Matte, nickel

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 30 - November 20, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Reference 2

Reference Type:

publication

Title:

Acute Oral Toxicity of Nickel Compounds

Author:

Henderson RG, Durando J, Oller A, Merkel DJ, Marone PA, and Bates HK.

Year:

2012

Bibliographic source:

Regul Toxicol and Pharmacol (doi.org/10.1016/j.yrtph.2012.02.002)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Matte, nickel

EC Number:

273-749-6

EC Name:

Matte, nickel

Cas Number:

69012-50-6

Molecular formula:

Not applicable

IUPAC Name:

Nickel matte

Details on test material:

- Name of test material (as cited in study report): nickel matte, Code #N101
- Physical state: grey, black course granules
- Composition of test material, percentage of components: Nickel Subsulfides <60%, Nickel Iron Sulfides <40%, Copper >10%, Cobalt <1%, Arsenic <0.1%, and Magnesium Oxide 4%.
- Solubility: insoluble in water
- Expiration date of the lot/batch: Not Applicable
- Stability under test conditions: test substance was expected to be stable for the duration of testing
- Storage condition of test material: stored under nitrogen
- Test substance preparation: The test substance was ground in a coffee mill (Cuisinart, Model #DCG-20) every time prior to dosing. A tissue homogenizer (Tissue Tearor, Biospec, Model 985370) was used to facilitate the preparation of a homogeneous mixture.
- Other: Documentation of the methods, synthesis, fabrication, or derivation of the test substance retained by Sponsor.

Test animals

Species:

rat

Strain:

other: Sprague-Dawley derived, albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA. July 21, August 4, and 26, 2009.
- Age at study initiation: young adult (9-10 weeks).
- Weight at study initiation: 177-201 grams at experiment start
- Fasting period before study: overnight prior to dosing
- Housing: singly housed in suspended stainless steel caging with mesh floors; litter paper was placed beneath the cage and was changed at least three times per week
- Diet (e.g. ad libitum): Purina Rodent Chow #5012 ad libitum
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: 6-15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24 °C
- Humidity (%): Test 1: 51-78%
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: test substance administered as a 50% w/w mixture in a 0.5 % w/w mixture of CMC in distilled water

Doses:

790, 1000, 1260, 1580, 2000, 2510, 3200, 4000, and 5000 mg/kg bw

No. of animals per sex per dose:

1 female at each dose of 790 -4000 mg/kg bw nickel matte
3 females at 5000 mg/kg bw nickel matte

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: cage-side observations during the first several hours post-dosing and at least once daily thereafter for 14 days
- Necropsy of survivors performed: yes; gross necropsies performed on all animals, tissues and organs of the thoracic and abdominal cavities were examined
- Other examinations performed: clinical signs, body weight, other: individual body weights were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing. Cage-side observations included mortality, signs of gross toxicity, and behavioral changes including: gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

The Acute Oral Toxicity(Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LDso and confidence limit calculations.

Results and discussion

Preliminary study:

All animals survived (short-term and long-term outcomes indicated “survival”)

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

All animals survived

Clinical signs:

other: No signs of abnormal behavior were observed. All animals appeared active and healthy during the study.

Gross pathology:

No signs of gross toxicity or adverse pharmacologic effects were observed. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

Not Applicable

Any other information on results incl. tables

Main Test - Weight and Survival Outcomes

Dose Sequence	Animal No.	Dose Level (mg/kg)	Short-term Outcome	Long-term Outcome	BW-I	BW-7D	BW-14D
1	3101	790	Survived	Survived	177	193	244
2	3102	1,000	Survived	Survived	177	193	231
3	3103	1,260	Survived	Survived	201	260	283
4	3104	1,580	Survived	Survived	195	216	244
5	3105	2,000	Survived	Survived	180	229	253
6	3106	2,510	Survived	Survived	179	201	220
7	3107	3,200	Survived	Survived	178	193	208
8	3108	4,000	Survived	Survived	181	212	233
9	3109	5,000	Survived	Survived	180	222	246
10	3110	5,000	Survived	Survived	192	223	250
11	3111	5,000	Survived	Survived	201	228	253

BW-I, Initial Body weight (grams) BW-7D, Body weight at 7 day (grams) BW-14D, Body weight at 14 day (grams). All animals healthy and active after 14 days. No gross abnormalities at necropsy for any animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

Under the conditions of this study, the acute oral LD50 of nickel matte is estimated to be greater than 5,000 milligrams per kilogram of body weight in female rats.

Executive summary:

Eurofins Product Safety Laboratory (EPSL) reported the findings of the acute oral toxicity of nickel matte as determined by the acute toxicity up and down procedures in female rats (carried out according to OECD Test # 425 guidelines and using GLP standards). The Main Test included the following dose levels: 790, 1000, 1260, 1580, 2000, 2510, 3200, 4000, and 5000 mg/kg bw. Young adult female rats were administered a single gavage dose of nickel matte (Code #N101, described as grey, black course granules). The test substance was administered as a 50% w/w mixture in a 0.5% w/w mixture of CMC in distilled water. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily; body weight was monitored prior to dosing and again on Days 7 and 14, and all animals were necropsied following death or at study termination (Day 14). Following a single oral exposure to nickel matte , all animals survived, gained body weight, and appeared healthy and active during the study. No signs of gross toxicity, adverse pharmacologic effects, abnormal behavior, or gross abnormalities were observed. Under the conditions of these studies, the acute oral LD50 of nickel matte was estimated to be greater than 5,000 milligrams per kilogram of body weight in female rats. STUDY RATED BY AN INDEPENDENT REVIEWER