Nickel(2+) propionate

Endpoint summary

Description of key information

Read across nickel acetate tetrahydrate (CAS 6018-89-9): LD50 (oral)= 550 mg/kg bw

Read across nickel sulfate hexahydrate (CAS 10101-97-0): LD50 (inhal)= 2.48 mg/L

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the read across justification (IUCLID6, section 13).

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD0

Effect level:

175 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

>= 192 - <= 1 680

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2006

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Specific details on test material used for the study:

Ni content 24 %

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc. (Boyertown, PA)
- Females nulliparous and non-pregnant: yes
- Housing: individually in suspended stainless steel cages with mesh floors
- Diet and Water: Purina Rodent Chow #5012 and filtered tap water ad ibitum.
- Acclimation period: 7-30 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 15-87
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Doses:

175, 550 and 2000 mg/kg bw

No. of animals per sex per dose:

total number of animals: 8

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, behaviour

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations. To more accurately determine the LD50, dose progressions were completed based on a sigma equal to 0.0 or 0.1.

Sex:

female

Dose descriptor:

LD0

Effect level:

175 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

>= 192 - <= 1 680

Mortality:

Mortality (number animals dead/surviving) during the 14 day observation period was 0/2, 2/4, and 2/2 for the 175, 550, and 2000 mg/kg dose groups, respectively.

Clinical signs:

Non-specific effects, such as hypoactivity and piloerection, were observed starting at
the 550 mg/kg dose level.

Gross pathology:

Red intestines were noted at necropsy in the two highest dose groups.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value of the test substance was determined to be 550 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

550 mg/kg bw

Quality of whole database:

Publication of studies conducted according to OECD Guidelines and in compliance with GLP. Sufficient for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

For justification of read-across please refer to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Species:

rat

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.48 mg/L air

95% CL:

> 1.3 - < 4.5

Exp. duration:

4 h

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 29, 2009 to July 13, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Specific details on test material used for the study:

- Name of test material: Nickel sulfate hexahydrate
- Substance type: Soluble in water
- Physical state: blue, crystalline solid
- Expiration date of the lot/batch: not applicable
- Stability under test conditions: Stable for duration of testing
- Storage condition of test material: Stored at room temperature with a nitrogen pad inserted into container after initial testing
-The sample was aerosolized after being ground in a coffee mill (Cuisinart, Model DCG-20N) until it passed through a 425 micron USA standard testing sieve and then further ground in a ball mill for 48 hours. Nitrogen was added to the ball mill prior to grinding for 48 hours.
Documentation of the methods of synthesis, fabrication, or derivation of the test substance is retained by Sigma-Aldrich, 3050 Spruce St., St. Louis, Mo 63103.

Species:

rat

Strain:

other: Sprague-Dawley derived, albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA
- Age at study initiation: Young adult (8-10 weeks)
- Weight at study initiation: Males 242-372 grams; Females 185-241 grams
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow #5012
- Water: Tap water was supplied ad libitum by an automatic water dispensing system except during exposure.
- Acclimation period: 8, 14 or 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 57-68 %
- Air changes (per hr): 284
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Route of administration:

other: aerosolized dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Remark on MMAD/GSD:

The MMAD was estimated based on the particle size distribution as measured with an Andersen Cascade Impactor.

0.063 mg/L; MMAD=2.4 µm, GSD=2.02 (sample #1)/2.13 (sample #2)
0.53 mg/L; MMAD=3.0 µm, GSD=2.00 (sample #1)/2.03 (sample #2)
2.12 mg/L; MMAD=2.8 µm(sample #1)/2.9 um(sample #2), GSD=1.93 (sample #1)/1.97 (sample #2)
5.08 mg/L; MMAD=2.7 µm, GSD=1.83 (sample #1)/1.83 (sample #2)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Mini Nose Only Inhalation Chamber, ADG Developments LTD
- Exposure chamber volume: 6.7 liters
- Method of holding animals in test chamber: Animals individually housed in polycarbonate holding tubes
- Source and rate of air: Air compressor (JUN-AIR, Model #6-15); Compressed air tank (Airgas); Average Total Air=31.7 Lpm
- System of generating particulates/aerosols: The test substance was aerosolized using a modified Wright Dust Generator driven by a variable speedmotor (Dayton, Model #4Z538A) D.C. speed control with 0-100 potentiometer. The test substance was packed into the dust container (Wright, Model OF 183 or 183A) and compressed to 250 Ibs/in^2 (Pound-force per square inch) using a lab press (Carver, Model C). The container was then fitted with a stainless steel cutting head (Model OF 1945S or 1935S) and cutting blade (Model OF 191 SS or 1905S). Compressed air was supplied to the dust generator at 30 psi. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.
- Method of particle size determination: An eight-stage Andersen cascade impactor was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals at two intervals during each exposure. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.
- Temperature, humidity, pressure in air chamber: Temperature Range 20-23 °C; Relative Humidity Range 62-72; Average Total Air 31.7 Lpm


TEST ATMOSPHERE
- Brief description of analytical method used: Compressed airflow was measured with a Mass Flowmeter (Omega, Model #FMA-5613). Chamber airflow was monitored throughout the exposure period and recorded periodically.

The temperature and relative humidity within the exposure tube as well as the room were monitored continuously during each exposure. The measurements inside the exposure tube were made with a Humidity-Temperature Indicator (Taylor, Model #5502) and room conditions were measured with a Temperature-Humidity Monitor (Dickson, Model #TH550). Temperature and relative humidity values were recorded every 15 minutes for the first hour of exposure and every 30 minutes thereafter.

Gravimetric samples were withdrawn at six intervals from the breathing zone of the animals during each exposure. Samples were collected using 25 mm glass fiber filters (GFIB Whatman) in a filter holder attached by 1/4 inch tygon tubing to a vacuum pump (Reliance Electric, Model #G557X). Filter papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. Sample airflows were measured using a Mass Flowmeter (Omega, Model #FMA-561 0).

- Samples taken from breathing zone: yes


VEHICLE -no vehicle was used


TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD was estimated based on the particle size distribution as measured with an Andersen Cascade Impactor.

0.063 mg/L; MMAD=2.4 µm, GSD=2.02 (sample #1)/2.13 (sample #2)
0.53 mg/L; MMAD=3.0 µm, GSD=2.00 (sample #1)/2.03 (sample #2)
2.12 mg/L; MMAD=2.8 µm(sample #1)/2.9 um(sample #2), GSD=1.93 (sample #1)/1.97 (sample #2)
5.08 mg/L; MMAD=2.7 µm, GSD=1.83 (sample #1)/1.83 (sample #2)


CLASS METHOD
- Rationale for the selection of the starting concentration: Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the targeted chamber concentration and desired particle size distribution (mass median aerodynamic diameter between 1 and 4 µm).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Target Exposure levels: 0.06, 0.5, 2.0, and 5.0 mg/L
Actual (Gravimetric) Exposure levels: 0.063, 0.53, 2.12, and 5.08 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: up to 14 days or until death occurred
- Frequency of observations and weighing: Observations occurred once daily; Body weights were recorded prior to exposure and again on Days 7 and 14 or after death.
- Necropsy of survivors performed: Yes - Surviving rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all decedents and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: body weight, gross toxicity, behavioral changes, gross evaluations

Statistics:

Biostat 2007 Professional Build 3.6.0.0, AnalystSoft, BioStat - statistical analysis program, Version
2007 was used for data analysis of LC50 and confidence limit calculations.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.48 mg/L air

95% CL:

> 1.3 - < 4.5

Exp. duration:

4 h

Mortality:

Cumulative mortality observed (number of mortalities observed/total number of animals tested) at each exposure level:
0.063 mg/L: 0/5 males; 0/5 females
0.53 mg/L: 0/5 males; 0/5 females
2.12 mg/L: 1/5 males; 0/5 females (death occurred one day after exposure)
5.08 mg/L: 5/5 males; 5/5 females (1 male and 1 female death occurred in exposure chamber; remaining deaths occurred within 3 days after exposure)

Clinical signs:

other: 0.063 mg/L: Immediately following exposure and throughout the 14-day observation period all animals appeared active and healthy. 0.53 mg/L: Immediately following exposure and throughout the 14-day observation period all animals appeared active.

Body weight:

Individual body weights of the animals were recorded prior to test substance exposure (initial) and
again on Days 7 and 14 (termination) or after death.

0.063 mg/L: Although five rats failed to gain or lose body weight through Day 7, all animals gained weight over the entire observation period.
0.53 mg/L: Although one rat failed to gain body weight through Day 7, all animals gained weight over the entire observation period.
2.12 mg/L: Although two male survivors lost body weight through Day 7, all survivors gained weight over the entire observation period.
5.08 mg/L: Although there were no survivors to weigh on Day 7, all decedents except for one had a lower weight at death than their initial starting weight.

Gross pathology:

0.063 mg/L: No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
0.53 mg/L: No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
2.12 mg/L: Gross necropsy of the decedent revealed discoloration of the lungs and liver, and rigor mortis. No gross abnormalities were noted for any of the euthanized animals necropsied at the conclusion of the 14-day observation period.
5.08 mg/L: Gross necropsy of most decedents revealed discoloration of the lungs, liver and/or intestines, distention of the stomach and/or intestines, and/or rigor mortis. For one male and one female decedent the thymus appeared gray with dark spots.

Other findings:

0.063 mg/L: There were no signs ofgross toxicity, adverse pharmacologic effects, or abnormal behavior.
0.53 mg/L: There were no signs ofgross toxicity, adverse pharmacologic effects, or abnormal behavior.
2.12 mg/L: There were no additional findings.
5.08 mg/L: There were no additional findings.

NOAEC was 0.53 mg NiSO4.6H2O/L air (or 120 mg Ni/m3)

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 for the test substance as aerosolized dust derived in this study was 2.48 mg/L.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

2.48 mg/L

Physical form:

inhalation: aerosol

Quality of whole database:

OECD Guideline-study. Sufficient for assessment.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

No data on acute oral toxicity of the target substance itself is available. Therefore, read across to nickel acetate tetrahydrate (CAS 6018-89-9) was applied.

To assess the acute oral toxicity of this substance a study was conducted according to OECD Guideline 425. The test substance was administered as a solution in distilled water by gavage. Animals (female Sprague Dawley rats) were observed for mortality, signs of gross toxicity, behavioural changes, and effects on body weight for 14 days after dosing or until death occurred. All rats were euthanized and gross necropsies were performed at the end of the 14-day observation period. Mortality (number animals dead/surviving) during the 14 day observation period was 0/2, 2/4, and 2/2 for the 175, 550, and 2000 mg/kg bw dose groups, respectively. Non-specific effects, such as hypoactivity and piloerection, were observed starting at the 550 mg/kg bw dose level. Red intestines were noted at necropsy in the two highest dose groups. The oral LD50 was estimated to be 550 mg/kg bw.

Inhalation:

No data on acute respiratory toxicity of the target substance itself is available. Therefore, read across to nickel sulphate hexahydrate (CAS 10101-97-0) was applied.

A study was conducted according to OECD Guideline 403 to assess the acute toxicity of nickel sulphate hexahydrate after inhalation. . 5 male and 5 female rats per dose were therefore exposed to different concentrations of aerosolized dusts (Target Exposure levels: 0.06, 0.5, 2.0, and 5.0 mg/L; Actual (Gravimetric) Exposure levels: 0.063, 0.53, 2.12, and 5.08 mg/L). The duration of exposure was 4 hours. An LC50 value of 2.48 mg/L was determined. Based on this value the test substance has to be classified into Category 4 (H332:Harmful if inhaled) for acute toxicity after inhalation.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on these data, the substance is considered to be classified for acute oral toxicity into Cat. 4, H302 (harmful if swallowed) and for acute inhalation toxicity into Cat. 4, H332 (harmful if inhaled) under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.