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Chemical hazard evaluation: the use of factual health and safety databanks
++'t -
r ~,
•
the Science of the Total Environment Aa t m r m e ~
ELSEVIER
J m n d t ~ a e m 0 f f l ,i t ~ o m b
The Science of the Total Environment 153 (1994) 211-217
Chemical hazard evaluation: the use of factual health and safety databanks M. Evangelisti *a, C. Bolognesi a, R. Rabboni a, D. U g o l i n i b aIsatuto Nazionale per la Ricerca sul Cancro IST, Servizio Informazione Documentazione Scientifica, Viale Benedetto XE, 10 16132 Genova, Italy blstituto di Oncologia Clinica e Sperimentale dell'Universit?t di Genova, Viale Benedetto XE, 10, 16132 Genova, Italy Received 1 September 1993; accepted 1 November 1993
Abstract
The usefulness of factual health and safety databanks is discussed in this paper. Four databanks have been selected for this study: HSDB (Hazardous Substances Data Bank), ECDIN (Environmental Chemicals Data Information Network), RTECS (Registry of the Toxic Effects of Chemical Substances) and CCRIS (Chemical Carcinogenesis Research Information). The quality of the information available in the databanks considered was examined for five different chemical compounds and the completeness of the information available was carried out by an analysis of carcinogenic and mutagenic data.
Keywords: Toxicological evaluation; Factual databanks; Carcinogenicity; Mutagenicity
1. Introduction Toxicological evaluation processes are based on a wide spectrum of information of all types; chemical, environmental, epidemiological, animal, toxicological, pharmacokinetics, pharmacodynamics, biochemical, structure-activity and exposure data. Original papers on toxicology are published in a wide range of journals, books, proceedings of various symposia and hearings. The most recent development in the retrieval of references and abstracts involves the use of computers; it is possible by means of a terminal device and a telephone with a modem to directly access the hostcomputers that house data within specific struc-
* Corresponding author.
tures, usually called databases and databanks, which can be searched using colloquial data retrieval software [1,2]. A variety of information is available in different toxicological information files [3,4]. Three main types of archives are available; bibliographic databases, numeric or factual databanks and fulltext databanks. In bibliographic databases (or reference databases) it is possible to retrieve bibliographic references about a specific subject. It is also possible to identify the primary information sources to which the user must refer in order to obtain the whole article. Factual databanks contain concise information and they offer immediate access to factual a n d / o r numeric data. Finally the full-text databanks report the whole article, book or report. Today a large number of environmental and chemical databases and databanks are available
0048-9697/94/$07.00 © 1994 Elsevier Science BV. All rights reserved. SSDI 0048-9697(94)4106-J
212
M. Evangelisti et al. / Sci. Total Environ. 153 (1994) 211-217
(Table 1). Many databases and databanks are an extensive collection of data (Excerpta Medica, Chemical Abstracts, Medline) subject to continuous expansion. Small databanks covering specialized topics are also available. The aim of our study is to evaluate the usefulness of the factual databanks for the hazard assessment process of environmental agents with regard to its ability to predict the carcinogenic and mutagenic risk of chemical substances.
2. Materials and methods For this study, four databanks were selected covering chemical hazard information:
HSDB --Hazardous Substances Data Bank; ECDIN--Environmental Chemicals Data Information Network; RTECS--Registry of Toxic Effects of Chemical Substances; CCRIS--Chemical Carcinogenesis Research Information System. In Table 2 characteristics of these databanks, such as the producer, the update and the sources are given [5]. These databanks are distributed online worldwide by different hosts. When the databank is resident on CD-ROM or on a magnetic tape it is possible to have the archive directly in-house. The identification of chemical substances and subject coverage provided by these
Table 1 Environmental and chemical databases and databanks Databases and databanks
Subject coverage
Type of database or databank
Time span
Acid rain Aquatic information retrieval Business and the environment Chemical carcinogenesis research information system Developmental and reproductive toxicology Ecocerved EMTOX (Excerpta medica) Enviroline Environment week Environmental chemicals data and information network
Environment Aquatic science, toxicology Environment Biomedicine, toxicology
Bibliographic Full-text, factual Full-text Factual
1975 to date 1970-1990 1990 to date 1971 to date
Biomedicine, toxicology
Bibliographic
1989 to date
Environment Toxicology Environment Environment Chemistry, occupational safety, toxicology water resources management Toxicology Chemistry, properties, safety, toxicology Toxicology
Full-text Bibliographic Bibliographic Full-text Factual
1974 to date 1971 to date February 23, 1989 to date 1970 to date
Full-text factual Factual
1970-1990 Current information
Genetic toxicity Hazardous substances data bank Phytotox Radioactivity environmental monitoring Registry of toxic effects of chemical substances Riskline Sciscan (ISI) Toxline
Environment, nuclear industry Toxicology Toxicology Biomedicine, chemistry, engineering, environment Biomedicine, chemistry, environment, occupational safety, waste management
Bibliographic, full-text, Current information factual Factual 1984 to date Factual
Current information
Bibliographic Bibliographic
1972 to date Current 4 weeks
Bibliographic
1965 to date
M. Evangelisti et al./ Sci. Total Entiron. 153 (1994) 211-217
databanks are summarised in Table 3. Information on manufacturing, chemical and physical properties and toxicology are covered by each databank. The CCRIS databank is restricted to carcinogenicity and mutagenicity test results. The record (data sheet) on a single compound can be, more or less, extensive reporting of a different number of fields. Each field deals with one aspect of the subject and can be used to limit the chosen search terms. Occasionally fields can be er~ty; this occurs where the information is
213
not yet available. The usefulness of the information available in the considered factual databanks was examined for five different chemicals, industrial compounds or pesticides. The study was carried out by searching for the substances using Chemical Abstract Service (CAS) registry numbers and retrieving the full records of the compound in each of the four databanks consulted through a connection with the host DIMDI (Deutsches Institut fur Medizinische Dokumentation und Information, Koln, DK).
Table 2 Databank characteristics HSDB
ECDIN
RTECS
CCRIS
Producer
National Library of Medicine (NLM), Toxicology Information Program (TIP)
Commission of the European Communities (CEC), Joint Research Centre (JRC)
U.S National Library of Medicine (NLM), Toxicology Information Program ('tiP)
U.S National Library of Medicine (NLM), Toxicology Information Program (TIP)
Hosts
DATA/STAR-DIMDI -NLM/TOXNET
CEC, Joint Research Centre--DIMDI
NLM/TIP-CCINFOLI NE-CIS-DIALOG DIMDI-BIOSIS-LIFE SCIENCE NETWORK
CIS-DIMDI-NLM/TIP
Support
Online-CD-ROM
Online-CD-ROM
Online-CD-ROM-magnetic tape
Online
Periodically
Quarterly
Quarterly
4200
104 000
100000
1400
Handbooks, monographs, government reports (USA), technical reports, journals
Handbooks, monographs, journals, research reports (CEC), data collections of the UN (United Nations E n v i r o n m e n t Program/International Register of Potentially Toxic Chemicals)--data collections of the Brandweer Informatiecentrum (BIG), Geel, Belgium--data collections of the CEC: European Inventory of Existing Commercial Chemical Substances (EINECS)
Journals, conferences, congress, papers, books, personal communications to National Institute for Occupational Health and Safety
Journals, current awareness tools, monographs, technical reports
Updating No. of chemical substances * Sources
As needed
(USA)(NIOSH)
* DIMDI (Deutsches Institut fur Medizinische Dokumentation und Information) 1991.
214
M. Evangelisti et al. / S c i Total Entiron. 153 0994) 211-217
3. Results and conclusions
The information available through factual databanks on chemical toxicology could be utilized to compile a provisional toxicological profile of a chemical compound. Records were available for all the chemicals selected for this study, varying substantially in length between databanks and also between chemical compounds. HSDB and ECDIN records are generally the most extensive.
The characteristics of the chemical substances, such as chemico-physical properties, toxicology and environmental hazard could be defined making use of all the available data present in the factual databanks. These banks could be considered to some extent complementary to each other. HSDB and RTECS provide a large number of synonyms for all the selected substances. HSDB is the best source of information concerning manufacture, chemical and physical properties, safety
Table 3 Identification of clinical substances and subjects coverage of factural databanks
HSDB
Identifications of substance
Subject coverage
Substance name
Manufacturing use information Chemical/physical properties Safety/handling Toxicity/biomedical effects
Synonyms Synonyms long CAS registry number RTECS number OHM-TADS number Ship(ping) name/number EPA hazardous wastes number STCC number ECDIN
Substance name Synonyms CAS registry number Old CAS registry number RTECS number EEC number EEC number EINECS number CCT number
Pharmacology Environmental fate Standards/regulations Monitoring/analysis methods
Ecology/ecotoxicology/ toxicology Occupational health Chemical hazard information Standards/regulations Analytical methods
RTECS
Substance name Synonyms CAS registry number RTECS number
Toxicity data Data on teratogenesis Data on mutagenicity Data on carcinogenicity Standards/regulations (USA) Threshold limit value
CCRIS
Substance name CAS registry number
Carcinogenicity studies Mutagenicity studies Tumor promotion studies Tumor inbihition studies
M. Eoangelisti et aL /ScL Total Ent#on. 153 (1994) 211-217
and handling. Data concerning EC consumption and production, standards and regulations of different countries are available in ECDIN records. A wide range of toxic and harmful effects, such as general toxicity, carcinogenicity, mutagenicity, teratogenicity and other reproductive effects are present in the examined records. HSDB gives the most comprehensive coverage of general animal toxicity, but RTECS is the best source for numerical lethal dose values. Hazard information, general recommendations for human safety, personal protections and data on environmental fate, biodegradation and ecotoxicity values are available in ECDIN and HSDB records. In ECDIN and RTECS experiments are described in synthetic form: the databank records contain details of dosage, test species and route of administration indexed by descriptors taken from a keyword list. HSDB records relate a summary of the information, often refering to a portion of the scientific paper. Access to the original source is made possible by the provision of the bibliographic reference to each piece of data. The evaluation of the completeness of the information available through the considered factual databanks was carried-out by the analysis of carcinogenic and mutagenic data. Table 4 shows the summary of the carcinogenicity of the reference chemical compounds.
215
Carcinogenic and mutagenic risk assessment is a complex process and implies the evaluation of a wide range of scientific data. The evaluation of the carcinogenic risk to humans is based not only on the analysis of all published studies of cancer in humans and experimental animals, but also on other data considered to be relevant, including information concerning chemical properties, metabolism and toxicity, particularly its activity in short-term tests for genotoxicity. International agencies have developed a classification system for the characterization of the overall weight of evidence for carcinogenicity (animal, human and other supportive data) [6,7]. The chemical carcinogens are classified as: Carcinogens to humans when a casual relationship has been established between exposure to the agent and human cancer. - - C a r c i n o g e n s in experimental animals with sufficient evidence of carcinogenicity when a casual relationship has been established between the agent and the increased incidence of tumors in two or more species of animals or in two or more independent studies of one species. These compounds could probably be considered carcinogenic to humans. - - C a r c i n o g e n s in experimental animals with limited evidence of carcinogenicity when the --
Table 4 Carcinogenicity of reference chemical compounds Chemical compound
Evidence derived from data available on the scientific literature
Information derived from different factual data banks CCRIS
Naphthalene, Inadequate CAS 91.20.3 Aniline, Limited evidence [8,9] -CAS 62.53.3 Di-2-ethylSufficient evidence [10] Positive (NCI) exylphthalate (21 scientific papers on CAS 117.81.7 the mechanisms of action) Captan Limited evidence [11] CAS 133.06.21 Methylparathion Inadequate evidence [12] CAS 298.00.0 NCI, National Cancer Institute.
RTECS
HSDB
Equivocal evidence
--
Limited evidence
Limited evidence
Sufficient evidence Positive (NCI), 7 (NCI), 3 scientific scientific papers on papers on the the mechanism of mechanisms of action action Limited evidence Limited evidence
Negative
No evidence
ECDIN
2 old studies
Limited evidence
Evidence suggesting lack - of carcinogenicity
216
M. Eoangelisti et al. / Sci. Total Entiron. 153 (1994) 211-217
carcinogenic effects are limited to a single species or a single experiment. These compounds could be considered as probable carcinogens to humans. - - C h e m i c a l compounds with inadequate evidence of carcinogenicity when available studies cannot be interpreted because of the major qualitative and quantitative limitations.
and the results are not reported. Mutagenicity data obtained from RTECS include the lowest dose in a given assay reported to produce a specific effect. This databank reports only positive results, chemicals which are negative in a given short-term assay are not considered. In addition RTECS only distinguishes between the presence or absence of enzyme activations for mutation assays using microorganisms, for other short-term assays no such distinction is made. In ECDIN records the essential experimental details and the final results are present. Chemical toxicology was among the first of all the subject disciplines to be served by computerized databanks: there is now a wide range of these resources available [13-16]. A wealth of data on chemical hazard is constantly produced, but it remains difficult to collect and sometimes to evaluate in order to determine its significance in the risk assesment process. Factual databanks provide evaluated data and could be considered useful for a rapid survey of the information available on a chemical compound, but cannot be utilized as a substitute for the original sources. Databanks could also be a valuable complement to bibliographic databases in different subject areas, such as sources of human and environmental exposure, environmental transport, distribution and transformation, environmental level
This categorization provides useful information on the carcinogenic hazard to humans. Records from factual databanks classify all of the chemical compounds for carcinogenic risk. The information derived from the RTECS databank provides the categorization for all the chemicals analyzed. The evaluation of the oncogenic evidence could be carried-out using HSDB and ECDIN records for four and two chemicals, respectively. CCRIS records provide the results concerning only three chemical compounds. Table 5 reports the mutagenicity data of the studied chemical compounds. The number of scientific papers on mutagenicity citated from different databanks is very small in respect to the great amount of data available in the scientific literature. The information derived from the factual databanks, in only a few instances, defines the mutagenicity of the compounds. The highest number of citations occurs in RTECS records, but the data are not evaluated Table 5 Mutagenicity of reference chemical compounds Chemical compound
Evidence derived from data available on the scientific literature
Naphthalene CAS 91.20.3 Aniline CAS 62.53.3 Di-2-ethylexylphthalate CAS 117.81.7 Captan CAS 133.06.2 Methylparathion CAS 298.00.0
No mutagen (15 scientific papers) Weak mutagen (75 scientific papers) Mutagen (80 scientific papers) Mutagen (50 scientific papers) Mutagen (25 scientific papers)
Information derived from different factual databanks CCRIS
RTECS
HSDB
2 studies
--
2 reported studies
Positive, 4 studies
4 evaluated, 13 citated studies 15 citated studies
8 reported studies
18 evaluated studies
10 studies
1 evaluated study
13 evaluated, 43 citated studies 5 evaluated, (EPA), 14 citated
18 studies
3 evaluated studies 1 evaluated study
10 studies
10 studies
ECDIN
M. Evangelisti et al. /ScL Total Environ. 153 (1994)211-217
and human exposure, evaluation of human health risks and the effects on the environment.
9
References 1 W.A. Warr, Online acess to chemical information: a review, Database, 10 (1987) 122-129 2 D. Bawden, Chemical toxicology databanks, Aslib Proc., 40 (1988) 79-85. 3 D. Ugolini, C. Lombardo, A. Bogliolo and C. Fare, Online searches on Data Banks for Medicine, Proceedings of the 1st Congress of the European Accademy of Dermatology and Venereology, Florence, Italy, Blackwell Scientitle Pubhcations Oxford, 1989, pp. 79-82 4 A. Costigan, F.E. Wood and D. Bawden, Comparison of search techniques (printed and computerised) with specific reference to the RTECS databank, J. Inf. Sci., 10 (1985) 79-86. 5 Online Cuadra Directory of Databases, Cuadra Associates, Inc., Los Angeles, CA, USA, (1993). 6 EPA, Guidelines for Carcinogenic Risk Assesment, Federal Register, 51, 185 (1986)33993-34003. 7 IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, France, 56 (1993) 13-33. 8 National Cancer Institute (NCI), Bioassay of Aniline Hy-
10 11
12 13
14
15
16
217
drochloride for Possible Carcinogenicity, Tech. Rep. Ser. No. 130, DHEW Publ., No (NIH) (1978) 78-1385. Chemical Industry Institute of Toxicology (CIIT), 104Week Chronic Toxicity in Rats. Aniline Hydrochloride, Final Rep., vol. I and II, (1982). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, France, 29 (1982) 269-294. National Cancer Institute (NCI), Bioassay of Captan for Possible Carcinogenicity, Tech. Rep. Ser. No. 77, 1977, p. 815. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, France, 30 (1983) 131-152. D. Bawden and A.M. Brock, Chemical toxicology searching: a comparative study of online databases, J. Chem. Inf. Comput. Sci., 25 (1985) 31-35. F.E. Wood, A.T. Berrie, H.R. Plampin and M.L. Wilkinson-Tough, Evaluations using test queries of chemical hazards databases and databanks, J. Inf. Sci., 15 (1989) 269-276. M. Boni, F. Geiss and W. Penning, The ECDIN database for chemicals in the environment, Inf. Ser. Use, 10 (1990) 83 -86. J. Benz, K. Voigt and W. Mucke, Strategy for computeraided searches for information about chemicals, Online Rev., 13, 5 (1989) 383-393.
r ~,
•
the Science of the Total Environment Aa t m r m e ~
ELSEVIER
J m n d t ~ a e m 0 f f l ,i t ~ o m b
The Science of the Total Environment 153 (1994) 211-217
Chemical hazard evaluation: the use of factual health and safety databanks M. Evangelisti *a, C. Bolognesi a, R. Rabboni a, D. U g o l i n i b aIsatuto Nazionale per la Ricerca sul Cancro IST, Servizio Informazione Documentazione Scientifica, Viale Benedetto XE, 10 16132 Genova, Italy blstituto di Oncologia Clinica e Sperimentale dell'Universit?t di Genova, Viale Benedetto XE, 10, 16132 Genova, Italy Received 1 September 1993; accepted 1 November 1993
Abstract
The usefulness of factual health and safety databanks is discussed in this paper. Four databanks have been selected for this study: HSDB (Hazardous Substances Data Bank), ECDIN (Environmental Chemicals Data Information Network), RTECS (Registry of the Toxic Effects of Chemical Substances) and CCRIS (Chemical Carcinogenesis Research Information). The quality of the information available in the databanks considered was examined for five different chemical compounds and the completeness of the information available was carried out by an analysis of carcinogenic and mutagenic data.
Keywords: Toxicological evaluation; Factual databanks; Carcinogenicity; Mutagenicity
1. Introduction Toxicological evaluation processes are based on a wide spectrum of information of all types; chemical, environmental, epidemiological, animal, toxicological, pharmacokinetics, pharmacodynamics, biochemical, structure-activity and exposure data. Original papers on toxicology are published in a wide range of journals, books, proceedings of various symposia and hearings. The most recent development in the retrieval of references and abstracts involves the use of computers; it is possible by means of a terminal device and a telephone with a modem to directly access the hostcomputers that house data within specific struc-
* Corresponding author.
tures, usually called databases and databanks, which can be searched using colloquial data retrieval software [1,2]. A variety of information is available in different toxicological information files [3,4]. Three main types of archives are available; bibliographic databases, numeric or factual databanks and fulltext databanks. In bibliographic databases (or reference databases) it is possible to retrieve bibliographic references about a specific subject. It is also possible to identify the primary information sources to which the user must refer in order to obtain the whole article. Factual databanks contain concise information and they offer immediate access to factual a n d / o r numeric data. Finally the full-text databanks report the whole article, book or report. Today a large number of environmental and chemical databases and databanks are available
0048-9697/94/$07.00 © 1994 Elsevier Science BV. All rights reserved. SSDI 0048-9697(94)4106-J
212
M. Evangelisti et al. / Sci. Total Environ. 153 (1994) 211-217
(Table 1). Many databases and databanks are an extensive collection of data (Excerpta Medica, Chemical Abstracts, Medline) subject to continuous expansion. Small databanks covering specialized topics are also available. The aim of our study is to evaluate the usefulness of the factual databanks for the hazard assessment process of environmental agents with regard to its ability to predict the carcinogenic and mutagenic risk of chemical substances.
2. Materials and methods For this study, four databanks were selected covering chemical hazard information:
HSDB --Hazardous Substances Data Bank; ECDIN--Environmental Chemicals Data Information Network; RTECS--Registry of Toxic Effects of Chemical Substances; CCRIS--Chemical Carcinogenesis Research Information System. In Table 2 characteristics of these databanks, such as the producer, the update and the sources are given [5]. These databanks are distributed online worldwide by different hosts. When the databank is resident on CD-ROM or on a magnetic tape it is possible to have the archive directly in-house. The identification of chemical substances and subject coverage provided by these
Table 1 Environmental and chemical databases and databanks Databases and databanks
Subject coverage
Type of database or databank
Time span
Acid rain Aquatic information retrieval Business and the environment Chemical carcinogenesis research information system Developmental and reproductive toxicology Ecocerved EMTOX (Excerpta medica) Enviroline Environment week Environmental chemicals data and information network
Environment Aquatic science, toxicology Environment Biomedicine, toxicology
Bibliographic Full-text, factual Full-text Factual
1975 to date 1970-1990 1990 to date 1971 to date
Biomedicine, toxicology
Bibliographic
1989 to date
Environment Toxicology Environment Environment Chemistry, occupational safety, toxicology water resources management Toxicology Chemistry, properties, safety, toxicology Toxicology
Full-text Bibliographic Bibliographic Full-text Factual
1974 to date 1971 to date February 23, 1989 to date 1970 to date
Full-text factual Factual
1970-1990 Current information
Genetic toxicity Hazardous substances data bank Phytotox Radioactivity environmental monitoring Registry of toxic effects of chemical substances Riskline Sciscan (ISI) Toxline
Environment, nuclear industry Toxicology Toxicology Biomedicine, chemistry, engineering, environment Biomedicine, chemistry, environment, occupational safety, waste management
Bibliographic, full-text, Current information factual Factual 1984 to date Factual
Current information
Bibliographic Bibliographic
1972 to date Current 4 weeks
Bibliographic
1965 to date
M. Evangelisti et al./ Sci. Total Entiron. 153 (1994) 211-217
databanks are summarised in Table 3. Information on manufacturing, chemical and physical properties and toxicology are covered by each databank. The CCRIS databank is restricted to carcinogenicity and mutagenicity test results. The record (data sheet) on a single compound can be, more or less, extensive reporting of a different number of fields. Each field deals with one aspect of the subject and can be used to limit the chosen search terms. Occasionally fields can be er~ty; this occurs where the information is
213
not yet available. The usefulness of the information available in the considered factual databanks was examined for five different chemicals, industrial compounds or pesticides. The study was carried out by searching for the substances using Chemical Abstract Service (CAS) registry numbers and retrieving the full records of the compound in each of the four databanks consulted through a connection with the host DIMDI (Deutsches Institut fur Medizinische Dokumentation und Information, Koln, DK).
Table 2 Databank characteristics HSDB
ECDIN
RTECS
CCRIS
Producer
National Library of Medicine (NLM), Toxicology Information Program (TIP)
Commission of the European Communities (CEC), Joint Research Centre (JRC)
U.S National Library of Medicine (NLM), Toxicology Information Program ('tiP)
U.S National Library of Medicine (NLM), Toxicology Information Program (TIP)
Hosts
DATA/STAR-DIMDI -NLM/TOXNET
CEC, Joint Research Centre--DIMDI
NLM/TIP-CCINFOLI NE-CIS-DIALOG DIMDI-BIOSIS-LIFE SCIENCE NETWORK
CIS-DIMDI-NLM/TIP
Support
Online-CD-ROM
Online-CD-ROM
Online-CD-ROM-magnetic tape
Online
Periodically
Quarterly
Quarterly
4200
104 000
100000
1400
Handbooks, monographs, government reports (USA), technical reports, journals
Handbooks, monographs, journals, research reports (CEC), data collections of the UN (United Nations E n v i r o n m e n t Program/International Register of Potentially Toxic Chemicals)--data collections of the Brandweer Informatiecentrum (BIG), Geel, Belgium--data collections of the CEC: European Inventory of Existing Commercial Chemical Substances (EINECS)
Journals, conferences, congress, papers, books, personal communications to National Institute for Occupational Health and Safety
Journals, current awareness tools, monographs, technical reports
Updating No. of chemical substances * Sources
As needed
(USA)(NIOSH)
* DIMDI (Deutsches Institut fur Medizinische Dokumentation und Information) 1991.
214
M. Evangelisti et al. / S c i Total Entiron. 153 0994) 211-217
3. Results and conclusions
The information available through factual databanks on chemical toxicology could be utilized to compile a provisional toxicological profile of a chemical compound. Records were available for all the chemicals selected for this study, varying substantially in length between databanks and also between chemical compounds. HSDB and ECDIN records are generally the most extensive.
The characteristics of the chemical substances, such as chemico-physical properties, toxicology and environmental hazard could be defined making use of all the available data present in the factual databanks. These banks could be considered to some extent complementary to each other. HSDB and RTECS provide a large number of synonyms for all the selected substances. HSDB is the best source of information concerning manufacture, chemical and physical properties, safety
Table 3 Identification of clinical substances and subjects coverage of factural databanks
HSDB
Identifications of substance
Subject coverage
Substance name
Manufacturing use information Chemical/physical properties Safety/handling Toxicity/biomedical effects
Synonyms Synonyms long CAS registry number RTECS number OHM-TADS number Ship(ping) name/number EPA hazardous wastes number STCC number ECDIN
Substance name Synonyms CAS registry number Old CAS registry number RTECS number EEC number EEC number EINECS number CCT number
Pharmacology Environmental fate Standards/regulations Monitoring/analysis methods
Ecology/ecotoxicology/ toxicology Occupational health Chemical hazard information Standards/regulations Analytical methods
RTECS
Substance name Synonyms CAS registry number RTECS number
Toxicity data Data on teratogenesis Data on mutagenicity Data on carcinogenicity Standards/regulations (USA) Threshold limit value
CCRIS
Substance name CAS registry number
Carcinogenicity studies Mutagenicity studies Tumor promotion studies Tumor inbihition studies
M. Eoangelisti et aL /ScL Total Ent#on. 153 (1994) 211-217
and handling. Data concerning EC consumption and production, standards and regulations of different countries are available in ECDIN records. A wide range of toxic and harmful effects, such as general toxicity, carcinogenicity, mutagenicity, teratogenicity and other reproductive effects are present in the examined records. HSDB gives the most comprehensive coverage of general animal toxicity, but RTECS is the best source for numerical lethal dose values. Hazard information, general recommendations for human safety, personal protections and data on environmental fate, biodegradation and ecotoxicity values are available in ECDIN and HSDB records. In ECDIN and RTECS experiments are described in synthetic form: the databank records contain details of dosage, test species and route of administration indexed by descriptors taken from a keyword list. HSDB records relate a summary of the information, often refering to a portion of the scientific paper. Access to the original source is made possible by the provision of the bibliographic reference to each piece of data. The evaluation of the completeness of the information available through the considered factual databanks was carried-out by the analysis of carcinogenic and mutagenic data. Table 4 shows the summary of the carcinogenicity of the reference chemical compounds.
215
Carcinogenic and mutagenic risk assessment is a complex process and implies the evaluation of a wide range of scientific data. The evaluation of the carcinogenic risk to humans is based not only on the analysis of all published studies of cancer in humans and experimental animals, but also on other data considered to be relevant, including information concerning chemical properties, metabolism and toxicity, particularly its activity in short-term tests for genotoxicity. International agencies have developed a classification system for the characterization of the overall weight of evidence for carcinogenicity (animal, human and other supportive data) [6,7]. The chemical carcinogens are classified as: Carcinogens to humans when a casual relationship has been established between exposure to the agent and human cancer. - - C a r c i n o g e n s in experimental animals with sufficient evidence of carcinogenicity when a casual relationship has been established between the agent and the increased incidence of tumors in two or more species of animals or in two or more independent studies of one species. These compounds could probably be considered carcinogenic to humans. - - C a r c i n o g e n s in experimental animals with limited evidence of carcinogenicity when the --
Table 4 Carcinogenicity of reference chemical compounds Chemical compound
Evidence derived from data available on the scientific literature
Information derived from different factual data banks CCRIS
Naphthalene, Inadequate CAS 91.20.3 Aniline, Limited evidence [8,9] -CAS 62.53.3 Di-2-ethylSufficient evidence [10] Positive (NCI) exylphthalate (21 scientific papers on CAS 117.81.7 the mechanisms of action) Captan Limited evidence [11] CAS 133.06.21 Methylparathion Inadequate evidence [12] CAS 298.00.0 NCI, National Cancer Institute.
RTECS
HSDB
Equivocal evidence
--
Limited evidence
Limited evidence
Sufficient evidence Positive (NCI), 7 (NCI), 3 scientific scientific papers on papers on the the mechanism of mechanisms of action action Limited evidence Limited evidence
Negative
No evidence
ECDIN
2 old studies
Limited evidence
Evidence suggesting lack - of carcinogenicity
216
M. Eoangelisti et al. / Sci. Total Entiron. 153 (1994) 211-217
carcinogenic effects are limited to a single species or a single experiment. These compounds could be considered as probable carcinogens to humans. - - C h e m i c a l compounds with inadequate evidence of carcinogenicity when available studies cannot be interpreted because of the major qualitative and quantitative limitations.
and the results are not reported. Mutagenicity data obtained from RTECS include the lowest dose in a given assay reported to produce a specific effect. This databank reports only positive results, chemicals which are negative in a given short-term assay are not considered. In addition RTECS only distinguishes between the presence or absence of enzyme activations for mutation assays using microorganisms, for other short-term assays no such distinction is made. In ECDIN records the essential experimental details and the final results are present. Chemical toxicology was among the first of all the subject disciplines to be served by computerized databanks: there is now a wide range of these resources available [13-16]. A wealth of data on chemical hazard is constantly produced, but it remains difficult to collect and sometimes to evaluate in order to determine its significance in the risk assesment process. Factual databanks provide evaluated data and could be considered useful for a rapid survey of the information available on a chemical compound, but cannot be utilized as a substitute for the original sources. Databanks could also be a valuable complement to bibliographic databases in different subject areas, such as sources of human and environmental exposure, environmental transport, distribution and transformation, environmental level
This categorization provides useful information on the carcinogenic hazard to humans. Records from factual databanks classify all of the chemical compounds for carcinogenic risk. The information derived from the RTECS databank provides the categorization for all the chemicals analyzed. The evaluation of the oncogenic evidence could be carried-out using HSDB and ECDIN records for four and two chemicals, respectively. CCRIS records provide the results concerning only three chemical compounds. Table 5 reports the mutagenicity data of the studied chemical compounds. The number of scientific papers on mutagenicity citated from different databanks is very small in respect to the great amount of data available in the scientific literature. The information derived from the factual databanks, in only a few instances, defines the mutagenicity of the compounds. The highest number of citations occurs in RTECS records, but the data are not evaluated Table 5 Mutagenicity of reference chemical compounds Chemical compound
Evidence derived from data available on the scientific literature
Naphthalene CAS 91.20.3 Aniline CAS 62.53.3 Di-2-ethylexylphthalate CAS 117.81.7 Captan CAS 133.06.2 Methylparathion CAS 298.00.0
No mutagen (15 scientific papers) Weak mutagen (75 scientific papers) Mutagen (80 scientific papers) Mutagen (50 scientific papers) Mutagen (25 scientific papers)
Information derived from different factual databanks CCRIS
RTECS
HSDB
2 studies
--
2 reported studies
Positive, 4 studies
4 evaluated, 13 citated studies 15 citated studies
8 reported studies
18 evaluated studies
10 studies
1 evaluated study
13 evaluated, 43 citated studies 5 evaluated, (EPA), 14 citated
18 studies
3 evaluated studies 1 evaluated study
10 studies
10 studies
ECDIN
M. Evangelisti et al. /ScL Total Environ. 153 (1994)211-217
and human exposure, evaluation of human health risks and the effects on the environment.
9
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