Calcium (S)-2-hydroxypropionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1987-06-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

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

Specific details on test material used for the study:

- 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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 120 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 361 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 518 - <= 3 191

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 301 mg/kg bw

Based on:

test mat.

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:

other: 2000 mg/kg 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.

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

Interpretation of results:

other: CLP criteria not met

Conclusions:

Calcium chloride is not toxic when tested for acute oral toxicity in rats. The LD50 is higher than 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study conducted according to OECD TG 401, groups of young Crj:CF(SD) rats (5/sex/dose) were given single oral doses of calcium chloride in water of 2000, 2800 and 3920 mg/kg bw and were observed for 14 days. Mortality occured in all three dosage groups.

Based on the results from this study, an oral LD50 in rats was determined to be 2120 mg/kg bw for males and 2361 mg/kg bw for females (combined LD50 = 2301 mg/kg bw). In accordance with CLP Regulation 1272/2008 no classifcation for acute oral toxicity is warranted based on the LD50 values (greater 2000 mg/kg bw).