reaction mass of neodymium carbonate and praseodymium carbonate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29-MAY-2013 to 10-FEB-2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in compliance with GLP and according to the OECD guideline 436.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

yes

Remarks:

(see below)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

yes

Remarks:

(see below)

Principles of method if other than guideline:

Deviations:
The temperatures in the inhalation chamber were slightly increased (not more than +1.0°C) during the second part of the exposure (from 1h45 of the 4-h exposure period) and thus exceeded the required range of 22 ± 3°C.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

reaction mass of neodymium carbonate and praseodymium carbonate

Molecular formula:

(Nd,Pr)2 (CO3)3

IUPAC Name:

reaction mass of neodymium carbonate and praseodymium carbonate

Constituent 2

Reference substance name:

937-221-5

IUPAC Name:

937-221-5

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: 336-353 g (males); 203-213 g (females)
- Fasting period before study: No
- Housing: 3 animals per polycarbonate solid floor cage (type III) with stainless steel mesh lids (L x W x H in cm = 38 x 38 x 18)
- Diet: Ad libitum, ssniff SM R/M "Autoclavable complete feed for rats and mice - breeding and maintenance" (sniff Spezialdiäten GmbH, Soest, Germany)
- Water: Ad libitum, tap water from the muncipal supply
- Acclimation period: At least 5 days prior to involvement in the study (additional acclimation to the test apparatus [restrain procedures] for a short period prior to testing to lessen the stress during exposure)
- Other: Lignocel Hygienic Animal Bedding (J. Rettenmaier & Söhne GmbH + Co.KG, Rosenberg, Germany)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): At least 15 air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 h of continuous artificial light in each 24-h period (from 6.00 a.m. to 6 p.m.)

IN-LIFE DATES: From 17-OCT-2013 to 07-NOV-2013

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only exposure unit (TSE Systems GmbH, Bad Homburg, Germany)
- Exposure chamber volume: 3.85 L
- Method of holding animals in test chamber: Animals held in polycarbonate restraint tubes located around the chamber
- Source and rate of air: At least 0.5 L/min (with O2 > 19% and CO2 < 1%)
- Method of conditioning air: No data available
- System of generating particulates/aerosols: In a dust generator according to Wright (TSE GmbH, Bad Homburg, Germany) located at the top of the exposure chamber
- Method of particle size determination: 7-stage cascade impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany), performed three times during the exposure period
- Treatment of exhaust air: No data available
- Temperature, humidity, pressure in air chamber: 24.1-26.0°C; 4.1-4.2% relative humidity
TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric measurements at regular intervals during exposure by pulling a suitable, known volume of test atmosphere, from the exposure chamber, through GF10 glass fibre filters (Whatman, Whatman GmbH, Dassel, Germany Ref No: 10370302 or similar)
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: analysis using a 7-stage casacde impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany); collection of samples three times during each exposure period with one during the first hour and one during the last hour (at animal's beathing zone)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.72 µm / 2.36

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Based on available test material toxicity data (from an OECD 436 study with praseodymium carbonate constituent) no morbidity or mortality was expected to occur at the dose-level of 5 mg/L. This was therefore chosen as the starting dose-level.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

5.03 mg/L (analytical concentration)

No. of animals per sex per dose:

3, by sex, per cage

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Morbidity/mortality checked twice daily, early and late during the normal working day; weighing on the day of exposure (day 0) prior to exposure, on days 1, 3, 7, 14, and at death
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs (after 1-, 2-, 3-h exposure, at least twice on the day of exposure, and then at least once daily for 14 days), body weight, macroscopic examination (of the respiratory tract notably), other: changes in skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous system, somato-motor activity, behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep, and coma

Statistics:

not included

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.03 mg/L air (analytical)

Based on:

test mat.

Mortality:

Among male and female rats exposed, no animals died during the entire study period.

Clinical signs:

other: Slight laboured respiration was observed in all exposed animals on the day of exposure. Additionally, wet fur and/or ruffled fur and/or red-brown staining were commonly observed in all animals on Day 0. All these observations were considered to be relate

Body weight:

Slight bodyweight loss (1.0-6.3%) was observed between Day 0 and Day 1 in all animals with exception of a single female rat (3843) on Day 1. All rats returned to the initial values by Day 7 at the latest.

Gross pathology:

Dark/red diffuse discoloration of the lungs was recorded in all animals at necropsy, which effect was considered to be related to the test item. No other macroscopic findings were observed in exposed animals.

Any other information on results incl. tables

Table 1: Test Atmosphere Concentrations

Exposure Duration (minutes)	Sample Volume (L)	Test Material Collected (mg)	Atmospheric Concentration of reaction mass of neodymium carbonate and praseodymium carbonate (mg/L)
0	1.0	4.86	4.86
11	1.0	4.91	4.91
23	1.0	4.97	4.97
38	1.0	5.08	5.08
51	1.0	4.82	4.82
67	1.0	5.11	5.11
82	1.0	5.06	5.06
99	1.0	4.92	4.92
114	1.0	4.97	4.97
129	1.0	5.29	5.29
144	1.0	5.08	5.08
164	1.0	5.31	5.31
177	1.0	4.99	4.99
188	1.0	4.86	4.86
200	1.0	4.94	4.94
215	1.0	5.29	5.29
230	1.0	5.09	5.09

 

Mean achieved atmosphere concentration: 5.03 mg/L (standard deviation 0.15)

 

Nominal Concentration

- Amount of test material used: 117.11 g

- Total volume of air used: 5360 L

- Nominal concentration: 21.85 mg/L

 

Table 2: Test atmosphere particle size distribution data

Stage Number	Cut Point (µm)	Amount Collected (mg)					Total Collected per Stage (mg)
		Sample 1		Sample 2	Sample 3
1	10.550	0.14		0.40	0.39		0.93
2	6.655	0.13		0.43	0.45		1.01
3	3.555	0.69		1.65	1.45		3.79
4	2.105	1.01		2.26	2.11		5.38
5	1.550	0.50		0.94	0.81		2.25
6	0.960	0.34		0.54	0.51		1.39
7	0.550	0.22		0.25	0.29		0.76
Filter	< 0.550	0.27		0.31	0.30		0.88
Total Amount Collected (mg)							16.39
Size Range (µm)			Total Mass/stage (mg)			Cumulative Mass (%)
< 0.550			0.88			5.37
0.550 – 0.960			0.76			10.01
0.960 – 1.550			1.39			18.49
1.5550 – 2.105			2.25			32.21
2.105 – 3.555			5.38			65.04
3.555 – 6.655			3.79			88.16
6.655 – 10.550			1.01			94.33
> 10.550			0.93			100.00

 

MMAD: 2.72 µm

Geometric standard deviation: 2.36

Predicted amount <4 µm: 67.3%

 

Table 3: Individual Bodyweights

Animal Sex and Number	Bodyweight (g) on days					Bodyweight gain (g) between days
	0	1	3	7	14	0-1	1-3	3-7	0-7	7-14	0-14
Male 3826	336	315	330	368	402	-21	15	38	32	34	66
Male 3827	340	330	340	378	413	-10	10	38	38	35	73
Male 3828	353	331	355	390	434	-22	24	35	37	44	81
Female 3841	213	203	215	229	242	-10	12	14	16	13	29
Female 3842	203	201	212	226	240	-2	11	14	23	14	37
Female 3843	207	308	213	224	249	1	5	11	17	25	42

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The 4 hour LC50 was determined to be > 5.03 mg/L, therefore the reaction mass of neodymium carbonate and praseodymium carbonate requires no classification under the conditions of this study in accordance with EU criteria.

Executive summary:

An acute inhalation study was conducted to assess the toxicity potential of the reaction mass of neodymium carbonate and praseodymium carbonate, in accordance with the standardised OECD guideline 436.

 

Male and female Wistar rats (3 per sex) were exposed (nose only) for 4 hours to a dust atmosphere containing the test material at a mean concentration of 5.03 mg/L, with a MMAD of 2.72 µm. Following exposure, the animals were observed for 14 days for signs of mortality and toxicity. At the end of the observation period, all animals were subjected to necropsy.

 

No deaths occurred throughout the study and the 4-h LC50 was therefore determined to be > 5.03 mg/L. The reaction mass of neodymium carbonate and praseodymium carbonate requires no classification under the conditions of this study in accordance with criteria of Annex VI of Directive 67/548/EEC, Regulation (EC) No. 1272/2008 and UN GHS.