Poor Preservative NOAEL Data SCCS/CIR Reviewed Sensitization Data

Methylisothiazolinone

Also known as: Caswell No. 572A, EINECS 220-239-6, UNII-229D0E1QFA, MI, MIT

INCI: METHYLISOTHIAZOLINONE

Methylisothiazolinone (CAS 2682-20-4) is a cosmetic preservative functioning as preservative. NOAEL 19 mg/kg bw/day (cross-referenced against ToxValDB ECHA IUCLID); EU Regulation 1223/2009 status: restricted, max 0.0015% in rinse-off cosmetics only; banned in all leave-on cosmetics; 5 safety opinions reviewed (cir). Industrial safety data is also available in the chemical safety database. Same-CAS public records also appear in industrial chemical safety and pharmaceutical data.

View industrial chemical safety profile for CAS 2682-20-4 →

Auto-generated CPSR Part A draft with source citations
CAS Number
2682-20-4
View industrial chemical safety profile →
Function
preservative
Safety Rating
POOR

Chemistry & Identifiers

EC Number
220-239-6
ChEBI: CHEBI:53620 UNII: 229D0E1QFA Wikidata: Q423870

Regulatory Status

EU EU Status restricted
EU Max Conc. 0.0015% in rinse-off cosmetics only; banned in all leave-on cosmetics
US US Status permitted
US Notes Still permitted in leave-on products in the US, Canada, and Australia — no federal ban. Sensitization rate 6–12% in clinical dermatitis populations. Industry self-restriction strongly recommended for all leave-on products globally. Decline in usage has produced measurable population-level reduction in sensitization rates in EU-compliant markets.

For full compliance data across multiple jurisdictions, use the Substance Compliance tool.

Safety Data

Margin of Safety, dermal absorption, and sensitization profile summaries for Methylisothiazolinone.

Calculate MoS for your specific formulation with the MoS Calculator.

Toxicological Studies

10 study endpoints found for Methylisothiazolinone. NOAEL (No Observed Adverse Effect Level) values are used to calculate the Margin of Safety per SCCS methodology.

Endpoint Value Route Species Study Type Source
NOAEL =10 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex
NOAEL =10 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex
NOAEL =10 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex
NOAEL =10 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex
NOAEL =28.6 mg/kg bw/d - - NOAEL study CIR_vision_codex
NOAEL =28.6 mg/kg bw/d - - NOAEL study CIR_vision_codex
NOAEL =28.6 mg/kg bw/d - - NOAEL study CIR_vision_codex
NOAEL =28.6 mg/kg bw/d - - NOAEL study CIR_vision_codex
NOAEL =30 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex
NOAEL =30 mg/kg/d oral rat repeated dose toxicity CIR_vision_codex

Safety Opinions

Official safety assessments from the Scientific Committee on Consumer Safety (SCCS) and Cosmetic Ingredient Review (CIR).

cir
Verdict: unknown
NOAEL: 1500 ppm (oral)
cir
Verdict: unknown
NOAEL: 30 mg/kg/d (oral)
cir
Verdict: unknown
NOAEL: 28.6 mg/kg bw/d (not specified)
cir
Verdict: unknown
NOAEL: 30.09 mg/kg bw/d (oral)
cir
Verdict: unknown
NOAEL: 10 mg/kg/d (oral)

Pre-Calculated Safety Assessment

Pre-calculated NOAEL → SED → MoS audit trail for Methylisothiazolinone across SCCS product categories, with measured dermal absorption where available.

Sensitization Profile

Contact sensitization data for Methylisothiazolinone based on clinical patch test studies and IFRA standards.

Sensitization Rate
very-high
Allergen Class
preservative
EU Allergen Listed
no
Patch Test Positive Rate
11.5%
Cross-reactivity Group
isothiazolinone-group
Reaction Type
contact-dermatitis

Source: NACDG 2021-22; ESSCA 2019/20

EPA ToxValDB — Toxicity Values

10 toxicity values from EPA ToxValDB (aggregated from CCTE, HPV, ToxRefDB, IRIS, and other regulatory dossiers).

Endpoint Value Species Route Duration Source
LC50 =110 mg/m3 Rat inhalation - ECHA IUCLID
LC50 =130 mg/m3 Rat inhalation - ECHA IUCLID
LC50 =100 mg/m3 Rat inhalation - ECHA IUCLID
LC50 =384 mg/m3 Rat inhalation - ECHA IUCLID
LC50 =422 mg/m3 Rat inhalation - ECHA IUCLID
LC50 =354 mg/m3 Rat inhalation - ECHA IUCLID
LD50 >2000 mg/kg Rat dermal acute ECHA IUCLID
LD50 =242 mg/kg Rat dermal acute ECHA IUCLID
LD50 =285.5 mg/kg Rat oral - ECHA IUCLID
LD50 =327.7 mg/kg Rat oral - ECHA IUCLID

EU CLP Annex VI Harmonized Classification

Legally binding harmonized classification per Regulation (EC) No 1272/2008 (CLP) Annex VI.

Signal Word
Danger
Pictograms
Acute ToxicityCorrosiveEnvironmental Hazard
Hazard Class and Category
Acute Tox. 2; Acute Tox. 3; Acute Tox. 3; Skin Corr. 1B; Eye Dam. 1; Skin Sens. 1A; Aquatic Acute 1; Aquatic Chronic 1
Hazard Statements
  • H330 Fatal if inhaled
  • H311 Toxic in contact with skin
  • H301 Toxic if swallowed
  • H314 Causes severe skin burns and eye damage
  • H318 Causes serious eye damage
  • H317 May cause an allergic skin reaction
  • H400 Very toxic to aquatic life
  • H410 Very toxic to aquatic life with long lasting effects
Specific Concentration Limits / M-factors
Skin Sens. 1A; H317: C ≥ 0.0015%; M = 10; M = 1

Inserted via ATP: ATP13

Sensitization AOP Dashboard

Adverse Outcome Pathway data across 5 assays (DPRA, KeratinoSens, hCLAT, LLNA, NESIL) aggregated from public sources.

DPRA Cys %
98.95%
DPRA Lys %
-2.25%
KeratinoSens IC50
138.98 µM
hCLAT CV75
24.7 µg/mL
LLNA EC3
1.3%
NESIL
325 µg/cm²
LLNA: Strong (1A) GHS: 1A

Source: LLNA: Basketter et al (2001); DPRA: Gerberick et al. 2007 [DOI:10.1093/toxsci/kfm064] | Nukada et al. 2013 [DOI:10.1016/j.tiv.2012.11.006]; KS: Natsch et al. 2013 [DOI:10.1002/jat.2868]; hCLAT: Ashikaga et al. 2010 [DOI:10.1177/026119291003800403]

HRIPT Human Patch Test Studies

5 human repeat insult patch tests aggregated from dermatological literature.

Test Type N Sensitized Dose µg/cm² NESIL µg/cm² Potency
HRIPT 97 0 100 100 -
Clinical / epidemiol - 0 - - strong
HRIPT - 0 100 100 strong
HRIPT - 0 - - -
HRIPT - 0 10 - -

Endocrine Disruptor Evidence (Expanded)

Cross-referenced EDC classifications, mechanism data, and dose-response evidence from EDLists, SIN List, and cosmetic-specific detail sources.

Cosmetic-Specific Mechanism
Category: preservative
Receptor targets: ERα (indirect)
LOEC: N/A
EU status: banned in leave-on; restricted in rinse-off (max 0.0015%)

indirect modulator (immune/dermal)

Dose-Response Data Points
Endpoint Target Value Direction
Thyroid hormone levels (T3/T4 ↓); tshβ upregulation Thyroid axis (TR / TSH feedback) EC50/IC50: LOEC = 30 µg/L (zebrafish whole-body T3/T4 decrease); LOEC: 30 µg/L (zebrafish); NOEC: not established mixed thyroid disruptor
AR and ER receptor activity screening AR / ERα EC50/IC50: No significant ER/AR activity below cytotoxic threshold (~1 µM in many cell lines); LOEC: not established; NOEC: N/A mixed not active in standard ER/AR screens at sub-cytotoxic concentrations
AhR transactivation AhR EC50/IC50: No AhR activity reported at sub-cytotoxic concentrations; LOEC: not established; NOEC: N/A mixed not active in standard AhR assays below cytotoxic threshold
E2 and T production in H295R cells Steroidogenesis EC50/IC50: LOEC ≈ 0.1 µM for E2 increase (H295R, 48 h; preliminary); LOEC: ~0.1 µM; NOEC: not established mixed active (E2 production ↑ at 0.1 µM LOEC in some studies)

ECHA REACH Registration

European Chemicals Agency REACH dossier and Substances of Very High Concern listing.

Registration Type
Full
Tonnage Band
10 - 100 tonnes
Substance Type
SUBSTANCE
SVHC Candidate
No
Hazard classification: Restricted (Annex XVII)

EU CosIng Annex Listing

European Commission CosIng database Annex references per Regulation (EC) No 1223/2009.

Annex V — Permitted Preservatives
Max: 0,0015 % Rinse-off products

Expanded Jurisdictional Detail

Additional regulatory detail beyond the 7-jurisdiction summary: Saudi SFDA, Korea MFDS, ASEAN ACD, Japan/Korea, Brazil/India, and cross-jurisdictional restriction entries.

KR Korea MFDS Annex 2 (Restricted)
Category: Preservative. Max: 0.0015% (rinse-off only). Leave-on prohibited; no mixing with MCI/MI blend
SA Saudi SFDA (V - Preservatives)
Max: 0,0015 % Rinse-off products.
JPKR Japan/Korea Cosmetics
Japan (Positive (Preservative)): max 0.01
Japan (Restricted): max Wash-away: 0.01% | Leave-on: 0.01% | Mucosa: Prohibited
Korea (Restricted): max 0.01%
BRIN Brazil/India Cosmetics
Brazil: Permitted Preservative · max 0,0015% em produtos que se enxáguem.
India: Permitted Preservative · max 0,0015 % Rinse-off products
Additional Jurisdictional Restrictions (9)
Jurisdiction Status Max % Product Type
JP restricted Wash-away: 0.01% | Leave-on: 0.01% | Mucosa: Prohibited Wash-away: 0.01% | Leave-on: 0.01% | Mucosa: Prohibited
CN permitted_preservative 0.0015 Rinse-off products only
IN permitted_preservative 0.01 rinse-off products (per IS 4707 2017)
AU restricted 0.0015 rinse-off products
AU restricted 0.01 rinse-off (historical)
GCC restricted 0.0015 Rinse-off products only
SA banned - Leave-on products
BR permitted_preservative 0.0015 Rinse-off products only; prohibited in leave-on products; cannot be combined with MCI/MI mixture in same product

Typical Use Concentrations

Reported concentration ranges per product category from SCCS/CIR/industry sources.

Product Category Typical Range Max Reported Source
Shampoo 0.0015 0.01 CIR (2014 amended, cited PCPC 2014)

Additional Ingredient Properties

7 property records from structured ingredient metadata.

allergen_detail
{"eu_allergen_listed": "no", "allergen_class": "preservative", "cross_reactivity_group": "isothiazolinone-group", "patch_test_frequency_pct": "11.5", "sensitization_rate": "very-high", "common_reaction_type": "contact-dermatitis", "ifra_restricted": "no", "source": "NACDG 2021-22; ESSCA 2019/20"}
baby_pediatric
{"cas_number": "2682-20-4", "ingredient_class": "preservative_baby_safe", "pediatric_safety_rating": "avoid", "minimum_age_months": "0", "neonatal_safe": "no", "premature_infant_safe": "no", "skin_barrier_maturity_consideration": "BANNED: EU leave-on ban 2017; potent sensitizer; allergic dermatitis epidemic", "transepidermal_absorption_risk_pediatric": "high", "systemic_exposure_concern_pediatric"…
comedogenicity_detail
{"comedogenicity_rating": "0", "irritancy_rating": "4", "acne_safe": "caution", "source": "Strong sensitizer"}
concentration
{"min_concentration_pct": "0.01", "max_concentration_pct": "0.01", "typical_concentration_pct": "0.01", "product_type": "Rinse-off Product", "function_at_concentration": "Preservative", "source": "EU Annex V (rinse-off only)"}
deodorant
{"cas_number": "2682-20-4", "ingredient_class": "antimicrobial_deodorant", "mechanism_of_action": "bacterial_growth_inhibition", "antiperspirant_efficacy_sweat_reduction_pct": "0", "deodorant_efficacy_hours": "24", "odor_reduction_pct": "60-80", "bacteriostatic": "yes", "bactericidal": "yes", "target_bacteria": "broad_spectrum", "microbiome_impact": "broad", "axillary_microbiome_effect": "varies b…
self_tanning
{"cas_number": "2682-20-4", "ingredient_class": "other", "tanning_mechanism": "other", "color_development_onset_hours": "0.0", "full_color_development_hours": "0", "color_duration_days": "0", "DHA_concentration_if_applicable_pct": "0", "erythrulose_concentration_pct": "0", "pH_dependent_color": "no", "formaldehyde_release_concern": "no", "formaldehyde_release_ppm": "0", "AGE_formation_concern": "n…
uv_stability
{"uv_stable": "yes", "uv_degradation_rate": "stable", "photosensitizer": "no", "phototoxic": "no", "photoallergic": "no", "requires_uv_protection_packaging": "no", "color_change_uv": "no", "odor_change_uv": "no", "efficacy_loss_uv_pct": "0", "spf_contribution": "no", "uva_protection": "no", "uvb_protection": "no", "photostable_sunscreen": "no", "boost_spf_of_others": "no", "antioxidant_under_uv": …

Function Categories & List Membership

Cosmetic/Chemical Function Categories
Antioxidant Biocide Fragrance Preservative Processing aids not otherwise specified
Regulatory List Membership (6)
EU Regulated in Personal Care EU Restricted for Children (Cosmetics) IFRA Fragrance Transparency List EPA Safer Chemical Ingredients List (SCIL) FDA Indirect Food Contact Additives EU CosIng Cosmetics Ingredient Database

Expert Verdict

Expert safety assessment and concern-level summary for Methylisothiazolinone.

Regulatory Flags

preservative eu-banned-leave-on contact-allergen high-sensitization potent-sensitizer rinse-off-only-eu 6-12pct-sensitization-rate pandemic-allergen avoid-leave-on us-permitted-leave-on endocrine_disruptor eu_children_restricted epa_safer_alternative ifra_fragrance eu_cosing_listed

NOAEL Studies Summary

View details ->

Public NOAEL study rows linked to Methylisothiazolinone by CAS number or substance name.

Studies
34
Lowest NOAEL
10
Highest NOAEL
49.8

Units vary across source rows: mg/kg bw/day, mg/kg bw/d, mg/kg/d

ToxValDB_ECHA_IUCLID CIR_vision_codex SCCNFP_vision_codex

Known Synonyms

Caswell No. 572A EINECS 220-239-6 UNII-229D0E1QFA MI MIT

Chemical Function

Preservative Antioxidant

Regulatory Lists

active_ingredient; Europe; Pesticides Arts and crafts/Office supplies - general arts and crafts supplies - arts and crafts paint; Europe Arts and crafts/Office supplies - general arts and crafts supplies - arts and crafts paint; Europe active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides active_ingredient; Pesticides

Australian Status

AICIS status: listed

Cross-Vertical Safety Context

Same-CAS public records found in pharmaceutical data.

SOURCE ChEMBL / DrugCentral / FAERS DB_PHARMA CAS match

Pharmaceutical Data

Same-CAS rows from the pharmaceutical spoke database.

ChEMBL ID
CHEMBL1620780
View full pharmaceutical profile →

Frequently Asked Questions

Is Methylisothiazolinone safe in cosmetics?

Methylisothiazolinone has a safety rating of "POOR" in our database. EU status: restricted. US status: permitted. 10 toxicological study endpoint(s) are available in our database. This ingredient has been reviewed by cir.

Is Methylisothiazolinone allowed in the EU?

Methylisothiazolinone EU regulatory status: restricted. Maximum allowed concentration: 0.0015% in rinse-off cosmetics only; banned in all leave-on cosmetics. This is based on EU Regulation 1223/2009 and its amendments.

What does Methylisothiazolinone do in cosmetics?

Methylisothiazolinone functions as: preservative. It is classified as a Preservative in our database. CAS number: 2682-20-4.

What is the NOAEL for Methylisothiazolinone?

The NOAEL (No Observed Adverse Effect Level) for Methylisothiazolinone is =10 mg/kg/d based on a repeated dose toxicity study via oral route in rat. A total of 10 study endpoints are available. Source: CIR_vision_codex.

Is Methylisothiazolinone used outside cosmetics?

Methylisothiazolinone also appears in industrial chemical safety and pharmaceutical data. The cross-vertical cards on this page render same-CAS public rows from the matched databases.

Does Methylisothiazolinone have different safety status in cosmetics vs industrial chemicals?

Methylisothiazolinone is classified GHS Danger (H301, H311, H302, H314, H317, H318, H330, H331) in the chemicals database but is restricted in EU cosmetics at max 0.0015% in rinse-off cosmetics only; banned in all leave-on cosmetics.

Compliance Tools

Check Methylisothiazolinone compliance across multiple jurisdictions:

Ingredient Decoder
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82 Allergen Checker
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Substance Compliance
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MoS Calculator
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Heavy Metal Limits
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