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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 open access journal

Data source

Reference
Reference Type:
publication
Title:
Toxicology of Chloral Hydrate in the Mouse
Author:
Virginia M. Sanders,* Bernadine M. Kauffmann,* Kimber L. White, Jr.,* Kathryn A. Douglas,* Donald W. Barnes,t Larry E. Sain,* Thomas J. Bradshaw,*Joseph F. Borzelleca* and Albert E. Munson
Year:
1982
Bibliographic source:
Environmental Health Perspectives Vol. 44, pp. 137-146, 1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The purpose of this study was to evaluate the acute and subchronic toxicology of chloral hydrate in the random-bred CD-1 mouse, to provide data for risk assessment.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Chloral Hydrate
- Molecular formula (if other than submission substance): C2 H3C13O2
- Molecular weight (if other than submission substance): 165.403 g/mol
- Smiles notation (if other than submission substance):C(C(O)O)(Cl)(Cl)Cl
- InChl (if other than submission substance):1S/C2H3Cl3O2/c3-2(4,5)1(6)7/h1,6-7H
- Substance type: Organic
- Physical state: crystalline
-Purity-99%

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA.
- Age at study initiation:6 week old
- Weight at study initiation: No data available
- Fasting period before study: 18 hr
- Housing: Mice were housed four per cage in plastic shoebox cages containing sawdust bedding (PWI Hardwood Sawdust, Lowville, N.Y.).
- Diet (e.g. ad libitum): Agway Lab Chow ad libitum
- Water (e.g. ad libitum):drinking water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%):40-60%
- Air changes (per hr):No data available
- Photoperiod (hrs dark / hrs light): The light/dark cycle was maintained on 12-hr intervals.

IN-LIFE DATES: From: To:No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0, 300, 600, 900, 1200, 1500 and 1800 mg/kg
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle: No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: 0.01 mL/g bw

DOSAGE PREPARATION (if unusual): Solutions of chloral hydrate were prepared fresh daily in deionized water

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A 14 day range finding study was conducted using chloral hydrate by oral gavage at doses of 14.4 and 144 mg/Kg which were 1/100 and 1/10 the LD50 value.
Doses:
0, 300, 600, 900, 1200, 1500 and 1800 mg/kg
No. of animals per sex per dose:
8/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Following gavage, the mice were observed continuously for 4 hr and then twice daily for 14 days.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, Neurobehavioral and gross pathology were examined.
Statistics:
Log probit analysis was used to determine the LD50, 95% confidence limits and the LOG probit slope.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
1 265 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 097 - <= 1 405
Sex:
male
Dose descriptor:
LD50
Effect level:
1 442 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 290 - <= 1 605
Mortality:
Find the details in tables mentioned below for male and female.
Clinical signs:
Within 10 min of gavage, the mice became sedated at the low doses, while at the intermediate and higher doses, the animals became lethargic and exhibited loss of righting reflex. Respiration was markedly inhibited with the higher dosages; this inhibition appeared to be the immediate cause of death.

For female:
Within 10 min of gavage, the mice became sedated at the low doses, while at the intermediate and higher doses, the animals became lethargic and exhibited loss of righting reflex. Respiration was markedly inhibited with the higher dosages; this inhibition appeared to be the immediate cause of death.
Body weight:
No data available
Gross pathology:
Animals necropsied after death showed gastric hypermia, but were otherwise unremarkable.
Other findings:
No data available

Any other information on results incl. tables

Table for results on mortality:(for male)

Concentration mg/kg

Mortality observed (8)

1200

1

1500

4

Table for results on mortality:(for female)

Concentration mg/kg

Mortality observed (8)

1200

3

1500

7

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Acute oral LD50 value for the test compound Chloral hydrate in random bred CD1- male mice is 1442 mg/kg/bw with 95% C.I. (1290-1605 mg/kg/bw ) and 1265 mg/kg/bw with 95% C.I. (1097-1405 mg/Kg/bw) in female mice.
Executive summary:

Acute oral toxicity study was conducted on random-bred CD-1 male/female mice to evaluate the toxicity effect of the test compound Chloral hydrate during the 14 days study period.

 

Seven doses of the test compound were administered: 0, 300, 600, 900, 1200, 1500 and 1800 mg/kg. Eight mice of each sex were in each dose group. Following gavage, the mice were observed for behavioral and toxicological effects and gross pathology was performed at the end of 14 days.

 

Within 10 min of gavage, the mice became sedated at the low doses, while at the intermediate and higher doses, the animals became lethargic and exhibited loss of righting reflex. Respiration was markedly inhibited with the higher dosages; this inhibition appeared to be the immediate cause of death. Animals necropsied after death showed gastric hypermia, but were otherwise unremarkable. Most deaths occurred within 4 hr at the highest dose. At lower dosages, some deaths occurred after 4 hr, with all deaths occurring within 24 hr.

Acute oral LD50 value for the test compound Chloral hydrate in random bred  CD1- male mice is 1442 mg/kg/bw  with 95% C.I. (1290-1605  mg/kg/bw ) and 1265  mg/kg/bw  with 95% C.I. (1097-1405 mg/Kg/bw) in female mice.

Acute toxicity of chloral hydrate to rat by oral (gavage) route indicates that chloral hydrate is likely to exhibit acute toxicity by the oral route in Toxicity Category IV as per the CLP classification criteria. However, the chemical has harmonized classification as Acute toxicity 3 (oral route) and this dossier agrees to the harmonized classification as per the CLP regulation.