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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
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 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:
In range finding Study the toxic effect of Chloral Hydrate was observed in CD1-male mice for 14 days by gavage.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- 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
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

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA.
- Age at study initiation: 6 week old mice.
- Weight at study initiation: 25.1 ± 0.2 to 25.5 ± 0.2 g
- Fasting period before study: No data available.
- Housing: Mice were housed four per cage in plastic shoebox cages containing sawdust bedding (PWI Hardwood Sawdust, Lowville, N.Y.). Identified by ear punching
- Diet (e.g. ad libitum): Agway Lab Chow ad libitum
- Water (e.g. ad libitum): Deionized water, ad libitum
- Acclimation period: 1 week

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

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


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Deionized water
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: Chloral hydrate was diluted in deionized water in the concentrations of 14.4 and 144 mg/kg and administered by gavage in a volume of 0.01 ml/g body weight.
Drinking water solutions were maintained at room temperature in amber-colored bottles fitted with sipper spouts and was changed twice weekly.

VEHICLE
- Justification for use and choice of vehicle (if other than water): Deionized water
- Concentration in vehicle: 0, 14.4 and 144 mg/kg body weight/day
- Amount of vehicle (if gavage): 0.01 ml/g
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Dose was analysis by using GLC and head space analysis.
Duration of treatment / exposure:
14 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0(control),14.4 and 144 mg/kg/bw/day
Basis:
no data
No. of animals per sex per dose:
Total animals: 188
Control: 68 males
14.4 mg/kg/day: 60 males
144 mg/kg/day: 60 males
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included: Mortality was observed.

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: On day 1, 8 and 15 of treatment.

FOOD CONSUMPTION : No data available

COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):
- Time schedule for examinations: No data available: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes,
- Time schedule for collection of blood: At the termination of study.
- Anaesthetic used for blood collection: Yes, chloroform was used.
- Animals fasted: No data available
- How many animals: All 188 animals were examined.
- Parameters checked in table [No.?] were examined: Hematocrit, Hemoglobin, Leukocytes, Fibrinogen and Prothombin time were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of study.
- Anaesthetic used for blood collection: Yes, chloroform was used.
- Animals fasted: No data available
- How many animals: All 188 animals were examined.
- Parameters checked in table [No.?] were examined: Lactic dehydrogenase, serum glutamic pyruvic transaminase, blood urea nitrogen were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: At the termination of study.
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available

NEUROBEHAVIOURAL
EXAMINATION: No data available

OTHER:
Organ weight: Yes

Organ examined: Brain, Liver, Spleen, Lungs, Thymus, Kidneys and Testes were examined.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes ,The organs (brain, liver, spleen, lungs, thymus, kidneys, and testes) were removed,trimmed, weighed, and gross pathological examinations were performed on all mice.
HISTOPATHOLOGY: No data available
Statistics:
Statistical analysis is performed by using one-way analysis of variance, If a one-way analysis of variance of the means showed treatment effects; a Dunnett's T-test was performed. Values which differ from vehicle control at p < 0.05 are noted. Each of the values is given as the mean +standard error (SE) of the mean.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS:No data available

MORTALITY:One male mice from both 14.4 and 144 mg/kg body weight /day died on second week.
Death were probably not compound-related since two mice of control group were also died during 14 day treatment period.

BODY WEIGHT AND WEIGHT GAIN:No effect was observed on body weight and body weight gain of treated mice as compared to control.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):No data available

FOOD EFFICIENCY:No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):No data available

OPHTHALMOSCOPIC EXAMINATION:No data available

HAEMATOLOGY:No effect was observed on Hematological and coagulation values of treated mice as compared to control.

CLINICAL CHEMISTRY:When treated with 144 mg/kg body weight/day, statistically significant decreased in lacticdehydrogenase activity were observed in treated mice as compared to control.

URINALYSIS:No data available

NEUROBEHAVIOUR:No data available

ORGAN WEIGHTS:When treated with 144 mg/kg body weight/day, significant increased in absolute and relative liver weight and significant decreased in relative spleen weight were observed as compared to control.

When treated with 14.4 mg/kg body weight/day, decreased in relative kidneys weight was observed in treated mice as compared to control.

The observed changes for 14.4 mg/kg bw/day treated mice are not significantly different from control.

GROSS PATHOLOGY:Increase in liver size and decrease in spleen size were observed in 144 mg/kg bw/day treated mice as compared to control.

Changes were also observed in 14.4 mg/kg bw/day treated mice but the changes are not significantly different from control.


HISTOPATHOLOGY: NON-NEOPLASTIC:No data available

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
14.4 other: mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No adverse effect on Body weight and weight gain, haematology, clinical chemistry, organ weights and gross pathology.

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 14.4 mg/kg bw/day in male mice when exposed to Chloral Hydrate for 14 days by (oral) gavage.
Executive summary:

In repeated dose toxicity study, Random – bred CD1 male mice were exposed to Chloral Hydrate by oral gavage in the concentrations of 0 (control), 14.4 and 144 mg/kg//body weight/day.

Result shows statistically significant decreased in  lactic dehydrogenase activity, increased  in absolute and relative liver weight and significant decreased in relative spleen weight. In addition, Increase in liver size and decrease in spleen size was observed in 144 mg/kg bw/day treated mice as compared to control. Changes were also observed in organ weight and gross pathology of 14.4 mg/kg bw/day treated mice but the changes are not significantly different from control.

Therefore, NOAEL was considered to be 14.4 mg/kg body weight/day in male mice when exposed to Chloral Hydrate for 14 days by oral gavage.