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Description of key information

Based on a reliable acute oral toxicity study (OECD 423) the LD50 is determined to be >300 mg/kg bw and <2000 mg/kg bw for CN-Nitcal. No reliable acute dermal toxicity study is available. An acute dermal toxicity study with Nitcal-K showed an LD50>2000 mg/kg bw.  An acute inhalation study is not considered necessary as the vapour pressure is assumed to be very low and the particle size of CN-Nitcal is very high with an MMAD > 2000 micrometer. The read-across rationale can be found in the document attached to the target record.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 14 - October 3, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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 Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Wistar strain Crl:WI
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 176 - 221 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): ad libitum to pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany)
- Water (e.g. ad libitum): ad libitum to tap water
- Acclimation period: at least 5 days before start of treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.8
- Humidity (%): 46 - 91
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 14 September 2006 To: 03 October 2006
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: see dosage preparation
- Amount of vehicle (if gavage): see dosage preparation
- 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.
- Lot/batch no. (if required): not applicable
- Purity: not applicable


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual): The formulation (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The first group was treated at a dose level of 300 mg/kg (according to OECD 423 guideline). The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval beween the dose groups.
Doses:
300 mg/kg (10 ml/kg) body weight
2000 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: mortality: twice daily - body weight: day 1, 8, 15 and at death - clinical signs: once daily from day 1-15
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Mortality:
300 mg/kg (1 dose group) = 0/3
300 mg/kg (2 dose group) = 0/3
2000 mg/kg = 3/3
Clinical signs:
other: 300 mg/kg: Hunched posture 2000 mg/kg: Lethargy, hunged/flat posture, laboured respiration, piloerection, ptosis, hypothermia The surviving animals had recovered from the symptoms by day 2.
Gross pathology:
Abnormalities of the stomach (dark red discolouration of glandular mucosa) were found in the animals that died during the study, at macroscopic post mortem examination. No adnormalities were found in the surviving animals.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of CN-Nitcal 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 500 mg/kg body weight.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The study has klimisch code 1.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 April - 2 May 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: indivvidually in labeled Macrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8-22.9
- Humidity (%): 31-68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 April 2007 To: 02 May 2007
Type of coverage:
occlusive
Vehicle:
water
Remarks:
selection based on trial formulations
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 square cm for males and 18 square cm for females
- % coverage: 10% of total body surface
- Type of wrap if used: surgical gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with tap water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 ml/kg) body weigh
- Constant volume or concentration used: yes

Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation for clinical signs, weekly determination of body weight
- Necropsy of survivors performed: yes (macroscopic examination only)
- Other examinations performed: none
Preliminary study:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
other: Males (recovery from these signs by day 3): lethargy, flat/hunched posture, uncoordinated movements, shallow respiration, piloerection, chromodacryorrhoea (snout), ptosis, hypothermia; Females (recovery from these signs by day 3): hunched posture, chromod
Gross pathology:
No abnormalities
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an acute dermal toxicity study in rats, Nitcal /K does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to Regulation (EC) 1272/2008 and under GHS.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Additional information

Oral

In an acute oral toxicity study with rats performed according to OECD 423, EU B.1tris and EPA and JMAFF guidelines, nitric acid, ammonium calcium salt gave an LD50 of >300 and <2000 mg/kg bw. At 300 mg/kg bw no animals died, but at 2000 mg/kg bw all animals died. At 300 mg/kg bw a hunched posture was observed, at 2000 mg/kg bw, lethargy, hunged/flat posture, laboured respiration, piloerection, ptosis, hypothermia were noted. Abnormalities of the stomach (dark red discolouration of glandular mucosa) were found in the animals that died during the study, at macroscopic post mortem examination. No abnormalities were found in the surviving animals.

Dermal

No reliable study with nitric acid, ammonium calcium salt is available. In an OECD 402 acute dermal toxicity study with rats, Nitcal-K (potassium pentacalcium nitrate decahydrate) did show some signs of toxicity, but no mortality was observed at 2000 mg/kg bw. Therefore, the LD50 >2000 mg/kg bw. Clinical signs that were noted in males (recovery from these signs by day 3): lethargy, flat/hunched posture, uncoordinated movements, shallow respiration, piloerection, chromodacryorrhoea (snout), ptosis, hypothermia; Females (recovery from these signs by day 3): hunched posture, chromodacryorrhea. Treated skin showed signs of irritation (scales, scabs, maculate erythema) during observation period. The mean body weight gain during the observation period was within the expected range, no abnormalities at gross pathology, and no mortalities were noted.

Inhalation

No study is considered necessary. Nitric acid, ammonium calcium salt has an assumed very low vapour pressure, and its particle size is very high. Only 0.1% has a size <100 micrometer, and the MMAD is >2000 micrometer. Therefore, inhalation is not a likely route of exposure.

Justification for selection of acute toxicity – oral endpoint

One acute oral study is available.

Justification for selection of acute toxicity – dermal endpoint

One acute dermal study on the read-across substance Nitcal/K is available.

Justification for classification or non-classification

Based on the available data, nitric acid, ammonium calcium salt does not have to be classified according to Directive 67/548/EC and the CLP Regulation with regard to acute dermal and inhalation toxicity.

However, the substance does need to be classified according to Directive 67/548/EC with Xn, R22 'Harmful if swallowed' and according to the CLP Regulation with Cat.4, H302 'Harmful if swallowed'.