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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 May 2010 - 16 Juni 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministery of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
calcium dinitrate tetrahydrate
EC Number:
603-865-8
Cas Number:
13477-34-4
Molecular formula:
Ca(NO3)2*4H20
IUPAC Name:
calcium dinitrate tetrahydrate
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): Calcium nitrate tetrahydrate
- Substance type: White flakes
- Physical state: Solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 12 weeks old
- Weight at study initiation: body weights variation did not exceed +/- 20% of the sex mean.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted roden diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimatization period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 – 21.5ºC
- Humidity (%): 41 - 81%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:2000 mg/kg (10 mL/kg) body weight and 300 mg/kg (10 mL/kg) body weight in water.
- Justification for choice of vehicle:The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
Doses:
2000 mg/kg (10 mL/kg) body weight.
300 mg/kg (10 mL/kg) body weight.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs At periodic intervals (0, 2 and 4 hours) on the day of dosing (Day 1) and once daily thereafter, until Day 15.
Body weights Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed:Mortality/Viability, clinical signs, body weight,

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals at 2000 mg/kg were found dead on Day 2 and no mortality occurred at 300 mg/kg.
Clinical signs:
other: Clinical signs observed during the study period were as follows: Dose level Clinical signs 2000 mg/kg Lethargy, flat and/or hunched posture, slow breathing and/or piloerection were noted in all animals on Day 1. In addition the surviving animal showed hun
Gross pathology:
One animal that died on Day 2 at 2000 mg/kg showed many dark red foci in the glandular mucosa of the stomach and gelatinous state of the glandular mucosa. No abnormalities were found at macroscopic post mortem examination of the animals at 300 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Classified as Category 4 according to Regulation (EC) 1272/2008
Conclusions:
The oral LD50 value of CALCIUM NITRATE TETRAHYDRATE in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.


Based on these results:
-according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007), CALCIUM NITRATE TETRAHYDRATE should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.
-according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, CALCIUM NITRATE TETRAHYDRATE should be classified as Category 4 and should be labeled as H302: Harmful if swallowed