more than one, i.e. those compounds that need further scrutiny.

Concentrations

The concentration code allows to calculate the mean and median value of the concentration of each compound that appear in table. In addition, it is possible to plot the concentration (expressed as percentage of essential oil) of each compound reported in the data table. Each single value is reported in the chart.

Data

This is an example data to show what kind of information is used by the tool. It is also used to calculate the example results. Some of the actual data for PFSs is proprietary and is currently only available to the partners of the Plantlibra project.

Example data(%)
ObsExtraction.techniqueCompoundResultReference
1Superheated water extraction, 100 °C2-Carene0.08; 0.1; 0.12Jayawardena & Smith, 2010
2Superheated water extraction, 100 °CZ-Cinnamaldehyde1.63; 2.1; 2.57Jayawardena & Smith, 2010
3Superheated water extraction, 100 °CCinnamaldehyde81.14; 83.7; 86.26Jayawardena & Smith, 2010
4Superheated water extraction, 100 °CEugenol0.45; 0.8; 1.15Jayawardena & Smith, 2010
5Hydrodistillation1,8-Cineole0.2Chericoni et al, 2005
6Superheated water extraction, 100 °CCinnamyl acetate5.47; 7.2; 8.93Jayawardena & Smith, 2010

Calculations

This is the code for the actual compound intake estimator model. You need to run the code below only if you update the guidance value tables on this page.

+ Show code


Using different data on different layers: [4].

Extraction techniques

Extraction techniques(-)
ObsExtraction.techniqueNotes
1Not known
2Hydrodistillation
3Solvent extraction
4Steam distillation
5Supercritical fluid extraction, 120 bar, 40 °C
6Supercritical fluid extraction, 90 bar, 40 °C
7Supercritical fluid extraction, 90 bar, 50 °C
8Superheated water extraction, 100 °C
9Superheated water extraction, 150 °C
10Superheated water extraction, 200 °C
11Solid phase
1270% ethanol (1:5)
13Acetone and water mixture (35 to 67:1)
14Commercial product
15Methanol (40%) and water
16Not reported
17Ultrasound assisted extraction
1870% methanol, Ultrasound assisted extraction
19ddH2O and Na2HPO4,partitioning with ethyl acetate, organic phases dried and redissolved in methanol
20Maceration
21Soxhlet extraction

Data about guidance values

Generic data about guidance values

Safety factors(-)
ObsGuidanceSafety factor
1ADI1
2BMDL1010000
3TDI1
4TTC1
Cramer values(µg /kg-BW /d)
ObsCramer classThreshold of toxicological concernDescription
1130
221.5
331.5
440.0025This value is the TTC for compounds having a structural alert for genotoxicity

Values 30, 1.5 and 0.025 µg /kg /d come from EFSA (2012)[5]


Compound-specific data about guidance values

[6]

Guidance values(mg /kg-BW /d)
ObsCompoundGuidanceResultNotes
11,8-CineoleADI2.8
24-TerpineolADI1.2
3BenzylbenzoateADI5
4CinnamaldehydeADI0.7
5CoumarinTDI0.1
6EstragoleBMDL103.3-6.5
7EugenolADI2.5
8FenchoneADI10.64
9LimoneneADI1
10LinaloolADI0.5
11MyrceneADI2.5
12Trans-anetholeADI2
13SafroleBMDL101.9-5.1
14α-TerpineolADI1.2

See also

References

  1. Segen's Medical Dictionary. 2012 Farlex, Inc. [1] accessed 15th April, 2014.
  2. Wikipedia: Tolerable daily intake accessed 15th April 2014
  3. U.S.EPA: Benchmark Dose (BMD) Methodology [2] accessed 15th April, 2014.
  4. Opinion on the Use of the Threshold of Toxicological Concern (TTC) Approach for Human Safety Assessment of Chemical Substances with focus on Cosmetics and Consumer Products. European Union (2012) SCCP/1171/08. [3] accessed 15th April 2014.
  5. EFSA (2012). Scientific Opinion on Exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC). EFSA Journal 2012;10(7):2750
  6. van den Berg SJPL, Restani P, Boersma MG, Delmulle L, Rietjens IMCM (2011) Levels of Genotoxic and Carcinogenic Ingredients in Plant Food Supplements and Associated Risk Assessment. Food and Nutrition Sciences, 2(9): 989-1010.

Give comments about the content or approach

Current comments that have not yet been included in the main page or talk page.


You can give comments about the content without login simply by writing your comments into the text box below. The page moderator will include your comments in the actual content of the page and then moves the comment to the archive: Show results


Your comment about the page content or discussion:

To what part of the page does you comment refer?:

Comments to be removed (after they have been moved to the page text)

ID of the comment to be removed:

Reason to remove: