(Health Hazard)

GHS / CLP FRAMEWORK FOR HEALTH HAZARDS

• GHS (Globally Harmonised System) / CLP (Classification, Labelling & Packaging) divides hazards into three broad classes:

• Physical Hazard

• Health Hazard (focus of this lecture)

• Environmental Hazard

• Hazard pictograms employed for Health Hazards

• Skull & cross-bones (acute, severe toxicity)

• Exclamation mark (moderate toxicity / irritation)

• Health-hazard torso (carcinogen, mutagen, STOT, etc.)

• Corrosion (skin corrosion, serious eye damage)

• Environment pictogram shown for completeness, though environmental endpoints are not covered here.

• Regulations recognise 13 Health-Hazard classes (see detailed sections below).

1. ACUTE TOXICITY (Oral ‑ Dermal ‑ Inhalation)

1.1 Definition

• "Acute toxicity" = adverse effects after a single dose (oral/dermal), multiple doses within $24\ \text{h}$, or a $4\ \text{h}$ inhalation exposure.

1.2 Sub-routes and categories

• Oral, Dermal, Inhalation – each with 5 categories (Cat 1 very toxic → Cat 5 very low toxicity; Cat 5 not adopted in Malaysian CLASS Regs).

1.3 Special terminology

• Dust = solid particles suspended in a gas.
• Mist = liquid droplets suspended in a gas.
• Vapour = gaseous form evolved from liquid/solid.
• Dust & mist particle-size range: <1 \ \mu m to $\approx 100 \ \mu m$.

2. SKIN CORROSION / IRRITATION

2.1 Definitions

• Skin Corrosion = irreversible tissue damage (visible necrosis) within up to $4\ \text{h}$ contact; observations up to day 14 (ulcers, scabs, scars, blanching, alopecia).
• Skin Irritation = reversible inflammation within the same exposure window.

2.2 Substance classification

• Cat 1A/1B/1C (corrosive, differing severity)
• Cat 2 (irritant)
• Cat 3* (mild irritant – not in CLASS Regs)

• Additional decision rules:

• “Severe” findings → treat as Cat 1 unless lesions are reversible, then Cat 2.

2.3 Mixture classification

1. Tested mixture – use data directly.

2. Bridging – apply principles if sufficient analogue info.

3. Ingredient method (when full/partial data):

   • (i) Generic conc. limits (additivity)

   • (ii) Generic limits for non-additive ingredients.

2.4 Hazard communication – apply correct signal word, pictogram (corrosion / exclamation), H- & P-statements.

3. SERIOUS EYE DAMAGE / EYE IRRITATION

3.1 Definitions

• Serious eye damage = irreversible ocular effects / loss of vision not fully reversible within $21\ \text{d}$.
• Eye irritation = changes fully reversible within the same period.

3.2 Substance criteria

• Cat 1 (Irreversible)
• Cat 2 (Reversible)

• Cross-reference rule: Any substance classified Skin Corrosion Cat 1 is automatically Serious Eye Damage Cat 1.

3.3 Mixture approach

Same 3-step hierarchy as for skin corrosion (tested mixture ➔ bridging ➔ ingredient limits).

4. RESPIRATORY SENSITISATION

4.1 Definition

• A respiratory sensitiser causes airway hypersensitivity after inhalation exposure.

4.2 Substance classification

• Single category (Cat 1).

4.3 Mixture rules

• Mixture is a respiratory sensitiser if ≥ 1 ingredient is classified Cat 1 and is present ≥ generic conc. limit (see GHS table).

5. SKIN SENSITISATION

5.1 Definition

• A skin sensitiser elicits an allergic response after dermal contact.

5.2 Classification principles (substances & mixtures)

• Single category (Cat 1).
• Mixture rule mirrors respiratory: classify when ≥ 1 sensitising ingredient at/above limit.

6. GERM CELL MUTAGENICITY

6.1 Definitions

• Mutation = permanent alteration of genetic material.
• Mutagenic agent ➔ ↑ mutation frequency.
• Genotoxicity = broader term including DNA damage, replication errors, chromosomal effects.

6.2 Substance categories

• Cat 1A (known human)
• Cat 1B (presumed human)
• Cat 2 (suspected).

6.3 Mixture criteria

• Classify if ≥ 1 ingredient in Cat 1A/1B/2 at or above limits in Table 2.45 (ICOP p196).

7. CARCINOGENICITY

7.1 Definition

• Carcinogen = substance/mixture inducing cancer or increasing incidence.
• Animal studies (benign & malignant tumours) generally presume human relevance unless mechanism non-relevant.

7.2 Categories & mixture rules

• Cat 1A / 1B / 2 parallels mutagenicity.
• Mixture classified if ≥ 1 carcinogenic ingredient at generic conc. limit (Table 2.48, p202).

8. REPRODUCTIVE TOXICITY

8.1 Definition

• Covers adverse effects on sexual function, fertility, and developmental toxicity in offspring; includes effects on/ via lactation.

8.2 Categories

• Cat 1A / 1B / 2
• Additional “Effects on or via lactation”.

8.3 Mixture rule

• Classify if ≥ 1 ingredient Cat 1A/1B/2 at limit values in Table 2.52 (ICOP p209).

9. SPECIFIC TARGET ORGAN TOXICITY (STOT)

9.1 STOT – Single Exposure (SE)

• Non-lethal, specific organ toxicity after one exposure; may be reversible/irreversible, immediate/delayed.
• Excludes effects already covered under Acute toxicity, Corrosion/Irritation, Sensitisation, etc.

9.2 STOT – Repeated Exposure (RE)

• Analogous definition but for repeated or continuous exposures.

9.3 Categories

• Cat 1 (serious)
• Cat 2 (less severe)
• Cat 3 (transient respiratory irritation or narcotic effects – only for SE).

9.4 Mixture classification (SE & RE)

• If bridging cannot be applied, classify when ≥ 1 ingredient Cat 1 or Cat 2 ≥ generic limits (Table 2.56, p219).
• Mixtures to be assessed independently for SE & RE.

10. ASPIRATION HAZARD

10.1 Definition

• Aspiration = entry of liquid/solid into trachea/lungs via mouth/nose or subsequent vomiting, causing chemical pneumonia or fatal injury.

10.2 Substance category

• Cat 1 (only category adopted).

10.3 Mixture rules

• Single-phase mixture → Cat 1 when:

• ≥ $10\%$ Cat 1 ingredient(s) and

• Kinematic viscosity $\le 20.5\ \text{mm}^2\,\text{s}^{-1}$ at $40^{\circ}\text{C}$.
  • Phase-separating mixture → Cat 1 if any layer meets above condition.