Registration Dossier

Administrative data

Description of key information

Skin irritation:

Chloral hydrate induced moderate erythma at two induction concentrations of 1 and 5% in primary Irritation study.. GHS classification of the substance also indicates the substance to be irritating to skin and hence is classified as Skin irritant 2.

Eye irritation:

Moderate doses of chloral hydrate affects eye movements, particularly interfering with convergence, and sometimes causing ptosis. It may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing. GHS classification of the substance also indicates the substance to be irritating to eye and hence classified as Eye irritant 2.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from peer reviewed publication.
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Primary Irritation Study had been performed as part of Guniea Pig Maximixation Test (GPMT) for evaluating contact allergenic activity of Chloral hydrate in Albino guinea pigs.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2,2,2-Trichloroethane-1,1-diol (Chloral hydrate)
- Molecular formula: C2-H3-Cl3-O2
- Molecular weight: 165.4026g/mol
- Smiles notation: C(C(O)O)(Cl)(Cl)Cl
- InChl: RNFNDJAIBTYOQL-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid
Species:
guinea pig
Strain:
other: FMMU strain
Details on test animals and environmental conditions:
- Source: Medical laboratory animal center (China).
- Age at study initiation: No data available
- Weight at study initiation: 300-350g
- Housing: Housed in an animal rooms.
- Diet (e.g. ad libitum): Standard guinea pig diet and Fresh vegetable
- Water (e.g. ad libitum): Tap water
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23°C±1.5 °C
- Humidity (%): 55% ±10%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12 h day/night cycle

IN-LIFE DATES: From: To: No data available
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
other: distilled water
Controls:
yes
Amount / concentration applied:
Induction: Intradermal concentration: 1%
Topical concentration: 5%

Challenge topical concentration : 2%
Duration of treatment / exposure:
24 hrs
Observation period:
not specified
Number of animals:
4
Details on study design:
- Area of exposure: back of animals
- % coverage: 4cm x 6 cm
- Type of wrap if used: not specified

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

SCORING SYSTEM: not specified
Irritation parameter:
erythema score
Basis:
animal: induction exposure animals
Time point:
24 h
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Remarks:
moderate erythma
Irritant / corrosive response data:
moderate erythma at two induction concentrations
Other effects:
not specified
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Chloral hydrate induced moderate erythma at two induction concentrations of 1 and 5% in primary Irritation study.
Executive summary:

Primary Irritation Study had been performed as part of Guniea Pig Maximixation Test (GPMT) for evaluating contact allergenic activity of Chloral hydrate in Albino guinea pigs. An area of 4cm x 6 cm on the back of animals were clipped free of hair. 24 h later, the intact animals were selected in the test. The moderate irritant concentration of 1% and 5% for intrademal and topical induction application respectively, and the non-irritant concentration of 2% for challenge were established in guinea pigs. The vehicle used was distilled water. Chloral hydrate was observed to induce moderate erythma at two induction concentrations of 1 and 5% but the challenge topical concentration did not induce any abnormal appearance in primary Irritation study.

Thus on the above result the test substance Chloral hydrate is considered to be moderately irritating to skin and hence can be classified as Skin Irritant 2 as per CLP classification criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from authoritative database
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Chloral hydrate eye irritation data from HSDB database
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 2,2,2-Trichloroethane-1,1-diol (Chloral hydrate)
- Molecular formula: C2-H3-Cl3-O2
- Molecular weight: 165.4026g/mol
- Smiles notation: C(C(O)O)(Cl)(Cl)Cl
- InChl: RNFNDJAIBTYOQL-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid
Species:
other: not specified
Strain:
not specified
Details on test animals or tissues and environmental conditions:
not specified
Vehicle:
not specified
Amount / concentration applied:
not specified
Duration of treatment / exposure:
not specified
Observation period (in vivo):
not specified
Duration of post- treatment incubation (in vitro):
not specified
Number of animals or in vitro replicates:
not specifiednot specified
Details on study design:
not specified
Irritation parameter:
overall irritation score
Remarks on result:
other: Moderate doses affects eye movements, particularly interfering with convergence, and sometimes causing ptosis. It may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing.
Irritant / corrosive response data:
Moderate doses affects eye movements, particularly interfering with convergence, and sometimes causing ptosis. It may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Moderate dose of chloral hydrate is found to irritating to the eye.
Executive summary:

Moderate doses of chloral hydrate affects eye movements, particularly interfering with convergence, and sometimes causing ptosis. It may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing. GHS classification of the substance also indicates the substance to be irritating to eye and hence classified as Eye irritant 2.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Available data for the target substance Chloral hydrate (CAS 302 -17 -0) and data for its read across substances Chloral (CAS 75 -87 -6) and 1,1,1-trichloroethane (CAS 71 -55 -6) were reviewed to classify the target substance for skin irritation. The same is presented below as key and supporting studies:

In key study by Tang et. al. from Biomedical and Environmental Sciences 15, 113-118 (2002), Primary Irritation Study had been performed as part of Guniea Pig Maximixation Test (GPMT) for evaluating contact allergenic activity of Chloral hydrate in Albino guinea pigs. An area of 4cm x 6 cm on the back of animals were clipped free of hair. 24 h later, the intact animals were selected in the test. The moderate irritant concentration of 1% and 5% for intrademal and topical induction application respectively, and the non-irritant concentration of 2% for challenge were established in guinea pigs. The vehicle used was distilled water.Chloral hydrate was observed to induce moderate erythma at two induction concentrations of 1 and 5% but the challenge topical concentration did not induce any abnormal appearance in primary Irritation study.

Thus on the above result the test substance Chloral hydrate is considered to be moderately irritating to skin and hence can be classified as Skin Irritant 2 as per CLP classification criteria.

As per available information from IPCS monograph;2000, the target substance chloral hydrate is irritating to the skin and mucous membranes.

Supporting the above data, the data from IPCS monograph - EHS criteria -136 ;1990 and OECD HPV dossier-2009, indicates skin irritation study of read across substance 1, 1, 1-trichloroethane (CAS No: 71-55-6) was conducted on three rabbits to observe its irritation potential in accordance with OECD Guide-line 404 "Acute Dermal Irritation/Corrosion". In this study,0.5 ml of undilutedthe test chemical was appliedto the clipped and intact trunk skin of three rabbits for 4 hours under semi-occlusive dressing. Dermal responses were evaluated for erythema and edema at 60 minutes and at 24, 48 and 72 hours.

Since the test chemical was able to elicit skin reactions,the test material1,1,1-trichloroethane(CAS No:- 71-55-6)can be considered to be irritating to the skin of rabbits.

Further data obtained from TSCATS low detailed report; 1992, suggests that skin irritation test was conducted on guinea pigs to evaluate the skin irritant potency of read across chemical 2,2,2-trichloroacetaldehyde (CAS No: 75-87-6). The test chemical was applied skin of guinea pigs at concentration of 2,5 and 10% of test chemical solution and the reactions were read. A 10% was strongly irritating, a 5% solution was mildly to moderately irritating, and a 2% solution was not irritating. On the basis of results obtained, it can be concluded that 2,2,2-trichloroacetaldehyde (CAS No: 75-87-6) can cause irritation at higher concentration and can be considered as irritating to the skin of guinea pigs.

Thus from the above data for target as well as its read across substance and considering the Harmonised classification of target, it can be concluded that the substance Chloral hydrate is irritating to skin and hence is classified as Skin irritant 2.

Eye irritation:

Available data for the target substance Chloral hydrate (CAS 302 -17 -0) and data for its read across substance 1,1,1-trichloroethane (CAS 71 -55 -6) were reviewed to classify the target substance for eye irritation. The same is presneted below as weight of evidence approach:

Available data from autgoritative database HSDB indicates moderate doses of chloral hydrate affects eye movements, particularly interfering with convergence, and sometimes causing ptosis. It may cause swelling of lids, hyperemia and edema of the conjunctivae, plus a sensation of irritation and tearing.

Supporting the above data, the data from IPCS monograph - EHS criteria -136 ;1990 and OECD HPV dossier-2009, indicates an eye irritation study of read across substance 1, 1, 1-trichloroethane (CAS No: 71-55-6) was conducted in rabbits to observe its irritation efficacy.The inhibited and unhibited material was installed in rabbit's eye by introducing two drops of liquid onto the right eyeball. Visual observations of irritation and corneal injury (both internal and external) were made upon the treated eye at the following times after treatment: three minutes, one hour, and one, two, and seven days. A 5% water solution of fluorescein dye was used to stain and render visible the external injury of the cornea in all observations after the first (three minutes). One application of uninhibited or inhibited 1,1,1-trichloroethane caused slight to moderate pain, slight conjunctival irritation but essentially no corneal damage. On the basis of observed effects,1,1,1-trichloroethane(CAS No:- 71-55-6) can be considered as slightly irritating to the eye of rabbits.

Further from the same source an eye irritation study of 1, 1, 1 -trichloroethane (CAS No: 71-55-6) was conducted in rabbits to observe its irritation efficacy. In this test, 0.1ml of 1,1,1- trichloroethane was applied into one eye and observations were made for 14 days. Moderate conjunctivitis is noted. Epithelial keratitis was observed at day 7, but resolved by day 14. Since the chemical produced slight ocular lesions,1,1,1-trichloroethane(CAS No:- 71-55-6)can be considered as slightly irritating to the rabbits’ eye.

Thus from the above data for target as well as its read across substance, by applying weight of evidence approach and considering the Harmonised classification of target, it can be concluded that the substance Chloral hydrate is irritating to eye and hence is classified as Eye irritant 2.

Justification for classification or non-classification

Based on the above data for target as well as its read across substance and considering the Harmonised classification of target, it can be concluded that the substance Chloral hydrate is irritating to skin and eye and hence is classified as Skin irritant 2 and Eye irritant 2.