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Toxicological Profile for Dinitrocresols. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2018 Jan.
Toxicological Profile for Dinitrocresols.
Show detailsThe objective of the toxicological profile is to evaluate the potential for human exposure and the potential health hazards associated with inhalation, oral, or dermal/ocular exposure to dinitrocresols.
B.1. LITERATURE SEARCH AND SCREEN
A literature search and screen was conducted to identify studies examining health effects, toxicokinetics, mechanisms of action, susceptible populations, biomarkers, and chemical interactions data for dinitrocresols. ATSDR primarily focused on peer-reviewed articles without publication date or language restrictions. Non-peer-reviewed studies that were considered relevant to the assessment of the health effects of dinitrocresols have undergone peer review by at least three ATSDR-selected experts who have been screened for conflict of interest. The inclusion criteria used to identify relevant studies examining the health effects of dinitrocresols are presented in Table B-1.
Table B-1Inclusion Criteria for the Literature Search and Screen
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Health Effects Species Human Laboratory mammals Route of exposure Inhalation Oral Dermal (or ocular) Parenteral (these studies will be considered supporting data) Health outcome Death Systemic effects Body weight effects Respiratory effects Cardiovascular effects Gastrointestinal effects Hematological effects Musculoskeletal effects Hepatic effects Renal effects Dermal effects Ocular effects Endocrine effects Immunological effects Neurological effects Reproductive effects Developmental effects Other noncancer effects Cancer |
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Toxicokinetics Absorption Distribution Metabolism Excretion PBPK models Biomarkers Biomarkers of exposure Biomarkers of effect Interactions with other chemicals |
B.1.1. Literature Search
The current literature search was intended to update the health effects sections of the existing toxicological profile for dinitrocresols (ATSDR 1995), thus, the literature search was restricted to studies published between January 1993 to March 2017. The following main databases were searched in March 2017:
- PubMed
- National Library of Medicine’s TOXLINE
- Scientific and Technical Information Network’s TOXCENTER
The search strategy used the chemical names, Chemical Abstracts Service (CAS) numbers, synonyms, Medical Subject Headings (MeSH) headings, and keywords for dinitrocresols. The query strings used for the literature search are presented in Table B-2.
The search was augmented by searching the Toxic Substances Control Act Test Submissions (TSCATS), NTP website, and National Institute of Health Research Portfolio Online Reporting Tools Expenditures and Results (NIH RePORTER) databases using the queries presented in Table B-3. Additional databases were searched in the creation of various tables and figures, such as the TRI Explorer, the Substance Priority List (SPL) resource page, and other items as needed. Regulations applicable to dinitrocresols were identified by searching international and U.S. agency websites and documents.
Review articles were identified and used for the purpose of providing background information and identifying additional references. ATSDR also identified reports from the grey literature, which included unpublished research reports, technical reports from government agencies, conference proceedings and abstracts, and theses and dissertations.
Table B-2Database Query Strings
| Database search date | Query string |
|---|---|
| PubMed | |
| 03/2017 | (((“2,4-Dinitro-5-methylphenol”[tw] OR “3-Methyl-4,6-dinitrophenol”[tw] OR “4,6-Dinitro-m-cresol”[tw] OR “5-methyl-2,4-dinitro-Phenol”[tw]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[crdat] OR 1993/01/01 : 3000[edat])) OR ((534-52-1[rn] OR 1604ZJR09T[rn] OR “4,6-dinitro-o-cresol”[supplementary concept] OR “4,6-dinitro-o-cresol”[nm]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[mhda])) OR ((“3,5-Dinitro-o-cresol”[tw] OR “2-methyl-3,5-dinitro-Phenol”[tw] OR “3,5-Dinitro-ortho-cresol”[tw]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[crdat] OR 1993/01/01 : 3000[edat])) OR ((609-93-8[rn] OR L572BVH6NF[rn] OR “2,6-dinitro-p-cresol”[supplementary concept] OR “2,6-dinitro-p-cresol”[nm]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[mhda])) OR (((“2,4-Dinitro-6-methylphenol”[tw] OR “2,4-Dinitro-o-cresol”[tw] OR “2-Methyl-4,6-dinitrophenol”[tw] OR “3,5-Dinitro-2-hydroxytoluene”[tw] OR “4,6-dinitro-2-cresol”[tw] OR “4,6-Dinitro-o-cresol”[tw] OR “4,6-dinitro-ortho-cresol”[tw] OR “4,6-Dinitro-o-cresolo”[tw] OR “4,6-Dinitro-o-kresol”[tw] OR “4,6-Dinitrokresol”[tw] OR “6-Methyl-2,4-dinitrophenol”[tw] OR “Antinonin”[tw] OR “Antinonnin”[tw] OR “Arborol”[tw] OR “Capsine”[tw] OR “Chemsect DNOC”[tw] OR “Degrassan”[tw] OR “Dekrysil”[tw] OR “Detal”[tw] OR “Dillex”[tw] OR “Dinitro”[tw] OR “Dinitro-o-cresol”[tw] OR “Dinitrocresol”[tw] OR “Dinitrodendtroxal”[tw] OR “Dinitrol”[tw] OR “Dinoc”[tw] OR “Dinurania”[tw] OR “Ditrosol”[tw] OR “Dn-dry mix no. 2”[tw] OR “DNOC”[tw] OR “DNOK”[tw] OR “Dwunitro-o-krezol”[tw] OR “Effusan”[tw] OR “Effusan 3436”[tw] OR “Elgetol”[tw] OR “Elgetol 30”[tw] OR “Elipol”[tw] OR “Extrar”[tw] OR “Flavin-Samdoz”[tw] OR “Hedolit”[tw] OR “Hedolite”[tw] OR “Kreozan”[tw] OR “Kresamone”[tw] OR “Kresonite-E”[tw] OR “Krezotol 50”[tw] OR “LE dinitrocresol-4,6”[tw] OR “Lipan”[tw] OR “Neudorff DN 50”[tw] OR “Nitrador”[tw] OR “Nitrofan”[tw] OR “Oranz viktoria”[tw] OR “Prokarbol”[tw] OR “Rafex”[tw] OR “Rafex 35”[tw] OR “Raphatox”[tw] OR “Sandolin”[tw] OR “Sandolin A”[tw] OR “Selinon”[tw] OR “Sinox”[tw] OR “3,5-dinitro-2-hydroxy-Toluene”[tw] OR “Trifocide”[tw] OR “Trifrina”[tw] OR “Winterwash”[tw] OR “Zahlreiche bezeichnungen”[tw]) NOT medline[sb]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[crdat] OR 1993/01/01 : 3000[edat])) OR ((“2,6-Dinitro-4-methylphenol”[tw] OR “2,6-Dinitro-p-cresol”[tw] OR “4-Methyl-2,6-dinitrophenol”[tw] OR “Dinitro-p-cresol”[tw] OR “DNPC”[tw] OR “3,5-dinitro-4-hydroxy-Toluene”[tw] OR “Victoria Orange”[tw] OR “Victoria Yellow”[tw] OR “Dinitro-para-cresol”[tw]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[crdat] OR 1993/01/01 : 3000[edat]))) OR ((Dinitrocresols[MeSH] AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[mhda])) OR ((“Dinitrocresols”[tw] NOT medline[sb]) AND (1993/01/01 : 3000[dp] OR 1993/01/01 : 3000[crdat] OR 1993/01/01 : 3000[edat]))) |
| Toxline | |
| 03/2017 | ( 616-73-9 [rn] OR 534-52-1 [rn] OR 497-56-3 [rn] OR 609-93-8 [rn] OR “2 4 dinitro 5 methylphenol” OR “3 methyl 4 6 dinitrophenol” OR “4 6 dinitro m cresol” OR “5 methyl 2 4 dinitro phenol” OR “2 4 dinitro 6 methylphenol” OR “2 4 dinitro o cresol” OR “2 methyl 4 6 dinitrophenol” OR “3 5 dinitro 2 hydroxytoluene” OR “4 6 dinitro 2 cresol” OR “4 6 dinitro o cresol” OR “4 6 dinitro ortho cresol” OR “4 6 dinitro o cresolo” OR “4 6 dinitro o kresol” OR “4 6 dinitrokresol” OR “6 methyl 2 4 dinitrophenol” OR “antinonin” OR “antinonnin” OR “arborol” OR “capsine” OR “chemsect dnoc” OR “degrassan” OR “dekrysil” OR “detal” OR “dillex” OR “dinitro” OR “dinitro o cresol” OR “dinitrocresol” OR “dinitrodendtroxal” OR “dinitrol” OR “dinoc” OR “dinurania” OR “ditrosol” OR “dn dry mix no 2” OR “dnoc” OR “dnok” OR “dwunitro o krezol” OR “effusan” OR “effusan 3436” OR “elgetol” OR “elgetol 30” OR “elipol” OR “extrar” OR “flavin samdoz” OR “hedolit” OR “hedolite” OR “kreozan” OR “kresamone” OR “kresonite e” OR “krezotol 50” OR “le dinitrocresol 4 6” OR “lipan” OR “neudorff dn 50” OR “nitrador” OR “nitrofan” OR “oranz viktoria” OR “prokarbol” OR “rafex” OR “rafex 35” OR “raphatox” OR “sandolin” OR “sandolin a” OR “selinon” OR “sinox” OR “3 5 dinitro 2 hydroxy toluene” OR “trifocide” OR “trifrina” OR “winterwash” OR “zahlreiche bezeichnungen” OR “3 5 dinitro o cresol” OR “2 methyl 3 5 dinitro phenol” OR “3 5 dinitro ortho cresol” OR “2 6 dinitro 4 methylphenol” OR “2 6 dinitro p cresol” OR “4 methyl 2 6 dinitrophenol” OR “dinitro p cresol” OR “dnpc” OR “3 5 dinitro 4 hydroxy toluene” OR “victoria orange” OR “victoria yellow” OR “dinitro para cresol”) AND 1993:2017 [yr] AND ( ANEUPL [org] OR BIOSIS [org] OR CIS [org] OR DART [org] OR EMIC [org] OR EPIDEM [org] OR HEEP [org] OR HMTC [org] OR IPA [org] OR RISKLINE [org] OR MTGABS [org] OR NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB [org] ) AND NOT PubMed [org] AND NOT pubdart [org] |
| Toxcenter | |
| 03/2017 |
FILE ‘TOXCENTER’ ENTERED AT 09:29:55 ON 29 MAR 2017 L1 1948 SEA 616-73-9 OR 534-52-1 OR 497-56-3 OR 609-93-8 L2 14 SEA 12167-18-9 L3 1960 SEA L1 OR L2 L4 1937 SEA L3 NOT TSCATS/FS L5 1752 SEA L4 NOT PATENT/DT L6 694 SEA L5 AND PY>=1993 ACTIVATE TOXQUERY/Q ------- L7 QUE (CHRONIC OR IMMUNOTOX? OR NEUROTOX? OR TOXICOKIN? OR BIOMARKER? OR NEUROLOG?) L8 QUE (PHARMACOKIN? OR SUBCHRONIC OR PBPK OR EPIDEMIOLOGY/ST,CT, IT) L9 QUE (ACUTE OR SUBACUTE OR LD50# OR LD(W)50 OR LC50# OR LC(W)50) L10 QUE (TOXICITY OR ADVERSE OR POISONING)/ST,CT,IT L11 QUE (INHAL? OR PULMON? OR NASAL? OR LUNG? OR RESPIR?) L12 QUE ((OCCUPATION? OR WORKPLACE? OR WORKER?) AND EXPOS?) L13 QUE (ORAL OR ORALLY OR INGEST? OR GAVAGE? OR DIET OR DIETS OR DIETARY OR DRINKING(W)WATER?) L14 QUE (MAXIMUM AND CONCENTRATION? AND (ALLOWABLE OR PERMISSIBLE)) L15 QUE (ABORT? OR ABNORMALIT? OR EMBRYO? OR CLEFT? OR FETUS?) L16 QUE (FOETUS? OR FETAL? OR FOETAL? OR FERTIL? OR MALFORM? OR OVUM?) L17 QUE (OVA OR OVARY OR PLACENTA? OR PREGNAN? OR PRENATAL?) L18 QUE (PERINATAL? OR POSTNATAL? OR REPRODUC? OR STERIL? OR TERATOGEN?) L19 QUE (SPERM OR SPERMAC? OR SPERMAG? OR SPERMATI? OR SPERMAS? OR SPERMATOB? OR SPERMATOC? OR SPERMATOG?) L20 QUE (SPERMATOI? OR SPERMATOL? OR SPERMATOR? OR SPERMATOX? OR SPERMATOZ? OR SPERMATU? OR SPERMI? OR SPERMO?) L21 QUE (NEONAT? OR NEWBORN? OR DEVELOPMENT OR DEVELOPMENTAL?) L22 QUE (ENDOCRIN? AND DISRUPT?) L23 QUE (ZYGOTE? OR CHILD OR CHILDREN OR ADOLESCEN? OR INFANT?) L24 QUE (WEAN? OR OFFSPRING OR AGE(W)FACTOR?) L25 QUE (DERMAL? OR DERMIS OR SKIN OR EPIDERM? OR CUTANEOUS?) L26 QUE (CARCINOG? OR COCARCINOG? OR CANCER? OR PRECANCER? OR NEOPLAS?) L27 QUE (TUMOR? OR TUMOUR? OR ONCOGEN? OR LYMPHOMA? OR CARCINOM?) L28 QUE (GENETOX? OR GENOTOX? OR MUTAGEN? OR GENETIC(W)TOXIC?) L29 QUE (NEPHROTOX? OR HEPATOTOX?) L30 QUE (ENDOCRIN? OR ESTROGEN? OR ANDROGEN? OR HORMON?) L31 QUE (OCCUPATION? OR WORKER? OR WORKPLACE? OR EPIDEM?) L32 QUE L7 OR L8 OR L9 OR L10 OR L11 OR L12 OR L13 OR L14 OR L15 OR L16 OR L17 OR L18 OR L19 OR L20 OR L21 OR L22 OR L23 OR L24 OR L25 OR L26 OR L27 OR L28 OR L29 OR L30 OR L31 L33 QUE (RAT OR RATS OR MOUSE OR MICE OR GUINEA(W)PIG? OR MURIDAE OR DOG OR DOGS OR RABBIT? OR HAMSTER? OR PIG OR PIGS OR SWINE OR PORCINE OR MONKEY? OR MACAQUE?) L34 QUE (MARMOSET? OR FERRET? OR GERBIL? OR RODENT? OR LAGOMORPHA OR BABOON? OR CANINE OR CAT OR CATS OR FELINE OR MURINE) L35 QUE L32 OR L33 OR L34 L36 QUE (NONHUMAN MAMMALS)/ORGN L37 QUE L35 OR L36 L38 QUE (HUMAN OR HUMANS OR HOMINIDAE OR MAMMALS OR MAMMAL? OR PRIMATES OR PRIMATE?) L39 QUE L37 OR L38 ------- L40 344 SEA L6 AND L39 L41 24 SEA L40 AND MEDLINE/FS L42 17 SEA L40 AND BIOSIS/FS L43 297 SEA L40 AND CAPLUS/FS L44 6 SEA L40 NOT (MEDLINE/FS OR BIOSIS/FS OR CAPLUS/FS) L45 321 DUP REM L41 L42 L44 L43 (23 DUPLICATES REMOVED) L*** DEL 24 S L40 AND MEDLINE/FS L*** DEL 24 S L40 AND MEDLINE/FS L46 24 SEA L45 L*** DEL 17 S L40 AND BIOSIS/FS L*** DEL 17 S L40 AND BIOSIS/FS L47 14 SEA L45 L*** DEL 297 S L40 AND CAPLUS/FS L*** DEL 297 S L40 AND CAPLUS/FS L48 278 SEA L45 L*** DEL 6 S L40 NOT (MEDLINE/FS OR BIOSIS/FS OR CAPLUS/FS) L*** DEL 6 S L40 NOT (MEDLINE/FS OR BIOSIS/FS OR CAPLUS/FS) L49 5 SEA L45 L50 297 SEA (L46 OR L47 OR L48 OR L49) NOT MEDLINE/FS L51 278 SEA L50 AND CAPLUS/FS D SCAN L50 |
Table B-3Strategies to Augment the Literature Search
| Source | Query and number screened when available |
|---|---|
| TSCATS a | |
| 03/2017 | Compounds searched: 616-73-9, 534-52-1, 497-56-3, 609-93-8, 12167-18-9 |
| NTP | |
| 03/2017 |
616-73-9 534-52-1 497-56-3 609-93-8 12167-18-9 2,4-Dinitro-5-methylphenol 3-Methyl-4,6-dinitrophenol 4,6-Dinitro-m-cresol 5-methyl-2,4-dinitro-Phenol 2,4-Dinitro-6-methylphenol 2,4-Dinitro-o-cresol 2-Methyl-4,6-dinitrophenol 3,5-Dinitro-2-hydroxytoluene 4,6-dinitro-2-cresol 4,6-Dinitro-o-cresol 4,6-dinitro-ortho-cresol 6-Methyl-2,4-dinitrophenol DNOC 3,5-Dinitro-o-cresol 2-methyl-3,5-dinitro-Phenol 3,5-Dinitro-ortho-cresol 2,6-Dinitro-4-methylphenol 2,6-Dinitro-p-cresol 4-Methyl-2,6-dinitrophenol Dinitro-p-cresol Dinitro-para-cresol DNPC 3,5-dinitro-4-hydroxy-Toluene Dinitrocresols Dinitrocresol |
| NIH RePORTER | |
| 06/2017 | Text Search: “2,4-Dinitro-6-methylphenol” OR “2,4-Dinitro-o-cresol” OR “2-Methyl-4,6-dinitrophenol ” OR “3,5-Dinitro-2-hydroxytoluene” OR “4,6-dinitro-2-cresol” OR “4,6-Dinitro-o-cresol” OR “4,6-dinitro-ortho-cresol” OR “4,6-Dinitro-o-cresolo” OR “4,6-Dinitro-o-kresol” OR “4,6-Dinitrokresol” OR “6-Methyl-2,4-dinitrophenol” OR “Antinonin” OR “Antinonnin” OR “Arborol” OR “Capsine” OR “Chemsect DNOC” OR “Degrassan” OR “Dekrysil” OR “Detal” OR “Dillex” OR “Dinitro” OR “Dinitro-o-cresol” OR “Dinitrocresol” OR “Dinitrodendtroxal” OR “Dinitrol” OR “Dinoc” OR “Dinurania” OR “Ditrosol” OR “Dn-dry mix no. 2” OR “DNOC” OR “DNOK” OR “Dwunitro-o-krezol” OR “Effusan” OR “Effusan 3436” OR “Elgetol” OR “Elgetol 30” OR “Elipol” OR “Extrar” OR “Flavin-Samdoz” OR “Hedolit” OR “Hedolite” OR “Kreozan” OR “Kresamone” OR “Kresonite-E” OR “Krezotol 50” OR “LE dinitrocresol-4,6” OR “Lipan” OR “Neudorff DN 50” OR “Nitrador” OR “Nitrofan” OR “Oranz viktoria” OR “Prokarbol” OR “Rafex” OR “Rafex 35” OR “Raphatox” OR “Sandolin” OR “Sandolin A” OR “Selinon” OR “Sinox” OR “Trifocide” OR “Trifrina” OR “Winterwash” OR “Zahlreiche bezeichnungen” (Advanced), Search in: Projects AdminIC: All, Fiscal Year: Active Projects |
| Other | Identified throughout the assessment process |
- a
Several versions of the TSCATS database were searched, as needed, by CASRN including TSCATS1 via Toxline (no date limit), TSCATS2 via https://yosemite
.epa .gov/oppts/epatscat8 .nsf/ReportSearch?OpenForm (date restricted by EPA receipt date), and TSCATS via CDAT (date restricted by ‘Mail Received Date Range’), as well as google for recent TSCA submissions.
The 2017 results were:
- Number of records identified from PubMed, TOXLINE, and TOXCENTER (after duplicate removal): 1,003
- Number of records identified from other strategies: 35
- Total number of records to undergo literature screening: 1,038
B.1.2. Literature Screening
A two-step process was used to screen the literature search to identify relevant studies on dinitrocresols:
- Title and abstract screen
- Full text screen
Title and Abstract Screen. Within the reference library, titles and abstracts were screened manually for relevance. Studies that were considered relevant (see Table B-1 for inclusion criteria) were moved to the second step of the literature screening process. Studies were excluded when the title and abstract clearly indicated that the study was not relevant to the toxicological profile.
- Number of titles and abstracts screened: 1,038
- Number of studies considered relevant and moved to the next step: 47
Full Text Screen. The second step in the literature screening process was a full text review of individual studies considered relevant in the title and abstract screen step. Each study was reviewed to determine whether it was relevant for inclusion in the toxicological profile.
- Number of studies undergoing full text review: 47
- Number of studies cited in the health effects sections of the existing toxicological profile (August, 1995): 78
- Total number of studies cited in the health effects sections of the updated profile: 90
A summary of the results of the literature search and screening is presented in Figure B-1.
Figure B-1March 2017 Literature Search Results and Screen for Dinitrocresols
- LITERATURE SEARCH FRAMEWORK FOR DINITROCRESOLS - Toxicological Profile for Dinit...LITERATURE SEARCH FRAMEWORK FOR DINITROCRESOLS - Toxicological Profile for Dinitrocresols
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