Cerium(3+) neodecanoate

Endpoint summary

Description of key information

No acute toxicity studies with cerium neodecanoate are available, thus the acute toxicity will be addressed with existing data on the dissociation products cerium and neodecanoate.

Signs of acute oral toxicity are not expected for cerium neodecanoate, since the two moieties cerium and neodecanoic acid have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000mg/kg).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 4 February 1991 until 18 February 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study performed according to Code of Federal Regulations 16:1500.3 and equivalent to OECD Guideline 401.

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations 16:1500.3

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ
- Age at study initiation: no data
- Weight at study initiation: males body weight range: 217 - 228 g; females body weight range: 206-221 g
- Fasting period before study: Rats were fasted on the day before dosing for approximately 18 hours by removing feed from their cages. During fasting, water was provided ad-libitum. After the 18 hour fast period, the rats were examined and weighed again.
- Housing: Individually in suspended stainless steel caging with mesh floors.
- Diet (e.g. ad libitum): Pelleted Purina Rat Chow ad-libitum
- Water (e.g. ad libitum): Tap water supplied by automatic water system
- Acclimation period: 6, 12 or 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 °C - 22.8°C
- Humidity (%): No data
- Air changes (per hr): No data

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% w/w solution in distilled water
- Amount of vehicle (if gavage): 10 g

Doses:

The dose levels were 2500 and 3500 mg/kg

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: The rats were observed at 1, 2 and 4 hours after dosing and at least once daily thereafter for signs of gross toxicity and mortality. Body weights were recorded initially and at termination (day 14) or after death.
- Necropsy of survivors performed: yes, all survivors to termination were euthanized by CO2 inhalation. Gross necropsies were performed on all decedents.

Statistics:

LD50 calculated by the Litchfield-Wilcoxon Method of Probit Analysis; J. Pharmacology and Experimental Therapeutics 96: 99-115 (1949)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 800 mg/kg bw

Based on:

test mat.

95% CL:

2 360 - 3 320

Mortality:

Dosage 2500 mg/kg: 30% mortality occurred by day 2.
Dosage 3500 mg/kg: 90% mortality occurred by day 3.

Clinical signs:

other: Dosage 2500 mg/kg: Following test material administration all animals appeared lethargic. Most had a hunched posture and two had ano-genital staining. All surviving animals recovered from the above symptoms by day 6 and gained weight over the 14-day obser

Gross pathology:

Dosage 2500 mg/kg: Necropsy of the decedents revealed distention of the stomach with reddish-white discoloration of the pyloric region, discoloration of the intestines and dark-colored fluid in the bladder.
Dosage 3500 mg/kg: Necropsy of the decedents revealed distention of the stomach with discoloration of the pyloric region in most animals. Discoloration of the intestines and dark-colored fluid in the bladder was also noted in most animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral, single dose LD50 calculated by Probit Analysis was 2800 mg cerium trichloride per kilogram body weight with 95% confidence limits of 2360 and 3320 mg/kg. Based on the criteria of the CLP Regulation, the substance should not be classified for acute oral toxicity as the LD50 value is > 2000 mg/kg.

Reference 2

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: Study report contains limited information, pre-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1, 1.5, 2, 3, or 4 ml/kg

No. of animals per sex per dose:

4 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 10 days post dosing
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

LD50 value and 95% confidence intervals were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 066 mg/kg bw

95% CL:

1 693 - 2 530

Mortality:

Animals that died did so within 3 days post exposure.

Clinical signs:

other: Lethargy, hypothermia, piloerection, dyspnea, ataxia

Gross pathology:

No data

Other findings:

No data

4 Animals per sex per dose group

	Daily Mortality
Dose ml/kg	1		2		3
	M	F	M	F	M	F
1
1.5
2			3	1		1
3	2	1		1		1
4		1	4	3

Interpretation of results:

Toxicity Category V

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 is approximately 2.27 ml/kg (2066 mg/kg).

Executive summary:

In this study, male and female rats were gavage with neodecanoic acid at concentrations of 1, 1.5, 2, 3, or 4 ml/kg. All animals that died during the study did so within 3 days of exposure. Signs of toxicity included lethargy, hypothermia, piloerection, dyspnea, and ataxia. Based on these results, it is concluded that the LD50 is approximately 2.27 ml/kg (2066 mg/kg). 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Cerium

The acute oral toxicity of cerium chloride was assessed in an OECD 401 study conducted in Sprague Dawley rats. Cerium chloride was solved in water and dose levels of 2500 mg/kg and 3500 mg/kg were administered via gavage to five animals per sex and dose. All animals were observed for 14 days and necropsy was performed as final examination. 3 animals of the 2500 mg/kg dose level died after 2 days and 9 animals of the 3500 mg/kg dose level died after 3 days. The acute oral, single dose LD50 calculated by Probit Analysis was 2800 mg cerium chloride per kilogram body weight with 95% confidence limits of 2360 and 3320 mg/kg. Based on the criteria of the CLP Regulation, the substance should not be classified for acute oral toxicity as the LD50 value is > 2000 mg/kg.

 

Neodecanoate

Neodecanoic acid has a low potential for toxicity via the oral route. 

Male and female rats were gavaged with neodecanoic acid at concentrations of 1, 1.5, 2, 3, or 4 ml/kg to assess acute oral toxicity. All animals that died during the study did so within 3 days of exposure. Signs of toxicity included lethargy, hypothermia, piloerection, dyspnea, and ataxia. Based on these results, it is concluded that the LD50 is approximately 2.27 ml/kg (2066 mg/kg). 

Cerium neodecanoate

Signs of acute oral toxicity are not expected for cerium neodecanoate, since the two moieties cerium and neodecanoic acid have not shown signs of acute oral toxicity in experimental testing (both LD50 > 2000mg/kg). Under the assumption that the moieties of cerium neodecanoate show their toxicological profile individually upon dissolution, the acute oral (systemic) toxicity of cerium neodecanoate can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

A study for acute toxicity via inhalation was not conducted with cerium neodecanoate, since it is produced and placed on the market in a form in which no inhalation hazard is anticipated, thus acute toxic effects are not likely to occur during manufacture and handling of that substance. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

The calculated oralLD50 for cerium neodecanoate is >2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

Justification for classification or non-classification

Based on in vivo oral LD50 data on the moieties, acute toxicity estimates for cerium neodecanoate have been calculated resulting in LD50 values > 2000 mg/kg bw.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, cerium neodecanoate does neither have to be classified and has no obligatory labelling requirement for acute oral toxicity nor for specific target organ toxicity after single exposure (STOT SE).