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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, minor restrictions in reporting (lacking information on test substance purity), but otherwise acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Calcium chloride
EC Number:
233-140-8
EC Name:
Calcium chloride
Cas Number:
10043-52-4
Molecular formula:
CaCl2
IUPAC Name:
calcium dichloride
Details on test material:
- Name of test material (as cited in study report): calcium chloride
- Physical state: solid in the form of grey chips, received in a plastic bottle with a screw top
- Analytical purity: no data
- Date of receipt: 23rd February 1987
- Storage condition of test material: in the dark at room temperature

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, England
- Weight at study initiation: males 107-127 g, females 106-121 g
- Fasting period before study: overnight
- Housing: in groups of 5, by sex, in grid bottomed popypropylene cages
- Diet: pelleted diet (SQC Rat and Mouse Maintenance Diet No. 1, Expanded, Special Diets Services Limited, Witham, England), as libitum
- Water (e.g. ad libitum): Mains tap water, in polypropylene bottles, ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 34-68, except one occasion when it rose to 75%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw

DOSAGE PREPARATION (if unusual): the test article was formulated freshly on the day of use in distilled water. For each dose level separately, a weighed amount of test article was made up to the required final volume. Preparations were mixed thoroughly by use of a pestle and mortar before use and shaking during use
Doses:
In the range-finding study: 2000, 2800, 3920, 5490 and 7680 mg/kg bw
In the main study: 2000, 2800 and 3920 mg/kg bw
No. of animals per sex per dose:
In the range-finding study: 2/sex/dose
In the main study: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed continuously for the first 30 min after dosing and then 1, 2 and 4 hours after dose administration on day 1. Subsequently, animals were observed at least once daily for all visible signs of reaction to treatment and twice daily for mortality and morbidity. Animals were weighed on days 1, 8 and 15 of the sutdy. In addition, decedent animals were weighed at necropsy.
- Necropsy of survivors performed: yes
Statistics:
The acute oral median lethal dose and 95% fiducial limits were calculated using a probit method (Finney, D. J. (1964), Statistical Methods for Biological Assay, 2nd Edition, London, Charles Griffin). Values were calculated for each sex separately and also for combined male and female animals.

Results and discussion

Preliminary study:
All animals dosed 2000 mg/kg bw survived. One out of 2 animals of each sex dosed at 2800 mg/kg bw died. Dose levels of 3920 and 7860 mg/kg bw caused death.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 120 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
2 361 mg/kg bw
95% CL:
>= 1 518 - <= 3 191
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 301 mg/kg bw
95% CL:
>= 1 455 - <= 2 781
Mortality:
2000 mg/kg bw: 2 males and one female were found dead on day 2 of the study.
2800 mg/kg bw: one male died on the day of dosing. Two males and 4 females were found dead on day 2 of the study, during which a further male died.
3920 mg/kg bw: one male died within one hour of dosing, a futher male died within 4 hours. Two males and 3 females were found dead on day 1 of the study after the 4 hour observation time. The remaining two females were found dead on day 2.
Clinical signs:
2000 mg/lg bw: all animals showed lethargy, incoordination and piloerection on day 1 between 1 and 4 hours after dosing. In addition, hunced posture was seen in 4 females and excessive salivation in one male. Clinical signs observed on day 2 were piloerection in 3 males and 4 females, lethargy in 2 males and isolated incidences of hunched posture and cranial fur staining in males. Piloerection was seen in 2 males until day 5 and in one male on day 6 as was lethargy until day 6. Surviving males were normal from day 7, surviving females from day 3.
2800 mg/kg bw: the main clinical signs observed on day 1 were lethargy, incoordination, piloerection and hunched posture in all animals and diarrhoea in a few. Hypothermia was seen in 2 males and lateral recumbency in one male. On day 2 additional clinical signs were dyspnoea in 2 males and periorbital fur staining in one. Most clinical signs regressed by day 6 in the surviving male and day 3 in the female. However, piloerection persisted in both animals until day 10. Lethargy was seen in the male on days 6 to 9 and recurred with piloerection on days 14 and 15.
3920 mg/kg bw: lethargy, incoordination, piloerection and hunched posture were the main clinical signs on day 1. Cranial fur staining was seen in most females and generalised fur staining in one. Isolated incidences of prostration, tremors, dyspnoea and bradypnoea were seen in males. The surviving males showed cranial fur staining until day 5, piloerection until day 10 and lethargy on days 2 and 6.
Body weight:
The bodyweight in each surviving male dosed 2800 and 3920 mg/kw bw was reduced compared to the group average for those dosed 2000 mg/kg bw. Bodyweight gains in surviving females were comparable. No significant weight loss was seen in decedents.
Gross pathology:
Pale and inflated lungs, reddened and thickened stomach mucosa with rugae absent, reddened mucosa with jejenum and fluid distension of the gastro-intestinal tract were observed at necropsy in decedents. The incidence of these increased with increasing dose level. In addition, red fluid contents were seen in one animal dosed 3920 mg/kg bw. An accetuated lobular pattern was seen in the livers of one animal dosed 2800 mg/kg bw and 3 dosed 3920 mg/kg bw.
In 4 animals examined at terminal necropsy the liver was pale, the stomach showed adhesions to the liver and had a thickened mucosa. In 2 animals the stomach contents were gelatinous.

Applicant's summary and conclusion