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EC number: 200-317-6 | CAS number: 57-15-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Skin irritation
The performed in-vitro test according to OECD guideline 439 addresses the human health endpoint skin irritation shows that the mean value of relative tissue viability was reduced to 3.8 %. This value is below the threshold for skin irritation potential (50%). Test items that induce values below the threshold of 50% are considered at least irritant to skin.
One in vivo supporting study on rabbits concluded that Chlorobutanol is a mild skin irritant, therefore the substance is classified as skin irritatant Cat. 2.
Eye irritation:
In the performed in vitro test according to the OECD Guideline 492, the EpiOcularTMEye Irritation Test, the mean value of relative tissue viability was 1.6 %. This value is well below the threshold for eye irritation potential (≤ 60%). Test items that induce values below the threshold are considered either eye irritant or inducing serious eye damage. In vivo supporting studies on rabbits concluded that Chlorobutanol is a mild eye irritant, therefore the substance is classified as eye irritant Cat. 2.
This classification is also supported by the use in eye drops, usually in 0.5% concentrations, whithout producing clinically significant ocular disturbance even though applied serveral time per day for several years.
However, certain precautions in use of Chlorobutanol in eyedrops are necessary. Hydrolysis destroys Chlorobutanol in alkaline solution. It is usually employed in solutions of pH 5 or lower, which is stable for at least many months. If unbuffered solutions are autoclaved, or allowed to stand at room temperature for several years, the pH may drop as low as 2.4. Furthermore, although fresh solutions containing 0.5% Chlorobutanol are quite satisfactory and innoculous for the brief applications involved in the ordinary use of eyedrops, they appear to be unsuited for prolonged bathing of the outer surface of the cornea.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not specified
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- review data, access to original study not available
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- not specified
- Type of coverage:
- not specified
- Preparation of test site:
- not specified
- Vehicle:
- not specified
- Controls:
- not specified
- Irritation parameter:
- other: MLD
- Basis:
- other: not specified
- Time point:
- other: not specified
- Reversibility:
- not specified
- Remarks on result:
- probability of mild irritation
- Remarks:
- probability of mild irritation
- Irritant / corrosive response data:
- skn-rbt 850 µg MLD
- Interpretation of results:
- Category 3 (mild irritant) based on GHS criteria
- Conclusions:
- results of a skin irritation test on rabbits available
mild irritation has been observed resulting in a category 3 classification - Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: he EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis
- Details on animal used as source of test system:
- The EpiDermTM tissue consists of human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers representing main lipid classes analogous to those found in vivo. The EpiDermTM tissues are cultured on specially prepared cell culture inserts.
- Vehicle:
- unchanged (no vehicle)
- Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- Tissue Amount
1 25.8 mg
2 25.5 mg
3 24.7 mg - Duration of treatment / exposure:
- 1 hour
- Duration of post-treatment incubation (if applicable):
- 23 hours 25 minutes
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Mean
- Value:
- 3.8
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- The test item Chlorobutanol Hemihydrate is considered as at least irritant to skin.
After the treatment, the mean value of relative tissue viability was reduced to 3.8%. This value is below the threshold for skin irritation (50%).
The optical density of the negative control was well within the required acceptability criterion of 0.8 ≤ mean OD ≤ 2.8.
The positive control has met the acceptance criterion too, for thus ensuring the validity of the test system.
Variation within replicates was within the accepted range for negative control, positive control and test item (required: ≤ 18%).
For these reasons, the result of the test is considered valid. - Executive summary:
One valid experiment was performed.
Three tissues of the human skin model EpiDermTMwere treated with Chlorobutanol Hemihydrate for 60 minutes.
The test item was applied directly to each tissue and spread to match the tissue size (0.63 cm2; as indicated by the supplier).
DPBS-buffer was used as negative control and 5% SDS solution was used as positive control.
After treatment with the negative control, the mean absorbance value was within the required acceptability criterion of 0.8 ≤ mean OD ≤ 2.8, OD was 1.2. The positive control showed clear irritating effects. The mean value of relative tissue viability was reduced to 4.1 % (required:<20%).
The variation within the tissue replicates of negative control, positive control and test item was acceptable (required: ≤ 18%).
After the treatment with the test item, the mean value of relative tissue viability was reduced to 3.8 %. This value is below the threshold for skin irritation potential (50%). Test items that induce values below the threshold of 50% are considered at least irritant to skin.
The OECD guideline 439 addresses the human health endpoint skin irritation and does not allow discrimination between skin irritation (category 2) and skin corrosion (category 1). For these purposes, further testing with other suitable test methods is required.
Therefore, Chlorobutanol Hemihydrate is considered at least irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.
Referenceopen allclose all
Designation |
Chlorobutanol Hemihydrate |
Positive Control |
% Tissue viability (tissue 1) |
4.1% |
3.9% |
% Tissue viability (tissue 2) |
3.7% |
4.3% |
% Tissue viability (tissue 3) |
3.6% |
4.3% |
% Tissue viability (mean) |
3.8% |
4.1% |
± SD of mean tissue viability (%) |
0.3% |
0.2% |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- human
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- Replicate Amount
Tissue 1 50.2 mg
Tissue 2 51.0 mg - Duration of treatment / exposure:
- 6 hours
- Duration of post- treatment incubation (in vitro):
- 18 hours
- Number of animals or in vitro replicates:
- 2
- Irritation parameter:
- in vitro irritation score
- Remarks:
- % Viability Mean
- Run / experiment:
- Mean
- Value:
- 1.6
- Vehicle controls validity:
- not examined
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- Criterion Demanded Found
Mean OD of negative control > 0.8 and < 2.5 1.7
% mean relative viability of positive control < 50% of negative control 40.0%
Variation within replicates < 20% 0.1% (negative control)
4.1% (positive control)
0.1% (test item) - Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- Under the conditions of the test, Chlorobutanol Hemihydrate is considered either eye irritant or inducing serious eye damage in the EpiOcularTM Eye Irritation Test.
After treatment with the test item, the mean value of relative tissue viability was reduced to 1.6 %. This value is well below the threshold for eye irritation potential (≤ 60%).
All validity criteria were met. The criterion for optical density of the negative control was fulfilled: The OD value was 1.7 (> 0.8 and < 2.5).
The positive control induced a decrease in tissue viability as compared to the negative control to 40.0 %. Variation within the replicates was acceptable (< 20%).
For these reasons, the result of the test is considered valid. - Executive summary:
One valid experiment was performed.
The test item Chlorobutanol Hemihydrate was applied to a three-dimensional human cornea tissue model in duplicate for an exposure time of 6 hours.
After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution.
Demineralised water was used as negative control and methyl acetate was used as positive control.
The controls showed the following results: After treatment with the negative control, the absorbance values were within the required acceptability criterion of mean OD>0.8 and < 2.5, OD was 1.7. The positive control showed clear eye irritating effects, the mean value of the relative tissue viability was 40.0 % (< 50%).
Variation within tissue replicates was acceptable (< 20%).
After treatment with the test item, the mean value of relative tissue viability was 1.6 %.
This value is well below the threshold for eye irritation potential (≤ 60%). Test items that induce values below the threshold are considered either eye irritant or inducing serious eye damage.
According to the OECD Guideline 492, the EpiOcularTMEye Irritation Test does not allow discrimination between eye irritation/reversible effects on the eye (Category 2) and serious eye damage/irreversible effects on the eye (Category 1). For these purposes, further testing with other suitable test methods is required.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- review data, no access to original study report
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- not specified
- Vehicle:
- not specified
- Irritation parameter:
- other: MLD
- Basis:
- other: not specified
- Time point:
- other: 30S
- Reversibility:
- not specified
- Remarks on result:
- probability of mild irritation
- Interpretation of results:
- Category 2B (mildly irritating to eyes) based on GHS criteria
- Conclusions:
- eye-rbt 9180 µg/30S MLD
- Executive summary:
mild eye irritation observed after application of chlorobutanol. No further information available.
supporting studies on humans with ophthalmic preservative result in slight but reversible irritation.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- other: review data
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Chlorobutanol has been widely used as a detergent preservative in ophthalmic preservatives. observation from ophthalmic administration are reported and are considered as supporting
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- review data, no access to original study available
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- not specified
- Vehicle:
- other: aqueous solution containing 1.4% sodium chloride
- Controls:
- yes, concurrent vehicle
- Amount / concentration applied:
- 0.4%
- Duration of treatment / exposure:
- several minutes
- Irritation parameter:
- other: visual fogging, haloes around lights, and a foreign body sensation
- Basis:
- other:
- Time point:
- other: several minutes
- Reversibility:
- fully reversible within: 1-2 days
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- Gonioscopy solutions containing 0.4% Chlorobutanol, applied under the contact lens, have been associated with visual fogging, haloes around lights, and a foreign body sensation, which intesifies over several hours and recovers spontaneously in 1 or 2 days
- Other effects:
- Chlorobutanol has been widely employed as a preservative in eye drops, usually in 0.5% concentrations, whithout producing clinically significant ocular disturbance. However, certain precautions in use of Chlorobutanol in eyedrops are necessary. hydrolysis destroys Chlorobutanol in alkaline solution. It is usually employed in solutions of pH 5 or lower, which is stable for at least many months. However, if unbuffered solutions are autoclaved, or allowed to stand at room temperature for several years, the pH may drop as low as 2.4. Furthermore, although fresh solutions containing 0.5% Chlorobutanol are quite satisfactory and innoculous for the brief applications inveolved in the ordinary use of eyedrops, they appear to be unsuited for prolonged bathing of the outer surface of the cornea.
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Chlorobutanol containing solutions applied under contact lens to humans show mild and reversible irritation
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- other: review
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Chlorobutanol has been widely used as a detergent preservative in ophthalmic preservatives. observation from ophthalmic administration are reported and are considered as supporting
- Qualifier:
- no guideline available
- GLP compliance:
- not specified
- Species:
- human
- Strain:
- not specified
- Vehicle:
- other: opthalmic solution cotaining polyvinylalcoghol 1.4%
- Controls:
- yes, concurrent vehicle
- Amount / concentration applied:
- 0.5%
- Duration of treatment / exposure:
- several hours
- Observation period (in vivo):
- several ours
- Irritation parameter:
- other: conjunctival erythema
- Basis:
- other: 9 of 16
- Time point:
- other: not specified
- Reversibility:
- fully reversible
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- It was suggested that the irritation was due to crystallisation of Chlorobutanol, which is close saturation at this concentration
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Ophthalmic administration of Chlorobutanol containing solutions to humans show mild and reversible irritation
Referenceopen allclose all
Designation |
Positive Control |
Chlorobutanol Hemihydrate |
% Viability (Tissue 1) |
37.9% |
1.6% |
% Viability (Tissue 2) |
42.0% |
1.6% |
% Viability Mean |
40.0% |
1.6% |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
Chlorobutanol is considered as skin and eye irritant, since the key in-vitro studies showed the irritant effects on skin and eye and the supporting in vivo studies also showed
that the substance is a mild eye and skin irritant.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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