CASE Ultra Models

CASE Ultra models cover a wide variety of toxicity end points and is the largest collection of high quality in-silico toxicity models

Statistical Models & Expert Rules

Licensing Options

New Additions

Latest additions to CASE Ultra models

Expert Rules for Mutagenicity • New E. coli mutagenicity models • New Skin Sensitization Models

Bacterial Mutagenicity Models (ICH M7)

Bacterial mutagenicity models are part of the ICH M7 guidlines, 
they are based on the experimental data from Ames test.

Main ICH M7 Models

GT_EXPERT
Expert Rules for Mutagenicity
GT1_A7B
Mutagenicity for 7 major strains of S. typhimurium, FDA data source
GT1_AT_ECOLI
Mutagenicity by A-T site mutation in E. coli / TA102, FDA data source
PHARM_SALM
Aggregated Salmonella mutagenicity from public and proprietary sources
PHARM_ECOLI
Aggregated E. coli mutagenicity from public and proprietary sources

Supporting ICH M7 Models

A9L
Salmonella mutagenicity, GENETOX data source
A9M
Salmonella mutagenicity, NTP data source
A6E
Mutagenicity in E. coli, CCRIS data source

Salmonella Strain Specific Mutagenicity Models

TA_97
S. typhimurium (TA97) mutation, with and without S9
TA_98
S. typhimurium (TA98) mutation, with and without S9
TA_100
S. typhimurium (TA100) mutation, with and without S9
TA_102
S. typhimurium (TA102) mutation, with and without S9
TA_104
S. typhimurium (TA104) mutation, with and without S9
TA_1535
S. typhimurium (TA1535) mutation, with and without S9
TA_1537
S. typhimurium (TA1537) mutation, with and without S9
TA_1538
S. typhimurium (TA1538) mutation, with and without S9

Salmonella Site Specific Mutagenicity Models

HISC3076
S. typhimurium HISC3076 mutation, with and without S9
HISD3052
S. typhimurium HISD3052 mutation, with and without S9
HISG46
S. typhimurium HISG46 mutation, with and without S9
HISG428
S. typhimurium HISG428 mutation, with and without S9
HISO1242
S. typhimurium HISO1242 mutation, with and without S9

Genotoxicity Models

Mutagenicity as well as other genotoxicity-relevant  in vitro and in vivo phenotypes, such as micronucleus, chromosomal aberrations, sister chromatid exchange and more. Models denoted as RCA are based on FDA data as part of Research Cooperation Agreement (RCA).

RCA Genotoxicity Models

GT_EXPERT
E‍xpert rules for mutagenicity
GT1_A7B
Mutagenicity for 7 major strains of S. typhimurium
GT1_AT_ECOLI
Mutagenicity by A-T site mutation in E. coli / TA102
GT2_CHROM_CHO
Clastogenicity, in-vitro, chromosome aberrations, CHO cells
GT2_CHROM_CHL
Clastogenicity, in-vitro, chromosome aberrations, CHL cells
GT3_MNT_MOUSE
Clastogenicity, micronucleus, in-vivo, mouse
GT4_L5178Y
G‍ene mutations, in-vitro, mouse lymphoma L5178Y cells

Research Only Genotoxicity Models

A7E - A7F
Yeast mutagenicity
A7G - A7I
Drosophila mutagenicity
A7J – A7K
Mammalian mutagenicity, in vivo
A7O
Mammalian mutagenicity in vitro, CHO V79 HGPRT loci
A8A - A8C
DNA effects, unscheduled DNA synthesis
A7Y, A7Z, A8I
Clastogenicity, in vitro, sister chromatid exchange

Additional Genotoxicity Models

A2D
Drosophila mutation
A6J
Mouse lymphoma L5178Y (NTP, GENETOX, CCRIS data sources)
A61
Chromosomal aberration, NTP data source
A62
Micronuclei induction
A60
Sister chromatid exchange, NTP data source
A6A
Aneuploidy in yeast
SOS
SOS chromotest

Carcinogenicity Models

Cancer-related endpoints in human and rodents.
Models denoted as RCA are based on FDA data as part of Research Cooperation Agreement (RCA).

RCA Rodent Carcinogenicity (ICH M7 compatible)

CARC_RAT_M
Rodent carcinogenicity, male rat
CARC_RAT_F
Rodent carcinogenicity, female rat
CARC_MOUSE_M
Rodent carcinogenicity, male mouse
CARC_MOUSE_F
Rodent carcinogenicity, female mouse

Additional Carcinogenicity Models

A8D - A8G
RCA cell transformation
A0C - A0E
Rodent carcinogenicity, CPDB data source
A0L
Two stage skin carcinogenicity, mouse
A0F - A0I
Rodent carcinogenicity by specie and gender, NTP data source
A07 - A09
Rodent carcinogenicity, NTP data source 
A0J
Human carcinogenicity, IARC data source (ICH M7 compatible)
AX1
Hepatocarcinogenicity, male rat
AX2
Hepatocarcinogenicity, female rat
AX3
Hepatocarcinogenicity, male mouse
AX4
Hepatocarcinogenicity, female mouse

HepaTox Models

Hepatobiliary adverse effects and general liver toxicity in human.
Models denotes as RCA are based on FDA data as part of Research Cooperation Agreement.

LIVER_DAMAGE
RCA human acute liver damage
LIVER_FTEST
RCA human liver function tests (liver enzymes release)
LIVER_BDUCT
RCA human bile duct disorders
LIVER_CHOLEST
RCA human cholestasis
LIVER_JAUNDICE
Human liver jaundice
LIVER_GALL
Human gall bladder disorders

RenalTox Models

Kidney and urinary tract adverse effects in human.
These models are based on FDA data as part of Research Cooperation Agreement (RCA).

RENAL_DISORD
RCA human renal disorders
RENAL_NPATHY
RCA human nephropathy
RENAL_FTEST
RCA human kidney function tests
RENAL_BLOOD
RCA human blood in urine disorders
RENAL_UROLITH
RCA human urolithiasis
RENAL_BLADDER
RCA human bladder disorders

CardioTox Models

Adverse effects of the heart and cardiovascular system disorders in human. These models are based on FDA data as part of Research Cooperation Agreement (RCA).

HEART_CONDUCT
RCA human cardiac conduction disorders
HEART_CORONARY
RCA human coronary artery disorders
HEART_ECG
RCA human electrocardiogram disorders
HEART_FAIL
RCA human cardiac failure
HEART_MYOCARD
RCA human myocardial disorders
HEART_RATE
RCA human cardiac rate rhythm disorders
HEART_PALPIT
RCA human cardiac palpitations
HEART_ARRHYTHM
RCA human cardiac arrhythmia disorders
HEART_QT
RCA human cardiac QT-prolongation
HEART_TACHY
RCA human tachycardia
HEART_BRADY
RCA human bradycardia
HEART_INFARCT
RCA human myocardial infarction
HEART_TORSADES
RCA human cardiac Torsades de pointes

SkinEye Toxicity Models

Irritation and sensitization potential upon contact with skin or eye. These models can help in managing environmental impact and in cosmetics research.

EYE_IRR
Sensory irritation
EYE_DRAIZE
Eye irritation Draize test, Avon & Carpenter, rabbit
SKIN_ACD
Allergic contact dermatitis, guinea pig and human
SKIN_DRAIZE
Draize skin test, 24h, rabbit
SKIN_LLNA_W
Local lymph node assay (LLNA), mouse, weak sensitizers (EC3 < 100%)
SKIN_LLNA_M
Local lymph node assay (LLNA), mouse, moderate sensitizers (EC3 < 10%)
SKIN_LLNA_X
Local lymph node assay (LLNA), mouse, extreme sensitizers (EC3 < 1%)
SKIN_HAPTEN
Haptenation (DPRA, SH test)
SKIN_HCLAT
Dendritic cell activation at 1mM (CD86,CD54)
SKIN_HCLATX
Dendritic cell activation at 100uM (CD86,CD54)
SKIN_ARE
ARE activation in keratinocytes at 1mM
SKIN_AREX
ARE activation in keratinocytes at 100uM

DevTox Models

Developmental toxicity, general

A44 – A48
Developmental toxicity in human and mammals
A4A
Risk of developmetal toxicity in human
A4B
Developmental toxicants, hamster

Mammalian ReproTox Models

Reproductive sytem disorders and adverse effects. These models are based on FDA data as part of Research Cooperation Agreement (RCA).

RP_AO1
Fertility in males, rodent
RP_AO4
Fertility in males, rat
RP_AO7
Fertility in males, mouse
RP_AP1
Sperm toxicity, mammal
RP_AP4
Sperm toxicity, rat
RP_AP7
Sperm toxicity, mouse
RP_AN1
Fertility in females, rodent
RP_AN5
Fertility in females, rat
RP_AN9
Fertility in females, mouse
RP_AQ1
Newborn behavioral toxicity, rodent
RP_AQ4
Newborn behavioral toxicity, rat
RP_AQ9
Newborn behavioral toxicity, mouse

Fetal Dysmorphogenesis Models

Developmental anomalies in fetal morphogenesis. These models are based on FDA data as part of Research Cooperation Agreement (RCA).

DT_AL1
Fetal dysmorphogenesis, rodent
DT_AL4
Fetal dysmorphogenesis, rat
DT_AL7
Fetal dysmorphogenesis, mouse
DT_AX6
Fetal dysmorphogenesis, rabbit
DT_AM1
Visceral and other soft tissue fetal defects, rodent
DT_AM5
Visceral and other soft tissue fetal defects, rat
DT_AT1
Visceral and other soft tissue fetal defects, mouse

Fetal Development Models

Anomalies in fetal development. These models are based on FDA data as part of Research Cooperation Agreement (RCA).

FD_AH1
Fetal development fetal growth retardation, rodent
FD_AH4
Fetal development fetal growth retardation, rat
FD_AH7
Fetal development fetal growth retardation, mouse
FD_AX1
Fetal development fetal growth retardation, rabbit
FD_AI1
Fetal development fetal weight decrease, rodent
FD_AI4
Fetal development fetal weight decrease, rat
FD_AI7
Fetal development fetal weight decrease, mouse
FD_AW1
Fetal development fetal weight decrease, rabbit

Fetal Survival Models

Developmental toxicity affecting fetal survival. These models are based on FDA data as part of Research Cooperation Agreement (RCA).

FS_AR1
Fetal survival fetal death, rodent
FS_AR4
Fetal survival fetal death, rat
FS_AR5
Fetal survival fetal death, mouse
FS_AR6
Fetal survival fetal death, rabbit
FS_AG1
Fetal survival post-implantation, rodent
FS_AG4
Fetal survival post-implantation, rat
FS_AG7
Fetal survival post-implantation, mouse
FS_AV1
Fetal survival post-implantation, rabbit
FS_AJ1
Fetal survival pre-implantation, rodent
FS_AJ4
Fetal survival pre-implantation, rat
FS_AJ8
Fetal survival pre-implantation, mouse
FS_AU3
Fetal survival pre-implantation, rabbit

Teratogenicity Models

Teratogenicity in rabbits, rats, mice and mammals. Data source is Teratogen Information System (TERIS).

A50
Teratogenicity, rabbit
A51
Teratogenicity, rat
A52
Teratogenicity, mouse
A53
Teratogenicity, mammal

AcuteTox Models

Acute toxicity endpoints. Models denoted as RCA are based on FDA data as part of Research Cooperation Agreement (RCA).

LD50**
Rat acute toxicity, LD50, from NTP, WHO, RTECS and other data sources
MTD_RAT, MTD_MOUSE
Maximum tolerated dose, rat and mouse, NTP data source
HIMTD_**
RCA maximum tolerated dose > 500mg/kg, rat and mouse, by gender
LOMTD_**
RCA maximum tolerated dose < 50mg/kg, rat and mouse, by gender

EcoTox Models

Endpoints related to ecotoxicity and environmental hazard.

BCF_RK
Bioconcentration factor for Red Killifish (CITI)
BCF_CC
Bioconcentration factor for Common Carp CITI)
DSLUG
Biodegradability in sludge
DBOD5
Biodegradability (biological oxygen demand after 5 days)
DMITI
Ready biodegradation (MITI)
TX_EB
Toxicity to environmental bacteria (MICROTOX EPA)
TX_PB
Toxicity to photobacteria, 15min
TX_BG
Toxicity to fish, Blue Gill
TX_GU
Toxicity to fish, 14 days, Guppy
TX_FM
Toxicity to fish, 96h, Minnow
TX_RT
Toxicity to fish, 48h, Rainbow Trout
TX_RK
Toxicity to fish, 48h, Red Killifish
TX_GF
Toxicity to fish, in vitro, Goldfish cells

Therapeutic Models

Endpoints related to drug development and drug side-effects.

MDR1_INH
Multi-drug resistance reversal (P-gp inhibition)
AA6
Antitumor activity, 9-anilinoacridines
AAC
Antimalarial activity againt P. falciparum
AAD
Anti-HIV activity, NCI data source
AA8
Anticancer activity, NCI data source
AAF
Tubulin polymerization ihibition
AAH
Estrogen disruption

ADME models

Pharmacokinetic and pharmacological endpoints (Absorption, Metabolism, Distribution, Excretion).

ADME_OB, OB_HI
Human oral bioavailability, %F
ADME_PPB
Human plasma protein binding, %bound
ADME_URINE
Human urinary excretion, %
ADME_METAB
Extent of human metabolism, %
ADME_VD
Human volume of distribution, L/kg

ADME transporter models

Interactions with membrane transport proteins.  Transporters modulate permeability of chemicals and can mediate drug-drug and drug-food interactions, as well as drug side-effects.

ASBT, ASBT_INH
Apical sodium-dependent bile acid transporter (IBAT, SLC10A2)
BCRP, BCRP_INH
Breast cancer resistance protein (ABCG2)
BSEP, BSEP_INH
Bile salt export pump (ABCB11)
MCT1, MCT1_INH
Monocarboxylate transporter 1 (SLC16A1)
MDR1, MDR1_INH
Multridrug resistance protein 1 (P-gp, ABCB1)
MRP1 - MRP5
Multridrug resistance-associated proteins 1 - 5 (ABCC1 - ABCC5)
NTCP, NTCP_INH
Na+-taurocholate cotransporting polypeptide (LBAT, SLC10A1)
OATP2B1, OATP2B1_INH
Organic anion transporting polypeptide 2B1 (OATP-B, SLCO2B1, SLC21A9)
OCT1, OCT1_INH
Organic cation transporter 1 (SLC22A1)
PEPT1, PEPT1_INH
Peptide tarnsporter 1 (SLC15A1)