Chemical Safety & Toxicology Assessment

Comprehensive chemical safety analysis integrating predictive AI models, curated toxicogenomics databases, regulatory safety data, and chemical-biological interaction networks.

When to Use This Skill

Triggers

:

"Is this chemical toxic?" / "Assess the safety profile of [drug/chemical]"

"What are the ADMET properties of [SMILES]?"

"What genes does [chemical] interact with?" / "What diseases are linked to [chemical] exposure?"

"Drug safety assessment" / "Environmental health risk" / "Chemical hazard profiling"

Use Cases

:

Predictive Toxicology

AI-predicted endpoints (AMES, DILI, LD50, carcinogenicity, hERG) via SMILES

ADMET Profiling

Absorption, distribution, metabolism, excretion, toxicity

Toxicogenomics

Chemical-gene-disease mapping from CTD

Regulatory Safety

FDA label warnings, contraindications, adverse reactions

Drug Safety

DrugBank safety + FDA labels combined

Chemical-Protein Interactions

STITCH-based interaction networks

Environmental Toxicology

Chemical-disease associations for contaminants

KEY PRINCIPLES

Report-first approach

- Create report file FIRST, then populate progressively

Tool parameter verification

- Verify params via

get_tool_info

before calling unfamiliar tools

Evidence grading

- Grade all safety claims by evidence strength (T1-T4)

Citation requirements

- Every toxicity finding must have inline source attribution

Mandatory completeness

- All sections must exist with data or explicit "No data" notes

Disambiguation first

- Resolve compound identity (name -> SMILES, CID, ChEMBL ID) before analysis

Negative results documented

- "No toxicity signals found" is data; empty sections are failures

Conservative risk assessment

- When evidence is ambiguous, flag as "requires further investigation"

English-first queries

- Always use English chemical/drug names in tool calls

Evidence Grading System (MANDATORY)

Tier

Symbol

Criteria

Examples

T1

[T1]

Direct human evidence, regulatory finding

FDA boxed warning, clinical trial toxicity

T2

[T2]

Animal studies, validated in vitro

Nonclinical toxicology, AMES positive, animal LD50

T3

[T3]

Computational prediction, association data

ADMET-AI prediction, CTD association

T4

[T4]

Database annotation, text-mined

Literature mention, unvalidated database entry

Evidence grades MUST appear in: Executive Summary, Toxicity Predictions, Regulatory Safety, Chemical-Gene Interactions, Risk Assessment.

Core Strategy: 8 Research Phases

Chemical/Drug Query

|

+-- PHASE 0: Compound Disambiguation (ALWAYS FIRST)

| Resolve name -> SMILES, PubChem CID, ChEMBL ID, formula, weight

|

+-- PHASE 1: Predictive Toxicology (ADMET-AI)

| AMES, DILI, ClinTox, carcinogenicity, LD50, hERG, skin reaction

| Stress response pathways, nuclear receptor activity

|

+-- PHASE 2: ADMET Properties

| BBB penetrance, bioavailability, clearance, CYP interactions, physicochemical

|

+-- PHASE 3: Toxicogenomics (CTD)

| Chemical-gene interactions, chemical-disease associations

|

+-- PHASE 4: Regulatory Safety (FDA Labels)

| Boxed warnings, contraindications, adverse reactions, nonclinical tox

|

+-- PHASE 5: Drug Safety Profile (DrugBank)

| Toxicity data, contraindications, drug interactions

|

+-- PHASE 6: Chemical-Protein Interactions (STITCH)

| Direct binding, off-target effects, interaction confidence

|

+-- PHASE 7: Structural Alerts (ChEMBL)

| PAINS, Brenk, Glaxo structural alerts

|

+-- SYNTHESIS: Integrated Risk Assessment

Risk classification, evidence summary, data gaps, recommendations

See

phase-procedures-detailed.md

for complete tool parameters, decision logic, output templates, and fallback strategies for each phase.

Tool Summary by Phase

Phase 0: Compound Disambiguation

PubChem_get_CID_by_compound_name

(

name

str)

PubChem_get_compound_properties_by_CID

(

cid

int)

ChEMBL_get_molecule

(if ChEMBL ID available)

Phase 1: Predictive Toxicology

ADMETAI_predict_toxicity

(

smiles

list[str]) - AMES, DILI, ClinTox, LD50, hERG, etc.

ADMETAI_predict_stress_response

(

smiles

list[str])

ADMETAI_predict_nuclear_receptor_activity

(

smiles

list[str])

Phase 2: ADMET Properties

ADMETAI_predict_BBB_penetrance

/

_bioavailability

/

_clearance_distribution

/

_CYP_interactions

/

_physicochemical_properties

/

_solubility_lipophilicity_hydration

(all take

smiles

list[str])

Phase 3: Toxicogenomics

CTD_get_chemical_gene_interactions

(

input_terms

str)

CTD_get_chemical_diseases

(

input_terms

str)

Phase 4: Regulatory Safety

FDA_get_boxed_warning_info_by_drug_name

/

contraindications

/

adverse_reactions

/

warnings

/

nonclinical_toxicology

/

carcinogenic_mutagenic_fertility

(all take

drug_name

str)

Phase 5: Drug Safety

drugbank_get_safety_by_drug_name_or_drugbank_id

(

query

,

case_sensitive

,

exact_match

,

limit

- all 4 required)

Phase 6: Chemical-Protein Interactions

STITCH_resolve_identifier

(

identifier

str,

species

9606)

STITCH_get_chemical_protein_interactions

(

identifiers

list[str],

species

int,

required_score

int)

Phase 7: Structural Alerts

ChEMBL_search_compound_structural_alerts

(

molecule_chembl_id

str) Risk Classification Matrix Risk Level Criteria CRITICAL FDA boxed warning OR multiple [T1] toxicity findings OR active DILI + active hERG HIGH FDA warnings OR [T2] animal toxicity OR multiple active ADMET endpoints MEDIUM Some [T3] predictions positive OR CTD disease associations OR structural alerts LOW All ADMET endpoints negative AND no FDA/DrugBank flags AND no CTD concerns INSUFFICIENT DATA Fewer than 3 phases returned data Report Structure

Chemical Safety & Toxicology Report: [Compound Name]

Generated: YYYY-MM-DD | SMILES: [...] | CID: [...]

Executive Summary (risk classification + key findings, all graded)

1. Compound Identity (disambiguation table)

2. Predictive Toxicology (ADMET-AI endpoints)

3. ADMET Profile (absorption, distribution, metabolism, excretion)

4. Toxicogenomics (CTD chemical-gene-disease)

5. Regulatory Safety (FDA label data)

6. Drug Safety Profile (DrugBank)

7. Chemical-Protein Interactions (STITCH network)

8. Structural Alerts (ChEMBL)

9. Integrated Risk Assessment (classification, evidence summary, gaps, recommendations)

Appendix: Methods and Data Sources

See

report-templates.md

for full section templates with example tables.

Mandatory Completeness Checklist

Phase 0: Compound disambiguated (SMILES + CID minimum)

Phase 1: At least 5 toxicity endpoints or "prediction unavailable"

Phase 2: ADMET A/D/M/E sections or "not available"

Phase 3: CTD queried; results or "no data in CTD"

Phase 4: FDA labels queried; results or "not FDA-approved"

Phase 5: DrugBank queried; results or "not found"

Phase 6: STITCH queried; results or "no data available"

Phase 7: Structural alerts checked or "ChEMBL ID not available"

Synthesis: Risk classification with evidence summary

Evidence Grading: All findings have [T1]-[T4] annotations

Data Gaps: Explicitly listed

Common Use Patterns

Novel Compound

SMILES -> Phase 0 (resolve) -> Phase 1 (toxicity) -> Phase 2 (ADMET) -> Phase 7 (structural alerts) -> Synthesis

Approved Drug Review

Drug name -> All phases (0-7) -> Complete safety dossier

Environmental Chemical

Chemical name -> Phase 0 -> Phase 1-2 -> Phase 3 (CTD, key) -> Phase 6 (STITCH) -> Synthesis

Batch Screening

Multiple SMILES -> Phase 0 -> Phase 1-2 (batch) -> Comparative table -> Synthesis

Toxicogenomic Deep-Dive

Chemical + gene/disease interest -> Phase 0 -> Phase 3 (expanded CTD) -> Literature -> Synthesis

Limitations

ADMET-AI

Computational [T3]; should not replace experimental testing

CTD

May lag behind latest literature by 6-12 months

FDA

Only covers FDA-approved drugs; not applicable to environmental chemicals

DrugBank

Primarily drugs; limited industrial chemical coverage

STITCH

Lower score thresholds increase false positives

ChEMBL

Structural alerts require ChEMBL ID; not all compounds have one

Novel compounds

May only have ADMET-AI predictions (no database evidence)

SMILES validity

Invalid SMILES cause ADMET-AI failures

Reference Files

phase-procedures-detailed.md

- Complete tool parameters, decision logic, output templates, fallback strategies per phase

evidence-grading.md

- Evidence grading details and examples

report-templates.md

- Full report section templates with example tables

phase-details.md

- Additional phase context

test_skill.py

- Test suite

Summary

Total tools integrated

25+ tools across 6 databases (ADMET-AI, CTD, FDA, DrugBank, STITCH, ChEMBL)

Best for

Drug safety assessment, chemical hazard profiling, environmental toxicology, ADMET characterization, toxicogenomic analysis

Outputs

Structured markdown report with risk classification (Critical/High/Medium/Low), evidence grading [T1-T4], and actionable recommendations