Reaction mass of cobalt sulphide and nickel sulphide and trinickel disulphide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Comparative Acute Toxicity of Four Nickel Compounds to F344 Rat Lung

Author:

Benson JM, Henderson RF, McClellan RO, Hanson RL, Rebar AH

Year:

1986

Bibliographic source:

FUNDAMENTAL AND APPLIED TOXICOLOGY. 7: 340-347

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Rats were intubated and exposed to Ni3S2 by instillation. Tissues were harvested and analyzed at 1 and 7 days post exposure.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trinickel disulphide

EC Number:

234-829-6

EC Name:

Trinickel disulphide

Cas Number:

12035-72-2

Molecular formula:

Ni3S2

IUPAC Name:

trinickel disulfide

Details on test material:

- Name of test material (as cited in study report): Ni3S2
- Analytical purity: 97%

Test animals

Species:

rat

Strain:

other: F344/Crl

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lovelace Inhalation Toxicology Research Institute facility
- Age at study initiation: 12-15 wks
- Weight at study initiation: 250 g
- Housing:2-3 per cage in polycarbonate cages with sterilized hardwood chip bedding and filter tops.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22 C
- Humidity (%): 20-50%
- Photoperiod (hrs dark / hrs light): 12 hr on 12 hr off

Administration / exposure

Route of administration:

other: intratracheal instillation

Vehicle:

physiological saline

Details on exposure:

Rats were anesthetized, using halothane, and intubated intratracheally. The dose was delivered to the lung in a maximum volume of 0.2 ml by Luer-Lok syringe through a 16-gauge Telfon catheter.

Doses:

0, 0.01, 0.1, 1.0 umol Ni

No. of animals per sex per dose:

12 male and 12 female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 1 and 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology, lung Ni concentration, biochemical analyses: lactate dehydrogenase, beta-glucuronidase, glutathione peroxidase, glutathione reductase, total protein, and sialic acid.

Statistics:

Mean values were calculated for all parameters evaluated for each exposure group, and statistical significance when compared to controls was
evaluated using Student's t test adjusted for multipe comparisons (Games, 1977). The criterion for significance was p < 0.05.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: no observable effect level

Effect level:

0.01 other: umol Ni

Remarks on result:

other: compared to control levels of lactate dehydrogenase, β-glucuronidase, glutathione peroxidase, glutathione reductase, total protein, sialic acid, total nucleated cells, neutrophils, macrophages, lymphocytes, and eosinophils

Mortality:

None.

Clinical signs:

Not applicable.

Body weight:

Not reported.

Gross pathology:

Not reported.

Other findings:

- Ni Lung burden: Ni lung levels were virtually identical after 1 and 7 days of exposure to 1 μmol Ni as Ni3S2 (~0.4 μmol), but elevated relative to untreated animals (1.83 nmol).

- Biochemical: Biochemical changes were also examined for lactate dehydrogenase, β-glucuronidase, glutathione peroxidase, glutathione reductase, total protein, and sialic acid.

No significant biochemical, cytological, or histopathological changes were detected in nickel-exposed animals 1 day following administration. However, all biochemical endpoints were significantly elevated after 7 days of exposure to 1 μmol Ni as Ni3S2. In addition, total protein and sialic acid were also elevated at 0.1 μmol. Total nucleated cells, neutrophils and macrophages were significantly elevated in lavage fluid at the highest dose of Ni3S2.

- Histopathology: Histopathological lesions primarily comprised of multifocal alveolitis. Scoring of this effect on a scale of 0 to 4 resulted in values less than 1 (very mild) at the low and intermediate doses but 3 (moderate alveolitis) at the highest dose.

Any other information on results incl. tables

Summary of Select Responses to Ni3S2

	Mean Percent Control Response						Mean Cells x 10^3/g Lung					Mean (SD)
umol Ni	LDH	BG	GP	GR	TP	SA	TN	N	M	L	E	Alveolitis
0							1200	8.5	1200	0	0	0.17 (0.2)
0.01	110	110	100	110	110	90	1200	16.4	1200	1	0	0.17 (0.2)
0.1	170	150	140	120	310*	270*	1300	7.5	1300	2.7	0	0.83 (0.4)
1.0	490*	400*	240*	280*	210*	260*	1800*	380*	1400*	0	0	3.0 (0.3)*

*, significantly different from control

LDH, lactate dehydrogenase; BG, β-glucuronidase; GP, glutathione peroxidase; GR, glutathione reductase; TP, total protein; SA, sialic acid; TN, total nucleated cells; N, neutrophils, M, macrophages, L, lymphocytes, E, eosinophils

Applicant's summary and conclusion

Conclusions:

Among the Ni compounds in this study, acute toxicity was ranked as Ni3S2 = NiSO4 = NiCl2 >> NiO.

Executive summary:

Benson et al. (1986) reported on the acute toxicity of Ni3S2 and other nickel compounds instilled into the lungs of rodents. Compounds were dissolved in physiological saline to 0, 0.01, 0.1, and 1.0 μmol Ni and administered in a 0.2 mL volume in anesthetized intubated F344 rats. Ninety-six rats were exposed to each compound (or vehicle) and were sacrificed at 1 and 7 days post exposure. At each time point, 6 animals (3 male and 3 female) were used to determine the concentration of Ni remaining in the lung via atomic absorption spectrophotometry. In 6 additional animals, the right lung lobe was lavaged for cellular and biochemical analyses and the left lobe fixed for histopathological examination. Levels of Ni in the lung were virtually identical after 1 and 7 days of exposure to 1 μmol Ni as Ni3S2 (~0.4 μmol), but elevated relative to untreated animals (1.83 nmol). Biochemical changes were also examined for lactate dehydrogenase, β-glucuronidase, glutathione peroxidase, glutathione reductase, total protein, and sialic acid.

No significant biochemical, cytological, or histopathological changes were detected in nickel-exposed animals 1 day following administration. However, all biochemical endpoints were significantly elevated after 7 days of exposure to 1 μmol. In addition, total protein and sialic acid were also elevated at 0.1 μmol. Total nucleated cells, neutrophils and macrophages were significantly elevated in lavage fluid at the highest dose of Ni3S2. Histopathological lesions primarily comprised of multifocal alveolitis. Scoring of this effect on a scale of 0 to 4 resulted in values less than 1 (very mild) at the low and intermediate doses but 3 (moderate alveolitis) at the highest dose. Collectively, these data indicate dose-related toxicity associated with exposure to Ni3S2. Among the Ni compounds in this study, acute toxicity was ranked as Ni3S2 ≈ NiSO4 ≈ NiCl2 >> NiO. STUDY RATED BY AN INDEPENDENT REVIEWER